Cardiovascular studies using the chimpanzee (Pan troglodytes)

NASA Technical Reports Server (NTRS)

Hinds, J. E.; Cothran, L. N.; Hawthorne, E. W.

1977-01-01

Despite the phylogenetic similarities between chimpanzees and man, there exists a paucity of reliable data on normal cardiovascular function and the physiological responses of the system to standard interventions. Totally implanted biotelemetry systems or hardwire analog techniques were used to examine the maximum number of cardiovascular variables which could be simultaneously monitored without significantly altering the system's performance. This was performed in order to acquire base-line data not previously obtained in this species, to determine cardiovascular response to specific forcing functions such as ventricular pacing, drug infusions, and lower body negative pressure. A cardiovascular function profile protocol was developed in order to adjust independently the three major factors which modify ventricular performance, namely, left ventricular performance, left ventricular preload, afterload, and contractility. Cardiac pacing at three levels above the ambient rate was used to adjust end diastolic volume (preload). Three concentrations of angiotensin were infused continuously to evaluate afterload in a stepwide fashion. A continuous infusion of dobutamine was administered to raise the manifest contractile state of the heart.

Cardiovascular response to acute normovolemic hemodilution in patients with coronary artery diseases: Assessment with transesophageal echocardiography.

PubMed

Licker, Marc; Ellenberger, Christoph; Sierra, Jorge; Christenson, Jan; Diaper, John; Morel, Denis

2005-03-01

Preoperative acute normovolemic hemodilution induces an increase in circulatory output that is thought to be limited in patients with cardiac diseases. Using multiple-plane transesophageal echocardiography, we investigated the mechanisms of cardiovascular adaptation during acute normovolemic hemodilution in patients with severe coronary artery disease. Prospective case-control study. Operating theater in a university hospital. Consecutive patients treated with beta-blockers, scheduled to undergo coronary artery bypass (n = 50). After anesthesia induction, blood withdrawal and isovolemic exchange with iso-oncotic starch (1:1.15 ratio) to achieve a hematocrit value of 28%. In addition to heart rate and intravascular pressures, echocardiographic recordings were obtained before and after acute normovolemic hemodilution to assess cardiac preload, afterload, and contractility. In a control group, not subjected to acute normovolemic hemodilution, hemodynamic variables remained stable during a 20-min anesthesia period. Following acute normovolemic hemodilution, increases in cardiac stroke volume (+28 +/- 4%; mean +/- sd) were correlated with increases in central venous pressure (+2.0 +/- 1.3 mm Hg; R = .56) and in left ventricular end-diastolic area (+18 +/- 5%, R = .39). The unchanged left ventricular end-systolic wall stress and preload-adjusted maximal power indicated that neither left ventricular afterload nor contractility was affected by acute normovolemic hemodilution. Diastolic left ventricular filling abnormalities (15 of 22 cases) improved in 11 patients and were stable in the remaining four patients. Despite reduction in systemic oxygen delivery (-20.5 +/- 7%, p < .05), there was no evidence for myocardial ischemia (electrocardiogram, left ventricular wall motion abnormalities). In anesthetized patients with coronary artery disease, moderate acute normovolemic hemodilution did not compromise left ventricular systolic and diastolic function. Lowering blood viscosity resulted in increased stroke volume that was mainly related to increased venous return and higher cardiac preload.

Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy

USDA-ARS?s Scientific Manuscript database

Chronic hypobaric hypoxia (CHH) increases load on the right ventricle (RV) resulting in RV hypertrophy. We hypothesized that CHH elicits distinct responses, i.e., the hypertrophied RV, unlike the left ventricle (LV), displaying enhanced mitochondrial respiratory and contractile function. Wistar rats...

Short-term in vivo inhibition of nitric oxide synthase with L-NAME influences the contractile function of single left ventricular myocytes in rats.

PubMed

Lunz, Wellington; Natali, Antônio José; Carneiro, Miguel Araújo; Dos Santos Aggum Capettini, Luciano; Baldo, Marcelo Perim; de Souza, Matheus Ornelas; Quintão, Judson Fonseca; Bozi, Luiz Henrique Marchesi; Lemos, Virginia Soares; Mill, José Geraldo

2011-04-01

The main purpose of this study was to investigate the effects of short-term L-NAME treatment on the contractile function of left ventricle (LV) myocytes and the expression of proteins related to Ca(2+) homeostasis. Data from Wistar rats treated with L-NAME (L group, n = 20; 0.7 g/L in drinking water; 7 days) were compared with results from untreated controls (C group, n = 20). Cardiomyocytes from the L group showed increased (p < 0.05) fractional shortening (23%) and maximum rate of shortening (20%) compared with the C group. LV from the L group also showed increased (p < 0.05) expression of the ryanodine receptor 2 and Na(+)/Ca(2+) exchanger proteins (76% and 83%, respectively; p < 0.05). However, the L and C groups showed similar in vivo hemodynamic parameters of cardiac function. In conclusion, short-term NOS inhibition determines an increased expression of Ca(2+) regulatory proteins, which contributes to improving cardiomyocyte contractile function, preserving left ventricular function.

Afterload mismatch in aortic and mitral valve disease: implications for surgical therapy.

PubMed

Ross, J

1985-04-01

In the management of patients with valvular heart disease, an understanding of the effects of altered loading conditions on the left ventricle is important in reaching a proper decision concerning the timing of corrective operation. In acquired valvular aortic stenosis, concentric hypertrophy generally maintains left ventricular chamber size and ejection fraction within normal limits, but in late stage disease function can deteriorate as preload reserve is lost and aortic stenosis progresses. In this setting, even when the ejection fraction is markedly reduced (less than 25%), it can improve to normal after aortic valve replacement, suggesting that afterload mismatch rather than irreversibly depressed myocardial contractility was responsible for left ventricular failure. Therefore, patients with severe aortic stenosis and symptoms should not be denied operation because of impaired cardiac function. In chronic severe aortic and mitral regurgitation, operation is generally recommended when symptoms are present, but whether to recommend operation to prevent irreversible myocardial damage in patients with few or no symptoms has remained controversial. In aortic regurgitation, left ventricular function generally improves postoperatively, even if it is moderately impaired preoperatively, indicating correction of afterload mismatch. Most such patients can be carefully followed by echocardiography. However, in some patients, severe left ventricular dysfunction fails to improve postoperatively. Therefore, when echocardiographic studies in the patient with severe aortic regurgitation show an ejection fraction of less than 40% (fractional shortening less than 25%) plus enlarging left ventricular end-diastolic diameter (approaching 38 mm/m2 body surface area) and end-systolic diameter (approaching 50 mm or 26 mm/m2), confirmation of these findings by cardiac catheterization and consideration of operation are advisable even in patients with minimal symptoms. In chronic mitral regurgitation, maintenance of a normal ejection fraction can mask depressed myocardial contractility. Pre- and postoperative studies in such patients have shown a poor clinical result after mitral valve replacement, associated with a sharp decrease in the ejection fraction after operation. This response appears to reflect unmasking of decreased myocardial contractility by mitral valve replacement, with ejection of the total stroke volume into the high impedance of the aorta (afterload mismatch produced by operation).(ABSTRACT TRUNCATED AT 400 WORDS)

The overloaded right heart and ventricular interdependence.

PubMed

Naeije, Robert; Badagliacca, Roberto

2017-10-01

The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Single plane angiography: Current applications and limitations

NASA Technical Reports Server (NTRS)

Falsetti, H. L.; Carroll, R. J.

1975-01-01

Technical errors in measurement of one plane cineangiography are identified. Examples of angiographic estimates of left ventricular geometry are given. These estimates of contractility are useful in evaluating myocardial performance.

Left ventricular function during lower body negative pressure

NASA Technical Reports Server (NTRS)

Ahmad, M.; Blomqvist, C. G.; Mullins, C. B.; Willerson, J. T.

1977-01-01

The response of the human left ventricle to lower body negative pressure (LBNP) and the relation between left ventricular function and hemodynamic response were investigated. Ventricular function curves relating stroke volume to end-diastolic volume were obtained in 12 normal men. Volume data were derived from echocardiographic measurements of left ventricular end-systolic and end-diastolic diameters at rest and during lower body negative pressure (LBNP) at minus 40 mm Hg. End-diastolic volume decreased by 19% and stroke volume by 22%. There were no significant changes in heart rate, arterial blood pressure, or end-systolic volume. Thus, moderate levels of LBNP significantly reduce preload and stroke volume without affecting contractile state. The absence of significant changes in heart rate and arterial blood pressure in the presence of a significant reduction in stroke volume is consistent with an increase in systemic peripheral resistance mediated by low-pressure baroreceptors.

Use of a Doppler pulmonary artery catheter for continuous measurement of right ventricular pump function and contractility during single lung transplantation.

PubMed

Heerdt, P M; Pond, C G; Kussman, M K; Triantafillou, A N

1993-01-01

Despite numerous technologic advances in intraoperative monitoring, the only methods routinely available for assessment of right ventricular function in lung transplant recipients are continuous measurement of right heart pressures and intermittent thermodilution determination of cardiac output and ejection fraction. Additional data may now be obtained with transesophageal echocardiography, although this technology is expensive and not widely available and requires diverting attention from a potentially unstable patient for data acquisition and analysis. Recently, a Doppler pulmonary artery catheter was introduced that measures beat-to-beat pulmonary artery blood flow-velocity, cross sectional area, and volume flow. Because of data indicating that acceleration of blood in the pulmonary artery (measured as the first derivative of either the velocity or flow waveform) is a sensitive indicator of right ventricular contractility, we have used waveforms obtained with the catheter for assessment of right ventricular pump function (stroke volume and peak pulmonary artery flow rate) and contractility in heart surgery patients. We report here our experience with this method in two patients undergoing left single lung transplantation.

Relative refractoriness of left ventricular contraction underlies human tachycardia-induced mechanical and electrical alternans.

PubMed

Kashimura, Takeshi; Kodama, Makoto; Watanabe, Tohru; Tanaka, Komei; Hayashi, Yuka; Ohno, Yukako; Obata, Hiroaki; Ito, Masahiro; Hirono, Satoru; Hanawa, Haruo; Minamino, Tohru

2014-02-01

Mechanical alternans (MA) and electrical alternans (EA) are predictors of cardiac events. Experimental studies have suggested that refractoriness of calcium cycling underlies these cardiac alternans. However, refractoriness of left ventricular contraction has not been examined in patients with cardiac alternans. In 51 patients with miscellaneous heart diseases, incremental right atrial pacing was performed to induce MA and EA. MA was quantified by alternans amplitude (AA: the difference between left ventricular dP/dt of a strong beat and that of a weak beat), and AA at 100/min (AA100) and maximal AA (AAmax) were measured. EA was defined as alternation of T wave morphology in 12-lead electrocardiogram. Relative refractoriness of left ventricular contraction was examined by drawing the mechanical restitution curve under a basal coupling interval (BCL) of 600 ms (100/min) and was assessed by the slope at BCL (Δmechanical restitution). Postextrasystolic potentiation (PESP) was also examined and the slope of PESP curve (ΔPESP) was assessed as a property to alternate strong and weak beats. MA and EA were induced in 19 patients and in none at 100/min or less, and at any heart rate in 32 and in 10, respectively. AA100 and AAmax correlated positively with Δmechanical restitution and negatively with ΔPESP. Patients with EA had a significantly larger Δmechanical restitution and a significantly larger absolute value of ΔPESP than those without. In patients with MA and EA, the left ventricular contractile force during tachycardia is under relative refractoriness and prone to cause large fluctuation of contractile force. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

Relationship between shortening load, contractility, and myocardial energetics in intact dog.

PubMed

Dell'Italia, L J; Evanochko, W T; Blackwell, G G; Pearce, D J; Pohost, G M

1993-06-01

A canine model was developed to estimate left ventricular wall stress, volumes, contractility, and high-energy phosphate metabolites without the need for major surgery. A percutaneously inserted catheter-tip manometer was used to record high-fidelity left ventricular pressure while gradient echo cinemagnetic resonance (cine-MR) imaging alternated with in vivo 31P-nuclear magnetic resonance (NMR) spectroscopy during pharmacological maneuvers to increase cardiac work. Left ventricular circumferential wall stress, volumes, maximum rate of pressure development (dP/dtmax), and the ratio of phosphocreatine (PCr) to gamma-ATP (PCr/gamma-ATP) were recorded sequentially during control 1, dobutamine infusion, control 2, angiotensin infusion, and control 3 in five anesthetized, closed-chest dogs. PCr/gamma-ATP did not change significantly during controls 1-3, angiotensin, and dobutamine infusion. Left ventricular peak positive dP/dt (+dP/dtmax) increased significantly during dobutamine (3,338 +/- 831 mmHg/s, P < 0.001) but was unchanged during angiotensin (1,818 +/- 317 mmHg/s) and controls 1-3 (1,915 +/- 434 vs. 1,808 +/- 478 vs. 1,859 +/- 414 mmHg/s). However, dobutamine decreased the total systolic stress integral (area under the wall stress-time relationship) and end-diastolic and end-systolic volumes, whereas angiotensin increased these parameters compared with control conditions. The unchanged PCr/gamma-ATP is in accord with the results from other open-chest surface coil 31P-NMR experiments in the normal heart. Our assessment of left ventricular functional parameters provides new information that complements these more invasive studies in which heart rate-pressure product was measured during increases in cardiac work.(ABSTRACT TRUNCATED AT 250 WORDS)

WEB downloadable software for training in cardiovascular hemodynamics in the (3-D) stress echo lab

PubMed Central

2010-01-01

When a physiological (exercise) stress echo is scheduled, interest focuses on wall motion segmental contraction abnormalities to diagnose ischemic response to stress, and on left ventricular ejection fraction to assess contractile reserve. Echocardiographic evaluation of volumes (plus standard assessment of heart rate and blood pressure) is ideally suited for the quantitative and accurate calculation of a set of parameters allowing a complete characterization of cardiovascular hemodynamics (including cardiac output and systemic vascular resistance), left ventricular elastance (mirroring left ventricular contractility, theoretically independent of preload and afterload changes heavily affecting the ejection fraction), arterial elastance, ventricular arterial coupling (a central determinant of net cardiovascular performance in normal and pathological conditions), and diastolic function (through the diastolic mean filling rate). All these parameters were previously inaccessible, inaccurate or labor-intensive and now become, at least in principle, available in the stress echocardiography laboratory since all of them need an accurate estimation of left ventricular volumes and stroke volume, easily derived from 3 D echo. Aims of this paper are: 1) to propose a simple method to assess a set of parameters allowing a complete characterization of cardiovascular hemodynamics in the stress echo lab, from basic measurements to calculations 2) to propose a simple, web-based software program, to learn and training calculations as a phantom of the everyday activity in the busy stress echo lab 3) to show examples of software testing in a way that proves its value. The informatics infrastructure is available on the web, linking to http://cctrainer.ifc.cnr.it PMID:21073738

Detrimental effect of hypothermia during acute normovolaemic haemodilution in anaesthetized cats

NASA Astrophysics Data System (ADS)

Talwar, A.; Fahim, Mohammad

Haemodynamic responses to hypothermia were studied at normal haematocrit and following the induction of acute normovolaemic haemodilution. Experiments were performed on 20 cats anaesthetized with a mixture of chloralose and urethane in two groups. In one group (n=10) the effects of hypothermia on various haemodynamic variables were studied at normal haematocrit (41.0+/-1.7%) and in the second group of cats (n=10) the effects of hypothermia on various haemodynamic variables were studied after the induction of acute normovolaemic haemodilution (14.0+/-1.0%). The haemodynamic variables left ventricular pressure, left ventricular contractility, arterial blood pressure, heart rate and right atrial pressure were recorded on a polygraph. Cardiac output was measured using a cardiac output computer. In both groups hypothermia was induced by surface cooling with the help of ice. Cardiovascular variables were recorded at each 1° C fall in body temperature. Hypothermia produced a significant (P<0.05) drop in heart rate, cardiac output, arterial blood pressure and left ventricular contractility in both groups. However, the percentage decrease in these variables in response to hypothermia was significantly (P<0.05) higher in cats with low haematocrit than in those with normal haematocrit. The severity of hypothermia - induced cardiovascular effects is evident from the drastic decrease in heart rate, cardiac output, arterial blood pressure and myocardial contractility in cats with low haematocrit, indicating a higher risk of circulatory failure under anaemic conditions at low temperatures.

Assessment of left ventricular myocardial deformation by cardiac MRI strain imaging reveals myocardial dysfunction in patients with primary cardiac tumors.

PubMed

Chen, Jing; Yang, Zhi-Gang; Xu, Hua-Yan; Shi, Ke; Guo, Ying-Kun

2018-02-15

To assess left ventricular myocardial deformation in patients with primary cardiac tumors. MRI was retrospectively performed in 61 patients, including 31 patients with primary cardiac tumors and 30 matched normal controls. Left ventricular strain and function parameters were then assessed by MRI-tissue tracking. Differences between the tumor group and controls, left and right heart tumor groups, left ventricular wall tumor and non-left ventricular wall tumor groups, and tumors with and without LV enlargement groups were assessed. Finally, the correlations among tumor diameter, myocardial strain, and LV function were analyzed. Left ventricular myocardial strain was milder for tumor group than for normal group. Peak circumferential strain (PCS) and its diastolic strain rate, longitudinal strains (PLS) and its diastolic strain rates, and peak radial systolic and diastolic velocities of the right heart tumor group were lower than those of the left heart tumor group (all p<0.050), but the peak radial systolic strain rate of the former was higher than that of the latter (p=0.017). The corresponding strains were lower in the left ventricular wall tumor groups than in the non-left ventricular wall tumor group (p<0.050). Peak radial systolic velocities were generally higher for tumors with LV enlargement than for tumors without LV enlargement (p<0.050). Peak radial strain, PCS, and PLS showed important correlations with the left ventricular ejection fraction (all p<0.050). MRI-tissue tracking is capable of quantitatively assessing left ventricular myocardial strain to reveal sub-clinical abnormalities of myocardial contractile function. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanical Circulatory Support of the Right Ventricle for Adult and Pediatric Patients With Heart Failure.

PubMed

Chopski, Steven G; Murad, Nohra M; Fox, Carson S; Stevens, Randy M; Throckmorton, Amy L

2018-05-10

The clinical implementation of mechanical circulatory assistance for a significantly dysfunctional or failing left ventricle as a bridge-to-transplant or bridge-to-recovery is on the rise. Thousands of patients with left-sided heart failure are readily benefitting from these life-saving technologies, and left ventricular failure often leads to severe right ventricular dysfunction or failure. Right ventricular failure (RVF) has a high rate of mortality caused by the risk of multisystem organ failure and prolonged hospitalization for patients after treatment. The use of a blood pump to support the left ventricle also typically results in an increase in right ventricular preload and may impair right ventricular contractility during left ventricular unloading. Patients with RVF might also suffer from severe pulmonary dysfunction, cardiac defects, congenital heart disease states, or a heterogeneity of cardiophysiologic challenges because of symptomatic congestive heart failure. Thus, the uniqueness and complexity of RVF is emerging as a new domain of significant clinical interest that motivates the development of right ventricular assist devices. In this review, we present the current state-of-the-art for clinically used blood pumps to support adults and pediatric patients with right ventricular dysfunction or failure concomitant with left ventricular failure. New innovative devices specifically for RVF are also highlighted. There continues to be a compelling need for novel treatment options to support patients with significant right heart dysfunction or failure.

Temporal Fourier analysis applied to equilibrium radionuclide cineangiography. Importance in the study of global and regional left ventricular wall motion.

PubMed

Cardot, J C; Berthout, P; Verdenet, J; Bidet, A; Faivre, R; Bassand, J P; Bidet, R; Maurat, J P

1982-01-01

Regional and global left ventricular wall motion was assessed in 120 patients using radionuclide cineangiography (RCA) and contrast angiography. Functional imaging procedures based on a temporal Fourier analysis of dynamic image sequences were applied to the study of cardiac contractility. Two images were constructed by taking the phase and amplitude values of the first harmonic in the Fourier transform for each pixel. These two images aided in determining the perimeter of the left ventricle to calculate the global ejection fraction. Regional left ventricular wall motion was studied by analyzing the phase value and by examining the distribution histogram of these values. The accuracy of global ejection fraction calculation was improved by the Fourier technique. This technique increased the sensitivity of RCA for determining segmental abnormalities especially in the left anterior oblique view (LAO).

Testosterone deficiency prevents left ventricular contractility dysfunction after myocardial infarction.

PubMed

Ribeiro Júnior, R F; Ronconi, K S; Jesus, I C G; Almeida, P W M; Forechi, L; Vassallo, D V; Guatimosim, S; Stefanon, I; Fernandes, A A

2018-01-15

Testosterone may affect myocardial contractility since its deficiency decreases the contraction and relaxation of the heart. Meanwhile, testosterone replacement therapy has raised concerns because it may worsen cardiac dysfunction and remodeling after myocardial infarction (MI). In this study, we evaluate cardiac contractility 60 days after MI in rats with suppressed testosterone. Male Wistar rats underwent bilateral orchidectomy one week before the ligation of the anterior descending left coronary artery. The animals were divided into orchidectomized (OCT); MI; orchidectomized + MI (OCT + MI); orchidectomized + MI + testosterone (OCT + MI + T) and control (Sham) groups. Eight weeks after MI, papillary muscle contractility was analyzed under increasing calcium (0.62, 1.25, 2.5 and 3.75 mM) and isoproterenol (10 -8 to 10 -2  M) concentrations. Ventricular myocytes were isolated for intracellular calcium measurements and assessment of Ca 2+ handling proteins. Contractility was preserved in the orchidectomized animals after myocardial infarction and was reduced when testosterone was replaced (Ca 2+ 3.75 mM: Sham: 608 ± 70 (n = 11); OCT: 590 ± 37 (n = 16); MI: 311 ± 33* (n = 9); OCT + MI: 594 ± 76 (n = 7); OCT + MI + T: 433 ± 38* (n=4), g/g *p < 0.05 vs Sham). Orchidectomy also increased the Ca 2+ transient amplitude of the ventricular myocytes and SERCA-2a protein expression levels. PLB phosphorylation levels at Thr 17 were not different in the orchidectomized animals compared to the Sham animals but were reduced after testosterone replacement. CAMKII phosphorylation and protein nitrosylation increased in the orchidectomized animals. Our results support the view that testosterone deficiency prevents MI contractility dysfunction by altering the key proteins involved in Ca 2+ handling. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of commonly used inotropes on myocardial function and oxygen consumption under constant ventricular loading conditions

PubMed Central

DeWitt, Elizabeth S.; Black, Katherine J.; Thiagarajan, Ravi R.; DiNardo, James A.; Colan, Steven D.; McGowan, Francis X.

2016-01-01

Inotropic medications are routinely used to increase cardiac output and arterial blood pressure during critical illness. However, few comparative data exist between these medications, particularly independent of their effects on venous capacitance and systemic vascular resistance. We hypothesized that an isolated working heart model that maintained constant left atrial pressure and aortic blood pressure could identify load-independent differences between inotropic medications. In an isolated heart preparation, the aorta and left atrium of Sprague Dawley rats were cannulated and placed in working mode with fixed left atrial and aortic pressure. Hearts were then exposed to common doses of a catecholamine (dopamine, epinephrine, norepinephrine, or dobutamine), milrinone, or triiodothyronine (n = 10 per dose per combination). Cardiac output, contractility (dP/dtmax), diastolic performance (dP/dtmin and tau), stroke work, heart rate, and myocardial oxygen consumption were compared during each 10-min infusion to an immediately preceding baseline. Of the catecholamines, dobutamine increased cardiac output, contractility, and diastolic performance more than clinically equivalent doses of norepinephrine (second most potent), dopamine, or epinephrine (P < 0.001). The use of triiodothyronine and milrinone was not associated with significant changes in cardiac output, contractility or diastolic function, either alone or added to a baseline catecholamine infusion. Myocardial oxygen consumption was closely related to dP/dtmax (r2 = 0.72), dP/dtmin (r2 = 0.70), and stroke work (r2 = 0.53). In uninjured, isolated working rodent hearts under constant ventricular loading conditions, dobutamine increased contractility and cardiac output more than clinically equivalent doses of norepinephrine, dopamine, and epinephrine; milrinone and triiodothyronine did not have significant effects on contractility. PMID:27150829

Passive and active ventricular elastances of the left ventricle

PubMed Central

Zhong, Liang; Ghista, Dhanjoo N; Ng, Eddie YK; Lim, Soo T

2005-01-01

Background Description of the heart as a pump has been dominated by models based on elastance and compliance. Here, we are presenting a somewhat new concept of time-varying passive and active elastance. The mathematical basis of time-varying elastance of the ventricle is presented. We have defined elastance in terms of the relationship between ventricular pressure and volume, as: dP = EdV + VdE, where E includes passive (Ep) and active (Ea) elastance. By incorporating this concept in left ventricular (LV) models to simulate filling and systolic phases, we have obtained the time-varying expression for Ea and the LV-volume dependent expression for Ep. Methods and Results Using the patient's catheterization-ventriculogram data, the values of passive and active elastance are computed. Ea is expressed as: ; Epis represented as: . Ea is deemed to represent a measure of LV contractility. Hence, Peak dP/dt and ejection fraction (EF) are computed from the monitored data and used as the traditional measures of LV contractility. When our computed peak active elastance (Ea,max) is compared against these traditional indices by linear regression, a high degree of correlation is obtained. As regards Ep, it constitutes a volume-dependent stiffness property of the LV, and is deemed to represent resistance-to-filling. Conclusions Passive and active ventricular elastance formulae can be evaluated from a single-beat P-V data by means of a simple-to-apply LV model. The active elastance (Ea) can be used to characterize the ventricle's contractile state, while passive elastance (Ep) can represent a measure of resistance-to-filling. PMID:15707494

Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat.

PubMed

Garjani, Alireza; Andalib, Sina; Biabani, Sajjad; Soraya, Hamid; Doustar, Yousef; Garjani, Afagh; Maleki-Dizaji, Nasrin

2011-09-01

The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 ± 94 to +1588 ± 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 ± 190 to -2939 ± 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 ± 1 and 4 ± 1.4 versus 8 ± 3.5 and 14 ± 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration. Copyright © 2011 Elsevier B.V. All rights reserved.

Diastolic blood pressure-estimated left ventricular dp/dt.

PubMed

Yilmaz, Hüseyin; Minareci, Kenan; Kabukçu, Mehmet; Sancaktar, Oktay

2002-02-01

Peak dp/dt is one of the best isovolumic phase indexes of the myocardial contractile state requiring invasive procedures or presence of mitral regurgitation severe enough to measure in clinical practice by Doppler echocardiography. In this study, we sought the correlation between two noninvasive methods of measurements for left ventricular dp/dt-diastolic blood pressure- (DBP) estimated and continuous-wave Doppler-derived dp/dt-min electrocardiographic/echocardiographic study to emphasize the clinical feasibility of the DBP-estimated method. Thirty-six randomized patients (27 male, 9 female; 58 +/- 8 years) with mild mitral regurgitation were enrolled in this study. DBP-estimated dp/dt was calculated from DBP minus the left ventricular end-diastolic pressure (LVEDP) over the isovolumetric contraction time (IVCT). LVEDP was assumed to be 10 mmHg for all patients. Doppler-determined left ventricular dp/dt was derived from the continuous-wave Doppler spectrum of mitral regurgitation jet by dividing the magnitude of the left ventricular atrial pressure gradient rise between 1 mm/sec-3 mm/sec of mitral regurgitant velocity signal by the time taken for this change. Left ventricular dp/dt by Doppler was 1122 +/- 303 mmHg/sec and blood pressure-estimated dp/dt was 1063 +/- 294 mmHg/sec. There was a high correlation (r = 0.97, P < 0.001) of dp/dt between the two techniques. DBP and IVCT can generate left ventricular dp/dt without invasive procedures, even in the absence of mitral regurgitation in clinical practice.

First report on an inotropic peptide activating tetrodotoxin-sensitive, "neuronal" sodium currents in the heart.

PubMed

Kirchhof, Paulus; Tal, Tzachy; Fabritz, Larissa; Klimas, Jan; Nesher, Nir; Schulte, Jan S; Ehling, Petra; Kanyshkova, Tatayana; Budde, Thomas; Nikol, Sigrid; Fortmueller, Lisa; Stallmeyer, Birgit; Müller, Frank U; Schulze-Bahr, Eric; Schmitz, Wilhelm; Zlotkin, Eliahu; Kirchhefer, Uwe

2015-01-01

New therapeutic approaches to improve cardiac contractility without severe risk would improve the management of acute heart failure. Increasing systolic sodium influx can increase cardiac contractility, but most sodium channel activators have proarrhythmic effects that limit their clinical use. Here, we report the cardiac effects of a novel positive inotropic peptide isolated from the toxin of the Black Judean scorpion that activates neuronal tetrodotoxin-sensitive sodium channels. All venoms and peptides were isolated from Black Judean Scorpions (Buthotus Hottentotta) caught in the Judean Desert. The full scorpion venom increased left ventricular function in sedated mice in vivo, prolonged ventricular repolarization, and provoked ventricular arrhythmias. An inotropic peptide (BjIP) isolated from the full venom by chromatography increased cardiac contractility but did neither provoke ventricular arrhythmias nor prolong cardiac repolarization. BjIP increased intracellular calcium in ventricular cardiomyocytes and prolonged inactivation of the cardiac sodium current. Low concentrations of tetrodotoxin (200 nmol/L) abolished the effect of BjIP on calcium transients and sodium current. BjIP did not alter the function of Nav1.5, but selectively activated the brain-type sodium channels Nav1.6 or Nav1.3 in cellular electrophysiological recordings obtained from rodent thalamic slices. Nav1.3 (SCN3A) mRNA was detected in human and mouse heart tissue. Our pilot experiments suggest that selective activation of tetrodotoxin-sensitive neuronal sodium channels can safely increase cardiac contractility. As such, the peptide described here may become a lead compound for a new class of positive inotropic agents. © 2014 American Heart Association, Inc.

Oxidative stress contributes to methamphetamine-induced left ventricular dysfunction.

PubMed

Lord, Kevin C; Shenouda, Sylvia K; McIlwain, Elizabeth; Charalampidis, Dimitrios; Lucchesi, Pamela A; Varner, Kurt J

2010-07-01

Our aim was to test the hypothesis that the repeated, binge administration of methamphetamine would produce oxidative stress in the myocardium leading to structural remodeling and impaired left ventricular function. Echocardiography and Millar pressure-volume catheters were used to monitor left ventricular structure and function in rats subjected to four methamphetamine binges (3 mg/kg, iv for 4 days, separated by a 10-day drug-free period). Hearts from treated and control rats were used for histological or proteomic analysis. When compared with saline treatment, four methamphetamine binges produced eccentric left ventricular hypertrophy. The drug also significantly impaired systolic function (decreased fractional shortening, ejection fraction, and adjusted maximal power) and produced significant diastolic dysfunction (increased -dP/dt and tau). Dihydroethedium staining showed that methamphetamine significantly increased (285%) the levels of reactive oxygen species in the left ventricle. Treatment with methamphetamine also resulted in the tyrosine nitration of myofilament (desmin, myosin light chain) and mitochondrial (ATP synthase, NADH dehydrogenase, cytochrome c oxidase, prohibitin) proteins. Treatment with the superoxide dismutase mimetic, tempol in the drinking water prevented methamphetamine-induced left ventricular dilation and systolic dysfunction; however, tempol (2.5 mM) did not prevent the diastolic dysfunction. Tempol significantly reduced, but did not eliminate dihydroethedium staining in the left ventricle, nor did it prevent the tyrosine nitration of mitochondrial and contractile proteins. This study shows that oxidative stress plays a significant role in mediating methamphetamine-induced eccentric left ventricular dilation and systolic dysfunction.

Oxidative stress contributes to methamphetamine-induced left ventricular dysfunction

PubMed Central

Lord, Kevin C.; Shenouda, Sylvia K.; McIlwain, Elizabeth; Charalampidis, Dimitrios; Lucchesi, Pamela A.; Varner, Kurt J.

2010-01-01

Aims Our aim was to test the hypothesis that the repeated, binge administration of methamphetamine would produce oxidative stress in the myocardium leading to structural remodeling and impaired left ventricular function. Methods and results Echocardiography and Millar pressure–volume catheters were used to monitor left ventricular structure and function in rats subjected to four methamphetamine binges (3 mg/kg, iv for 4 days, separated by a 10-day drug-free period). Hearts from treated and control rats were used for histological or proteomic analysis. When compared with saline treatment, four methamphetamine binges produced eccentric left ventricular hypertrophy. The drug also significantly impaired systolic function (decreased fractional shortening, ejection fraction, and adjusted maximal power) and produced significant diastolic dysfunction (increased −dP/dt and tau). Dihydroethedium staining showed that methamphetamine significantly increased (285%) the levels of reactive oxygen species in the left ventricle. Treatment with methamphetamine also resulted in the tyrosine nitration of myofilament (desmin, myosin light chain) and mitochondrial (ATP synthase, NADH dehydrogenase, cytochrome c oxidase, prohibitin) proteins. Treatment with the superoxide dismutase mimetic, tempol in the drinking water prevented methamphetamine-induced left ventricular dilation and systolic dysfunction; however, tempol (2.5 mM) did not prevent the diastolic dysfunction. Tempol significantly reduced, but did not eliminate dihydroethedium staining in the left ventricle, nor did it prevent the tyrosine nitration of mitochondrial and contractile proteins. Conclusion This study shows that oxidative stress plays a significant role in mediating methamphetamine-induced eccentric left ventricular dilation and systolic dysfunction. PMID:20139112

Congenital left ventricular wall abnormalities in adults detected by gated cardiac multidetector computed tomography: clefts, aneurysms, diverticula and terminology problems.

PubMed

Erol, Cengiz; Koplay, Mustafa; Olcay, Ayhan; Kivrak, Ali Sami; Ozbek, Seda; Seker, Mehmet; Paksoy, Yahya

2012-11-01

Our aim was to evaluate congenital left ventricular wall abnormalities (clefts, aneurysms and diverticula), describe and illustrate imaging features, discuss terminology problems and determine their prevalence detected by cardiac CT in a single center. Coronary CT angiography images of 2093 adult patients were evaluated retrospectively in order to determine congenital left ventricular wall abnormalities. The incidence of left ventricular clefts (LVC) was 6.7% (141 patients) and statistically significant difference was not detected between the sexes regarding LVC (P=0.5). LVCs were single in 65.2% and multiple in 34.8% of patients. They were located at the basal to mid inferoseptal segment of the left ventricle in 55.4%, the basal to mid anteroseptal segment in 24.1%, basal to mid inferior segment in 17% and septal-apical septal segment in 3.5% of cases. The cleft length ranged from 5 to 22 mm (mean 10.5 mm) and they had a narrow connection with the left ventricle (mean 2.5 mm). They were contractile with the left ventricle and obliterated during systole. Congenital left ventricular septal aneurysm that was located just under the aortic valve was detected in two patients (0.1%). No case of congenital left ventricular diverticulum was detected. Cardiac CT allows us to recognize congenital left ventricular wall abnormalities which have been previously overlooked in adults. LVC is a congenital structural variant of the myocardium, is seen more frequently than previously reported and should be differentiated from aneurysm and diverticulum for possible catastrophic complications of the latter two. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Minoxidil accelerates heart failure development in rats with ascending aortic constriction.

PubMed

Turcani, M; Jacob, R

1998-06-01

To test the ability of the heart to express characteristic geometric features of concentric and eccentric hypertrophy concurrently, constriction of the ascending aorta was performed in 4-week-old rats. Simultaneously, these rats were treated with an arteriolar dilator minoxidil. An examination 6 weeks after induction of the hemodynamic overload revealed no signs of congestion in systemic or pulmonary circulation in rats with aortic constriction or minoxidil-treated sham-operated rats. The magnitude of hemodynamic overload caused by aortic constriction or minoxidil treatment could be considered as equivalent, because the same enlargement of left ventricular pressure-volume area was necessary to compensate for either pressure or volume overload. Myocardial contractility decreased in rats with aortic constriction, and the compensation was achieved wholly by the marked concentric hypertrophy. Volume overload in minoxidil-treated rats was compensated partially by the eccentric hypertrophy and partially by the increased myocardial contractility. In contrast, increased lung weight and pleural effusion were found in all minoxidil-treated rats with aortic constriction. Unfavorable changes in left ventricular mass and geometry, relatively high chamber stiffness, and depressed ventricular and myocardial function were responsible for the massive pulmonary congestion.

Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in an animal model with right ventricular failure after pulmonary artery banding.

PubMed

Hyldebrandt, Janus Adler; Sivén, Eleonora; Agger, Peter; Frederiksen, Christian Alcaraz; Heiberg, Johan; Wemmelund, Kristian Borup; Ravn, Hanne Berg

2015-07-01

Right ventricular (RV) failure due to chronic pressure overload is a main determinant of outcome in congenital heart disease. Medical management is challenging because not only contractility but also the interventricular relationship is important for increasing cardiac output. This study evaluated the effect of milrinone alone and in combination with epinephrine or dopamine on hemodynamics, ventricular performance, and the interventricular relationship. RV failure was induced in 21 Danish landrace pigs by pulmonary artery banding. After 10 wk, animals were reexamined using biventricular pressure-volume conductance catheters. The maximum pressure in the RV increased by 113% (P < 0.0001) and end-diastolic volume by 43% (P < 0.002), while left ventricular (LV) pressure simultaneously decreased (P = 0.006). Concomitantly, mean arterial pressure (MAP; -16%, P = 0.01), cardiac index (CI; -23%, P < 0.0001), and mixed venous oxygen saturation (SvO2 ; -40%, P < 0.0001) decreased. Milrinone increased CI (11%, P = 0.008) and heart rate (HR; 21%, P < 0.0001). Stroke volume index (SVI) decreased (7%, P = 0.03), although RV contractility was improved. The addition of either epinephrine or dopamine further increased CI and HR in a dose-dependent manner but without any significant differences between the two interventions. A more pronounced increase in biventricular contractility was observed in the dopamine-treated animals. LV volume was reduced in both the dopamine and epinephrine groups with increasing doses In the failing pressure overloaded RV, milrinone improved CI and increased contractility. Albeit additional dose-dependent effects of both epinephrine and dopamine on CI and contractility, neither of the interventions improved SVI due to reduced filling of the LV. Copyright © 2015 the American Physiological Society.

Doppler-derived myocardial systolic strain rate is a strong index of left ventricular contractility

NASA Technical Reports Server (NTRS)

Greenberg, Neil L.; Firstenberg, Michael S.; Castro, Peter L.; Main, Michael; Travaglini, Agnese; Odabashian, Jill A.; Drinko, Jeanne K.; Rodriguez, L. Leonardo; Thomas, James D.; Garcia, Mario J.

2002-01-01

BACKGROUND: Myocardial fiber strain is directly related to left ventricular (LV) contractility. Strain rate can be estimated as the spatial derivative of velocities (dV/ds) obtained by tissue Doppler echocardiography (TDE). The purposes of the study were (1) to determine whether TDE-derived strain rate may be used as a noninvasive, quantitative index of contractility and (2) to compare the relative accuracy of systolic strain rate against TDE velocities alone. METHODS AND RESULTS: TDE color M-mode images of the interventricular septum were recorded from the apical 4-chamber view in 7 closed-chest anesthetized mongrel dogs during 5 different inotropic stages. Simultaneous LV volume and pressure were obtained with a combined conductance-high-fidelity pressure catheter. Peak elastance (Emax) was determined as the slope of end-systolic pressure-volume relationships during caval occlusion and was used as the gold standard of LV contractility. Peak systolic TDE myocardial velocities (Sm) and peak (epsilon'(p)) and mean (epsilon'(m)) strain rates obtained at the basal septum were compared against Emax by linear regression. Emax as well as TDE systolic indices increased during inotropic stimulation with dobutamine and decreased with the infusion of esmolol. A stronger association was found between Emax and epsilon'(p) (r=0.94, P<0.01, y=0.29x+0.46) and epsilon'(m) (r=0.88, P<0.01) than for Sm (r=0.75, P<0.01). CONCLUSIONS: TDE-derived epsilon'(p) and epsilon'(m) are strong noninvasive indices of LV contractility. These indices appear to be more reliable than S(m), perhaps by eliminating translational artifact.

Cardiovascular haemodynamics and cardiac autonomic control in patients with subclinical and overt hyperthyroidism.

PubMed

Petretta, M; Bonaduce, D; Spinelli, L; Vicario, M L; Nuzzo, V; Marciano, F; Camuso, P; De Sanctis, V; Lupoli, G

2001-12-01

To characterize cardiac structure and function and cardiac autonomic control in patients with subclinical and overt hyperthyroidism. Thirty patients with subclinical hyperthyroidism and 30 with overt disease were selected from patients never previously treated for endocrinological disease in the outpatient clinic of our institution. Twenty normal individuals were studied as control group. Left ventricular structure and function and cardiac autonomic control were evaluated, respectively, by two-dimensional Doppler echocardiography and by 24-h Holter recording with heart rate variability analysis. Patients with overt hyperthyroidism showed greater values of left ventricular end-diastolic volume (P<0.05) and left ventricular mass (P<0.05) than patients with subclinical disease. In addition, the mean velocity of left ventricular fibre shortening (P<0.05) and left ventricular ejection fraction (P<0.05) were greater in patients with overt hyperthyroidism than in patients with subclinical disease. No difference in any of these parameters was detectable between normal subjects and patients with subclinical disease. The isovolumic relaxation period was shorter in patients with subclinical hyperthyroidism than in control individuals (P<0.05) and in patients with overt hyperthyroidism (P<0.05). As regards cardiac autonomic control, all time and frequency domain measures decreased progressively from control individuals to patients with subclinical hyperthyroidism and those with overt disease (P<0.001). Thyrotoxic patients show changes in left ventricular structure and increased echocardiographic indexes of myocardial contractility, whereas the only echocardiographic feature detectable in patients with subclinical hyperthyroidism is an increased velocity of left ventricular relaxation. Cardiac parasympathetic withdrawal is evident in patients with overt hyperthyroidism and in patients with subclinical disease.

Cardiac AAV9-S100A1 gene therapy rescues postischemic heart failure in a preclinical large animal model

PubMed Central

Pleger, Sven T.; Shan, Changguang; Ksienzyk, Jan; Bekeredjian, Raffi; Boekstegers, Peter; Hinkel, Rabea; Schinkel, Stefanie; Leuchs, Barbara; Ludwig, Jochen; Qiu, Gang; Weber, Christophe; Kleinschmidt, Jürgen A.; Raake, Philip; Koch, Walter J.; Katus, Hugo A.; Müller, Oliver J.; Most, Patrick

2014-01-01

As a prerequisite to clinical application, we determined the long-term therapeutic effectiveness and safety of adeno-associated viral (AAV) S100A1 gene therapy in a preclinical, large animal model of heart failure. S100A1, a positive inotropic regulator of myocardial contractility, becomes depleted in failing cardiomyocytes in humans and various animal models, and myocardial-targeted S100A1 gene transfer rescues cardiac contractile function by restoring sarcoplasmic reticulum calcium Ca2+ handling in acutely and chronically failing hearts in small animal models. We induced heart failure in domestic pigs by balloon-occlusion of the left circumflex coronary artery, resulting in myocardial infarction. After 2 weeks, when the pigs displayed significant left ventricular contractile dysfunction, we administered through retrograde coronary venous delivery, AAV9-S100A1 to the left ventricular non-infarcted myocardium. AAV9-luciferase and saline treatment served as control. At 14 weeks, both control groups showed significantly decreased myocardial S100A1 protein expression along with progressive deterioration of cardiac performance and left ventricular remodeling. AAV9-S100A1 treatment prevented and reversed this phenotype by restoring cardiac S100A1 protein levels. S100A1 treatment normalized cardiomyocyte Ca2+ cycling, sarcoplasmic reticulum calcium handling and energy homeostasis. Transgene expression was restricted to cardiac tissue and extra-cardiac organ function was uncompromised indicating a favorable safety profile. This translational study shows the pre-clinical feasibility, long-term therapeutic effectiveness and a favorable safety profile of cardiac AAV9-S100A1 gene therapy in a preclinical model of heart failure. Our study presents a strong rational for a clinical trial of S100A1 gene therapy for human heart failure that could potentially complement current strategies to treat end-stage heart failure. PMID:21775667

Ventricular distension and diastolic coronary blood flow in the anaesthetized dog.

PubMed

Gattullo, D; Linden, R J; Losano, G; Pagliaro, P; Westerhof, N

1993-01-01

There appears to be no agreement as to whether or not an increase in diastolic left ventricular pressure and/or volume can cause a decrease in diastolic coronary blood flow. We investigated the problem in the anaesthetized dog using a flaccid freely distensible latex balloon inserted into the left ventricle with the animal on extracorporeal circulation and the coronary perfusion pressure constant at about 45 mm Hg. Maximal vasodilatation and suppression of autoregulation in coronary vasculature was obtained by the intracoronary infusion of dipyridamole (10-40 mg/h). Ventricular volume was changed in steps of 10 ml from 10 to 70 ml and back to 10 ml, whilst recording coronary blood flow and left ventricular pressure in the left circumflex coronary artery. Over a range of ventricular volumes from 20 to 50 ml and a concomitant rise in diastolic ventricular pressure to about 20 mm Hg there was no change in the diastolic coronary flow. Only when the ventricular volume was more than two times the control value (i.e. exceeded 50 ml) and left ventricular pressure was more than 20 mm Hg, was there a decrease in coronary flow. During the return of the volume to the control level there was a fall in diastolic flow and ventricular contractility with respect to the values obtained when the volume was increased; these two effects were transient lasting less than 10 min. It was not considered that any of the three models of the coronary circulation, waterfall, intramyocardial pump or varying elastance model could explain our results.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular mechanics in isolated mild mitral stenosis: a three dimensional speckle tracking study.

PubMed

Poyraz, Esra; Öz, Tuğba Kemaloğlu; Zeren, Gönül; Güvenç, Tolga Sinan; Dönmez, Cevdet; Can, Fatma; Güvenç, Rengin Çetin; Dayı, Şennur Ünal

2017-09-01

In a fraction of patients with mild mitral stenosis, left ventricular systolic function deteriorates despite the lack of hemodynamic load imposed by the dysfunctioning valve. Neither the predisposing factors nor the earlier changes in left ventricular contractility were understood adequately. In the present study we aimed to evaluate left ventricular mechanics using three-dimensional (3D) speckle tracking echocardiography. A total of 31 patients with mild rheumatic mitral stenosis and 27 healthy controls were enrolled to the study. All subjects included to the study underwent echocardiographic examination to collect data for two- and three-dimensional speckle-tracking based stain, twist angle and torsion measurements. Data was analyzed offline with a echocardiographic data analysis software. Patients with rheumatic mild MS had lower global longitudinal (p < 0.001) circumferential (p = 0.02) and radial (p < 0.01) strain compared to controls, despite ejection fraction was similar for both groups [(p = 0.45) for three dimensional and (p = 0.37) for two dimensional measurement]. While the twist angle was not significantly different between groups (p = 0.11), left ventricular torsion was significantly higher in mitral stenosis group (p = 0.03). All strain values had a weak but significant positive correlation with mitral valve area measured with planimetry. Subclinical left ventricular systolic dysfunction develops at an early stage in rheumatic mitral stenosis. Further work is needed to elucidate patients at risk for developing overt systolic dysfunction.

Acute Heart Failure Triggered by Coronary Spasm With Transient Left Ventricular Dysfunction.

PubMed

Adachi, Yusuke; Sakakura, Kenichi; Ibe, Tatsuro; Yoshida, Nanae; Wada, Hiroshi; Fujita, Hideo; Momomura, Shin-Ichi

2017-04-06

Coronary spasm is abnormal contraction of an epicardial coronary artery resulting in myocardial ischemia. Coronary spasm induces not only depressed myocardial contractility, but also incomplete myocardial relaxation, which leads to elevated ventricular filling pressure. We herein report the case of a 55-year-old woman who had repeated acute heart failure caused by coronary spasm. Acetylcholine provocation test with simultaneous right heart catheterization was useful for the diagnosis of elevated ventricular filling pressure as well as coronary artery spasm. We should add coronary spasm to a differential diagnosis for repeated acute heart failure.

Relationship between improvement in left ventricular dyssynchrony and contractile function and clinical outcome with cardiac resynchronization therapy: the MADIT-CRT trial.

PubMed

Pouleur, Anne-Catherine; Knappe, Dorit; Shah, Amil M; Uno, Hajime; Bourgoun, Mikhail; Foster, Elyse; McNitt, Scott; Hall, W Jackson; Zareba, Wojciech; Goldenberg, Ilan; Moss, Arthur J; Pfeffer, Marc A; Solomon, Scott D

2011-07-01

To assess long-term effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) dyssynchrony and contractile function, by two-dimensional speckle-tracking echocardiography, compared with implantable cardioverter defibrillator (ICD) only in MADIT-CRT. We studied 761 patients in New York Heart Association I/II, ejection fraction ≤30%, and QRS ≥130 ms [n = 434, CRT-defibrillator (CRT-D), n = 327, ICD] with echocardiographic studies available at baseline and 12 months. Dyssynchrony was determined as the standard deviation of time to peak transverse strain between 12 segments of apical four- and two-chamber views, and contractile function as global longitudinal strain (GLS) by averaging longitudinal strain over these 12 segments. We compared changes in LV dyssynchrony and contractile function between treatment groups and assessed relationships between these changes over the first year and subsequent outcomes (median post 1-year follow-up = 14.9 months). Mean changes in LV dyssynchrony and contractile function measured by GLS in the overall population were, respectively, -29 ± 83 ms and -1 ± 2.9%. However, both LV dyssynchrony (CRT-D: -47 ± 83 ms vs. ICD: -6 ± 76 ms, P < 0.001) and contractile function (CRT-D: -1.4 ± 3.1% vs. ICD: -0.4 ± 2.5%, P < 0.001) improved to a greater extent in the CRT-D group compared with the ICD-only group. A greater improvement in dyssynchrony and contractile function at 1 year was associated with lower rates of the subsequent primary outcome of death or heart failure, adjusting for baseline dyssynchrony and contractile function, treatment arm, ischaemic status, and change in LV end-systolic volume. Each 20 ms decrease in LV dyssynchrony was associated with a 7% reduction in the primary outcome (P = 0.047); each 1% improvement in GLS over the 12-month period was associated with a 24% reduction in the primary outcome (P < 0.001). Cardiac resynchronization therapy resulted in a significant improvement in both LV dyssynchrony and contractile function measured by GLS compared with ICD only and these improvements were associated with better subsequent outcomes.

Is everything clear about Tako-tsubo syndrome?

PubMed

Petrov, Ivo S; Tokmakova, Mariya P; Marchov, Daniel N; Kichukov, Kostadin N

2011-01-01

Tako-tsubo syndrome is a novel cardio-vascular disease affecting predominantly postmenopausal women exposed to unexpected strong emotional or physical stress, in the absence of significant coronary heart disease. It is characterized by acute onset of severe chest pain and/or acute left ventricular failure, ECG-changes, typical left ventricular angiographic findings, good prognosis and positive resolution of the morphological and clinical manifestations. First described in 1990 in Japan by Sato, Tako-tsubo cardiomyopathy is characterized by transient contractile abnormalities of the left ventricle, causing typical left ventricular apical ballooning at end-systole with concomitant compensatory basal hyperkinesia. There are also atypical forms, presenting with left ventricular systolic dysfunction which affects the mid-portions of the left ventricle. The etiology of the disease still remains unclear. Many theories have been put forward about the potential underlying pathophysiological mechanisms that may trigger this syndrome among which are the theory of catecholamine excess, the theory of multivessel coronary vasospasm, the ischemic theory, and the theory of microvascular dysfunction and dynamic left ventricular gradient induced by elevated circulating catecholamine levels. Adequate management of Tako-tsubo syndrome demands immediate preparation for coronary angiography. Once the diagnosis is made, treatment is primarily symptomatic and includes monitoring for complications. Patients with Tako-tsubo syndrome most frequently develop acute LV failure, pulmonary edema, rhythm and conductive disturbances and apical thrombosis. Treatment is symptomatic and includes administration of diuretics, vasodilators and mechanical support of circulation with intra-aortic balloon counterpulsation.

Putative β4-adrenoceptors in rat ventricle mediate increases in contractile force and cell Ca2+: comparison with atrial receptors and relationship to (−)-[3H]-CGP 12177 binding

PubMed Central

Sarsero, Doreen; Molenaar, Peter; Kaumann, Alberto J; Freestone, Nicholas S

1999-01-01

We identified putative β4-adrenoceptors by radioligand binding, measured increases in ventricular contractile force by (−)-CGP 12177 and (±)-cyanopindolol and demonstrated increased Ca2+ transients by (−)-CGP 12177 in rat cardiomyocytes.(−)-[3H]-CGP 12177 labelled 13–22 fmol mg−1 protein ventricular β1, β2-adrenoceptors (pKD ∼9.0) and 50–90 fmol mg−1 protein putative β4-adrenoceptors (pKD ∼7.3). The affinity values (pKi) for (β1,β2-) and putative β4-adrenoceptors, estimated from binding inhibition, were (−)-propranolol 8.4, 5.7; (−)-bupranolol 9.7, 5.8; (±)-cyanopindolol 10.0,7.4.In left ventricular papillary muscle, in the presence of 30 μM 3-isobutyl-1-methylxanthine, (−)-CGP 12177 and (±)-cyanopindolol caused positive inotropic effects, (pEC50, (−)-CGP 12177, 7.6; (±)-cyanopindolol, 7.0) which were antagonized by (−)-bupranolol (pKB 6.7–7.0) and (−)-CGP 20712A (pKB 6.3–6.6). The cardiostimulant effects of (−)-CGP 12177 in papillary muscle, left and right atrium were antagonized by (±)-cyanopindolol (pKP 7.0–7.4).(−)-CGP 12177 (1 μM) in the presence of 200 nM (−)-propranolol increased Ca2+ transient amplitude by 56% in atrial myocytes, but only caused a marginal increase in ventricular myocytes. In the presence of 1 μM 3-isobutyl-1-methylxanthine and 200 nM (−)-propranolol, 1 μM (−)-CGP 12177 caused a 73% increase in Ca2+ transient amplitude in ventricular myocytes. (−)-CGP 12177 elicited arrhythmic transients in some atrial and ventricular myocytes.Probably by preventing cyclic AMP hydrolysis, 3-isobutyl-1-methylxanthine facilitates the inotropic function of ventricular putative β4-adrenoceptors, suggesting coupling to Gs protein-adenylyl cyclase. The receptor-mediated increases in contractile force are related to increases of Ca2+ in atrial and ventricular myocytes. The agreement of binding affinities of agonists with cardiostimulant potencies is consistent with mediation through putative β4-adrenoceptors labelled with (−)-[3H]-CGP 12177. PMID:10602323

Effects of systolic anterior motion of the mitral valve on haemodynamics. Evaluation by a direct method.

PubMed

Kaku, T; Sakurai, S; Furuno, Y; Yashiro, A; Nakashima, Y; Kuroiwa, A

1995-08-01

We evaluated the effects of systolic anterior motion systolic anterior motion of the mitral valve on cardiac haemodynamics. Seven adult mongrel dogs in which systolic anterior motion-septal contact was observed after dobutamine administration were used. To exclude the effects of left ventricular function and morphology, a stone removal basket catheter was placed in the left ventricular outflow tract, and haemodynamics were compared with the basket closed and opened. The basket was opened five times in three dogs not showing systolic anterior motion-septal contact, but the basket itself did not effect the haemodynamics. In the seven dogs that showed systolic anterior motion-septal contact without left ventricular hypertrophy, the basket was opened a total of 33 times in the presence of various degrees of systolic anterior motion-septal contact. After opening the basket, systolic anterior motion was reduced echocardiographically, and significant (P<0.01) changes were observed in the left ventricle-aorta pressure gradient (from 68 +/- 22 to 25 +/- 15 mm Hg), the systolic ejection period (from 146 +/- 19 to 135 +/- 16 ms), and the stroke volume (SV; from 9.4 +/- 2.9 to 10.1 +/- 3.3 ml). After basket inflation, aortic pressure and aortic flow waveforms changed but the peak pressure and flow velocity did not. The temporal distribution of left ventricular ejection also definitely changed after the basket was opened. No changes were observed in the peak dp/dt, peak negative dp/dt, time constant, left ventricular end-diastolic pressure, or left atrial pressure. These observations in this animal model of systolic anterior motion without left ventricular hypertrophy suggest that: (1) there is no potential for generation of an intra-cavity gradient in the absence of systolic anterior motion of the mitral valve, so that (2) systolic anterior motion narrowed the left ventricular outflow tract and, consequently, produced the systolic ejection period, and affected the left ventricular ejection dynamics, and that (3) the basket catheter is useful because it allows these assessments in the same heart with a nearly fixed left ventricular contractility, at least in our animal model.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samarel, A.M.; Parmacek, M.S.; Magid, N.M.

To determine the relative importance of protein degradation in the development of starvation-induced cardiac atrophy, in vivo fractional synthetic rates of total cardiac protein, myosin heavy chain, actin, light chain 1, and light chain 2 were measured in fed and fasted rabbits by continuous infusion of (/sup 3/H) leucine. In addition, the rate of left ventricular protein accumulation and loss were assessed in weight-matched control and fasted rabbits. Rates of total cardiac protein degradation were then estimated as the difference between rates of synthesis and growth. Fasting produced left ventricular atrophy by decreasing the rate of left ventricular protein synthesismore » (34.8 +/- 1.4, 27.3 +/- 3.0, and 19.3 +/- 1.2 mg/day of left ventricular protein synthesized for 0-, 3-, and 7-day fasted rabbits, respectively). Inhibition of contractile protein synthesis was evident by significant reductions in the fractional synthetic rates of all myofibrillar protein subunits. Although fractional rates of protein degradation increased significantly within 7 days of fasting, actual amounts of left ventricular protein degraded per day were unaffected. Thus, prolonged fasting profoundly inhibits the synthesis of new cardiac protein, including the major protein constituents of the myofibril. Both this inhibition in new protein synthesis as well as a smaller but significant reduction in the average half-lives of cardiac proteins are responsible for atrophy of the heart in response to fasting.« less

Systolic Intrinsic Frequency and Various Measures of Left Ventricle Contractility

NASA Astrophysics Data System (ADS)

Pahlevan, Niema

2017-11-01

There has been growing interest during past six decades to introduce new indices for quantifying left ventricular (LV) contractility. We have recently introduced a new method, called intrinsic frequency (IF), for analyzing the dynamics of systemic circulation. IF method models LV and arterial network as an object rotating around an origin where the angular velocity of the rotation during systole (when LV and arterial network are coupled) and diastole (when arterial network is decoupled) are intrinsic frequencies, ω1 and ω2 respectively. ω1 and ω2 can be extracted from a carotid pulse waveform using IF method. In this study, Huntington Medical Research Institutes heart study data have been used to compare ω1 with various measures of LV contractility such as ejection fraction, mean velocity of circumferential fiber shortening, LV end-systolic meridional wall stress, and maximal LV power corrected for end-diastolic volume. Here, LV contractility indices were computed noninvasively from cardiac MRI and tonometry data. The results indicate that ω1 can be used as a surrogate of LV contractility. This is clinically significant since ω1 can be accurately obtained by a standard iPhone camera.

Cardiovascular pharmacology of quazodine (MJ-1988), with particular reference to effects of myocardial blood flow and metabolic heat production.

PubMed

Parratt, J R; Winslow, E

1971-06-01

1. The effects of intravenous infusions of quazodine (6,7-dimethoxy-4-ethylquinazoline; MJ-1988) on myocardial blood flow, myocardial metabolic heat production and on general haemodynamics have been studied in cats anaesthetized with sodium pentobarbitone.2. Quazodine (0.25 and 0.5 (mg/kg)/min for 10 min) decreased diastolic blood pressure, peripheral vascular resistance, systolic ejection time and left ventricular end-diastolic pressure. Heart rate, cardiac effort, output and external work and left ventricular dP/dt were markedly increased. These changes are indicative of increased myocardial contractility and peripheral vasodilatation.3. In a dose of (1.0 mg/kg)/min, quazodine had a more marked hypotensive effect, systolic pressure being significantly reduced, and had less effect on left ventricular dP/dt and cardiac effort. Calculated external cardiac work was slightly reduced and there were very occasional nodal arrhythmias.4. Changes in heart rate, aortic dP/dt and diastolic blood pressure induced by quazodine were unaffected by the previous administration of the beta-adrenoceptor blocking agent alprenolol in a dose (1.0 mg/kg) which abolished the effects of isoprenaline.5. In all doses, quazodine markedly increased local blood flow (by 70-540%) around an implanted myocardial heated thermocouple recorder. ;Corrected temperature', an index of local myocardial metabolic heat production, was almost unchanged and it is suggested that increased myocardial contractility, occurring with unchanged metabolic heat production and oxygen consumption, probably results from a concomitant decrease in intramural wall tension.

Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte Contractility in Β1 Adrenergic Receptor Knockout Mice.

PubMed

Rodrigues, Aurora Corrêa; Natali, Antônio José; Cunha, Daise Nunes Queiroz da; Costa, Alexandre Jayme Lopes Dantas; Moura, Anselmo Gomes de; Araújo Carneiro-Júnior, Miguel; Félix, Leonardo Bonato; Brum, Patrícia Chakur; Prímola-Gomes, Thales Nicolau

2018-03-01

The lack of cardiac β1-adrenergic receptors (β1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF. We tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from β1 adrenergic receptor knockout (β1ARKO) mice. Four- to five-month-old male wild type (WT) and β1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and β1ARKO control (β1ARKOc) and trained (β1ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. The β1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The β1ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from β1ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in β1ARKO mice. MCAE improves myocyte contractility in the left ventricle of β1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving β1-AR desensitization or reduction.

Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload.

PubMed

Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, Elena; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preissl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz

2016-12-01

Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading. Left ventricular pressure overload induced by transverse aortic constriction (TAC) in mice resulted in left ventricular dysfunction, fibrosis and increased biglycan expression. Fluorescence- and magnetic-assisted sorting of cardiac cell types revealed upregulation of biglycan in the fibroblast population, but not in cardiomyocytes, endothelial cells or leukocytes after TAC. Removal of the aortic constriction (rTAC) after short-term pressure overload (3weeks) improved cardiac contractility and reversed ventricular hypertrophy but not fibrosis in wild-type (WT) mice. Biglycan ablation (KO) enhanced functional recovery but did not resolve cardiac fibrosis. After long-term TAC for 9weeks, ablation of biglycan attenuated the development of cardiac hypertrophy and fibrosis. In vitro, biglycan induced hypertrophy of neonatal rat cardiomyocytes and led to activation of a hypertrophic gene program. Putative downstream mediators of biglycan signaling include Rcan1, Abra and Tnfrsf12a. These genes were concordantly induced by TAC in WT but not in biglycan KO mice. Left ventricular pressure overload induces biglycan expression in cardiac fibroblasts. Ablation of biglycan improves cardiac function and attenuates left ventricular hypertrophy and fibrosis after long-term pressure overload. In vitro biglycan induces hypertrophy of cardiomyocytes, suggesting that biglycan may act as a signaling molecule between cell types to modulate cardiac remodeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Altered in vivo left ventricular torsion and principal strains in hypothyroid rats

PubMed Central

Chen, Yong; Somji, Aleefia; Yu, Xin

2010-01-01

The twisting and untwisting motions of the left ventricle (LV) lead to efficient ejection of blood during systole and filling of the ventricle during diastole. Global LV mechanical performance is dependent on the contractile properties of cardiac myocytes; however, it is not known how changes in contractile protein expression affect the pattern and timing of LV rotation. At the myofilament level, contractile performance is largely dependent on the isoforms of myosin heavy chain (MHC) that are expressed. Therefore, in this study, we used MRI to examine the in vivo mechanical consequences of altered MHC isoform expression by comparing the contractile properties of hypothyroid rats, which expressed only the slow β-MHC isoform, and euthyroid rats, which predominantly expressed the fast α-MHC isoform. Unloaded shortening velocity (Vo) and apparent rate constants of force development (ktr) were measured in the skinned ventricular myocardium isolated from euthyroid and hypothyroid hearts. Increased expression of β-MHC reduced LV torsion and fiber strain and delayed the development of peak torsion and strain during systole. Depressed in vivo mechanical performance in hypothyroid rats was related to slowed cross-bridge performance, as indicated by significantly slower Vo and ktr, compared with euthyroid rats. Dobutamine infusion in hypothyroid hearts produced smaller increases in torsion and strain and aberrant transmural torsion patterns, suggesting that the myocardial response to β-adrenergic stress is compromised. Thus, increased expression of β-MHC alters the pattern and decreases the magnitude of LV rotation, contributing to reduced mechanical performance during systole, especially in conditions of increased workload. PMID:20729398

Calcineurin Regulates Myocardial Function during Acute Endotoxemia

PubMed Central

Joshi, Mandar S.; Julian, Mark W.; Huff, Jennifer E.; Bauer, John A.; Xia, Yong; Crouser, Elliott D.

2006-01-01

Rationale: Cyclosporin A (CsA) is known to preserve cardiac contractile function during endotoxemia, but the mechanism is unclear. Increased nitric oxide (NO) production and altered mitochondrial function are implicated as mechanisms contributing to sepsis-induced cardiac dysfunction, and CsA has the capacity to reduce NO production and inhibit mitochondrial dysfunction relating to the mitochondrial permeability transition (MPT). Objectives: We hypothesized that CsA would protect against endotoxin-mediated cardiac contractile dysfunction by attenuating NO production and preserving mitochondrial function. Methods: Left ventricular function was measured continuously over 4 h in cats assigned as follows: control animals (n = 7); LPS alone (3 mg/kg, n = 8); and CsA (6 mg/kg, n = 7), a calcineurin inhibitor that blocks the MPT, or tacrolimus (FK506, 0.1 mg/kg, n = 7), a calcineurin inhibitor lacking MPT activity, followed in 30 min by LPS. Myocardial tissue was then analyzed for NO synthase-2 expression, tissue nitration, protein carbonylation, and mitochondrial morphology and function. Measurements and Main Results: LPS treatment resulted in impaired left ventricular contractility, altered mitochondrial morphology and function, and increased protein nitration. As hypothesized, CsA pretreatment normalized cardiac performance and mitochondrial respiration and reduced myocardial protein nitration. Unexpectedly, FK506 pretreatment had similar effects, normalizing both cardiac and mitochondrial parameters. However, CsA and FK506 pretreatments markedly increased protein carbonylation in the myocardium despite elevated manganese superoxide dismutase activity during endotoxemia. Conclusions: Our data indicate that calcineurin is a critical regulator of mitochondrial respiration, tissue nitration, protein carbonylation, and contractile function in the heart during acute endotoxemia. PMID:16424445

A new "twist" on right heart failure with left ventricular assist systems.

PubMed

Houston, Brian A; Shah, Keyur B; Mehra, Mandeep R; Tedford, Ryan J

2017-07-01

Despite significant efforts to predict and prevent right heart failure, it remains a leading cause of morbidity and mortality after implantation of left ventricular assist systems (LVAS). In this Perspective, we review the underappreciated anatomic and physiologic principles that govern the relationship between left and right heart function and contribute to this phenomenon. This includes the importance of considering the right ventricle (RV) and pulmonary arterial circuit as a coupled system; the contribution of the left ventricle (LV) to RV contractile function and the potential negative impact of acutely unloading the LV; the influence of the pericardium and ventricular twist on septal function; the role of RV deformation in reduced mechanical efficiency after device placement; and the potential of ongoing stressors of an elevated right-sided preload. We believe an appreciation of these complex issues is required to fully understand the expression of the unique phenotypes of right heart failure after LVAS implantation and for developing better prognostic and therapeutic strategies. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy: pressure-volume analysis with a nonimaging scintillation probe.

PubMed

Bonow, R O; Ostrow, H G; Rosing, D R; Cannon, R O; Lipson, L C; Maron, B J; Kent, K M; Bacharach, S L; Green, M V

1983-11-01

To investigate the effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy, we studied 14 patients at catheterization with a nonimaging scintillation probe before and after serial intravenous infusions of low-, medium-, and high-dose verapamil (total dose 0.17 to 0.72 mg/kg). Percent change in radionuclide stroke counts after verapamil correlated well with percent change in thermodilution stroke volume (r = .87), and changes in diastolic and systolic counts were used to assess relative changes in left ventricular volumes after verapamil. Verapamil produced dose-related increases in end-diastolic counts (19 +/- 9% increase; p less than .001), end-systolic counts (91 +/- 54% increase; p less than .001), and stroke counts (7 +/- 10% increase; p less than .02). This was associated with a decrease in ejection fraction (83 +/- 8% control, 73 +/- 10% verapamil; p less than .001) and, in the 10 patients with left ventricular outflow tract gradients, a reduction in gradient (62 +/- 27 mm Hg control, 32 +/- 35 mm Hg verapamil; p less than .01). The end-systolic pressure-volume relation was shifted downward and rightward in all patients, suggesting a negative inotropic effect. In 10 patients, left ventricular pressure-volume loops were constructed with simultaneous micromanometer pressure recordings and the radionuclide time-activity curve. In five patients, verapamil shifted the diastolic pressure-volume curve downward and rightward, demonstrating improved pressure-volume relations despite the negative inotropic effect, and also increased the peak rate of rapid diastolic filling. In the other five patients, the diastolic pressure-volume relation was unaltered by verapamil, and increased end-diastolic volumes occurred at higher end-diastolic pressures; in these patients, the peak rate of left ventricular diastolic filling was not changed by verapamil. The negative inotropic effects of intravenous verapamil are potentially beneficial in patients with hypertrophic cardiomyopathy by decreasing left ventricular contractile function and increasing left ventricular volume. Verapamil also enhances left ventricular diastolic filling and improves diastolic pressure-volume relations in some patients despite its negative inotropic effect.

[Oligomeric procyanidins from hawthorn extract as supplementary therapy in patients with left ventricle systolic dysfunction].

PubMed

Rechciński, Tomasz; Kurpesa, Małgorzata

2005-01-01

The results of recent studies provide the evidence that extract of hawthorn (Crataegus sp.) may provide benefits in left ventricular systolic dysfunction. The authors present a number of in vitro and in vivo studies in which the influence of this herbal drug on contractility of impaired myocardium has been proved. This kind of supplementary therapy was well tolerated and no interactions with the other compounds for heart failure were reported.

Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts.

PubMed

Mori, M; Takeuchi, M; Takaoka, H; Hata, K; Hayashi, Y; Yamakawa, H; Yokoyama, M

1997-03-01

The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 +/- 1.26 to 5.37 +/- 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vo2 (from 0.22 +/- 0.08 to 0.27 +/- 0.09 ml O2, p < 0.05) and PVA-independent Vo2 (from 0.019 +/- 0.019 to 0.091 +/- 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p < 0.05). These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.

Left atrial strain predicts hemodynamic parameters in cardiovascular patients.

PubMed

Hewing, Bernd; Theres, Lena; Spethmann, Sebastian; Stangl, Karl; Dreger, Henryk; Knebel, Fabian

2017-08-01

We aimed to evaluate the predictive value of left atrial (LA) reservoir, conduit, and contractile function parameters as assessed by speckle tracking echocardiography (STE) for invasively measured hemodynamic parameters in a patient cohort with myocardial and valvular diseases. Sixty-nine patients undergoing invasive hemodynamic assessment were enrolled into the study. Invasive hemodynamic parameters were obtained by left and right heart catheterization. Transthoracic echocardiography assessment of LA reservoir, conduit, and contractile function was performed by STE. Forty-nine patients had sinus rhythm (SR) and 20 patients had permanent atrial fibrillation (AF). AF patients had significantly reduced LA reservoir function compared to SR patients. In patients with SR, LA reservoir, conduit, and contractile function inversely correlated with pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure, and mean pulmonary artery pressure (PAP), and showed a moderate association with cardiac index. In AF patients, there were no significant correlations between LA reservoir function and invasively obtained hemodynamic parameters. In SR patients, LA contractile function with a cutoff value of 16.0% had the highest diagnostic accuracy (area under the curve, AUC: 0.895) to predict PCWP ≥18 mm Hg compared to the weaker diagnostic accuracy of average E/E' ratio with an AUC of 0.786 at a cutoff value of 14.3. In multivariate analysis, LA contractile function remained significantly associated with PCWP ≥18 mm Hg. In a cohort of patients with a broad spectrum of cardiovascular diseases LA strain shows a valuable prediction of hemodynamic parameters, specifically LV filling pressures, in the presence of SR. © 2017, Wiley Periodicals, Inc.

Cardio-oncology: cardiovascular complications of cancer therapy.

PubMed

Henning, Robert J; Harbison, Raymond D

2017-07-01

This paper focuses on three classes of commonly used anticancer drugs, which can cause cardiotoxicity: anthracyclines, monoclonal antibodies exemplified by trastuzumab and tyrosine kinase inhibitors. Anthracyclines can induce cardiomyocyte necrosis and fibrosis. Trastuzumab can cause cardiac stunning. The tyrosine kinase inhibitors can increase systemic arterial pressure and impair myocyte contractility. In addition, radiation therapy to the mediastinum or left chest can exacerbate the cardiotoxicity of these anticancer drugs and can also cause accelerated atherosclerosis, myocardial infarction, heart failure and arrhythmias. Left ventricular ejection fraction measurements are most commonly used to assess cardiac function in patients who receive chemo- or radiation-therapy. However, echocardiographic determinations of global longitudinal strain are more sensitive for detection of early left ventricular systolic dysfunction. Information on patient-risk stratification and monitoring is presented and guidelines for the medical treatment of cardiac dysfunction due to cancer therapies are summarized.

Application of NASTRAN for stress analysis of left ventricle of the heart

NASA Technical Reports Server (NTRS)

Pao, Y. C.; Ritman, E. L.; Wang, H. C.

1975-01-01

Knowing the stress and strain distributions in the left ventricular wall of the heart is a prerequisite for the determination of the muscle elasticity and contractility in the process of assessing the functional status of the heart. NASTRAN was applied for the calculation of these stresses and strains and to help in verifying the results obtained by the computer program FEAMPS which was specifically designed for the plane-strain finite-element analysis of the left ventricular cross sections. Adopted for the analysis are the true shape and dimensions of the cross sections reconstructed from multiplanar X-ray views of a left ventricle which was surgically isolated from a dog's heart but metabolically supported to sustain its beating. A preprocessor was prepared to accommodate both FEAMPS and NASTRAN, and it has also facilitated the application of both the triangular element and isoparameteric quadrilateral element versions of NASTRAN. The stresses in several crucial regions of the left ventricular wall calculated by these two independently developed computer programs are found to be in good agreement. Such confirmation of the results is essential in the development of a method which assesses the heart performance.

Evaluation of left ventricular function by bedside ultrasound in acute toxic myocarditis.

PubMed

Brown, Cara; Budhram, Gavin

2013-10-01

Myocarditis can be difficult to diagnose in the Emergency Department (ED) due to the lack of classic symptoms and the wide variation in presentations. Poor cardiac contractility is a common finding in myocarditis and can be evaluated by bedside ultrasound. To demonstrate the utility of fractional shortening measurements as an estimation of left ventricular function during bedside cardiac ultrasound evaluation in the ED. A 54-year-old man presented to the ED complaining of 3 days of chest tightness, palpitations, and dyspnea, as well as persistent abdominal pain and vomiting. An electrocardiogram (ECG) showed sinus tachycardia with presumably new ST-segment elevation and signs of an incomplete right bundle branch block. A bedside echocardiogram was performed by the emergency physician that showed poor left ventricular function by endocardial fractional shortening measurements. On further questioning, the patient revealed that for the past 2 weeks he had been regularly huffing a commercially available compressed air duster. Based on these history and examination findings, the patient was given a presumptive diagnosis of toxic myocarditis. A follow-up echocardiogram approximately 7 weeks later demonstrated resolution of the left ventricular systolic dysfunction and his ECG findings normalized. Cardiac ultrasound findings of severely reduced global function measured by endocardial fractional shortening were seen in this patient and supported the diagnosis of myocarditis. Endocardial fractional shortening is a useful means of easily evaluating and documenting left ventricular function and can be performed at the bedside in the ED. Copyright © 2013 Elsevier Inc. All rights reserved.

Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.

PubMed

Frisk, Michael; Ruud, Marianne; Espe, Emil K S; Aronsen, Jan Magnus; Røe, Åsmund T; Zhang, Lili; Norseng, Per Andreas; Sejersted, Ole M; Christensen, Geir A; Sjaastad, Ivar; Louch, William E

2016-10-01

Invaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation-contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca(2+) release and reduced power of the heartbeat. The underlying mechanism is, however, unknown. We presently investigated whether elevated ventricular wall stress triggers remodelling of t-tubule structure and function. MRI and blood pressure measurements were employed to examine regional wall stress across the left ventricle of sham-operated and failing, post-infarction rat hearts. In failing hearts, elevated left ventricular diastolic pressure and ventricular dilation resulted in markedly increased wall stress, particularly in the thin-walled region proximal to the infarct. High wall stress in this proximal zone was associated with reduced expression of the dyadic anchor junctophilin-2 and disrupted cardiomyocyte t-tubular structure. Indeed, local wall stress measurements predicted t-tubule density across sham and failing hearts. Elevated wall stress and disrupted cardiomyocyte structure in the proximal zone were also associated with desynchronized Ca(2+) release in cardiomyocytes and markedly reduced local contractility in vivo. A causative role of wall stress in promoting t-tubule remodelling was established by applying stretch to papillary muscles ex vivo under culture conditions. Loads comparable to wall stress levels observed in vivo in the proximal zone reduced expression of junctophilin-2 and promoted t-tubule loss. Elevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca(2+) release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Exercise reveals impairments in left ventricular systolic function in patients with metabolic syndrome

PubMed Central

Fournier, Sara B.; Reger, Brian L.; Donley, David A.; Bonner, Daniel E.; Warden, Bradford E.; Gharib, Wissam; Failinger, Conard F.; Olfert, Melissa D.; Frisbee, Jefferson C.; Olfert, I. Mark; Chantler, Paul D.

2013-01-01

MetS is the manifestation of a cluster of cardiovascular (CV) risk factors and is associated with a three-fold increase risk of CV morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to comprehensively examine LV and arterial responses to exercise in MetS individuals without diabetes and/or overt CVD compared to a healthy control population. CV function was characterized using Doppler echocardiography and gas exchange in MetS (n=27) vs. healthy controls (n=20) at rest and during peak exercise. At rest, MetS individuals displayed normal LV systolic function but reduced LV diastolic function vs. healthy controls. During peak exercise, individuals with MetS had impaired contractility; pump performance, and vasodilator reserve capacity vs. controls. A blunted contractile reserve response resulted in diminished arterial-ventricular coupling reserve and limited aerobic capacity in MetS vs. controls. These findings possess clinical importance as they provide insight to the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of CV morbidity and mortality. PMID:24036595

Effects of respiratory alkalosis and acidosis on myocardial blood flow and metabolism in patients with coronary artery disease.

PubMed

Kazmaier, S; Weyland, A; Buhre, W; Stephan, H; Rieke, H; Filoda, K; Sonntag, H

1998-10-01

Variation of the arterial carbon dioxide partial pressure (PaCO2) is not uncommon in anesthetic practice. However, little is known about the myocardial consequences of respiratory alkalosis and acidosis, particularly in patients with coronary artery disease. The aim of the current study was to investigate the effects of variation in PaCO2 on myocardial blood flow (MBF), metabolism, and systemic hemodynamics in patients before elective coronary artery bypass graft surgery. In 10 male anesthetized patients, measurements of MBF, myocardial contractility, metabolism, and systemic hemodynamics were made in a randomized sequence at PaCO2 levels of 30, 40, and 50 mmHg, respectively. The MBF was measured using the Kety-Schmidt technique with argon as a tracer. End-diastolic left ventricular pressure and the maximal increase of left ventricular pressure were assessed using a manometer-tipped catheter. The cardiac index significantly changed with varying PaCO2 levels (hypocapnia, - 9%; hypercapnia, 13%). This reaction was associated with inverse changes in systemic vascular resistance index levels. The MBF significantly increased by 15% during hypercapnia, whereas no change was found during hypocapnia. Myocardial oxygen and glucose uptake and the maximal increase of left ventricular pressure were not affected by varying PaCO2 levels. In anesthetized patients with coronary artery disease, short-term variations in PaCO2 have significant effects on MBF but do not influence global myocardial oxygen and glucose uptake. Changes in systemic hemodynamics associated with respiratory alkalosis and acidosis are caused by changes in systemic vascular resistance rather than by alterations in myocardial contractility.

Left atrial volume and function in dogs with naturally occurring myxomatous mitral valve disease.

PubMed

Höllmer, M; Willesen, J L; Tolver, A; Koch, J

2017-02-01

Myxomatous mitral valve disease (MMVD) induces progressive left atrial (LA) enlargement. The LA modulates left ventricular filling and performance through its reservoir, conduit, and contractile function. Assessment of LA size and function may provide valuable information on the level of cardiac compensation. Left atrial function in dogs with naturally occurring MMVD remains largely unexplored. The objective of this study was to evaluate LA volume and function in dogs with naturally occurring MMVD. This prospective study included 205 client-owned dogs of different breeds, 114 healthy dogs, and 91 dogs with MMVD of different disease severities. Using two-dimensional echocardiography, the biplane area-length method was applied to assess LA volume and calculate volumetric indices of LA reservoir, conduit, and contractile function. Left atrial volume and LA stroke volume increased, whereas LA reservoir and contractile function decreased with increasing disease severity. A maximal LA volume <2.25mL/kg was the optimal cut off identified for excluding congestive heart failure in dogs with chronic MMVD with a sensitivity of 96% and a specificity of 100%. An active LA emptying fraction <24% and/or a LA expansion index <126% were suggestive of congestive heart failure in dogs with chronic MMVD with a sensitivity of 77% and a specificity of 89% and a sensitivity of 82% and a specificity of 82%, respectively. Dogs with MMVD appear to have larger LA volumes with poorer LA function. Deteriorating LA function, characterized by a decreasing reservoir and active contractile function, was evident in dogs with MMVD with increasing disease severity. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue.

PubMed

Jacob, Fabian; Yonis, Amina Y; Cuello, Friederike; Luther, Pradeep; Schulze, Thomas; Eder, Alexandra; Streichert, Thomas; Mannhardt, Ingra; Hirt, Marc N; Schaaf, Sebastian; Stenzig, Justus; Force, Thomas; Eschenhagen, Thomas; Hansen, Arne

2016-01-01

Left ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism. We studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time-dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy). This study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux.

Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue

PubMed Central

Cuello, Friederike; Luther, Pradeep; Schulze, Thomas; Eder, Alexandra; Streichert, Thomas; Mannhardt, Ingra; Hirt, Marc N.; Schaaf, Sebastian; Stenzig, Justus; Force, Thomas

2016-01-01

Introduction Left ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism. Methods and Results We studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time-dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy). Conclusion This study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux. PMID:26840448

[Takotsubo cardiomyopathy in the context of Staphylococcus aureus sepsis].

PubMed

Núñez, D; Bermejo, R; Rodríguez-Velasco, A

2014-03-01

Takotsubo cardiomyopathy consists of a transient dysfunction of the left ventricle. It is characterised by an impaired left ventricular segmentary contractility, without significant coronary lesions in the coronary angiography. It usually occurs after an episode of physical or emotional stress. We present the case of a 70 year-old woman, who, in the postoperative period of an ankle osteosynthesis, developed a Takotsubo cardiomyopathy in the context of a sepsis caused by Staphylococcus aureus. She presented with acute lung oedema and a clinical picture of low cardiac output. The echocardiogram showed left ventricular medioapical akinesia. Coronary angiography was normal. She was treated with supportive measures with good progress. At 33 days from onset she was able to be discharged from hospital to home with normal systolic function on echocardiography. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure.

PubMed

Hanft, Laurin M; Emter, Craig A; McDonald, Kerry S

2017-07-01

Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously undiscovered changes in myofibrillar power output were found and were associated with alterations in myofilament proteins, providing potential new targets to exploit for improved ventricular pump function in heart failure. Copyright © 2017 the American Physiological Society.

Improved Arterial–Ventricular Coupling in Metabolic Syndrome after Exercise Training

PubMed Central

Fournier, Sara B.; Donley, David A.; Bonner, Daniel E.; DeVallance, Evan; Olfert, I. Mark; Chantler, Paul D.

2014-01-01

Purpose The metabolic syndrome (MetS) is associated with a three-fold increase risk of cardiovascular (CV) morbidity and mortality, which is in part, due to a blunted CV reserve capacity, reflected by a reduced peak exercise left ventricular contractility and aerobic capacity, and a blunted peak arterial-ventricular coupling. To date, no study has examined whether aerobic exercise training in MetS can reverse the peak exercise CV dysfunction. Further, examining how exercise training alters CV function in a group of individuals with MetS prior to the development of diabetes and/or overt CVD, can provide insights into whether some of the pathophysiological changes to the CV can be delayed/reversed, lowering their CV risk. The objective of this study was to examine the effects of 8 weeks of aerobic exercise training in individuals with MetS on resting and peak exercise CV function. Methods Twenty MetS underwent either 8 weeks of aerobic exercise training (MetS-ExT; n=10) or remained sedentary (MetS-NonT; n=10) during this time period. Resting and peak exercise CV function was characterized using Doppler echocardiography and gas exchange. Results Exercise training did not alter resting left ventricular diastolic or systolic function and arterial-ventricular coupling in MetS. In contrast, at peak exercise an increase in LV contractility (40%, p<0.01), cardiac output (28%, p<0.05) and aerobic capacity (20%, p<0.01), while a reduction in vascular resistance (30%, p<0.05) and arterial-ventricular coupling (27%, p<0.01), were noted in the MetS-ExT but not the MetS-NonT group. Further, an improvement in Lifetime Risk Score was also noted in the MetS-ExT group. Conclusions These findings have clinical importance as they provide insight that some of the pathophysiological changes associated with MetS can be improved and lower the risk of CVD. PMID:24870568

Ecstasy produces left ventricular dysfunction and oxidative stress in rats

PubMed Central

Shenouda, Sylvia K.; Lord, Kevin C.; McIlwain, Elizabeth; Lucchesi, Pamela A.; Varner, Kurt J.

2008-01-01

Aims Our aim was to determine whether the repeated, binge administration of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) produces structural and/or functional changes in the myocardium that are associated with oxidative stress. Methods and results Echocardiography and pressure–volume conductance catheters were used to assess left ventricular (LV) structure and function in rats subjected to four ecstasy binges (9 mg/kg i.v. for 4 days, separated by a 10 day drug-free period). Hearts from treated and control rats were used for either biochemical and proteomic analysis or the isolation of adult LV myocytes. After the fourth binge, treated hearts showed eccentric LV dilation and diastolic dysfunction. Systolic function was not altered in vivo; however, the magnitude of the contractile responses to electrical stimulation was significantly smaller in myocytes from rats treated in vivo with ecstasy compared with myocytes from control rats. The magnitude of the peak increase in intracellular calcium (measured by Fura-2) was also significantly smaller in myocytes from ecstasy-treated vs. control rats. The relaxation kinetics of the intracellular calcium transients were significantly longer in myocytes from ecstasy-treated rats. Ecstasy significantly increased nitrotyrosine content in the left ventricle. Proteomic analysis revealed increased nitration of contractile proteins (troponin-T, tropomyosin alpha-1 chain, myosin light polypeptide, and myosin regulatory light chain), mitochondrial proteins (Ub-cytochrome-c reductase and ATP synthase), and sarcoplasmic reticulum calcium ATPase. Conclusion The repeated binge administration of ecstasy produces eccentric LV dilation and dysfunction that is accompanied by oxidative stress. These functional responses may result from the redox modification of proteins involved in excitation-contraction coupling and/or mitochondrial energy production. Together, these results indicate that ecstasy has the potential to produce serious cardiac toxicity and ventricular dysfunction. PMID:18495670

Left ventricular hypertrophy does not prevent heart failure in experimental hypertension.

PubMed

Hernán Gómez Llambí, H; Cao, G; Donato, M; Suárez, D; Ottaviano, G; Müller, A; Buchholz, B; Gelpi, R; Otero-Losada, M; Milei, J

2017-07-01

Left ventricular hypertrophy (LVH) secondary to hypertension has been accepted to prevent heart failure (HF) while paradoxically increasing cardiovascular morbi-mortality. To evaluate whether antihypertensive treatment inhibits LVH, restores beta-adrenergic response and affects myocardial oxidative metabolism. Ninety spontaneously hypertensive rats (SHR) were distributed into groups and treated (mg/kg, p.o.) with: losartan 30 (L), hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C). Hypertension control group comprised 18 normotensive rats (Wistar-Kyoto, WKY). Following euthanasia at 16months, contractility was measured in 50% of rats (Langendorff system) before and after isoproterenol (Iso) 10 -9 M, 10 -7 M and 10 -5 M stimulation. Left ventricular weight (LVW) was measured in the remaining hearts, and normalized by BW. Expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2), glutaredoxin 3 (Grx-3), caspase-3 and brain natriuretic peptide (BNP) was determined. Systolic blood pressure (mmHg): 154±3 (L), 137±1 (H), 190±3 (R)*, 206±3 (SHR)*, 183±1 (C)**, and 141±1 (WKY) (*p<0.05 vs. L, H, WKY, **p<0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p<0.05). Groups SHR, R and C evidenced baseline contractile depression. Response to Iso 10 -5 M was similar in WKY and L. Expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (p<0.01). Present findings argue against the traditional idea and support that LVH might not be required to prevent HF. Increased expression of thioredoxins by antihypertensive treatment might be involved in protection from HF. Copyright © 2017 Elsevier B.V. All rights reserved.

Exercise reveals impairments in left ventricular systolic function in patients with metabolic syndrome.

PubMed

Fournier, Sara B; Reger, Brian L; Donley, David A; Bonner, Daniel E; Warden, Bradford E; Gharib, Wissam; Failinger, Conard F; Olfert, Melissa D; Frisbee, Jefferson C; Olfert, I Mark; Chantler, Paul D

2014-01-01

Metabolic syndrome (MetS) is the manifestation of a cluster of cardiovascular risk factors and is associated with a threefold increase in the risk of cardiovascular morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to examine comprehensively the LV and arterial responses to exercise in individuals with MetS without diabetes and/or overt cardiovascular disease in comparison to a healthy control population. Cardiovascular function was characterized using Doppler echocardiography and gas exchange in individuals with MetS (n = 27) versus healthy control subjects (n = 20) at rest and during peak exercise. At rest, individuals with MetS displayed normal LV systolic function but reduced LV diastolic function compared with healthy control subjects. During peak exercise, individuals with MetS had impaired contractility, pump performance and vasodilator reserve capacity versus control subjects. A blunted contractile reserve response resulted in diminished arterial-ventricular coupling reserve and limited aerobic capacity in individuals with MetS versus control subjects. These findings are of clinical importance, because they provide insight into the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of cardiovascular morbidity and mortality.

Two-dimensional strain profiles in patients with physiological and pathological hypertrophy and preserved left ventricular systolic function: a comparative analyses.

PubMed

Afonso, Luis; Kondur, Ashok; Simegn, Mengistu; Niraj, Ashutosh; Hari, Pawan; Kaur, Ramanjit; Ramappa, Preeti; Pradhan, Jyotiranjan; Bhandare, Deepti; Williams, Kim A; Zalawadiya, Sandip; Pinheiro, Aurelio; Abraham, Theodore P

2012-01-01

This study was designed to examine the utility of two-dimensional strain (2DS) or speckle tracking imaging to typify functional adaptations of the left ventricle in variant forms of left ventricular hypertrophy (LVH). Cross-sectional study. Urban tertiary care academic medical centres. A total of 129 subjects, 56 with hypertrophic cardiomyopathy (HCM), 34 with hypertensive left ventricular hypertrophy (H-LVH), 27 professional athletes with LVH (AT-LVH) and 12 healthy controls in sinus rhythm with preserved left ventricular systolic function. Conventional echocardiographic and tissue Doppler examinations were performed in all study subjects. Bi-dimensional acquisitions were analysed to map longitudinal systolic strain (automated function imaging, AFI, GE Healthcare, Waukesha, Wisconsin, USA) from apical views. Subjects with HCM had significantly lower regional and average global peak longitudinal systolic strain (GLS-avg) compared with controls and other forms of LVH. Strain dispersion index, a measure of regional contractile heterogeneity, was higher in HCM compared with the rest of the groups. On receiver operator characteristics analysis, GLS-avg had excellent discriminatory ability to distinguish HCM from H-LVH area under curve (AUC) (0.893, p<0.001) or AT-LVH AUC (0.920, p<0.001). Tissue Doppler and LV morphological parameters were better suited to differentiate the athlete heart from HCM. 2DS (AFI) allows rapid characterisation of regional and global systolic function and may have the potential to differentiate HCM from variant forms of LVH.

Transcatheter closure of patent ductus arteriosus reverses left ventricular dysfunction in a septuagenarian.

PubMed

Rapacciuolo, Antonio; Losi, Maria Angela; Borgia, Francesco; De Angelis, Maria Carmen; Esposito, Francesca; Cavallaro, Massimo; De Rosa, Roberta; Piscione, Federico; Chiariello, Massimo

2009-04-01

A 70-year-old man was admitted because of a 6-month history of progressive dyspnoea on exertion. The medical history showed that he suffered from patent ductus arteriosus (PDA) that was closed at 35 years of age by surgical ligation. Subsequently, up to year 1992, no evidence of residual left-to-right shunt was found. When he first came to our attention, we performed an echocardiographic test evidencing left ventricular dilation and contractile dysfunction and a recurrence of PDA. To exclude other possible causes of congestive heart failure, we performed several tests, including a coronary angiogram that showed coronary atherosclerosis without significant lesions. The haemodynamic study confirmed that the PDA was associated with a mild pulmonary hypertension with a QP: QS of 2: 1. The patient did not report any cardiovascular risk factor. Therefore, we concluded that PDA was responsible for congestive heart failure in this patient. We performed percutaneous closure of PDA, which was able to reverse left ventricular dilation and dysfunction, improving the patient's symptoms, at 1 month as well as 4 months after the interventional procedure. Although this kind of device is frequently used in the paediatric population, adult patients may present different challenges in proper management, such as poor visualization, calcification and pulmonary hypertension. In the description of the case reported here, we show that a PDA can present as congestive heart failure in the elderly. Percutaneous closure can be very effective in ameliorating left ventricular performance as well as symptoms.

Pressure-volume analysis reveals characteristic sex-related differences in cardiac function in a rat model of aortic banding-induced myocardial hypertrophy.

PubMed

Ruppert, Mihály; Korkmaz-Icöz, Sevil; Loganathan, Sivakkanan; Jiang, Weipeng; Lehmann, Lorenz H; Oláh, Attila; Sayour, Alex Ali; Barta, Bálint András; Merkely, Béla; Karck, Matthias; Radovits, Tamás; Szabó, Gábor

2018-05-25

Sex differences in pressure overload (PO)-induced left ventricular (LV) myocardial hypertrophy (LVH) have been intensely investigated. Nevertheless, sex-related disparities of LV hemodynamics in LVH were not examined in detail. Therefore, we aimed to provide a detailed characterization of distinct aspects of LV function in male and female rats during different stages of LVH. Banding of the abdominal aorta (AB) was performed to induce PO for 6 or 12 weeks in male and female rats. Control animals underwent sham operation. The development of LVH was followed by serial echocardiography. Cardiac function was assessed by pressure-volume analysis. Cardiomyocyte hypertrophy and fibrosis were evaluated by histology. At week 6, increased LV mass index, heart weight-to-tibial length, cardiomyocyte diameter, concentric LV geometry and moderate interstitial fibrosis were detected in both male and female AB rats, indicating the development of an early stage of LVH. Functionally, at this time point, impaired active relaxation, increased contractility and preserved ventricular-arterial coupling were observed in the AB groups in both genders. In contrast, at week 12, progressive deterioration of LVH-associated structural and functional alterations occurred in male but not in female animals with sustained PO. Accordingly, at this later stage, LVH was associated with eccentric remodeling, exacerbated fibrosis and increased chamber stiffness in male AB rats. Furthermore, augmented contractility declined in male and not in female AB animals, resulting in contractility-afterload mismatch. Maintained contractility augmentation, preserved ventricular-arterial coupling and better myocardial compliance in female rats contribute to sex differences in LV function during the progression of PO-induced LVH.

[Correlation of the quantitative ECG and echocardiogram indices in left ventricular hypertrophy according to correlational analysis data].

PubMed

Alekperov, I I; Dorofeeva, Z Z; Iurenev, A P

1981-11-01

In 47 patients with arterial hypertension and clinicoroentgenological signs of hypertrophy of the left ventricle the echo- and electrocardiographic study (the McFee-Parungao system) was carried out. Highly significant (p less than 0.001) direct correlation was revealed between the index of the corrected ECG, such as sigma R x,y,z + + sigma S x,y,z and Rx + Sz with echocardiographic indices of mass r = +0.851 and +0.848, respectively, and the thickness of the left ventricle of the myocardium (r = +0.806 and +0.794, respectively). The above electrocardiographic indices do not correlate to the main echocardiographic indices of the contractile function of the left ventricle.

Age-related peculiarities of contractile activity of rat myocardium during blockade of hyperpolarization-activated currents.

PubMed

Zefirov, T L; Gibina, A E; Sergejeva, A M; Ziyatdinova, N I; Zefirov, A L

2007-09-01

Contractile activity of atrial and ventricular myocardial strips isolated from rats of various age was examined under conditions of blockade of non-selective hyperpolarization-activated cation currents. Addition of ZD7288, a blocker of non-selective hyperpolarization-activated cation currents, to the perfusion solution increased the contraction force of atrial and ventricular strips in 1-, 8-, and 20-week rats, but produced an opposite effect on contractile activity of atrial and ventricular strips in 3-week rats.

Integration of Wall Motion, Coronary Flow Velocity, and Left Ventricular Contractile Reserve in a Single Test: Prognostic Value of Vasodilator Stress Echocardiography in Patients with Diabetes.

PubMed

Cortigiani, Lauro; Huqi, Alda; Ciampi, Quirino; Bombardini, Tonino; Bovenzi, Francesco; Picano, Eugenio

2018-06-01

Coronary flow velocity reserve (CFVR) and left ventricular contractile reserve (LVCR) have demonstrated prognostic importance in patients with diabetes. The aim of this study was to investigate the prognostic contribution of combined evaluation of CFVR and LVCR in patients with diabetes with nonischemic stress echocardiography. Three hundred seventy-five patients with diabetes (mean age, 68 ± 9 years) with nonischemic dipyridamole stress echocardiography underwent assessment of CFVR of the left anterior descending coronary artery (prospectively) and LVCR with left ventricular force (retrospectively) in a multicenter study. On receiver operating characteristic analysis, LVCR ≤ 1.1 was the best prognostic predictor and was considered an abnormal value. CFVR was abnormal (≤2) in 139 patients (37%), LVCR in 156 (42%), neither in 157 (42%), and both in 77 (21%). During a median follow-up period of 16 months, 86 major adverse cardiac events occurred: 16 deaths, 13 myocardial infarctions, and 57 revascularizations. Multivariate prognostic indicators were CFVR ≤ 2 (P < .0001), age (P = .03), and LVCR ≤ 1.1 (P = .04). The 3-year rate of major adverse cardiac events was 63% in patients with both abnormal CFVR and LVCR, 42% in those with abnormal CFVR only, 19% in those with abnormal LVCR only, and 10% in patients with both normal CFVR and LVCR. The 3-year hard event rate was 3% in patients with both normal CFVR and LVCR, fivefold higher in patients with abnormal CFVR or LVCR only, and ninefold higher in patients with both abnormal CFVR and LVCR. Patients with diabetes with nonischemic dipyridamole stress echocardiography may still have significant risk in presence of abnormal CFVR and/or LVCR, which assess the underlying, largely unrelated, microvascular and myocardial components of coronary circulation. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Broken heart as work-related accident: Occupational stress as a cause of takotsubo cardiomyopathy in 55-year-old female teacher - Role of automated function imaging in diagnostic workflow.

PubMed

Mielczarek, Agnieszka; Kasprzak, Jarosław Damian; Marcinkiewicz, Andrzej; Kurpesa, Małgorzata; Uznańska-Loch, Barbara; Wierzbowska-Drabik, Karina

2015-01-01

Takotsubo cardiomiopathy (TTC) (known also as "ampulla cardiomyopathy," "apical ballooning" or "broken heart syndrome") is connected with a temporary systolic left ventricular dysfunction without the culprit coronary lesion. Takotsubo cardiomyopathy was first described in 1990 in Japan after octopus trapping pot with a round bottom and narrow neck similar in shape to left ventriculogram in TTC patients. The occurrence of TTC is usually precipitated by a stressful event with a clinical presentation mimicking myocardial infarction: chest pain, ST-T segment elevation or T-wave inversion, a rise in cardiac troponin, and contractility abnormalities in echocardiography. A left ventricular dysfunction is transient and improves within a few weeks. Takotsubo cardiomyopathy typically occurs in postmenopausal women and the postulated mechanism is catecholamine overstimulation. Moreover, the distribution of contractility impairments usually does not correspond with typical region supplied by a single coronary artery. Therefore, the assessment of regional pattern of systolic dysfunction with speckle-tracking echocardiography and automated function imaging (AFI) technique may be important in diagnosis of TTC and may improve our insight into its patophysiology. We described a 55-year-old female teacher with TTC diagnosed after acute psychological stress in workplace. The provoking factor related with occupational stress and pattern of contraction abnormalities documented with AFI technique including basal segments of left ventricle make this case atypical. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Comparative Effects of Urocortins and Stresscopin on Cardiac Myocyte Contractility

PubMed Central

Makarewich, Catherine A.; Troupes, Constantine D.; Schumacher, Sarah M.; Gross, Polina; Koch, Walter J.; Crandall, David L.; Houser, Steven R.

2015-01-01

Rationale There is a current need for development of new therapies for patients with heart failure. Objective To test the effects of members of the Corticotropin-Releasing Factor (CRF) family of peptides on myocyte contractility to validate them as potential heart failure therapeutics. Methods and Results Adult feline left ventricular myocytes (AFMs) were isolated and contractility was assessed in the presence and absence of CRF peptides Urocortin 2 (UCN2), Urocortin 3 (UCN3), Stresscopin (SCP), and the β-adrenergic agonist isoproterenol (Iso). An increase in fractional shortening and peak Ca2+ transient amplitude was seen in the presence of all CRF peptides. A decrease in Ca2+ decay rate (Tau) was also observed at all concentrations tested. cAMP generation was measured by ELISA in isolated AFMs in response to the CRF peptides and Iso and significant production was seen at all concentrations and time points tested. Conclusions The CRF family of peptides effectively increases cardiac contractility and should be evaluated as potential novel therapeutics for heart failure patients. PMID:26231084

Asymmetry in the control of cardiac performance by dorsomedial hypothalamus.

PubMed

Xavier, Carlos Henrique; Beig, Mirza Irfan; Ianzer, Danielle; Fontes, Marco Antônio Peliky; Nalivaiko, Eugene

2013-04-15

Dorsomedial hypothalamus (DMH) plays a key role in integrating cardiovascular responses to stress. We have recently reported greater heart rate responses following disinhibition of the right side of the DMH (R-DMH) in anesthetized rats and greater suppression of stress-induced tachycardia following inhibition of the R-DMH in conscious rats [both compared with similar intervention in the left DMH (L-DMH)], suggesting existence of right/left side asymmetry in controlling cardiac chronotropic responses by the DMH. The aim of the present study was to determine whether similar asymmetry is present for controlling cardiac contractility. In anesthetized rats, microinjections of the GABAA antagonist bicuculline methiodide (BMI; 40 pmol/100 nl) into the DMH-evoked increases in heart rate (HR), left ventricular pressure (LVP), myocardial contractility (LVdP/dt), arterial pressure, and respiratory rate. DMH disinhibition also precipitated multiple ventricular and supraventricular ectopic beats. DMH-induced increases in HR, LVP, LVdP/dt, and in the number of ectopic beats dependent on the side of stimulation, with R-DMH provoking larger responses. In contrast, pressor and respiratory responses did not depend on the side of stimulation. Newly described DMH-induced inotropic responses were rate-, preload- and (largely) afterload-independent; they were mediated by sympathetic cardiac pathway, as revealed by their sensitivity to β-adrenergic blockade. We conclude that recruitment of DMH neurons causes sympathetically mediated positive chronotropic and inotropic effects, and that there is an asymmetry, at the level of the DMH, in the potency to elicit these effects, with R-DMH > L-DMH.

Premorbid determinants of left ventricular dysfunction in a novel model of gradually induced pressure overload in the adult canine

NASA Technical Reports Server (NTRS)

Koide, M.; Nagatsu, M.; Zile, M. R.; Hamawaki, M.; Swindle, M. M.; Keech, G.; DeFreyte, G.; Tagawa, H.; Cooper, G. 4th; Carabello, B. A.

1997-01-01

BACKGROUND: When a pressure overload is placed on the left ventricle, some patients develop relatively modest hypertrophy whereas others develop extensive hypertrophy. Likewise, the occurrence of contractile dysfunction also is variable. The cause of this heterogeneity is not well understood. METHODS AND RESULTS: We recently developed a model of gradual proximal aortic constriction in the adult canine that mimicked the heterogeneity of the hypertrophic response seen in humans. We hypothesized that differences in outcome were related to differences present before banding. Fifteen animals were studied initially. Ten developed left ventricular dysfunction (dys group). Five dogs maintained normal function (nl group). At baseline, the nl group had a lower mean systolic wall stress (96 +/- 9 kdyne/cm2; dys group, 156 +/- 7 kdyne/cm2; P < .0002) and greater relative left ventricular mass (left ventricular weight [g]/body wt [kg], 5.1 +/- 0.36; dys group, 3.9 +/- 0.26; P < .02). On the basis of differences in mean systolic wall stress at baseline, we predicted outcome in the next 28 dogs by using a cutoff of 115 kdyne/cm2. Eighteen of 20 dogs with baseline mean systolic stress > 115 kdyne/cm2 developed dysfunction whereas 6 of 8 dogs with resting stress < or = 115 kdyne/cm2 maintained normal function. CONCLUSIONS: We conclude that this canine model mimicked the heterogeneous hypertrophic response seen in humans. In the group that eventually developed dysfunction there was less cardiac mass despite 60% higher wall stress at baseline, suggesting a different set point for regulating myocardial growth in the two groups.

Left atrial physiology and pathophysiology: Role of deformation imaging

PubMed Central

Kowallick, Johannes Tammo; Lotz, Joachim; Hasenfuß, Gerd; Schuster, Andreas

2015-01-01

The left atrium (LA) acts as a modulator of left ventricular (LV) filling. Although there is considerable evidence to support the use of LA maximum and minimum volumes for disease prediction, theoretical considerations and a growing body of literature suggest to focus on the quantification of the three basic LA functions: (1) Reservoir function: collection of pulmonary venous return during LV systole; (2) Conduit function: passage of blood to the left ventricle during early LV diastole; and (3) Contractile booster pump function (augmentation of ventricular filling during late LV diastole. Tremendous advances in our ability to non-invasively characterize all three elements of atrial function include speckle tracking echocardiography (STE), and more recently cardiovascular magnetic resonance myocardial feature tracking (CMR-FT). Corresponding imaging biomarkers are increasingly recognized to have incremental roles in determining prognosis and risk stratification in cardiac dysfunction of different origins. The current editorial introduces the role of STE and CMR-FT for the functional assessment of LA deformation as determined by strain and strain rate imaging and provides an outlook of how this exciting field may develop in the future. PMID:26131333

Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.

PubMed

Harjola, Veli-Pekka; Mebazaa, Alexandre; Čelutkienė, Jelena; Bettex, Dominique; Bueno, Hector; Chioncel, Ovidiu; Crespo-Leiro, Maria G; Falk, Volkmar; Filippatos, Gerasimos; Gibbs, Simon; Leite-Moreira, Adelino; Lassus, Johan; Masip, Josep; Mueller, Christian; Mullens, Wilfried; Naeije, Robert; Nordegraaf, Anton Vonk; Parissis, John; Riley, Jillian P; Ristic, Arsen; Rosano, Giuseppe; Rudiger, Alain; Ruschitzka, Frank; Seferovic, Petar; Sztrymf, Benjamin; Vieillard-Baron, Antoine; Yilmaz, Mehmet Birhan; Konstantinides, Stavros

2016-03-01

Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV-specific treatment approaches. © 2016 The Authors European Journal of Heart Failure © 2016 European Society of Cardiology.

Left ventricular remodeling in preclinical experimental mitral regurgitation of dogs.

PubMed

Dillon, A Ray; Dell'Italia, Louis J; Tillson, Michael; Killingsworth, Cheryl; Denney, Thomas; Hathcock, John; Botzman, Logan

2012-03-01

Dogs with experimental mitral regurgitation (MR) provide insights into the left ventricular remodeling in preclinical MR. The early preclinical left ventricular (LV) changes after mitral regurgitation represent progressive dysfunctional remodeling, in that no compensatory response returns the functional stroke volume (SV) to normal even as total SV increases. The gradual disease progression leads to mitral annulus stretch and enlargement of the regurgitant orifice, further increasing the regurgitant volume. Remodeling with loss of collagen weave and extracellular matrix (ECM) is accompanied by stretching and hypertrophy of the cross-sectional area and length of the cardiomyocyte. Isolated ventricular cardiomyocytes demonstrate dysfunction based on decreased cell shortening and reduced intracellular calcium transients before chamber enlargement or decreases in contractility in the whole heart can be clinically appreciated. The genetic response to increased end-diastolic pressure is down-regulation of genes associated with support of the collagen and ECM and up-regulation of genes associated with matrix remodeling. Experiments have not demonstrated any beneficial effects on remodeling from treatments that decrease afterload via blocking the renin-angiotensin system (RAS). Beta-1 receptor blockade and chymase inhibition have altered the progression of the LV remodeling and have supported cardiomyocyte function. The geometry of the LV during the remodeling provides insight into the importance of regional differences in responses to wall stress. Copyright © 2012 Elsevier B.V. All rights reserved.

Changes in left atrial deformation in hypertrophic cardiomyopathy: Evaluation by vector velocity imaging

PubMed Central

Badran, Hala Mahfouz; Soltan, Ghada; Hassan, Hesham; Nazmy, Ahmed; Faheem, Naglaa; Saadan, Haythem; Yacoub, Magdi H.

2012-01-01

Abstract: Objectives: Hypertrophic cardiomyopathy (HCM) represents a generalized myopathic process affecting both ventricular and atrial myocardium. We assessed the global and regional left atrial (LA) function and its relation to left ventricular (LV) mechanics and clinical status in patients with HCM using Vector Velocity Imaging (VVI). Methods: VVI of the LA and LV was acquired from apical four- and two-chamber views of 108 HCM patients (age 40 ± 19years, 56.5% men) and 33 healthy subjects, all had normal LV systolic function. The LA subendocardium was traced to obtain atrial volumes, ejection fraction, velocities, and strain (ϵ)/strain rate (SR) measurements. Results: Left atrial reservoir (ϵsys,SRsys) and conduit (early diastolic SRe) function were significantly reduced in HCM compared to controls (P < .0001). Left atrial deformation directly correlated to LVϵsys, SRsys and negatively correlated to age, NYHA class, left ventricular outflow tract (LVOT) gradient, left ventricular mass index (LVMI), LA volume index and severity of mitral regurge (P < 0.001). Receiver operating characterist was constructed to explore the cutoff value of LA deformation in differentiation of LA dysfunction; ϵsys < 40% was 75% sensitive, 50% specific, SRsys < 1.7s− 1 was 70% sensitive, 61% specific, SRe> − 1.8s− 1 was 81% sensitive and 30% specific, SRa> − 1.5s− 1 was 73% sensitive and 40% specific. By multivariate analysis global LVϵsys and LV septal thickness are independent predictors for LAϵsys, while end systolic diameter is the only independent predictor for SRsys, P < .001. Conclusion: Left atrial reservoir and conduit function as measured by VVI were significantly impaired while contractile function was preserved among HCM patients. Left atrial deformation was greatly influenced by LV mechanics and correlated to severity of phenotype. PMID:24688992

Effects of increased left ventricular wall thickness on the myocardium in severe aortic stenosis with normal left ventricular ejection fraction: Two- and three-dimensional multilayer speckle tracking echocardiography.

PubMed

Cho, Eun Jeong; Park, Sung-Ji; Kim, Eun Kyoung; Lee, Ga Yeon; Chang, Sung-A; Choi, Jin-Oh; Lee, Sang-Chol; Park, Seung Woo

2017-04-01

The aim of this study was to determine the capability of real time three-dimensional echocardiography (RT3DE) and two-dimensional (2D) multilayer speckle tracking echocardiography (MSTE) for evaluation of early myocardial dysfunction triggered by increased left ventricular (LV) wall thickness in severe aortic stenosis (AS) with normal LV ejection fraction (EF≥55%). Conventional, RT3D STE and 2D MSTE were performed in 45 patients (mean 68.9±9.0 years) with severe AS (aortic valve area <1 cm 2 , aortic velocity Vmax >4 m/s or mean PG >40 mm Hg) and normal left ventricular ejection fraction (LVEF) without overt coronary artery disease and in 18 age-, sex-matched healthy controls. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were calculated using RT3DE and MSTE. The severe AS group had lower 3D GLS, GRS, GAS and 2D epicardium, and mid-wall and endocardium GLS compared to healthy controls. In MSTE analysis, 2D LS and CS values decreased from the endocardial layer toward the epicardial layer. Severe AS patients with increased LV wall thickness had lower 3D GLS and 2D epicardium, and mid-wall and endocardium GLS compared with severe AS patients without LV wall thickening. GLS on RT3D STE was correlated with GLS on 2D MSTE, left ventricular mass index, LVEF, left atrial volume index, and lnNT-proBNP. RT3DE and 2D MSTE can be used to identify subtle contractile dysfunction triggered by increased LV wall thickness in severe AS with normal LVEF. Therefore, RT3D STE and 2D MSTE may provide additional information that can facilitate decision-making regarding severe AS patients with increased LV wall thickness and normal LV function. © 2017, Wiley Periodicals, Inc.

Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors.

PubMed

Pustovit, Ksenia B; Kuzmin, Vladislav S; Abramochkin, Denis V

2016-03-01

Diadenosine polyphosphates (Ap(n)As) are endogenously produced molecules which have been identified in various tissues of mammalian organism, including myocardium. Ap(n)As contribute to the blood clotting and are also widely accepted as regulators of blood vascular tone. Physiological role of Ap(n)As in cardiac muscle has not been completely elucidated. The present study aimed to investigate the effects of diadenosine tetra- (Ap4A) and penta- (Ap5A) polyphosphates on contractile function and action potential (AP) waveform in rat supraventricular and ventricular myocardium. We have also demonstrated the effects of A4pA and Ap5A in myocardial sleeves of pulmonary veins (PVs), which play a crucial role in genesis of atrial fibrillation. APs were recorded with glass microelectrodes in multicellular myocardial preparations. Contractile activity was measured in isolated Langendorff-perfused rat hearts. Both Ap4A and Ap5A significantly reduced contractility of isolated Langendorff-perfused heart and produced significant reduction of AP duration in left and right auricle, interatrial septum, and especially in right ventricular wall myocardium. Ap(n)As also shortened APs in rat pulmonary veins and therefore may be considered as potential proarrhythmic factors. Cardiotropic effects of Ap4A and Ap5A were strongly antagonized by selective blockers of P2 purine receptors suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), while P1 blocker DPCPX was not effective. We conclude that Ap(n)As may be considered as new class of endogenous cardioinhibitory compounds. P2 purine receptors play the central role in mediation of Ap4A and Ap5A inhibitory effects on electrical and contractile activity in different regions of the rat heart.

Clinical review: Positive end-expiratory pressure and cardiac output

PubMed Central

Luecke, Thomas; Pelosi, Paolo

2005-01-01

In patients with acute lung injury, high levels of positive end-expiratory pressure (PEEP) may be necessary to maintain or restore oxygenation, despite the fact that 'aggressive' mechanical ventilation can markedly affect cardiac function in a complex and often unpredictable fashion. As heart rate usually does not change with PEEP, the entire fall in cardiac output is a consequence of a reduction in left ventricular stroke volume (SV). PEEP-induced changes in cardiac output are analyzed, therefore, in terms of changes in SV and its determinants (preload, afterload, contractility and ventricular compliance). Mechanical ventilation with PEEP, like any other active or passive ventilatory maneuver, primarily affects cardiac function by changing lung volume and intrathoracic pressure. In order to describe the direct cardiocirculatory consequences of respiratory failure necessitating mechanical ventilation and PEEP, this review will focus on the effects of changes in lung volume, factors controlling venous return, the diastolic interactions between the ventricles and the effects of intrathoracic pressure on cardiac function, specifically left ventricular function. Finally, the hemodynamic consequences of PEEP in patients with heart failure, chronic obstructive pulmonary disease and acute respiratory distress syndrome are discussed. PMID:16356246

Andrographis paniculata extract protect against isoproterenol-induced myocardial injury by mitigating cardiac dysfunction and oxidative injury in rats.

PubMed

Ojha, Shreesh; Bharti, Saurabh; Golechha, Mahaveer; Sharma, Ashok K; Rani, Neha; Kumari, Santosh; Arya, Dharamvir Singh

2012-01-01

Present study evaluated the cardioprotective effect of Andrographis paniculata (100, 200 or 400 mg/kg) against isoproterenol (85 mg/kg, b.w.)-induced cardiotoxicity referred as myocardial infarction in rats. Isoproterenol significantly (p < 0.05) decreased mean arterial pressure, heart rate, contractility and relaxation and increased left ventricular end diastolic pressure. Isoproterenol also significantly (p < 0.05) decreased antioxidants, superoxide dismutase, catalase, glutathione peroxidase, glutathione and increased leakage of cardiac injury markers; creatine phosphokinase-MB isoenzyme, lactate dehydrogenase concomitant to increased lipid peroxidation and histopathological perturbations. However, pretreatment with A. paniculata favorably restored hemodynamic parameters and left ventricular function and significantly (p < 0.05) prevented the depletion of endogenous antioxidants and myocyte marker enzymes as well as inhibited lipid peroxidation. Significant (p < 0.05) reversal of almost all the hemodynamic, biochemical and histopathological parameters by A. paniculata pretreatment in isoproterenol-induced cardiotoxicity depicted the cardioprotective effect of A. paniculata. Results showed that A. paniculata protected heart against cardiotoxic effects of isoproterenol by boosting endogenous antioxidant network, restoring ventricular function and maintaining structural integrity of heart.

Akt2 Knockout Alleviates Prolonged Caloric Restriction-Induced Change in Cardiac Contractile Function through Regulation of Autophagy

PubMed Central

Zhang, Yingmei; Han, Xuefeng; Hu, Nan; Huff, Anna F.; Gao, Feng; Ren, Jun

2014-01-01

Caloric restriction leads to changes in heart geometry and function although the underlying mechanism remains elusive. Autophagy, a conserved pathway for degradation of intracellular proteins and organelles, preserves energy and nutrient in the face of caloric insufficiency. This study was designed to examine the role of Akt2 in prolonged caloric restriction-induced change in cardiac homeostasis and the underlying mechanism(s) involved. Wild-type (WT) and Akt2 knockout mice were caloric restricted (by 40%) for 30 weeks. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties, autophagy and its regulatory proteins were evaluated. Caloric restriction compromised echocardiographic indices (decreased left ventricular mass, left ventricular diameters and cardiac output), cardiomyocyte contractile and intracellular Ca2+ properties associated with dampened SERCA2a phosphorylation, upregulated phospholamban and autophagy (Beclin-1, Atg7, LC3BII-to-LC3BI ratio), increased autophagy adaptor protein p62, elevated phosphorylation of AMPK, Akt2 and the Akt downstream signal molecule TSC2, the effects of which with the exception of autophagy protein markers (Beclin-1, Atg7, LC3B) and AMPK were mitigated or significantly alleviated by Akt2 knockout. Lysosomal inhibition using bafilomycin A1 negated Akt2 knockout-induced protective effect on p62. Evaluation of downstream signaling molecules of Akt and AMPK including mTOR and ULK1 revealed that caloric restriction suppressed and promoted phosphorylation of mTOR and ULK1, respectively, without affecting total mTOR and ULK1 expression. Akt2 knockout significantly augmented caloric restriction-induced responses on mTOR and ULK1. Taken together, these data suggest a beneficial role of Akt2 knockout in preservation of cardiac homeostasis against prolonged caloric restriction-induced pathological changes possibly through facilitating autophagy. PMID:24368095

Superiority of desflurane over sevoflurane and isoflurane in the presence of pressure-overload right ventricle hypertrophy in rats.

PubMed

Blaudszun, Grégoire; Morel, Denis R

2012-11-01

Pulmonary hypertension and associated pressure-overload right ventricular (RV) hypertrophy represent a tremendous challenge for the anesthesiologist, as optimal perioperative management is mandatory. However, the ideal anesthetic agent remains unknown because scientific evidence is lacking. Twenty-eight rats were randomly assigned to a control or a monocrotaline group (60 mg kg). Four weeks later, animals were anesthetized, instrumented with a RV conductance catheter, and underwent well-controlled dose-responses to isoflurane, desflurane, and sevoflurane inhalation (minimum alveolar concentrations 0.5, 1.0, 1.5). Compared with controls, rats injected with monocrotaline presented with RV hypertrophy, increased afterload, and contractility, without change in cardiac output. The ratio of pressures in the right over the left circulation increased. The halogenated volatiles differently altered hemodynamics. Sevoflurane reduced RV contractility (more than 50%) and the right over left pressures ratio increased (from 0.41 ± 0.08 [SD] to 0.82 ± 0.14; P < 0.0001) secondary to profound concomitant systemic vasodilation, demonstrating a critical pressure gradient between right and left circulations. Despite significantly higher RV systolic pressures and afterload, desflurane decreased RV contractility much less (<10%; P < 0.0001 vs. sevoflurane) and maintained the right over left pressures ratio at more favorable values (0.47 ± 0.07; P < 0.0001 vs. sevoflurane). Isoflurane presented intermediate effects. In the presence of pressure-overload RV hypertrophy, hemodynamics are better preserved under desflurane inhalation, whereas sevoflurane-and to a lesser extent isoflurane-cause large discrepancies on the left and right circulations, raising the right over left pressures ratio to critical levels despite a conserved cardiac output.

The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats with streptozotocin-induced diabetes.

PubMed

Cheng, Xing; Xia, Zhengyuan; Leo, Joyce M; Pang, Catherine C Y

2005-09-05

We examined if myocardial depression at the acute phase of diabetes (3 weeks after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of inducible nitric oxide synthase and production of peroxynitrite, and if treatment with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac function. Four groups of rats were used: control, N-acetylcysteine-treated control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital-anaesthetized diabetic rats, relative to the controls, had reduced left ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats also had increased myocardial levels of thiobarbituric acid reactive substances, immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the control rats; but increased cardiac contractility to dobutamine, reduced myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine and level of 15-F2t-isoprostane, and increased cardiac contractility to dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces oxidative stress and improves cardiac function.

Electrical latency predicts the optimal left ventricular endocardial pacing site: results from a multicentre international registry.

PubMed

Sieniewicz, Benjamin J; Behar, Jonathan M; Sohal, Manav; Gould, Justin; Claridge, Simon; Porter, Bradley; Niederer, Steve; Gamble, James H P; Betts, Tim R; Jais, Pierre; Derval, Nicolas; Spragg, David D; Steendijk, Paul; van Gelder, Berry M; Bracke, Frank A; Rinaldi, Christopher A

2018-04-23

The optimal site for biventricular endocardial (BIVENDO) pacing remains undefined. Acute haemodynamic response (AHR) is reproducible marker of left ventricular (LV) contractility, best expressed as the change in the maximum rate of LV pressure (LV-dp/dtmax), from a baseline state. We examined the relationship between factors known to impact LV contractility, whilst delivering BIVENDO pacing at a variety of LV endocardial (LVENDO) locations. We compiled a registry of acute LVENDO pacing studies from five international centres: Johns Hopkins-USA, Bordeaux-France, Eindhoven-The Netherlands, Oxford-United Kingdom, and Guys and St Thomas' NHS Foundation Trust, London-UK. In all, 104 patients incorporating 687 endocardial and 93 epicardial pacing locations were studied. Mean age was 66 ± 11 years, mean left ventricular ejection fraction 24.6 ± 7.7% and mean QRS duration of 163 ± 30 ms. In all, 50% were ischaemic [ischaemic cardiomyopathy (ICM)]. Scarred segments were associated with worse haemodynamics (dp/dtmax; 890 mmHg/s vs. 982 mmHg/s, P < 0.01). Delivering BiVENDO pacing in areas of electrical latency was associated with greater improvements in AHR (P < 0.01). Stimulating late activating tissue (LVLED >50%) achieved greater increases in AHR than non-late activating tissue (LVLED < 50%) (8.6 ± 9.6% vs. 16.1 ± 16.2%, P = 0.002). However, the LVENDO pacing location with the latest Q-LV, was associated with the optimal AHR in just 62% of cases. Identifying viable LVENDO tissue which displays late electrical activation is crucial to identifying the optimal BiVENDO pacing site. Stimulating late activating tissue (LVLED >50%) yields greater improvements in AHR however, the optimal location is frequently not the site of latest activation.

Pressure-derived indices of left ventricular isovolumic relaxation in patients with hypertrophic cardiomyopathy.

PubMed Central

Thompson, D S; Wilmshurst, P; Juul, S M; Waldron, C B; Jenkins, B S; Coltart, D J; Webb-Peploe, M M

1983-01-01

High fidelity measurements of left ventricular pressure were made at increasing pacing rates in 21 patients with hypertrophic cardiomyopathy and a control group of 11 patients investigated for chest pain who proved to have normal hearts. In both groups the fall in pressure during isovolumic relaxation from the point of min dp/dt approximated closely to a monoexponential, and could be described by a time constant and asymptote. The time constant shortened and the asymptote increased as heart rate rose in both groups. The time constant was longer and min dp/dt less in the cardiomyopathy group than controls at all heart rates. In the cardiomyopathy patients min dp/dt, but not the time constant, was related to systolic pressure. During pacing, eight cardiomyopathy patients developed metabolic evidence of myocardial ischaemia, but indices of relaxation did not differ between these eight and the other 13 either at basal heart rate or the highest pacing rate. In 10 cardiomyopathy patients measurements were repeated at comparable pacing rates after propranolol (0.2 mg/kg). Left ventricular end-diastolic pressure and indices of contractility decreased after the drug, but the time constant did not change. Eight patients received verapamil (20 mg) after which there were substantial reductions in systolic pressure and contractility. Min dp/dt decreased in proportion to systolic pressure, but the time constant was unchanged. At the highest pacing rate before drug administration three patients had abnormal lactate extraction which was corrected by either propranolol (one patient) or verapamil (two patients). Despite abolition of metabolic evidence of ischaemia, relaxation did not improve. It is concluded that abnormal isovolumic relaxation is common in patients with hypertrophic cardiomyopathy, but its severity correlates poorly with other features of the disease. Abnormal relaxation is not the result of ischaemia, and pressure derived indices of relaxation do not improve after the administration of propranolol or verapamil. PMID:6681978

Gestational changes in left ventricular myocardial contractile function: new insights from two-dimensional speckle tracking echocardiography.

PubMed

Sengupta, Shantanu P; Bansal, Manish; Hofstra, Leonard; Sengupta, Partho P; Narula, Jagat

2017-01-01

The goal of this study was to evaluate the impact of pregnancy and labor on left ventricular (LV) myocardial mechanics using speckle tracking echocardiography (STE). Pregnancy is characterized by profound hormonal and hemodynamic alterations that directly or indirectly influence cardiac structure and function. However, the impact of these changes on left ventricular (LV) myocardial contractile function has not been fully elucidated. In this prospective, longitudinal study, 35 pregnant women underwent serial clinical and echocardiographic evaluation during each trimester and at labor. Two dimensional STE was performed to measure global LV longitudinal, circumferential and radial strain (GLS, GCS and GRS, respectively). Similar data obtained from 20 nulliparous, age-matched women were used as control. All strain values during pregnancy were adjusted for age and hemodynamic parameters. There was a progressive increase in heart rate, systolic and diastolic blood pressure, cardiac output and LV stroke-work during pregnancy. LV end-diastolic and end-systolic volumes also increased progressively but LV ejection fraction remained unaltered, except for slight reduction during the second trimester. Compared to the controls, GLS and GCS were reduced in the first trimester itself (GLS -22.39 ± 5.43 % vs. -18.66 ± 0.64 %, P 0.0002; GCS -20.84 ± 3.20 vs. -17.88 ± 0.09, P < 0.001) and remained so throughout the pregnancy and labor. In contrast, GRS showed an increase during pregnancy which peaked during the second trimester (24.18 ± 0.39 % vs. 18.06 ± 8.14 % in controls, P < 0.001). Alterations in loading conditions during pregnancy are associated with counterbalancing changes in the myocardial mechanics. LV longitudinal and circumferential strain are reduced whereas radial strain is increased. These counterbalancing changes serve to maintain overall LV ejection performance within a normal range and enable the maternal heart to meet the hemodynamic demands of pregnancy and labor.

Contribution of mammalian target of rapamycin in the pathophysiology of cirrhotic cardiomyopathy.

PubMed

Saeedi Saravi, Seyed Soheil; Ghazi-Khansari, Mahmoud; Ejtemaei Mehr, Shahram; Nobakht, Maliheh; Mousavi, Seyyedeh Elaheh; Dehpour, Ahmad Reza

2016-05-21

To explore the role of mammalian target of rapamycin (mTOR) in the pathogenesis of cirrhotic cardiomyopathy and the potential of rapamycin to improve this pathologic condition. Male albino Wistar rats weighing 100-120 g were treated with tetrachloride carbon (CCl4) for 8 wk to induce cirrhosis. Subsequently, animals were administered rapamycin (2 mg/kg per day). The QTc intervals were calculated in a 5-min electrocardiogram. Then, the left ventricular papillary muscles were isolated to examine inotropic responsiveness to β-adrenergic stimulation using a standard organ bath equipped by Powerlab system. Phosphorylated-mTOR localization in left ventricles was immunohistochemically assessed, and ventricular tumor necrosis factor (TNF)-α was measured. Western blot was used to measure levels of ventricular phosphorylated-mTOR protein. Cirrhosis was confirmed by hematoxylin and eosin staining of liver tissues, visual observation of lethargy, weight loss, jaundice, brown urine, ascites, liver stiffness, and a significant increase of spleen weight (P < 0.001). A significant prolongation in QTc intervals occurred in cirrhotic rats exposed to CCl4 (P < 0.001), while this prolongation was decreased with rapamycin treatment (P < 0.01). CCl4-induced cirrhosis caused a significant decrease of contractile responsiveness to isoproterenol stimulation and a significant increase in cardiac TNF-α. These findings were correlated with data from western blot and immunohistochemical studies on phosphorylated-mTOR expression in left ventricles. Phosphorylated-mTOR was significantly enhanced in cirrhotic rats, especially in the endothelium, compared to controls. Rapamycin treatment significantly increased contractile force and myocardial localization of phosphorylated-mTOR and decreased cardiac TNF-α concentration compared to cirrhotic rats with no treatment. In this study, we demonstrated a potential role for cardiac mTOR in the pathophysiology of cirrhotic cardiomyopathy. Rapamycin normalized the inotropic effect and altered phosphorylated-mTOR expression and myocardial localization in cirrhotic rats.

Left atrial function: evaluation by strain analysis

PubMed Central

Gan, Gary C. H.; Ferkh, Aaisha; Boyd, Anita

2018-01-01

The left atrium has an important role in modulating left ventricular filling and is an important biomarker of cardiovascular disease and adverse cardiovascular outcomes. While previously left atrial (LA) size was utilised, the role of LA function as a biomarker is increasingly being evaluated, both independently and also in combination with LA size. Strain analysis has been utilised for evaluation of LA function and can be measured throughout the cardiac cycle, thereby enabling the evaluation of LA reservoir, conduit and contractile function. Strain evaluates myocardial deformation while strain rate examines the rate of change in strain. This review will focus on the various types of strain analysis for evaluation of LA function, alterations in LA strain in physiological and pathologic states that alter LA function and finally evaluate its utility as a prognostic marker. PMID:29541609

Effects of 4 classes of cardiovascular drugs on ventricular function in dogs with mitral regurgitation.

PubMed

Nakayama, Tomohiro; Nishijima, Yoshinori; Miyamoto, Mutsumi; Hamlin, Robert L

2007-01-01

There have been few trials in which dogs with mitral regurgitation (MR) have been treated with various cardioactive drugs to determine effects on left ventricular (LV) function. Four classes of cardiovascular drugs may improve LV function in dogs with MR without increasing MR. Nine mature dogs were included in the study. MR was produced in 9 dogs. Five months later under butorphanol narcosis, parameters of LV function and left atrial dimension (LAD) were monitored by LV micromanometry and echocardiography/Doppler. Dogs were given (in random order) enalaprilat, nitroglycerine, ouabain, milrinone, and placebo. Nitroglycerin produced no significant change; milrinone and ouabain increased contractility; ouabain decreased heart rate; and there was evidence that enalaprilat and milrinone decreased LAD. Milrinone and ouabain decreased isovolumetric contraction time and therefore the time available for MR. There was no evidence that a positive inotrope increased MR despite increasing LV contractility and stroke volume. This study contradicts the hypotheses that (1) strengthening the left ventricle may increase MR and (2) treatment of MR (even before symptoms of heart failure develop) may decrease LAD. It is reasonable that strengthening the force of LV contraction should increase the driving pressure for MR; however, this effect did not appear to increase MR. Although some investigators believe that treating dogs with MR with afterload reducers and decreasing hindrance to ejection of blood from the LV to aorta may lengthen life by decreasing MR, there did not appear to be a reduction in MR, at least in response to the angiotensin-converting enzyme (ACE) inhibitor.

Pressure-volume Relationship in the Stress-echocardiography Laboratory: Does (Left Ventricular End-diastolic) Size Matter?

PubMed

Bombardini, Tonino; Mulieri, Louis A; Salvadori, Stefano; Costantino, Marco Fabio; Scali, Maria Chiara; Marzilli, Mario; Picano, Eugenio

2017-02-01

The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. Whether and to what extent it depends on end-diastolic volume remains unclear. The aim of this study was to assess the dependence of the delta rest-stress end-systolic pressure-volume relation on end-diastolic volume in patients with negative stress echo and all ranges of resting left ventricular function. We analyzed interpretable data obtained in 891 patients (593 men, age 63 ± 12 years) with ejection fraction 47% ± 12%: 338 were normal or near-normal or hypertensive; 229 patients had coronary artery disease; and 324 patients had ischemic or nonischemic dilated cardiomyopathy. They were studied with exercise (n = 172), dipyridamole (n = 482) or dobutamine (n = 237) stress echocardiography. The end-systolic pressure-volume relation was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson rule 2-dimensional echocardiography. Absolute values of delta rest-stress end-systolic pressure-volume relation were higher for exercise and dobutamine than for dipyridamole. In the overall population, an inverse relationship between end-systolic pressure-volume relation and end-diastolic volume was present at rest (r 2 = 0.69, P < .001) and peak stress (r 2 = 0.56, P < .001), but was absent if the delta rest-stress end-systolic pressure-volume relation was considered (r 2 = 0.13). Left ventricular end-diastolic volume does not affect the rest-stress changes in end-systolic pressure-volume relation in either normal or abnormal left ventricles during physical or pharmacological stress. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

[Adaptation to effort in patients with chronic cardiac insufficiency; study by post-exercise Doppler echocardiography, comparative results with a control population].

PubMed

Pouillart, F; Perchet, H; Duval-Moulin, A M; Heintz, J F; Hittinger, L; Brun, P; Castaigne, A; Dubois-Randé, J L

1995-04-01

Adaptation to exercise was studied by post-exercise Doppler echocardiography in patients with chronic cardiac failure and an apparently healthy control population matched for age. This post-exercise Doppler echocardiographic method initially introduced for the detection of myocardial ischaemia has already been validated in normal subjects for the analysis of haemodynamic changes caused by exercise providing the data is recorded in the first 5 minutes following recovery in the recumbent position. Eleven patients with chronic cardiac failure in NYHA classes II or III with a mean age of 54 +/- 11 years and 6 controls (mean age: 46 +/- 9 years) were investigated. The patients had been stabilised for at least 3 months with a vasodilator and diuretic therapy: the control subjects had no medication. After bicycle ergometry performed to 70% of maximum capacity, the subjects were positioned in the left lateral recumbent position. Doppler echocardiography was then performed in the immediate recovery phase. When compared to the control population, the patients with cardiac failure had a reduced chronotropic reserve, a smaller increase in the parameters of myocardial contractility (maximal aortic velocity, maximal aortic acceleration and left ventricular fractional shortening) without an increase in left ventricular end diastolic dimensions in subjects with severe dilatation under basal conditions (left ventricular end diastolic dimension 69 +/- 3 mm). This result suggests the absence of a Frank-Starling effect. The lack of adaptation of the peripheral vascular system was demonstrated by the lack of reduction of left ventricular end systolic stress, already greatly increased at rest (176 vs 77 +/- 10 g/cm2 for patients, compared with controls; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiohemodynamic and electrophysiological effects of a selective EP4 receptor agonist ONO--AE1--329 in the halothane-anesthetized dogs.

PubMed

Nomura, Hiroaki; Nakamura, Yuji; Cao, Xin; Honda, Atsushi; Katagi, Jun; Ohara, Hiroshi; Izumi-Nakaseko, Hiroko; Satoh, Yoshioki; Ando, Kentaro; Sugiyama, Atsushi

2015-08-15

Cardiovascular effects of a highly selective prostaglandin E2 type 4 (EP4) receptor agonist ONO-AE1-329 were assessed with the halothane-anesthetized dogs (n=6). ONO-AE1-329 was intravenously infused in three escalating doses of 0.3, 1 and 3ng/kg/min for 10min with a pause of 20min between the doses. The low dose of 0.3ng/kg/min significantly increased maximum upstroke velocity of left ventricular pressure by 18% at 20min, indicating increase of ventricular contractility. The middle dose of 1ng/kg/min significantly decreased total peripheral resistance by 24% and left ventricular end-diastolic pressure by 32% at 10min, indicating dilation of arteriolar resistance vessels and venous capacitance ones, respectively; and increased cardiac output by 25% at 10min in addition to the change induced by the low dose. The high dose of 3ng/kg/min increased heart rate by 34% at 10min; decreased mean blood pressure by 14% at 10min and atrioventricular nodal conduction time by 13% at 5min; and shortened left ventricular systolic period by 8% at 10min and electromechanical coupling defined as an interval from completion of repolarization to the start of ventricular diastole by 39% at 10min in addition to the changes induced by the middle dose. No significant change was detected in a ventricular repolarization period. These results indicate that ONO-AE1-329 may possess a similar cardiovascular profile to typical phosphodiesterase 3 inhibitors as an inodilator, and suggest that EP4 receptor stimulation can become an alternative strategy for the treatment of congestive heart failure. Copyright © 2015 Elsevier B.V. All rights reserved.

Rate-dependent electrical, contractile and restitution properties of isolated left ventricular myocytes in guinea-pig hypertrophy.

PubMed

Davey, P; Bryant, S; Hart, G

2001-01-01

Left ventricular hypertrophy predisposes to sudden cardiac death (SCD) and studies of human SCD suggest that the antecedent heart rate (HR) is usually < 100 beats min(-1). This is surprising in view of the known association between adrenergic receptor stimulation and SCD which by itself would suggest that it is more likely to occur from high rather than low HR. We therefore hypothesized that there may be electrical or mechanical abnormalities present in myocytes isolated from animals with left ventricular hypertrophy that predispose to SCD at low stimulation frequencies but which may not be present at high HR. Mild left ventricular hypertrophy was induced in guinea-pigs by infra-renal aortic banding. Electrical and mechanical properties of isolated myocytes were studied at different stimulation frequencies between 0.1 and 3 Hz. Action potential duration (APD) is prolonged in hypertrophy at stimulation frequencies < 1 Hz but not at faster rates. Contraction size, time-to-peak contraction (TTPC) and half-relaxation time are greatly enhanced in hypertrophy at all frequencies between 0.1 and 3 Hz. Electrical (50.3 +/- 5.2 ms in hypertrophy and 78.4 +/- 12.1 ms in control, P < 0.03) and mechanical (205 +/- 16 ms for hypertrophy and 266 +/- 24 ms for control cells, P < 0.03) restitution time constants are quicker in hypertrophy. The finding of APD prolongation at low but not at high frequencies is consistent with the finding that SCD arises from low and not high HR. This data supports the role of abnormal repolarization in SCD.

Cardiac contractility modulation in heart failure patients: Randomized comparison of signal delivery through one vs. two ventricular leads.

PubMed

Röger, Susanne; Said, Samir; Kloppe, Axel; Lawo, Thomas; Emig, Ulf; Rousso, Benny; Gutterman, David; Borggrefe, Martin; Kuschyk, Jürgen

2017-01-01

Cardiac contractility modulation (CCM) is an electrical stimulation treatment for symptomatic heart failure (HF) patients. The procedure involves implantation of two ventricular leads for delivery of CCM impulses. The purpose of this study is to compare the efficacy and safety of CCM when the signal is delivered through one vs. two ventricular leads. This prospective blinded randomized trial enrolled 48 patients. Eligible subjects had symptoms despite optimal HF medications, left ventricular ejection fraction <40% and peakVO 2 ≥9ml O 2 /kg/min. All patients received a CCM system with two ventricular leads, and were randomized to CCM active through both or just one ventricular lead; 25 patients were randomized to receive signal delivery through two leads (Group A) and 23 patients to signal delivery through one lead (Group B). The study compared the mean changes from baseline to 6 months follow-up in peakVO 2 , New York Heart Association (NYHA) classification, and quality of life (by MLWHFQ). Following 6 months, similar and significant (p<0.05) improvements from baseline in NYHA (-0.7±0.5 vs. -0.9±0.7) and MLWHFQ (-14±20 vs. -16±22) were observed in Group A and in Group B. PeakVO 2 showed improvement trends in both groups (0.34±1.52 vs. 0.10±2.21ml/kg/min; p=ns). No patient died. Serious adverse event rates (20 events in 10 subjects) were not different between groups. No statistically significant difference was found in any of the study endpoints. The efficacy and safety of CCM in this study were similar when the signal was delivered through either one or two ventricular leads. These results support the potential use of a single ventricular lead for delivery of CCM. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Effect of free fatty acids on myocardial function and metabolism in the ischemic dog heart

PubMed Central

Kjekshus, John K.; Mjøs, Ole D.

1972-01-01

Since elevation of plasma concentrations of free fatty acids (FFA) increases myocardial oxygen consumption without influencing mechanical performance in normal hearts, it was the purpose of this study to determine whether FFA would modify mechanical performance at limited oxygen supply. Left coronary blood flow was reduced by gradual clamping of a shunt from the left carotid artery until moderate ventricular dilatation supervened. Left ventricular systolic pressure (LVSP), its maximal rate of rise (dP/dt) and stroke volume (SV) were unchanged or slightly reduced. The ischemia resulted in a decrease in myocardial oxygen consumption (MVO2) from 9.7±1.1 ml/min to 7.9±0.8 ml/min, and myocardial lactate uptake was reduced or reversed to excretion. Increasing the plasma concentrations of FFA from 359±47 μEq/1 to 3688±520 μEq/1 by intravenous infusion of a triglyceride emulsion and heparin resulted in further ventricular dilatation, accompanied by increased excretion of lactate. The ventricular decompensation and enhancement of anaerobic myocardial metabolism associated with increased uptake of FFA was not related to changes in coronary flow, MVO2, or LVSP. dP/dt and SV were virtually unchanged. Intravenous infusion of glucose/insulin, which lowered plasma concentrations of FFA, reversed ventricular dilatation and lactate excretion. The data support the hypothesis that high concentrations of FFA play a significant role in increasing myocardial oxygen requirement and thereby promote depression of contractility of the hypoxic heart in experimental animals. Images PMID:5032525

A multi-scale cardiovascular system model can account for the load-dependence of the end-systolic pressure-volume relationship

PubMed Central

2013-01-01

Background The end-systolic pressure-volume relationship is often considered as a load-independent property of the heart and, for this reason, is widely used as an index of ventricular contractility. However, many criticisms have been expressed against this index and the underlying time-varying elastance theory: first, it does not consider the phenomena underlying contraction and second, the end-systolic pressure volume relationship has been experimentally shown to be load-dependent. Methods In place of the time-varying elastance theory, a microscopic model of sarcomere contraction is used to infer the pressure generated by the contraction of the left ventricle, considered as a spherical assembling of sarcomere units. The left ventricle model is inserted into a closed-loop model of the cardiovascular system. Finally, parameters of the modified cardiovascular system model are identified to reproduce the hemodynamics of a normal dog. Results Experiments that have proven the limitations of the time-varying elastance theory are reproduced with our model: (1) preload reductions, (2) afterload increases, (3) the same experiments with increased ventricular contractility, (4) isovolumic contractions and (5) flow-clamps. All experiments simulated with the model generate different end-systolic pressure-volume relationships, showing that this relationship is actually load-dependent. Furthermore, we show that the results of our simulations are in good agreement with experiments. Conclusions We implemented a multi-scale model of the cardiovascular system, in which ventricular contraction is described by a detailed sarcomere model. Using this model, we successfully reproduced a number of experiments that have shown the failing points of the time-varying elastance theory. In particular, the developed multi-scale model of the cardiovascular system can capture the load-dependence of the end-systolic pressure-volume relationship. PMID:23363818

Dependence of intramyocardial pressure and coronary flow on ventricular loading and contractility: a model study.

PubMed

Bovendeerd, Peter H M; Borsje, Petra; Arts, Theo; van De Vosse, Frans N

2006-12-01

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity.

The Achilles' heel of left ventricular assist device therapy: right ventricle.

PubMed

Ranganath, Neel K; Smith, Deane E; Moazami, Nader

2018-06-01

Many patients suffer from either persistent right ventricular failure (RVF) at the time of left ventricular assist device (LVAD) or have ongoing symptoms consistent with RVF during chronic mechanical circulatory support. The lack of long-term right ventricular assist devices (RVADs) has limited the impact that mechanical circulatory support can provide to patients with biventricular failure. We aim to review the entire spectrum of RVF in patients receiving LVADs and reflect on why this entity remains the Achilles' heel of LVAD therapy. In the early postoperative period, LVAD implantation reduces right ventricle (RV) afterload, but RV dysfunction may be exacerbated secondary to increased venous return. With prolonged therapy, the decreased RV afterload leads to improved RV contractile function. Bayesian statistical models outperform previously published preoperative risk scores by considering inter-relationships and conditional probabilities amongst independent variables. Various echocardiographic parameters and the pulmonary artery pulsatility index have shown promise in predicting post-LVAD RVF. Recent publications have delineated the emergence of 'delayed' RVF. Several devices are currently being investigated for use as RVADs. Post-LVAD RVF depends on the RV's ability to adapt to acute hemodynamic changes imposed by the LVAD. Management options are limited due to the lack of an easily implantable, chronic-use RVAD.

Microtubule Stabilization in Pressure Overload Cardiac Hypertrophy

PubMed Central

Sato, Hiroshi; Nagai, Toshio; Kuppuswamy, Dhandapani; Narishige, Takahiro; Koide, Masaaki; Menick, Donald R.; IV, George Cooper

1997-01-01

Increased microtubule density, for which microtubule stabilization is one potential mechanism, causes contractile dysfunction in cardiac hypertrophy. After microtubule assembly, α-tubulin undergoes two, likely sequential, time-dependent posttranslational changes: reversible carboxy-terminal detyrosination (Tyr-tubulin ↔ Glu-tubulin) and then irreversible deglutamination (Glu-tubulin → Δ2-tubulin), such that Glu- and Δ2-tubulin are markers for long-lived, stable microtubules. Therefore, we generated antibodies for Tyr-, Glu-, and Δ2-tubulin and used them for staining of right and left ventricular cardiocytes from control cats and cats with right ventricular hypertrophy. Tyr- tubulin microtubule staining was equal in right and left ventricular cardiocytes of control cats, but Glu-tubulin and Δ2-tubulin staining were insignificant, i.e., the microtubules were labile. However, Glu- and Δ2-tubulin were conspicuous in microtubules of right ventricular cardiocytes from pressure overloaded cats, i.e., the microtubules were stable. This finding was confirmed in terms of increased microtubule drug and cold stability in the hypertrophied cells. In further studies, we found an increase in a microtubule binding protein, microtubule-associated protein 4, on both mRNA and protein levels in pressure-hypertrophied myocardium. Thus, microtubule stabilization, likely facilitated by binding of a microtubule-associated protein, may be a mechanism for the increased microtubule density characteristic of pressure overload cardiac hypertrophy. PMID:9362514

AMP-Activated Protein Kinase Deficiency Rescues Paraquat-Induced Cardiac Contractile Dysfunction Through an Autophagy-Dependent Mechanism

PubMed Central

Wang, Qiurong; Yang, Lifang; Hua, Yinan; Nair, Sreejayan; Xu, Xihui; Ren, Jun

2014-01-01

Aim: Paraquat, a quaternary nitrogen herbicide, is a highly toxic prooxidant resulting in multi-organ failure including the heart although the underlying mechanism still remains elusive. This study was designed to examine the role of the cellular fuel sensor AMP-activated protein kinase (AMPK) in paraquat-induced cardiac contractile and mitochondrial injury. Results: Wild-type and transgenic mice with overexpression of a mutant AMPK α2 subunit (kinase dead, KD), with reduced activity in both α1 and α2 subunits, were administered with paraquat (45 mg/kg) for 48 h. Paraquat elicited cardiac mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic diameter and reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca2+ handling, reduced cell survival, and overt mitochondrial damage (loss in mitochondrial membrane potential). In addition, paraquat treatment promoted phosphorylation of AMPK and autophagy. Interestingly, deficiency in AMPK attenuated paraquat-induced cardiac contractile and intracellular Ca2+ derangement. The beneficial effect of AMPK inhibition was associated with inhibition of the AMPK-TSC-mTOR-ULK1 signaling cascade. In vitro study revealed that inhibitors for AMPK and autophagy attenuated paraquat-induced cardiomyocyte contractile dysfunction. Conclusion: Taken together, our findings revealed that AMPK may mediate paraquat-induced myocardial anomalies possibly by regulating the AMPK/mTOR-dependent autophagy. PMID:25092649

Dependence of Intramyocardial Pressure and Coronary Flow on Ventricular Loading and Contractility: A Model Study

PubMed Central

Borsje, Petra; Arts, Theo; van De Vosse, Frans N.

2006-01-01

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity. PMID:17048105

Increased cardiac alpha-myosin heavy chain in left atria and decreased myocardial insulin-like growth factor (Igf-I) expression accompany low heart rate in hibernating grizzly bears.

PubMed

Barrows, N D; Nelson, O L; Robbins, C T; Rourke, B C

2011-01-01

Grizzly bears (Ursus arctos horribilis) tolerate extended periods of extremely low heart rate during hibernation without developing congestive heart failure or cardiac chamber dilation. Left ventricular atrophy and decreased left ventricular compliance have been reported in this species during hibernation. We evaluated the myocardial response to significantly reduced heart rate during hibernation by measuring relative myosin heavy-chain (MyHC) isoform expression and expression of a set of genes important to muscle plasticity and mass regulation in the left atria and left ventricles of active and hibernating bears. We supplemented these data with measurements of systolic and diastolic function via echocardiography in unanesthetized grizzly bears. Atrial strain imaging revealed decreased atrial contractility, decreased expansion/reservoir function (increased atrial stiffness), and decreased passive-filling function (increased ventricular stiffness) in hibernating bears. Relative MyHC-α protein expression increased significantly in the atrium during hibernation. The left ventricle expressed 100% MyHC-β protein in both groups. Insulin-like growth factor (IGF-I) mRNA expression was reduced by ∼50% in both chambers during hibernation, consistent with the ventricular atrophy observed in these bears. Interestingly, mRNA expression of the atrophy-related ubiquitin ligases Muscle Atrophy F-box (MAFBx) and Muscle Ring Finger 1 did not increase, nor did expression of myostatin or hypoxia-inducible factor 1α (HIF-1α). We report atrium-specific decreases of 40% and 50%, respectively, in MAFBx and creatine kinase mRNA expression during hibernation. Decreased creatine kinase expression is consistent with lowered energy requirements and could relate to reduced atrial emptying function during hibernation. Taken together with our hemodynamic assessment, these data suggest a potential downregulation of atrial chamber function during hibernation to prevent fatigue and dilation due to excessive work against an optimally filled ventricle, a response unpredicted by the Frank-Starling mechanism.

Small interfering RNA targeting focal adhesion kinase prevents cardiac dysfunction in endotoxemia.

PubMed

Guido, Maria C; Clemente, Carolina F; Moretti, Ana I; Barbeiro, Hermes V; Debbas, Victor; Caldini, Elia G; Franchini, Kleber G; Soriano, Francisco G

2012-01-01

Sepsis and septic shock are associated with cardiac depression. Cardiovascular instability is a major cause of death in patients with sepsis. Focal adhesion kinase (FAK) is a potential mediator of cardiomyocyte responses to oxidative and mechanical stress. Myocardial collagen deposition can affect cardiac compliance and contractility. The aim of the present study was to determine whether the silencing of FAK is protective against endotoxemia-induced alterations of cardiac structure and function. In male Wistar rats, endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Cardiac morphometry and function were studied in vivo by left ventricular catheterization and histology. Intravenous injection of small interfering RNA targeting FAK was used to silence myocardial expression of the kinase. The hearts of lipopolysaccharide-injected rats showed collagen deposition, increased matrix metalloproteinase 2 activity, and myocyte hypertrophy, as well as reduced 24-h +dP/dt and -dP/dt, together with hypotension, increased left ventricular end-diastolic pressure, and elevated levels of FAK (phosphorylated and unphosphorylated). Focal adhesion kinase silencing reduced the expression and activation of the kinase in cardiac tissue, as well as protecting against the increased collagen deposition, greater matrix metalloproteinase 2 activity, and reduced cardiac contractility that occur during endotoxemia. In conclusion, FAK is activated in endotoxemia, playing a role in cardiac remodeling and in the impairment of cardiac function. This kinase represents a potential therapeutic target for the protection of cardiac function in patients with sepsis.

Intra-Aortic Balloon Counterpulsation in Patients with Chronic Heart Failure and Cardiogenic Shock: Clinical Response and Predictors of Stabilization

PubMed Central

Sintek, Marc A.; Gdowski, Mark; Lindman, Brian R.; Nassif, Michael; Lavine, Kory J.; Novak, Eric; Bach, Richard G.; Silvestry, Scott C.; Mann, Douglas L.; Joseph, Susan M.

2015-01-01

Objective To characterize the clinical response and identify predictors of clinical stabilization after intra-aortic balloon counterpulsation (IABP) support in patients with chronic systolic heart failure in cardiogenic shock prior to implantation of a left ventricular assist device (LVAD). Background Limited data exist regarding the clinical response to IABP in patients with chronic heart failure in cardiogenic shock. Methods We identified 54 patients supported with IABP prior to LVAD implantation. Criteria for clinical decompensation after IABP insertion and before LVAD included the need for more advanced temporary support, initiation of mechanical ventilation or dialysis, increase in vasopressors/inotropes, refractory ventricular arrhythmias, or worsening acidosis. The absence of these indicated stabilization. Results Clinical decompensation after IABP occurred in 23 (43%) patients. Both patients who decompensated and those who stabilized had similar hemodynamic improvements after IABP support but patients who decompensated required more vasopressors/inotropes. Clinical decompensation after IABP was associated with worse outcomes after LVAD implantation, including a 3-fold longer intensive care unit stay and 5-fold longer time on mechanical ventilation (p<0.01 for both). While baseline characteristics were similar between groups, right and left ventricular cardiac power indices (Cardiac power Index= Cardiac Index × Mean arterial pressure / 451)identified patients who were likely to stabilize (AUC=0.82). Conclusions Among patients with chronic systolic heart failure who develop cardiogenic shock, more than half of patients stabilized with IABP support as a bridge to LVAD. Baseline measures of right and left ventricular cardiac power, both measures of work performed for a given flow and pressure, may allow clinicians to identify patients with sufficient contractile reserve who will be likely to stabilize with an IABP versus those who may need more aggressive ventricular support. PMID:26164215

Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in right heart failure after pulmonary regurgitation.

PubMed

Hyldebrandt, Janus Adler; Agger, Peter; Sivén, Eleonora; Wemmelund, Kristian Borup; Heiberg, Johan; Frederiksen, Christian Alcaraz; Ravn, Hanne Berg

2015-09-01

Right ventricular failure (RVF) secondary to pulmonary regurgitation (PR) impairs right ventricular (RV) function and interrupts the interventricular relationship. There are few recommendations for the medical management of severe RVF after prolonged PR. PR was induced in 16 Danish landrace pigs by plication of the pulmonary valve leaflets. Twenty-three pigs served as controls. At reexamination the effect of milrinone, epinephrine, and dopamine was evaluated using biventricular conductance and pulmonary catheters. Seventy-nine days after PR was induced, RV end-diastolic volume index (EDVI) had increased by 33% (P = 0.006) and there was a severe decrease in the load-independent measurement of contractility (PRSW) (-58%; P = 0.003). Lower cardiac index (CI) (-28%; P < 0.0001), mean arterial pressure (-15%; P = 0.01) and mixed venous oxygen saturation (SvO2) (36%; P < 0.0001) were observed compared with the control group. The interventricular septum deviated toward the left ventricle (LV). Milrinone improved RV-PRSW and CI and maintained systemic pressure while reducing central venous pressure (CVP). Epinephrine and dopamine further improved biventricular PRSW and CI equally in a dose-dependent manner. Systemic and pulmonary pressures were higher in the dopamine-treated animals compared with epinephrine-treated animals. None of the treatments improved stroke volume index (SVI) despite increases in contractility. Strong correlation was detected between SVI and LV-EDVI, but not SVI and biventricular contractility. In RVF due to PR, milrinone significantly improved CI, SvO2, and CVP and increased contractility in the RV. Epinephrine and dopamine had equal inotropic effect, but a greater vasopressor effect was observed for dopamine. SV was unchanged due to inability of both treatments to increase LV-EDVI. Copyright © 2015 the American Physiological Society.

Acquired heart block: a possible complication of patent ductus arteriosus in a preterm infant.

PubMed

Grasser, Monika; Döhlemann, Christoph; Mittal, Rashmi; Till, Holger; Dietz, Hans-Georg; Münch, Georg; Holzinger, Andreas

2008-01-01

A large patent ductus arteriosus (PDA) is a frequently encountered clinical problem in extremely low birth weight (ELBW) infants. It leads to an increased pulmonary blood flow and in a decreased or reversed diastolic flow in the systemic circulation, resulting in complications. Here we report a possible complication of PDA not previously published. On day 8 of life, a male ELBW infant (birth weight 650 g) born at a gestational age of 23 weeks and 3 days developed an atrioventricular block (AV block). The heart rate dropped from 168/min to 90/min, and the ECG showed a Wenckebach second-degree AV block and intraventricular conduction disturbances. Echocardiography demonstrated a PDA with a large left-to-right shunt and large left atrium and left ventricle with high contractility. Within several minutes after surgical closure of the PDA, the heart rate increased, and after 30 min the AV block had improved to a 1:1 conduction ratio. Echocardiography after 2 h revealed a significant decrease of the left ventricular and atrial dimensions. Within 12 h, the AV block completely reversed together with the intraventricular conduction disturbances. We suggest that PDA with a large left-to-right shunt and left ventricular volume overload may lead to an AV block in an ELBW infant. Surgical closure of the PDA may be indicated. (c) 2007 S. Karger AG, Basel.

Evidence for increased cardiac compliance during exposure to simulated microgravity

NASA Technical Reports Server (NTRS)

Koenig, S. C.; Convertino, V. A.; Fanton, J. W.; Reister, C. A.; Gaffney, F. A.; Ludwig, D. A.; Krotov, V. P.; Trambovetsky, E. V.; Latham, R. D.

1998-01-01

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Impaired right ventricular contractile function in childhood obesity and its association with right and left ventricular changes: a cine DENSE cardiac magnetic resonance study.

PubMed

Jing, Linyuan; Pulenthiran, Arichanah; Nevius, Christopher D; Mejia-Spiegeler, Abba; Suever, Jonathan D; Wehner, Gregory J; Kirchner, H Lester; Haggerty, Christopher M; Fornwalt, Brandon K

2017-06-28

Pediatric obesity is a growing public health problem, which is associated with increased risk of cardiovascular disease and premature death. Left ventricular (LV) remodeling (increased myocardial mass and thickness) and contractile dysfunction (impaired longitudinal strain) have been documented in obese children, but little attention has been paid to the right ventricle (RV). We hypothesized that obese/overweight children would have evidence of RV remodeling and contractile dysfunction. One hundred and three children, ages 8-18 years, were prospectively recruited and underwent cardiovascular magnetic resonance (CMR), including both standard cine imaging and displacement encoding with stimulated echoes (DENSE) imaging, which allowed for quantification of RV geometry and function/mechanics. RV free wall longitudinal strain was quantified from the end-systolic four-chamber DENSE image. Linear regression was used to quantify correlations of RV strain with LV strain and measurements of body composition (adjusted for sex and height). Analysis of variance was used to study the relationship between RV strain and LV remodeling types (concentric remodeling, eccentric/concentric hypertrophy). The RV was sufficiently visualized with DENSE in 70 (68%) subjects, comprising 36 healthy weight (13.6 ± 2.7 years) and 34 (12.1 ± 2.9 years) obese/overweight children. Obese/overweight children had a 22% larger RV mass index (8.2 ± 0.9 vs 6.7 ± 1.1 g/m 2.7 , p < 0.001) compared to healthy controls. RV free wall longitudinal strain was impaired in obese/overweight children (-16 ± 4% vs -19 ± 5%, p = 0.02). Ten (14%) out of 70 children had LV concentric hypertrophy, and these children had the most impaired RV longitudinal strain compared to those with normal LV geometry (-13 ± 4% vs -19 ± 5%, p = 0.002). RV longitudinal strain was correlated with LV longitudinal strain (r = 0.34, p = 0.004), systolic blood pressure (r = 0.33, p = 0.006), as well as BMI z-score (r = 0.28, p = 0.02), waist (r = 0.31, p = 0.01), hip (r = 0.40, p = 0.004) and abdominal (r = 0.38, p = 0.002) circumference, height and sex adjusted. Obese/overweight children have evidence of RV remodeling (increased RV mass) and RV contractile dysfunction (impaired free wall longitudinal strain). Moreover, RV longitudinal strain correlates with LV longitudinal strain, and children with LV concentric hypertrophy show the most impaired RV function. These results suggest there may be a common mechanism underlying both remodeling and dysfunction of the left and right ventricles in obese/overweight children.

Akt2 knockout alleviates prolonged caloric restriction-induced change in cardiac contractile function through regulation of autophagy.

PubMed

Zhang, Yingmei; Han, Xuefeng; Hu, Nan; Huff, Anna F; Gao, Feng; Ren, Jun

2014-06-01

Caloric restriction leads to changes in heart geometry and function although the underlying mechanism remains elusive. Autophagy, a conserved pathway for degradation of intracellular proteins and organelles, preserves energy and nutrient in the face of caloric insufficiency. This study was designed to examine the role of Akt2 in prolonged caloric restriction-induced change in cardiac homeostasis and the underlying mechanism(s) involved. Wild-type (WT) and Akt2 knockout mice were calorie restricted (by 40%) for 30weeks. Echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, autophagy and its regulatory proteins were evaluated. Caloric restriction compromised echocardiographic indices (decreased left ventricular mass, left ventricular diameters and cardiac output), cardiomyocyte contractile and intracellular Ca(2+) properties associated with dampened SERCA2a phosphorylation, upregulated phospholamban and autophagy (Beclin-1, Atg7, LC3BII-to-LC3BI ratio), increased autophagy adaptor protein p62, elevated phosphorylation of AMPK, Akt2 and the Akt downstream signal molecule TSC2, the effects of which with the exception of autophagy protein markers (Beclin-1, Atg7, LC3B) and AMPK were mitigated or significantly alleviated by Akt2 knockout. Lysosomal inhibition using bafilomycin A1 negated Akt2 knockout-induced protective effect on p62. Evaluation of downstream signaling molecules of Akt and AMPK including mTOR and ULK1 revealed that caloric restriction suppressed and promoted phosphorylation of mTOR and ULK1, respectively, without affecting total mTOR and ULK1 expression. Akt2 knockout significantly augmented caloric restriction-induced responses on mTOR and ULK1. Taken together, these data suggest a beneficial role of Akt2 knockout in preservation of cardiac homeostasis against prolonged caloric restriction-induced pathological changes possibly through facilitating autophagy. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy." Copyright © 2013 Elsevier Ltd. All rights reserved.

Exposure to low mercury concentration in vivo impairs myocardial contractile function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furieri, Lorena Barros; Fioresi, Mirian; Junior, Rogerio Faustino Ribeiro

2011-09-01

Increased cardiovascular risk after mercury exposure has been described but cardiac effects resulting from controlled chronic treatment are not yet well explored. We analyzed the effects of chronic exposure to low mercury concentrations on hemodynamic and ventricular function of isolated hearts. Wistar rats were treated with HgCl{sub 2} (1st dose 4.6 {mu}g/kg, subsequent dose 0.07 {mu}g/kg/day, im, 30 days) or vehicle. Mercury treatment did not affect blood pressure (BP) nor produced cardiac hypertrophy or changes of myocyte morphometry and collagen content. This treatment: 1) in vivo increased left ventricle end diastolic pressure (LVEDP) without changing left ventricular systolic pressure (LVSP)more » and heart rate; 2) in isolated hearts reduced LV isovolumic systolic pressure and time derivatives, and {beta}-adrenergic response; 3) increased myosin ATPase activity; 4) reduced Na{sup +}-K{sup +} ATPase (NKA) activity; 5) reduced protein expression of SERCA and phosphorylated phospholamban on serine 16 while phospholamban expression increased; as a consequence SERCA/phospholamban ratio reduced; 6) reduced sodium/calcium exchanger (NCX) protein expression and {alpha}-1 isoform of NKA, whereas {alpha}-2 isoform of NKA did not change. Chronic exposure for 30 days to low concentrations of mercury does not change BP, heart rate or LVSP but produces small but significant increase of LVEDP. However, in isolated hearts mercury treatment promoted contractility dysfunction as a result of the decreased NKA activity, reduction of NCX and SERCA and increased PLB protein expression. These findings offer further evidence that mercury chronic exposure, even at small concentrations, is an environmental risk factor affecting heart function. - Highlights: > Unchanges blood pressure, heart rate, systolic pressure. > Increases end diastolic pressure. > Promotes cardiac contractility dysfunction. > Decreases NKA activity, NCX and SERCA, increases PLB protein expression. > Small concentrations constitutes environmental cardiovascular risk factor.« less

Chitosan hydrogels significantly limit left ventricular infarction and remodeling and preserve myocardial contractility.

PubMed

Henning, Robert J; Khan, Abraham; Jimenez, Ernesto

2016-04-01

Left ventricular myocardial infarctions (MIs) consist of a central area of myocardial necrosis that is surrounded by areas of myocardial injury and ischemia. We hypothesized that chitosan hydrogels, when injected around the perimeter of MIs in rats, could decrease left ventricle (LV) wall stress by the Law of LaPlace, and therefore myocardial oxygen requirements, and prevent the ischemic and injured myocardium from becoming necrotic. In this manner, chitosan gels could limit LV infraction size and LV remodeling. Chitosan hydrogels are liquid at 25°C but gel at 37°C. Seventy Sprague-Dawley rats with ligation of the left coronary artery were treated with either Dulbecco's Modified Eagle Medium (DMEM) or chitosan hydrogel in DMEM, which was injected around the infarct perimeter. Echocardiograms were obtained before MI and at 2, 4, 8, 12, and 16 wk after MI. Hearts from randomly selected rats were harvested at baseline and at the time of echocardiography for determinations of LV infarct size, remodeling, and histopathology. Infarct sizes as a percentage of the total ventricular myocardium in the DMEM group averaged 17% versus 14% in the chitosan group at 4 wk (P < 0.05), 18% versus 14% at 8 wk (P < 0.01), 19% versus 14% at 12 wk (P < 0.001), and 20% versus 14% at 16 wk (P < 0.001). Injection of chitosan into the infarctions produced LV wall thicknesses in the MI border zones that averaged 0.66 cm at 4 wk, which were greater than the LV wall thicknesses in the border zones of rats treated with DMEM, which averaged 0.33 cm (P < 0.01). Arteriole densities in the MI border zones were 160/mm(2) in the chitosan group but only 92/mm(2) in the DMEM rats (P < 0.01). The left ventricular end-diastolic diameters (LVEDs) in the rats averaged 0.73 cm before MI. After MI, LVED increased in the DMEM rats to 0.84 cm at 2 wk, then 0.89 cm at 4 wk, 0.89 cm at 8 wk, 0.89 m at 12 wk, and 0.87 cm at 16 wk. In contrast, LVED in the chitosan rats were on average 19% smaller in comparison with the DMEM rats (P < 0.05) and did not significantly change in comparison with their baseline LVEDs. Left ventricular ejection fraction (LVEF) in the rats averaged 83% before infarctions. In the infarction + DMEM group, the LVEFs significantly decreased after MI and averaged 59.7% at 2 wk, 52.5% at 4 wk, 46.1% at 8 wk, 52.4% at 12 wk, and 53.6% at 16 wk (P < 0.05). In the infarction + chitosan-treated rats, the LVEFs were greater and averaged 67.8% at 2 wk (P < 0.02), 68.9% (P < 0.02) at 4 wk, 69% (P < 0.003) at 8 wk, 65.2% at 12 wk (P < 0.05), and 67% at 16 wk (P < 0.05). Chitosan gel can increase LV myocardial wall thickness, decrease infarct size and LV remodeling, and preserve LV contractility. Copyright © 2016 Elsevier Inc. All rights reserved.

Protective effect of hydroalcoholic extract of Andrographis paniculata on ischaemia-reperfusion induced myocardial injury in rats.

PubMed

Ojha, Shreesh Kumar; Bharti, Saurabh; Joshi, Sujata; Kumari, Santosh; Arya, Dharamvir Singh

2012-03-01

Protecting myocardium from ischaemia-reperfusion (I-R) injury is important to reduce the complication of myocardial infarction (MI) and interventional revascularization procedures. In the present study, the cardioprotective potential of hydroalcoholic extract of Andrographis paniculata was evaluated against left anterior descending coronary artery (LADCA) ligation-induced I-R injury of myocardium in rats. MI was induced in rats by LADCA ligation for 45 min followed by reperfusion for 60 min. The rats were divided into five experimental groups viz., sham (saline treated, but LADCA was not ligated), I-R control (saline treated + I-R), benazepril (30 mg/kg + I-R), A. paniculata (200 mg/kg per se) and A. paniculata (200 mg/kg + I-R). A. paniculata was administered orally for 31 days. On day 31, rats were subjected to the I-R and cardiac function parameters were recorded. Further, rats were sacrificed and heart was excised for biochemical and histopathological studies. In I-R control group, LADCA ligation resulted in significant cardiac dysfunction evidenced by reduced haemodynamic parameters; mean arterial pressure (MAP) and heart rate (HR). The left ventricular contractile function was also altered. In I-R control group, I-R caused decline in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) as well as leakage of myocytes injury marker enzymes, creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH), and enhanced lipid peroxidation product, malonaldialdehyde (MDA). However, rats pretreated with A. paniculata 200 mg/kg showed favourable modulation of haemodynamic and left ventricular contractile function parameters, restoration of the myocardial antioxidants and prevention of depletion of myocytes injury marker enzymes along with inhibition of lipid peroxidation. Histopathological observations confirmed the protective effects of A. paniculata. The cardioprotective effects of A. paniculata were found comparable to that of benazepril treatment. Our results showed the cardioprotective effects of A. paniculata against I-R injury likely result from the suppression of oxidative stress and preserved histoarchitecture of myofibrils along with improved haemodynamic and ventricular functions.

Protective effect of hydroalcoholic extract of Andrographis paniculata on ischaemia-reperfusion induced myocardial injury in rats

PubMed Central

Ojha, Shreesh Kumar; Bharti, Saurabh; Joshi, Sujata; Kumari, Santosh; Arya, Dharamvir Singh

2012-01-01

Background & objectives: Protecting myocardium from ischaemia-reperfusion (I-R) injury is important to reduce the complication of myocardial infarction (MI) and interventional revascularization procedures. In the present study, the cardioprotective potential of hydroalcoholic extract of Andrographis paniculata was evaluated against left anterior descending coronary artery (LADCA) ligation-induced I-R injury of myocardium in rats. Methods: MI was induced in rats by LADCA ligation for 45 min followed by reperfusion for 60 min. The rats were divided into five experimental groups viz., sham (saline treated, but LADCA was not ligated), I-R control (saline treated + I-R), benazepril (30 mg/kg + I-R), A. paniculata (200 mg/kg per se) and A. paniculata (200 mg/kg + I-R). A. paniculata was administered orally for 31 days. On day 31, rats were subjected to the I-R and cardiac function parameters were recorded. Further, rats were sacrificed and heart was excised for biochemical and histopathological studies. Results: In I-R control group, LADCA ligation resulted in significant cardiac dysfunction evidenced by reduced haemodynamic parameters; mean arterial pressure (MAP) and heart rate (HR). The left ventricular contractile function was also altered. In I-R control group, I-R caused decline in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) as well as leakage of myocytes injury marker enzymes, creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH), and enhanced lipid peroxidation product, malonaldialdehyde (MDA). However, rats pretreated with A. paniculata 200 mg/kg showed favourable modulation of haemodynamic and left ventricular contractile function parameters, restoration of the myocardial antioxidants and prevention of depletion of myocytes injury marker enzymes along with inhibition of lipid peroxidation. Histopathological observations confirmed the protective effects of A. paniculata. The cardioprotective effects of A. paniculata were found comparable to that of benazepril treatment. Interpretation & Conclusions: Our results showed the cardioprotective effects of A. paniculata against I-R injury likely result from the suppression of oxidative stress and preserved histoarchitecture of myofibrils along with improved haemodynamic and ventricular functions. PMID:22561631

Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction.

PubMed

Wang, Jiaxing; Lu, Songhe; Zheng, Qijun; Hu, Nan; Yu, Wenjun; Li, Na; Liu, Min; Gao, Beilei; Zhang, Guoyong; Zhang, Yingmei; Wang, Haichang

2016-07-01

Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ETA) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ETA receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteins for biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, overt apoptosis and mitochondrial damage. ETA receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ETA receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ETA receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage.

Ineffective and prolonged apical contraction is associated with chest pain and ischaemia in apical hypertrophic cardiomyopathy.

PubMed

Stephenson, Edward; Monney, Pierre; Pugliese, Francesca; Malcolmson, James; Petersen, Steffen E; Knight, Charles; Mills, Peter; Wragg, Andrew; O'Mahony, Constantinos; Sekhri, Neha; Mohiddin, Saidi A

2018-01-15

To investigate the hypothesis that persistence of apical contraction into diastole is linked to reduced myocardial perfusion and chest pain. Apical hypertrophic cardiomyopathy (HCM) is defined by left ventricular (LV) hypertrophy predominantly of the apex. Hyperdynamic contractility resulting in obliteration of the apical cavity is often present. Apical HCM can lead to drug-refractory chest pain. We retrospectively studied 126 subjects; 76 with apical HCM and 50 controls (31 with asymmetrical septal hypertrophy (ASH) and 19 with non-cardiac chest pain and culprit free angiograms and structurally normal hearts). Perfusion cardiac magnetic resonance imaging (CMR) scans were assessed for myocardial perfusion reserve index (MPRi), late gadolinium enhancement (LGE), LV volumes (muscle and cavity) and regional contractile persistence (apex, mid and basal LV). In apical HCM, apical MPRi was lower than in normal and ASH controls (p<0.05). In apical HCM, duration of contractile persistence was associated with lower MPRi (p<0.01) and chest pain (p<0.05). In multivariate regression, contractile persistence was independently associated with chest pain (p<0.01) and reduced MPRi (p<0.001). In apical HCM, regional contractile persistence is associated with impaired myocardial perfusion and chest pain. As apical myocardium makes limited contributions to stroke volume, apical contractility is also largely ineffective. Interventions to reduce apical contraction and/or muscle mass are potential therapies for improving symptoms without reducing cardiac output. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiac Dysfunction in HIV-1 Transgenic Mouse: Role of Stress and BAG3.

PubMed

Cheung, Joseph Y; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Tilley, Douglas G; Gao, Erhe; Koch, Walter J; Rabinowitz, Joseph; Klotman, Paul E; Khalili, Kamel; Feldman, Arthur M

2015-08-01

Since highly active antiretroviral therapy improved long-term survival of acquired immunodeficiency syndrome (AIDS) patients, AIDS cardiomyopathy has become an increasingly relevant clinical problem. We used human immunodeficiency virus (HIV)-1 transgenic (Tg26) mouse to explore molecular mechanisms of AIDS cardiomyopathy. Tg26 mice had significantly lower left ventricular (LV) mass and smaller end-diastolic and end-systolic LV volumes. Under basal conditions, cardiac contractility and relaxation and single myocyte contraction dynamics were not different between wild-type (WT) and Tg26 mice. Ten days after open heart surgery, contractility and relaxation remained significantly depressed in Tg26 hearts, suggesting that Tg26 mice did not tolerate surgical stress well. To simulate heart failure in which expression of Bcl2-associated athanogene 3 (BAG3) is reduced, we down-regulated BAG3 by small hairpin ribonucleic acid in WT and Tg26 hearts. BAG3 down-regulation significantly reduced contractility in Tg26 hearts. BAG3 overexpression rescued contractile abnormalities in myocytes expressing the HIV-1 protein Tat. We conclude: (i) Tg26 mice exhibit normal contractile function at baseline; (ii) Tg26 mice do not tolerate surgical stress well; (iii) BAG3 down-regulation exacerbated cardiac dysfunction in Tg26 mice; (iv) BAG3 overexpression rescued contractile abnormalities in myocytes expressing HIV-1 protein Tat; and (v) BAG3 may occupy a role in pathogenesis of AIDS cardiomyopathy. © 2015 Wiley Periodicals, Inc.

Effects of temperature and calcium availability on ventricular myocardium from rainbow trout.

PubMed

Coyne, M D; Kim, C S; Cameron, J S; Gwathmey, J K

2000-06-01

We studied the mechanical and electrophysiological properties of ventricular myocardium from rainbow trout (Oncorhynchus mykiss) in vitro at 4, 10, and 18 degrees C from fish acclimated at 10 degrees C. Temperature alone did not significantly alter the contractile force of the myocardium, but the time to peak tension and time to 80% relaxation were prolonged at 4 degrees C and shortened at 18 degrees C. The duration of the action potential was also prolonged at 4 degrees C and progressively shortened at higher temperatures. An alteration of the stimulation frequency did not affect contraction amplitude at any temperature. Calcium influx via L-type calcium channels was increased by raising extracellular calcium concentration (¿Ca(2+)(o)) or including Bay K 8644 (Bay K) and isoproterenol in the bathing medium. These treatments significantly enhanced the contractile force at all temperatures. Calcium channel blockers had a reverse-negative inotropic effect. Unexpectedly, the duration of the action potential at 10 degrees C was shortened as ¿Ca(2+)(o) increased. However, Bay K prolonged the plateau phase at 4 degrees C. Caffeine, which promotes the release of sarcoplasmic reticulum (SR) calcium, increased contractile force eightfold at all three temperatures, but the SR blocker ryanodine was only inhibitory at 4 degrees C. Our results suggest that contractile force in ventricular myocardium from Oncorhynchus mykiss is primarily regulated by sarcolemmal calcium influx and that ventricular contractility is maintained during exposure to a wide range of temperatures.

Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise.

PubMed

Sanz-de la Garza, Maria; Rubies, Cira; Batlle, Montserrat; Bijnens, Bart H; Mont, Lluis; Sitges, Marta; Guasch, Eduard

2017-09-01

Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): -2.9 ± 0.5 vs. -3.3 ± 0.6 s -1 , SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: -3.3 ± 0.6 vs. -3.0 ± 0.4 s -1 and basal SR: -3.3 ± 0.7 vs. -2.7 ± 0.6 s -1 , MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive. NEW & NOTEWORTHY Exercise promotes left ventricular eccentric hypertrophy with no changes in systolic or diastolic function in healthy rats. Conversely, right ventricular adaptation to physical activity follows a biphasic, dose-dependent, and segmentary pattern. Moderate exercise promotes a mild systolic function enhancement at the right ventricular apex and more intense exercise impairs systolic and diastolic function. Copyright © 2017 the American Physiological Society.

Adenoviral gene transfer of Akt enhances myocardial contractility and intracellular calcium handling

PubMed Central

Cittadini, A; Monti, MG; Iaccarino, G; Di Rella, F; Tsichlis, PN; Di Gianni, A; Strömer, H; Sorriento, D; Peschle, C; Trimarco, B; Saccà, L; Condorelli, G

2010-01-01

The serine-threonine kinase Akt/PKB mediates stimuli from different classes of cardiomyocyte receptors, including the growth hormone/insulin like growth factor and the β-adrenergic receptors. Whereas the growth-promoting and antiapoptotic properties of Akt activation are well established, little is known about the effects of Akt on myocardial contractility, intracellular calcium (Ca2+) handling, oxygen consumption, and β-adrenergic pathway. To this aim, Sprague–Dawley rats were subjected to a wild-type Akt in vivo adenoviral gene transfer using a catheter-based technique combined with aortopulmonary crossclamping. Left ventricular (LV) contractility and intracellular Ca2+ handling were evaluated in an isolated isovolumic buffer-perfused, aequorin-loaded whole heart preparations 10 days after the surgery. The Ca2+–force relationship was obtained under steady-state conditions in tetanized muscles. No significant hypertrophy was detected in adenovirus with wild-type Akt (Ad.Akt) versus controls rats (LV-to-body weight ratio 2.6±0.2 versus 2.7±0.1 mg/g, controls versus Ad.Akt, P, NS). LV contractility, measured as developed pressure, increased by 41% in Ad.Akt. This was accounted for by both more systolic Ca2+ available to the contractile machinery (+19% versus controls) and by enhanced myofilament Ca2+ responsiveness, documented by an increased maximal Ca2+-activated pressure (+19% versus controls) and a shift to the left of the Ca2+–force relationship. Such increased contractility was paralleled by a slight increase of myocardial oxygen consumption (14%), while titrated dose of dobutamine providing similar inotropic effect augmented oxygen consumption by 39% (P<0.01). Phospholamban, calsequestrin, and ryanodine receptor LV mRNA and protein content were not different among the study groups, while sarcoplasmic reticulum Ca2+ ATPase protein levels were significantly increased in Ad.Akt rats. β-Adrenergic receptor density, affinity, kinase-1 levels, and adenylyl cyclase activity were similar in the three animal groups. In conclusion, our results support an important role for Akt/PKB in the regulation of myocardial contractility and mechanoenergetics. PMID:16094411

Evaluation of cardiac function in active and hibernating grizzly bears.

PubMed

Nelson, O Lynne; McEwen, Margaret-Mary; Robbins, Charles T; Felicetti, Laura; Christensen, William F

2003-10-15

To evaluate cardiac function parameters in a group of active and hibernating grizzly bears. Prospective study. 6 subadult grizzly bears. Indirect blood pressure, a 12-lead ECG, and a routine echocardiogram were obtained in each bear during the summer active phase and during hibernation. All measurements of myocardial contractility were significantly lower in all bears during hibernation, compared with the active period. Mean rate of circumferential left ventricular shortening, percentage fractional shortening, and percentage left ventricular ejection fraction were significantly lower in bears during hibernation, compared with the active period. Certain indices of diastolic function appeared to indicate enhanced ventricular compliance during the hibernation period. Mean mitral inflow ratio and isovolumic relaxation time were greater during hibernation. Heart rate was significantly lower for hibernating bears, and mean cardiac index was lower but not significantly different from cardiac index during the active phase. Contrary to results obtained in hibernating rodent species, cardiac index was not significantly correlated with heart rate. Cardiac function parameters in hibernating bears are opposite to the chronic bradycardic effects detected in nonhibernating species, likely because of intrinsic cardiac muscle adaptations during hibernation. Understanding mechanisms and responses of the myocardium during hibernation could yield insight into mechanisms of cardiac function regulation in various disease states in nonhibernating species.

Simulation of 'pathologic' changes in ICG waveforms resulting from superposition of the 'preejection' and ejection waves induced by left ventricular contraction

NASA Astrophysics Data System (ADS)

Ermishkin, V. V.; Kolesnikov, V. A.; Lukoshkova, E. V.; Sonina, R. S.

2013-04-01

The impedance cardiography (ICG) is widely used for beat-to-beat noninvasive evaluation of the left ventricular stroke volume and contractility. It implies the correct determination of the ejection start and end points and the amplitudes of certain peaks in the differentiated impedance cardiogram. An accurate identification of ejection onset by ICG is often problematic, especially in the cardiologic patients, due to peculiar waveforms. Using a simple theoretical model, we tested the hypothesis that two major processes are responsible for the formation of impedance systolic wave: (1) the changes in the heart geometry and surrounding vessels produced by ventricular contraction, which occur during the isovolumic phase and precede ejection, and (2) expansion of aorta and adjacent arteries during the ejection phase. The former process initiates the preejection wave WpE and the latter triggers the ejection wave WEj. The model predicts a potential mechanism of generating the abnormal shapes of dZ/dt due to the presence of preejection waves and explains the related errors in ICG time and amplitude parameters. An appropriate decomposition method is a promising way to avoid the masking effects of these waves and a further step to correct determination of the onset of ejection and the corresponding peak amplitudes from 'pathologically shaped' ICG signals.

SEA0400 fails to alter the magnitude of intracellular Ca2+ transients and contractions in Langendorff-perfused guinea pig heart.

PubMed

Szentandrássy, Norbert; Birinyi, Péter; Szigeti, Gyula; Farkas, Attila; Magyar, János; Tóth, András; Csernoch, László; Varró, András; Nánási, Péter P

2008-07-01

SEA0400 is a recently developed inhibitor of the Na+/Ca2+ exchanger (NCX) shown to suppress both forward and reverse mode operation of NCX. Present experiments were designed to study the effect of partial blockade of NCX on Ca handling and contractility in Langendorff-perfused guinea pig hearts loaded with the fluorescent Ca-sensitive dye fura-2. Left ventricular pressure and intracellular calcium concentration ([Ca2+]i) were synchronously recorded before and after cumulative superfusion with 0.3 and 1 muM SEA0400. SEA0400 caused no significant change in the systolic and diastolic values of left ventricular pressure and [Ca2+]i. Accordingly, pulse pressure and amplitude of the [Ca2+]i transient also remained unchanged in the presence of SEA0400. SEA0400 had no influence either on the time required to reach peak values of pressure and [Ca2+)]i or on half relaxation time. On the other hand, both 0.3 and 1 microM SEA0400 significantly increased the decay time constant of [Ca2+]i transients, obtained by fitting its descending limb between 30% and 90% of relaxation, from 127 +/- 7 to 165 +/- 7 and 177 +/- 14 ms, respectively (P < 0.05, n=6). In contrast to the guinea pig hearts, rat hearts responded to SEA0400 treatment with increased [Ca2+]i transients and contractility. These interspecies differences observed in the effect of SEA0400 can be explained by the known differences in calcium handling between the two species.

Ginsenoside Rb1 inhibits autophagy through regulation of Rho/ROCK and PI3K/mTOR pathways in a pressure-overload heart failure rat model.

PubMed

Yang, Tianrui; Miao, Yunbo; Zhang, Tong; Mu, Ninghui; Ruan, Libo; Duan, Jinlan; Zhu, Ying; Zhang, Rongping

2018-06-01

This study was designed to explore the relationship between ginsenoside Rb1 (Grb1) and high-load heart failure (HF) in rats. The parameters of cardiac systolic function (left ventricular posterior wall thickness (LVPWT), left ventricular internal diastolic diameter (LVID), fraction shortening (FS) and mitral valves (MVs)) of rat hearts in each group were inspected by echocardiogram. The expressions of rat myocardial contractile proteins, autophagy-related proteins and the activation of Rho/ROCK and PI3K/mTOR pathways were detected by Western blot. LVPWT, FS, MVs and the expression of myocardial contractile proteins α-MHC, apoptosis-related proteins Bcl-2 and signalling pathway involved proteins pAkt and mTOR were significantly reduced in the HF, HF+5 mg/kg Grb1 (HF+Grb1-5) and HF+Grb1+arachidonic acid (AA) groups with LVID, β-MHC, cell apoptosis, cell autophagy and Rho/ROCK significantly increased compared with the control group, of which the tendency was contrary to the HF+20 mg/kg Grb1 (HF+Grb1-20) group compared with the HF group (P < 0.05). In the HF+Grb1+AA group, there was no significant change in the above indexes compared with the HF group. The results indicated that Grb1 can exert anti-HF function by inhibiting cardiomyocyte autophagy of rats through regulation of Rho/ROCK and PI3K/mTOR pathways. © 2018 Royal Pharmaceutical Society.

Partitioned fluid-solid coupling for cardiovascular blood flow: left-ventricular fluid mechanics.

PubMed

Krittian, Sebastian; Janoske, Uwe; Oertel, Herbert; Böhlke, Thomas

2010-04-01

We present a 3D code-coupling approach which has been specialized towards cardiovascular blood flow. For the first time, the prescribed geometry movement of the cardiovascular flow model KaHMo (Karlsruhe Heart Model) has been replaced by a myocardial composite model. Deformation is driven by fluid forces and myocardial response, i.e., both its contractile and constitutive behavior. Whereas the arbitrary Lagrangian-Eulerian formulation (ALE) of the Navier-Stokes equations is discretized by finite volumes (FVM), the solid mechanical finite elasticity equations are discretized by a finite element (FEM) approach. Taking advantage of specialized numerical solution strategies for non-matching fluid and solid domain meshes, an iterative data-exchange guarantees the interface equilibrium of the underlying governing equations. The focus of this work is on left-ventricular fluid-structure interaction based on patient-specific magnetic resonance imaging datasets. Multi-physical phenomena are described by temporal visualization and characteristic FSI numbers. The results gained show flow patterns that are in good agreement with previous observations. A deeper understanding of cavity deformation, blood flow, and their vital interaction can help to improve surgical treatment and clinical therapy planning.

Heart failure—potential new targets for therapy

PubMed Central

Nabeebaccus, Adam; Zheng, Sean; Shah, Ajay M.

2016-01-01

Abstract Introduction/background Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. Sources of data A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Areas of agreement Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Areas of controversy Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Growing points Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Areas timely for developing research Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID:27365454

Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n-Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat.

PubMed

Li, S; Korkmaz-Icöz, S; Radovits, T; Ruppert, M; Spindler, R; Loganathan, S; Hegedűs, P; Brlecic, P; Theisinger, B; Theisinger, S; Höger, S; Brune, M; Lasitschka, F; Karck, M; Yard, B; Szabó, G

2017-07-01

Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-octanoyl-dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham-operated (n = 9). In BDD, decreased left-ventricular contractility (ejection fraction; maximum rate of rise of left-ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left-ventricular pressure; Tau), and increased end-diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD-treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin-6, tumor necrosis factor TNF-α, NF-kappaB-p65, and nuclear factor (NF)-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro-apoptotic factor caspase-3, pro-inflammatory cytokines, and NF-kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction

PubMed Central

Nelson, O. Lynne; Rourke, Bryan C.

2013-01-01

SUMMARY Deep hibernators such as golden-mantled ground squirrels (Callospermophilus lateralis) have multiple challenges to cardiac function during low temperature torpor and subsequent arousals. As heart rates fall from over 300 beats min−1 to less than 10, chamber dilation and reduced cardiac output could lead to congestive myopathy. We performed echocardiography on a cohort of individuals prior to and after several months of hibernation. The left ventricular chamber exhibited eccentric and concentric hypertrophy during hibernation and thus calculated ventricular mass was ~30% greater. Ventricular ejection fraction was mildly reduced during hibernation but stroke volumes were greater due to the eccentric hypertrophy and dramatically increased diastolic filling volumes. Globally, the systolic phase in hibernation was ~9.5 times longer, and the diastolic phase was 28× longer. Left atrial ejection generally was not observed during hibernation. Atrial ejection returned weakly during early arousal. Strain echocardiography assessed the velocity and total movement distance of contraction and relaxation for regional ventricular segments in active and early arousal states. Myocardial systolic strain during early arousal was significantly greater than the active state, indicating greater total contractile movement. This mirrored the increased ventricular ejection fraction noted with early arousal. However, strain rates were slower during early arousal than during the active period, particularly systolic strain, which was 33% of active, compared with the rate of diastolic strain, which was 67% of active. As heart rate rose during the arousal period, myocardial velocities and strain rates also increased; this was matched closely by cardiac output. Curiously, though heart rates were only 26% of active heart rates during early arousal, the cardiac output was nearly 40% of the active state, suggesting an efficient pumping system. We further analyzed proportions of cardiac myosin heavy-chain (MyHC) isoforms in a separate cohort of squirrels over 5 months, including time points before hibernation, during hibernation and just prior to emergence. Hibernating individuals were maintained in both a 4°C cold room and a 20°C warm room. Measured by SDS-PAGE, relative percentages of cardiac MyHC alpha were increased during hibernation, at both hibernacula temperatures. A potential increase in contractile speed, and power, from more abundant MyHC alpha may aid force generation at low temperature and at low heart rates. Unlike many models of cardiomyopathies where the alpha isoform is replaced by the beta isoform in order to reduce oxygen consumption, ground squirrels demonstrate a potential cardioprotective mechanism to maintain cardiac output during torpor. PMID:24072796

Age-dependent effects of milrinone and levosimendan on ventricular function and haemodynamics in newborn and mature pigs.

PubMed

Hyldebrandt, Janus A; Larsen, Signe H; Schmidt, Michael R; Hjortdal, Vibeke E; Ravn, Hanne B

2011-10-01

Inodilators are used in the treatment of low cardiac output, mainly after cardiac surgery. At present, there is little knowledge of the effect of inodilators in the newborn heart. Immediately after birth and in the neonatal period, the metabolism and physiology of the heart undergo major changes. We hypothesised that effects of the inodilators milrinone and levosimendan on myocardial contractility and haemodynamics under normal physiological conditions were age dependent. Animal studies were conducted on 48 pigs using a closed-chest biventricular conductance catheter method. Pigs in two age groups, that is, 5-6 days and 5-6 weeks, were assigned to milrinone, levosimendan, or a control group. We observed that both milrinone - 19.2% with a p value of 0.05 - and levosimendan - 25.7% with a p value of 0.03 compared with the control group increased cardiac output, as well as myocardial contractility with a maximum pressure development over time: milrinone 28.2%, p = 0.01 and levosimendan 19.4%, p = 0.05. Milrinone improved diastolic performance (p < 0.05) in the left ventricle in the 5-6-week-old animals. In the newborn animals, neither of the inodilators increased ventricular contractility or cardiac output; however, we observed a significant decrease in the mean arterial pressure: milrinone 34.6%, p < 0.01 and levosimendan 30.1%, p = 0.02. Both inodilators demonstrated age-dependent haemodynamic effects, and it is noteworthy that neither milrinone nor levosimendan was able to increase cardiac output in the newborn heart.

Thoracic Epidural Anesthesia Reduces Right Ventricular Systolic Function With Maintained Ventricular-Pulmonary Coupling.

PubMed

Wink, Jeroen; de Wilde, Rob B P; Wouters, Patrick F; van Dorp, Eveline L A; Veering, Bernadette Th; Versteegh, Michel I M; Aarts, Leon P H J; Steendijk, Paul

2016-10-18

Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia may affect right ventricular function and interfere with the coupling between right ventricular function and right ventricular afterload. Our main objectives were to study the effects of thoracic epidural anesthesia on right ventricular function and ventricular-pulmonary coupling. In 10 patients scheduled for lung resection, right ventricular function and its response to increased afterload, induced by temporary, unilateral clamping of the pulmonary artery, was tested before and after induction of thoracic epidural anesthesia using combined pressure-conductance catheters. Thoracic epidural anesthesia resulted in a significant decrease in right ventricular contractility (ΔESV 25 : +25.5 mL, P=0.0003; ΔEes: -0.025 mm Hg/mL, P=0.04). Stroke work, dP/dt MAX , and ejection fraction showed a similar decrease in systolic function (all P<0.05). A concomitant decrease in effective arterial elastance (ΔEa: -0.094 mm Hg/mL, P=0.004) yielded unchanged ventricular-pulmonary coupling. Cardiac output, systemic vascular resistance, and mean arterial blood pressure were unchanged. Clamping of the pulmonary artery significantly increased afterload (ΔEa: +0.226 mm Hg/mL, P<0.001). In response, right ventricular contractility increased (ΔESV 25 : -26.6 mL, P=0.0002; ΔEes: +0.034 mm Hg/mL, P=0.008), but ventricular-pulmonary coupling decreased (Δ(Ees/Ea) = -0.153, P<0.0001). None of the measured indices showed significant interactive effects, indicating that the effects of increased afterload were the same before and after thoracic epidural anesthesia. Thoracic epidural anesthesia impairs right ventricular contractility but does not inhibit the native positive inotropic response of the right ventricle to increased afterload. Right ventricular-pulmonary arterial coupling was decreased with increased afterload but not affected by the induction of thoracic epidural anesthesia. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2844. Unique identifier: NTR2844. © 2016 American Heart Association, Inc.

Improved arterial-ventricular coupling in metabolic syndrome after exercise training: a pilot study.

PubMed

Fournier, Sara B; Donley, David A; Bonner, Daniel E; Devallance, Evan; Olfert, I Mark; Chantler, Paul D

2015-01-01

The metabolic syndrome (MetS) is associated with threefold increased risk of cardiovascular (CV) morbidity and mortality, which is partly due to a blunted CV reserve capacity, reflected by a reduced peak exercise left ventricular (LV) contractility and aerobic capacity and a blunted peak arterial-ventricular coupling. To date, no study has examined whether aerobic exercise training in MetS can reverse peak exercise CV dysfunction. Furthermore, examining how exercise training alters CV function in a group of individuals with MetS before the development of diabetes and/or overt CV disease can provide insights into whether some of the pathophysiological CV changes can be delayed/reversed, lowering their CV risk. The objective of this study was to examine the effects of 8 wk of aerobic exercise training in individuals with MetS on resting and peak exercise CV function. Twenty participants with MetS underwent either 8 wk of aerobic exercise training (MetS-ExT, n = 10) or remained sedentary (MetS-NonT, n = 10) during this period. Resting and peak exercise CV function was characterized using Doppler echocardiography and gas exchange. Exercise training did not alter resting LV diastolic or systolic function and arterial-ventricular coupling in MetS. In contrast, at peak exercise, an increase in LV contractility (40%, P < 0.01), cardiac output (28%, P < 0.05), and aerobic capacity (20%, P < 0.01), but a reduction in vascular resistance (30%, P < 0.05) and arterial-ventricular coupling (27%, P < 0.01), were noted in the MetS-ExT but not in the MetS-NonT group. Furthermore, an improvement in lifetime risk score was also noted in the MetS-ExT group. These findings have clinical importance because they provide insight that some of the pathophysiological changes associated with MetS can be improved and can lower the risk of CV disease.

Post-hypothermic cardiac left ventricular systolic dysfunction after rewarming in an intact pig model

PubMed Central

2010-01-01

Introduction We developed a minimally invasive, closed chest pig model with the main aim to describe hemodynamic function during surface cooling, steady state severe hypothermia (one hour at 25°C) and surface rewarming. Methods Twelve anesthetized juvenile pigs were acutely catheterized for measurement of left ventricular (LV) pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were surface cooled to 25°C, while four animals were kept as normothermic time-matched controls. Results During progressive cooling and steady state severe hypothermia (25°C) cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), maximal deceleration of pressure in the cardiac cycle (dP/dtmin), indexes of LV contractility (preload recruitable stroke work, PRSW, and maximal acceleration of pressure in the cardiac cycle, dP/dtmax) and LV end diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen content in arterial and mixed venous blood increased significantly. LV end diastolic pressure (EDP) remained constant. After rewarming all the above mentioned hemodynamic variables that were depressed during 25°C remained reduced, except for CO that returned to pre-hypothermic values due to an increase in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming, while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac troponin T (TnT) and tumor necrosis factor-alpha (TNF-α) were significantly increased. Conclusions Progressive cooling to 25°C followed by rewarming resulted in a reduced systolic, but not diastolic left ventricular function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic increase in TnT indicates that hypothermia/rewarming may cause degradation of cardiac tissue. There were no signs of inadequate global oxygenation throughout the experiments. PMID:21092272

Isometric exercise: cardiovascular responses in normal and cardiac populations.

PubMed

Hanson, P; Nagle, F

1987-05-01

Isometric exercise produces a characteristic pressor increase in blood pressure which may be important in maintaining perfusion of muscle during sustained contraction. This response is mediated by combined central and peripheral afferent input to medullary cardiovascular centers. In normal individuals the increase in blood pressure is mediated by a rise in cardiac output with little or no change in systemic vascular resistance. However, the pressor response is also maintained during pharmacologic blockade or surgical denervation by increasing systemic vascular resistance. Left ventricular function is normally maintained or improves in normal subjects and cardiac patients with mild impairment of left ventricular contractility. Patients with poor left ventricular function may show deterioration during isometric exercise, although this pattern of response is difficult to predict from resting studies. Recent studies have shown that patients with uncomplicated myocardial infarction can perform submaximum isometric exercise such as carrying weights in the range of 30 to 50 lb without difficulty or adverse responses. In addition, many patients who show ischemic ST depression or angina during dynamic exercise may have a reduced ischemic response during isometric or combined isometric and dynamic exercise. Isometric exercises are frequently encountered in activities of daily living and many occupational tasks. Cardiac patients should be gradually exposed to submaximum isometric training in supervised cardiac rehabilitation programs. Specific job tasks that require isometric or combined isometric and dynamic activities may be evaluated by work simulation studies. This approach to cardiac rehabilitation may facilitate patients who wish to return to a job requiring frequent isometric muscle contraction. Finally, there is a need for additional research on the long-term effects of isometric exercise training on left ventricular hypertrophy and performance. The vigorous training regimens currently utilized by international class and professional athletes should stimulate longitudinal studies of physiologic and pathophysiologic outcomes of intense isometric exercise training programs.

Coronary wave energy: a novel predictor of functional recovery after myocardial infarction.

PubMed

De Silva, Kalpa; Foster, Paul; Guilcher, Antoine; Bandara, Asela; Jogiya, Roy; Lockie, Tim; Chowiencyzk, Phil; Nagel, Eike; Marber, Michael; Redwood, Simon; Plein, Sven; Perera, Divaka

2013-04-01

Revascularization after acute coronary syndromes provides prognostic benefit, provided that the subtended myocardium is viable. The microcirculation and contractility of the subtended myocardium affect propagation of coronary flow, which can be characterized by wave intensity analysis. The study objective was to determine in acute coronary syndromes whether early wave intensity analysis-derived microcirculatory (backward) expansion wave energy predicts late viability, defined by functional recovery. Thirty-one patients (58±11 years) were enrolled after non-ST elevation myocardial infarction. Regional left ventricular function and late-gadolinium enhancement were assessed by cardiac magnetic resonance imaging, before and 3 months after revascularization. The backward-traveling (microcirculatory) expansion wave was derived from wave intensity analysis of phasic coronary pressure and velocity in the infarct-related artery, whereas mean values were used to calculate hyperemic microvascular resistance. Twelve-hour troponin T, left ventricular ejection fraction, and percentage late-gadolinium enhancement mass were 1.35±1.21 µg/L, 56±11%, and 8.4±6.0%, respectively. The infarct-related artery backward-traveling (microcirculatory) expansion wave was inversely correlated with late-gadolinium enhancement infarct mass (r=-0.81; P<0.0001) and strongly predicted regional left ventricular recovery (r=0.68; P=0.001). By receiver operating characteristic analysis, a backward-traveling (microcirculatory) expansion wave threshold of 2.8 W m(-2) s(-2)×10(5) predicted functional recovery with sensitivity and specificity of 0.91 and 0.82 (AUC 0.88). Hyperemic microvascular resistance correlated with late-gadolinium enhancement mass (r=0.48; P=0.03) but not left ventricular recovery (r=-0.34; P=0.07). The microcirculation-derived backward expansion wave is a new index that correlates with the magnitude and location of infarction, which may allow for the prediction of functional myocardial recovery. Coronary wave intensity analysis may facilitate myocardial viability assessment during cardiac catheterization.

The impact of age and frailty on ventricular structure and function in C57BL/6J mice

PubMed Central

Feridooni, H. A.; Kane, A. E.; Ayaz, O.; Boroumandi, A.; Polidovitch, N.; Tsushima, R. G.; Rose, R. A.

2017-01-01

Key points Heart size increases with age (called hypertrophy), and its ability to contract declines. However, these reflect average changes that may not be present, or present to the same extent, in all older individuals.That aging happens at different rates is well accepted clinically. People who are aging rapidly are frail and frailty is measured with a ‘frailty index’.We quantified frailty with a validated mouse frailty index tool and evaluated the impacts of age and frailty on cardiac hypertrophy and contractile dysfunction.Hypertrophy increased with age, while contractions, calcium currents and calcium transients declined; these changes were graded by frailty scores.Overall health status, quantified as frailty, may promote maladaptive changes associated with cardiac aging and facilitate the development of diseases such as heart failure.To understand age‐related changes in heart structure and function, it is essential to know both chronological age and the health status of the animal. Abstract On average, cardiac hypertrophy and contractile dysfunction increase with age. Still, individuals age at different rates and their health status varies from fit to frail. We investigated the influence of frailty on age‐dependent ventricular remodelling. Frailty was quantified as deficit accumulation in adult (≈7 months) and aged (≈27 months) C57BL/6J mice by adapting a validated frailty index (FI) tool. Hypertrophy and contractile function were evaluated in Langendorff‐perfused hearts; cellular correlates/mechanisms were investigated in ventricular myocytes. FI scores increased with age. Mean cardiac hypertrophy increased with age, but values in the adult and aged groups overlapped. When plotted as a function of frailty, hypertrophy was graded by FI score (r = 0.67–0.55, P < 0.0003). Myocyte area also correlated positively with FI (r = 0.34, P = 0.03). Left ventricular developed pressure (LVDP) plus rates of pressure development (+dP/dt) and decay (−dP/dt) declined with age and this was graded by frailty (r = −0.51, P = 0.0007; r = −0.48, P = 0.002; r = −0.56, P = 0.0002 for LVDP, +dP/dt and −dP/dt). Smaller, slower contractions graded by FI score were also seen in ventricular myocytes. Contractile dysfunction in cardiomyocytes isolated from frail mice was attributable to parallel changes in underlying Ca2+ transients. These changes were not due to reduced sarcoplasmic reticulum stores, but were graded by smaller Ca2+ currents (r = −0.40, P = 0.008), lower gain (r = −0.37, P = 0.02) and reduced expression of Cav1.2 protein (r = −0.68, P = 0.003). These results show that cardiac hypertrophy and contractile dysfunction in naturally aging mice are graded by overall health and suggest that frailty, in addition to chronological age, can help explain heterogeneity in cardiac aging. PMID:28502095

Serca2a and Na(+)/Ca(2+) exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid.

PubMed

Nascimento, Andrews Marques do; Lima, Ewelyne Miranda de; Brasil, Girlandia Alexandre; Caliman, Izabela Facco; Silva, Josiane Fernandes da; Lemos, Virgínia Soares; Andrade, Tadeu Uggere de; Bissoli, Nazaré Souza

2016-06-15

Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20mg/kg/week for 4weeks); and NDE (trained and treated). The haemodynamic parameters (+dP/dtmax, -dP/dtmin and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na(+)/Ca(2+) exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. Copyright © 2016 Elsevier Inc. All rights reserved.

Macrophage migration inhibitory factor plays a permissive role in the maintenance of cardiac contractile function under starvation through regulation of autophagy.

PubMed

Xu, Xihui; Pacheco, Benjamin D; Leng, Lin; Bucala, Richard; Ren, Jun

2013-08-01

The cytokine macrophage migration inhibitory factor (MIF) protects the heart through AMPK activation. Autophagy, a conserved pathway for bulk degradation of intracellular proteins and organelles, helps preserve and recycle energy and nutrients for cells to survive under starvation. This study was designed to examine the role of MIF in cardiac homeostasis and autophagy regulation following an acute starvation challenge. Wild-type (WT) and MIF knockout mice were starved for 48 h. Echocardiographic data revealed little effect of starvation on cardiac geometry, contractile and intracellular Ca²⁺ properties. MIF deficiency unmasked an increase in left ventricular end-systolic diameter, a drop in fractional shortening associated with cardiomyocyte contractile and intracellular Ca²⁺ anomalies following starvation. Interestingly, the unfavourable effect of MIF deficiency was associated with interruption of starvation-induced autophagy. Furthermore, restoration of autophagy using rapamycin partially protected against starvation-induced cardiomyocyte contractile defects. In our in vitro model of starvation, neonatal mouse cardiomyocytes from WT and MIF-/- mice and H9C2 cells were treated with serum free-glucose free DMEM for 2 h. MIF depletion dramatically attenuated starvation-induced autophagic vacuole formation in neonatal mouse cardiomyocytes and exacerbated starvation-induced cell death in H9C2 cells. In summary, these results indicate that MIF plays a permissive role in the maintenance of cardiac contractile function under starvation by regulation of autophagy.

Left Ventricular Myocardial Function in Children With Pulmonary Hypertension: Relation to Right Ventricular Performance and Hemodynamics.

PubMed

Burkett, Dale A; Slorach, Cameron; Patel, Sonali S; Redington, Andrew N; Ivy, D Dunbar; Mertens, Luc; Younoszai, Adel K; Friedberg, Mark K

2015-08-01

Through ventricular interdependence, pulmonary hypertension (PH) induces left ventricular (LV) dysfunction. We hypothesized that LV strain/strain rate, surrogate measures of myocardial contractility, are reduced in pediatric PH and relate to invasive hemodynamics, right ventricular strain, and functional measures of PH. At 2 institutions, echocardiography was prospectively performed in 54 pediatric PH patients during cardiac catheterization, and in 54 matched controls. Patients with PH had reduced LV global longitudinal strain (LS; -18.8 [-17.3 to -20.4]% versus -20.2 [-19.0 to -20.9]%; P=0.0046) predominantly because of reduced basal (-12.9 [-10.8 to -16.3]% versus -17.9 [-14.5 to -20.7]%; P<0.0001) and mid (-17.5 [-15.5 to -19.0]% versus -21.1 [-19.1 to -23.0]%; P<0.0001) septal strain. Basal global circumferential strain was reduced (-18.7 [-15.7 to -22.1]% versus -20.6 [-19.0 to -22.5]%; P=0.0098), as were septal and free-wall segments. Mid circumferential strain was reduced within the free-wall. Strain rates were reduced in similar patterns. Basal septum LS, the combined average LS of basal and mid interventricular septal segments, correlated strongly with degree of PH (r=0.66; P<0.0001), pulmonary vascular resistance (r=0.60; P<0.0001), and right ventricular free-wall LS (r=0.64; P<0.0001). Brain natriuretic peptide levels correlated moderately with septal LS (r=0.48; P=0.0038). PH functional class correlated moderately with LV free-wall LS (r=-0.48; P=0.0051). The septum, shared between ventricles and affected by septal shift, was the most affected LV region in PH. Pediatric PH patients demonstrate reduced LV strain/strain rate, predominantly within the septum, with relationships to invasive hemodynamics, right ventricular strain, and functional PH measures. © 2015 American Heart Association, Inc.

Altered LV inotropic reserve and mechanoenergetics early in the development of heart failure.

PubMed

Prabhu, S D; Freeman, G L

2000-03-01

To test the hypothesis that alterations in left ventricular (LV) mechanoenergetics and the LV inotropic response to afterload manifest early in the evolution of heart failure, we examined six anesthetized dogs instrumented with LV micromanometers, piezoelectric crystals, and coronary sinus catheters before and after 24 h of rapid ventricular pacing (RVP). After autonomic blockade, the end-systolic pressure-volume relation (ESPVR), myocardial O(2) consumption (MVO(2)), and LV pressure-volume area (PVA) were defined at several different afterloads produced by graded infusions of phenylephrine. Short-term RVP resulted in reduced preload with proportionate reductions in stroke work and the maximum first derivative of LV pressure but with no significant reduction in baseline LV contractile state. In response to increased afterload, the baseline ESPVR shifted to the left with maintained end-systolic elastance (E(es)). In contrast, after short-term RVP, in response to comparable increases in afterload, the ESPVR displayed reduced E(es) (P < 0.05) and significantly less leftward shift compared with control (P < 0.05). Compared with the control MVO(2)-PVA relation, short-term RVP significantly increased the MVO(2) intercept (P < 0.05) with no change in slope. These results indicate that short-term RVP produces attenuation of afterload-induced enhancement of LV performance and increases energy consumption for nonmechanical processes with maintenance of contractile efficiency, suggesting that early in the development of tachycardia heart failure, there is blunting of length-dependent activation and increased O(2) requirements for excitation-contraction coupling, basal metabolism, or both. Rather than being adaptive mechanisms, these abnormalities may be primary defects involved in the progression of the heart failure phenotype.

The cardiovascular pharmacology of ICI 170777 ((6RS)-6-methyl-5-(pyrid-4-yl)-3H,6H-1,3,4- thiadiazin-2-one) a novel compound with positive inotropic and vasodilator effects.

PubMed Central

Collis, M. G.; Keddie, J. R.; Rouse, W.

1989-01-01

1. This paper describes the cardiovascular effects of ICI 170777, a novel compound which enhances cardiac contractility and causes arterial and venous dilatation. 2. The positive inotropic effects of ICI 170777 on the heart were demonstrated by an increase in left ventricular dP/dtmax in the anaesthetized and conscious dog, and by an increase in tension development in isolated papillary muscles from the cat. 3. In the anaesthetized dog, the positive inotropic effects of ICI 170777 and of isoprenaline were attenuated by atenolol (5 mg kg-1, i.v.). Atenolol displaced the dose-response curve to ICI 170777 to the right by 4 fold but displaced the isoprenaline dose-response curve to the right by 247 fold. In vitro, however, atenolol (10 microM) had no significant effect on the positive inotropic response to ICI 170777. In the ganglion-blocked anaesthetized dog, infusion of a low dose of ICI 170777 which had no effect on the basal left ventricular dP/dtmax, selectively potentiated the positive inotropic effects of isoprenaline. These results indicate that ICI 170777 has both a non-adrenoceptor-mediated positive inotropic effect on the heart and also facilitates the beta-adrenoceptor-mediated control of contractility. 4. In the denervated and perfused hind-limb of the dog, ICI 170777 reduced arterial perfusion pressure and increased limb circumference at a constant arterial flow and venous pressure. This indicates that ICI 170777 has direct dilator actions on both arterial and venous vessels. In this preparation, diazoxide exerted an arterial selective vasodilator effect and sodium nitroprusside was a relatively selective venous dilator.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2758224

Negative inotropic effects of diadenosine tetraphosphate are mediated by protein kinase C and phosphodiesterases stimulation in the rat heart.

PubMed

Pakhomov, Nikolai; Pustovit, Ksenia; Potekhina, Victoria; Filatova, Tatiana; Kuzmin, Vladislav; Abramochkin, Denis

2018-02-05

Extracellular diadenosine polyphosphates (Ap n A) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular Ap n A cause alteration of the heart functioning via purine receptors in different mammalian species. Nevertheless, principal intracellular pathways which underlie Ap n A action in the heart remain unknown. In the present study the role of the P2Y-associated intracellular regulatory pathway in the mediation of diadenosine tetraphosphate (Ap 4 A) effects in the rat heart has been investigated for the first time. Extracellular Ap 4 A caused significant decreasing of the ventricular inotropy. Ap 4 A evoked reduction of the left ventricle contractility in the isolated Langendorff-perfused rat hearts, decreasing of the Ca 2+ transients in the enzymatically isolated ventricular cardiomyocytes and induced shortening of action potentials in the ventricle multicellular preparations. The inhibitory effects of Ap 4 A in the rat heart were significantly attenuated by protein kinase C (PKC) inhibitor chelerythrine but these effects were not affected by NO-synthase inhibitor L-NAME and guanylyl cyclase (sGC) inhibitor ODQ. In addition, substantial attenuation of Ap 4 A-caused negative inotropy in the left ventricle was produced by nonselective phsophodiesterase (PDE) inhibitor IBMX, while PDE type 2 inhibitor EHNA was ineffective. In conclusion, our results allow suggesting that Ap 4 A-induced inhibitory effects in the rat heart are mediated by PKC, but not by NO/sGC/PKG-related signaling pathway. In addition, PDE stimulation may contribute to Ap 4 A-caused inhibition of the rat heart contractility. Copyright © 2017 Elsevier B.V. All rights reserved.

Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury.

PubMed

West, Christopher R; Crawford, Mark A; Poormasjedi-Meibod, Malihe-Sadat; Currie, Katharine D; Fallavollita, Andre; Yuen, Violet; McNeill, John H; Krassioukov, Andrei V

2014-04-15

Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day(-1), 5 days week(-1) for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFβ1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI.

Frequency-dependent left ventricular performance in women and men.

PubMed

Wainstein, Rodrigo V; Sasson, Zion; Mak, Susanna

2012-06-01

We aimed to determine whether sex differences in humans extend to the dynamic response of the left ventricular (LV) chamber to changes in heart rate (HR). Several observations suggest sex influences LV structure and function in health; moreover, this physiology is also affected in a sex-specific manner by aging. Eight postmenopausal women and eight similarly aged men underwent a cardiac catheterization-based study for force-interval relationships of the LV. HR was controlled by right atrial (RA) pacing, and LV +dP/dt(max) and volume were assessed by micromanometer-tipped catheter and Doppler echocardiography, respectively. Analysis of approximated LV pressure-volume relationships was performed using a time-varying model of elastance. External stroke work was also calculated. The relationship between HR and LV +dP/dt(max) was expressed as LV +dP/dt(max) = b + mHR. The slope (m) of the relationship was steeper in women compared with men (11.8 ± 4.0 vs. 6.1 ± 4.1 mmHg·s(-1)·beats(-1)·min(-1), P = 0.01). The greater increase in contractility in women was reproducibly observed after normalizing LV +dP/dt(max) to LV end-diastolic volume (LVVed) or by measuring end-systolic elastance. LVVed and stroke volume decreased more in women. Thus, despite greater increases in contractility, HR was associated with a lesser rise in cardiac output and a steeper fall in external stroke work in women. Compared with men, women exhibit greater inotropic responses to incremental RA pacing, which occurs at the same time as a steeper decline in external stroke work. In older adults, we observed sexual dimorphism in determinants of LV mechanical performance.

Alcohol and Apoptosis: Friends or Foes?

PubMed

Rodriguez, Ana; Chawla, Karan; Umoh, Nsini A; Cousins, Valerie M; Ketegou, Assama; Reddy, Madhumati G; AlRubaiee, Mustafa; Haddad, Georges E; Burke, Mark W

2015-11-19

Alcohol abuse causes 79,000 deaths stemming from severe organ damage in the United States every year. Clinical manifestations of long-term alcohol abuse on the cardiac muscle include defective contractility with the development of dilated cardiomyopathy and low-output heart failure; which has poor prognosis with less than 25% survival for more than three years. In contrast, low alcohol consumption has been associated with reduced risk of cardiovascular disease, however the mechanism of this phenomenon remains elusive. The aim of this study was to determine the significance of apoptosis as a mediating factor in cardiac function following chronic high alcohol versus low alcohol exposure. Adult rats were provided 5 mM (low alcohol), 100 mM (high alcohol) or pair-fed non-alcohol controls for 4-5 months. The hearts were dissected, sectioned and stained with cresyl violet or immunohistochemically for caspase-3, a putative marker for apoptosis. Cardiomyocytes were isolated to determine the effects of alcohol exposure on cell contraction and relaxation. High alcohol animals displayed a marked thinning of the left ventricular wall combined with elevated caspase-3 activity and decreased contractility. In contrast, low alcohol was associated with increased contractility and decreased apoptosis suggesting an overall protective mechanism induced by low levels of alcohol exposure.

Endocannabinoids Acting at Cannabinoid-1 Receptors Regulate Cardiovascular Function in Hypertension

PubMed Central

Bátkai, Sándor; Pacher, Pál; Osei-Hyiaman, Douglas; Radaeva, Svetlana; Liu, Jie; Harvey-White, Judith; Offertáler, László; Mackie, Ken; Audrey Rudd, M.; Bukoski, Richard D.; Kunos, George

2009-01-01

Background Endocannabinoids are novel lipid mediators with hypotensive and cardiodepressor activity. Here, we examined the possible role of the endocannabinergic system in cardiovascular regulation in hypertension. Methods and Results In spontaneously hypertensive rats (SHR), cannabinoid-1 receptor (CB1) antagonists increase blood pressure and left ventricular contractile performance. Conversely, preventing the degradation of the endocannabinoid anandamide by an inhibitor of fatty acid amidohydrolase reduces blood pressure, cardiac contractility, and vascular resistance to levels in normotensive rats, and these effects are prevented by CB1 antagonists. Similar changes are observed in 2 additional models of hypertension, whereas in normotensive control rats, the same parameters remain unaffected by any of these treatments. CB1 agonists lower blood pressure much more in SHR than in normotensive Wistar-Kyoto rats, and the expression of CB1 is increased in heart and aortic endothelium of SHR compared with Wistar-Kyoto rats. Conclusions We conclude that endocannabinoids tonically suppress cardiac contractility in hypertension and that enhancing the CB1-mediated cardiodepressor and vasodilator effects of endogenous anandamide by blocking its hydrolysis can normalize blood pressure. Targeting the endocannabinoid system offers novel therapeutic strategies in the treatment of hypertension. PMID:15451779

Antiarrhythmic Effects of Beta3-adrenergic Receptor Stimulation in a Canine Model of Ventricular Tachycardia

PubMed Central

Zhou, Shengmei; Tan, Alex Y.; Paz, Offir; Ogawa, Masahiro; Chou, Chung-Chuan; Hayashi, Hideki; Nihei, Motoki; Fishbein, Michael C.; Chen, Lan S.; Lin, Shien-Fong; Chen, Peng-Sheng

2009-01-01

Background Beta3-adrenergic receptor (beta3-AR) stimulation inhibits cardiac contractility. Objective To test the hypothesis that beta3-AR stimulation is antiarrhythmic. Methods We implanted a radiotransmitter for continuous ECG monitoring in 18 dogs with a tendency for high incidence of spontaneous ventricular tachycardia (VT). Ten of 18 had subcutaneous continuous BRL37344 (beta3-AR agonist) infusion (experimental group) for 1 month. The other dogs were controls. Western blotting studies were performed on tissues sampled from the noninfarcted left ventricular free wall of all dogs that survived the 60-day follow up period. Results Phase-2 VT appeared significantly later in the experimental group than in the control group (p<0.05). The number of VT episodes in the experimental group was significantly lower than control during both the first month (0.5 ± 0.95 episode/d vs. 2.6 ± 2.3 episode/d) and the second month (0.2 ± 0.2 episode/d vs. 1.2 ± 1.1 episode/d, p<0.05 for both). The experimental group had shorter QTc than control (p<0.002). The experimental group had decreased protein levels for sodium calcium exchanger and dihydropyridine receptor, increased beta3-AR expression, without changes in beta1-AR, beta2-AR. The average heart weight and the left ventricular free wall thickness in the experimental group (226 ± 17 g and 15.1 ± 1.2 mm, respectively) was significantly lower than control (265 ± 21 g and 17.4 ± 2.5 mm, respectively, p<0.05 for both). There was no difference in the incidences of sudden cardiac death (SCD) in these two groups of dogs. Conclusion Beta3-AR stimulation significantly reduces the occurrence of ventricular tachycardia. PMID:18242556

Continuous Flow Left Ventricular Assist Device Implant Significantly Improves Pulmonary Hypertension, Right Ventricular Contractility, and Tricuspid Valve Competence

PubMed Central

Atluri, Pavan; Fairman, Alexander S.; MacArthur, John W.; Goldstone, Andrew B.; Cohen, Jeffrey E.; Howard, Jessica L.; Zalewski, Christyna M.; Shudo, Yasuhiro; Woo, Y. Joseph

2014-01-01

Background Continuous flow left ventricular assist devices (CF LVAD) are being implanted with increasing frequency for end-stage heart failure. At the time of LVAD implant, a large proportion of patients have pulmonary hypertension, right ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy, edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased cardiopulmonary bypass time and bicaval cannulation, which should be reserved for the time of orthotopic heart transplantation. We hypothesized that CF LVAD implant would improve pulmonary artery pressures, enhance RV function, and minimize TR, obviating need for surgical tricuspid repair. Methods One hundred fourteen continuous flow LVADs implanted from 2005 through 2011 at a single center, with medical management of functional TR, were retrospectively analyzed. Pulmonary artery pressures were measured immediately prior to and following LVAD implant. RV function and TR were graded according to standard echocardiographic criteria, prior to, immediately following, and long-term following LVAD. Results There was a significant improvement in post-VAD mean pulmonary arterial pressures (26.6 ± 4.9 vs. 30.2 ± 7.4 mmHg, p = 0.008) with equivalent loading pressures (CVP = 12.0 ± 4.0 vs. 12.1 ± 5.1 p = NS). RV function significantly improved, as noted by right ventricular stroke work index (7.04 ± 2.60 vs. 6.05 ± 2.54, p = 0.02). There was an immediate improvement in TR grade and RV function following LVAD implant, which was sustained long term. Conclusion Continuous flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid regurgitation. TR may be managed nonoperatively during CF LVAD implant. PMID:24118109

A randomized hemodynamic comparison of intravenous amiodarone with and without Tween 80.

PubMed

Munoz, A; Karila, P; Gallay, P; Zettelmeier, F; Messner, P; Mery, M; Grolleau, R

1988-02-01

In 20 patients undergoing coronary arteriography, the hemodynamic effects of an experimental preparation of i.v. amiodarone 5 mg kg-1 without Tween 80 (N) (10 patients) were compared with those of the commercial form with Tween 80 (A) (10 patients). Analysis of variance demonstrated differences during the 3 min of injection and for 3 min afterwards: left ventricular systolic pressure decreased from 110 + 11 to 86 +/- 11 mmHg (P = 0.001) after A and from 114 +/- 22 to 106 +/- 19 (P = 0.05) after N (comparison P = 0.01) while related tachycardia was also more pronounced after A (comparison P = 0.001). Left ventricular end diastolic pressure transiently decreased after A while continuously increasing after N (P = 0.05). During the following 30 min both A and N caused similar bradycardia, increase in ventricular filling pressure, vascular resistance and decrease in cardiac and contractility indexes. Amiodarone blood levels were similar after A or N. These data document a significant initial short duration vasoplegia, mainly related to Tween 80, after A, when amiodarone itself after producing a similar very slight effect causes bradycardia, and a moderate and progressive negative inotropic effect. It was concluded that while the experimental form would be of interest, the risk of severe hypotension after i.v. Cordarone can be largely avoided by using a slower rate of infusion, especially in patients with hypovolemic status.

Xanthine Oxidase Inhibition with Febuxostat Attenuates Systolic Overload-induced Left Ventricular Hypertrophy and Dysfunction in Mice

PubMed Central

Xu, Xin; Hu, Xinli; Lu, Zhongbing; Zhang, Ping; Zhao, Lin; Wessale, Jerry L.; Bache, Robert J.; Chen, Yingjie

2008-01-01

The purine analog xanthine oxidase (XO) inhibitors (XOIs), allopurinol and oxypurinol, have been reported to protect against heart failure secondary to myocardial infarction or rapid ventricular pacing. Since these agents might influence other aspects of purine metabolism that could influence their effect, this study examined the effect of the non-purine XOI, febuxostat, on pressure overload-induced left ventricular (LV) hypertrophy and dysfunction. Transverse aortic constriction (TAC) in mice caused LV hypertrophy and dysfunction as well as increased myocardial nitrotyrosine at 8 days. TAC also caused increased phosphorylated Akt (p-AktSer473), p42/44 extracellular signal-regulated kinase (p-ErkThr202/Tyr204) and mammalian target of rapamycin (mTOR) (p-mTORSer2488). XO inhibition with febuxostat (5mg/kg/day by gavage for 8 days) beginning ~60 minutes after TAC attenuated the TAC-induced LV hypertrophy and dysfunction. Febuxostat blunted the TAC-induced increases in nitrotyrosine (indicating reduced myocardial oxidative stress), p-ErkThr202/Tyr204 and p-mTORSer2488, with no effect on total Erk or total mTOR. Febuxostat had no effect on myocardial p-AktSer473 or total Akt. The results suggest that XO inhibition with febuxostat reduced oxidative stress in the pressure overloaded LV, thereby diminishing the activation of pathways that result in pathologic hypertrophy and contractile dysfunction. PMID:18995179

Ca(2+)-related signaling and protein phosphorylation abnormalities play central roles in a new experimental model of electrical storm.

PubMed

Tsuji, Yukiomi; Hojo, Mayumi; Voigt, Niels; El-Armouche, Ali; Inden, Yasuya; Murohara, Toyoaki; Dobrev, Dobromir; Nattel, Stanley; Kodama, Itsuo; Kamiya, Kaichiro

2011-05-24

Electrical storm (ES), characterized by recurrent ventricular tachycardia/fibrillation, typically occurs in implantable cardioverter-defibrillator patients and adversely affects prognosis. However, the underlying molecular basis is poorly understood. In the present study, we report a new experimental model featuring repetitive episodes of implantable cardioverter-defibrillator firing for recurrent ventricular fibrillation (VF), in which we assessed involvement of Ca(2+)-related protein alterations in ES. We studied 37 rabbits with complete atrioventricular block for ≈80 days, all with implantable cardioverter-defibrillator implantation. All rabbits showed long-QT and VF episodes. Fifty-three percent of rabbits developed ES (≥3 VF episodes per 24-hour period; 103±23 VF episodes per rabbit). Expression/phosphorylation of Ca(2+)-handling proteins was assessed in left ventricular tissues from rabbits with the following: ES; VF episodes but not ES (non-ES); and controls. Left ventricular end-diastolic diameter increased comparably in ES and non-ES rabbits, but contractile dysfunction was significantly greater in ES than in non-ES rabbits. ES rabbits showed striking hyperphosphorylation of Ca(2+)/calmodulin-dependent protein kinase II, prominent phospholamban dephosphorylation, and increased protein phosphatase 1 and 2A expression versus control and non-ES rabbits. Ryanodine receptors were similarly hyperphosphorylated at Ser2815 in ES and non-ES rabbits, but ryanodine receptor Ser2809 and L-type Ca(2+) channel α-subunit hyperphosphorylation were significantly greater in ES versus non-ES rabbits. To examine direct effects of repeated VF/defibrillation, VF was induced 10 times in control rabbits. Repeated VF tissues showed autophosphorylated Ca(2+)/calmodulin-dependent protein kinase II upregulation and phospholamban dephosphorylation like those of ES rabbit hearts. Continuous infusion of a calmodulin antagonist (W-7) to ES rabbits reduced Ca(2+)/calmodulin-dependent protein kinase II hyperphosphorylation, suppressed ventricular tachycardia/fibrillation, and rescued left ventricular dysfunction. ES causes Ca(2+)/calmodulin-dependent protein kinase II activation and phospholamban dephosphorylation, which can explain the vicious cycle of arrhythmia promotion and mechanical dysfunction that characterizes ES.

Left atrial function in heart failure with impaired and preserved ejection fraction.

PubMed

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

Mechanisms underlying hypothermia-induced cardiac contractile dysfunction.

PubMed

Han, Young-Soo; Tveita, Torkjel; Prakash, Y S; Sieck, Gary C

2010-03-01

Rewarming patients after profound hypothermia may result in acute heart failure and high mortality (50-80%). However, the underlying pathophysiological mechanisms are largely unknown. We characterized cardiac contractile function in the temperature range of 15-30 degrees C by measuring the intracellular Ca(2+) concentration ([Ca(2+)](i)) and twitch force in intact left ventricular rat papillary muscles. Muscle preparations were loaded with fura-2 AM and electrically stimulated during cooling at 15 degrees C for 1.5 h before being rewarmed to the baseline temperature of 30 degrees C. After hypothermia/rewarming, peak twitch force decreased by 30-40%, but [Ca(2+)](i) was not significantly altered. In addition, we assessed the maximal Ca(2+)-activated force (F(max)) and Ca(2+) sensitivity of force in skinned papillary muscle fibers. F(max) was decreased by approximately 30%, whereas the pCa required for 50% of F(max) was reduced by approximately 0.14. In rewarmed papillary muscle, both total cardiac troponin I (cTnI) phosphorylation and PKA-mediated cTnI phosphorylation at Ser23/24 were significantly increased compared with controls. We conclude that after hypothermia/rewarming, myocardial contractility is significantly reduced, as evidenced by reduced twitch force and F(max). The reduced myocardial contractility is attributed to decreased Ca(2+) sensitivity of force rather than [Ca(2+)](i) itself, resulting from increased cTnI phosphorylation.

L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

PubMed

Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

2009-02-01

The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

Contractile reserve and calcium regulation are depressed in myocytes from chronically unloaded hearts

NASA Technical Reports Server (NTRS)

Ito, Kenta; Nakayama, Masaharu; Hasan, Faisal; Yan, Xinhua; Schneider, Michael D.; Lorell, Beverly H.

2003-01-01

BACKGROUND: Chronic cardiac unloading of the normal heart results in the reduction of left ventricular (LV) mass, but effects on myocyte contractile function are not known. METHODS AND RESULTS: Cardiac unloading and reduction in LV mass were induced by heterotopic heart transplantation to the abdominal aorta in isogenic rats. Contractility and [Ca(2+)](i) regulation in LV myocytes were studied at both 2 and 5 weeks after transplantation. Native in situ hearts from recipient animals were used as the controls for all experiments. Contractile function indices in myocytes from 2-week unloaded and native (control) hearts were similar under baseline conditions (0.5 Hz, 1.2 mmol/L [Ca(2+)](o), and 36 degrees C) and in response to stimulation with high [Ca(2+)](o) (range 2.5 to 4.0 mmol/L). In myocytes from 5-week unloaded hearts, there were no differences in fractional cell shortening and peak-systolic [Ca(2+)](i) at baseline; however, time to 50% relengthening and time to 50% decline in [Ca(2+)](i) were prolonged compared with controls. Severe defects in fractional cell shortening and peak-systolic [Ca(2+)](i) were elicited in myocytes from 5-week unloaded hearts in response to high [Ca(2+)](o). However, there were no differences in the contractile response to isoproterenol between myocytes from unloaded and native hearts. In 5-week unloaded hearts, but not in 2-week unloaded hearts, LV protein levels of phospholamban were increased (345% of native heart values). Protein levels of sarcoplasmic reticulum Ca(2+) ATPase and the Na(+)/Ca(2+) exchanger were not changed. CONCLUSIONS: Chronic unloading of the normal heart caused a time-dependent depression of myocyte contractile function, suggesting the potential for impaired performance in states associated with prolonged cardiac atrophy.

Activation of Akt rescues endoplasmic reticulum stress-impaired murine cardiac contractile function via glycogen synthase kinase-3β-mediated suppression of mitochondrial permeation pore opening.

PubMed

Zhang, Yingmei; Xia, Zhi; La Cour, Karissa H; Ren, Jun

2011-11-01

The present study was designed to examine the impact of chronic Akt activation on endoplasmic reticulum (ER) stress-induced cardiac mechanical anomalies, if any, and the underlying mechanism involved. Wild-type and transgenic mice with cardiac-specific overexpression of the active mutant of Akt (Myr-Akt) were subjected to the ER stress inducer tunicamycin (1 or 3 mg/kg). ER stress led to compromised echocardiographic (elevated left ventricular end-systolic diameter and reduced fractional shortening) and cardiomyocyte contractile function, intracellular Ca(2+) mishandling, and cell survival in wild-type mice associated with mitochondrial damage. In vitro ER stress induction in murine cardiomyocytes upregulated the ER stress proteins Gadd153, GRP78, and phospho-eIF2α, and promoted reactive oxygen species production, carbonyl formation, apoptosis, mitochondrial membrane potential loss, and mitochondrial permeation pore (mPTP) opening associated with overtly impaired cardiomyocyte contractile and intracellular Ca(2+) properties. Interestingly, these anomalies were mitigated by chronic Akt activation or the ER chaperon tauroursodeoxycholic acid (TUDCA). Treatment with tunicamycin also dephosphorylated Akt and its downstream signal glycogen synthase kinase 3β (GSK3β) (leading to activation of GSK3β), the effect of which was abrogated by Akt activation and TUDCA. The ER stress-induced cardiomyocyte contractile and mitochondrial anomalies were obliterated by the mPTP inhibitor cyclosporin A, GSK3β inhibitor SB216763, and ER stress inhibitor TUDCA. This research reported the direct relationship between ER stress and cardiomyocyte contractile and mitochondrial anomalies for the first time. Taken together, these data suggest that ER stress may compromise cardiac contractile and intracellular Ca(2+) properties, possibly through the Akt/GSK3β-dependent impairment of mitochondrial integrity.

Impact of Vitamin D on the Cardiovascular System in Advanced Chronic Kidney Disease (CKD) and Dialysis Patients.

PubMed

Gluba-Brzózka, Anna; Franczyk, Beata; Ciałkowska-Rysz, Aleksandra; Olszewski, Robert; Rysz, Jacek

2018-06-01

In patients suffering from chronic kidney disease (CKD), the prevalence of cardiovascular disease is much more common than in the general population. The role of vitamin D deficiency had been underestimated until a significant association was found between vitamin D therapy and survival benefit in haemodialysis patients. Vitamin D deficiency is present even in the early stages of chronic kidney disease. The results of experimental studies have revealed the relationship between vitamin D deficiency and impairment of cardiac contractile function, higher cardiac mass and increased myocardial collagen content. Experimental models propose that intermediate end points for the relationship between vitamin D deficiency and higher risk of cardiovascular disease comprise diminished left ventricular hypertrophy (LVH), enhanced left ventricular diastolic function, and decreased frequency of heart failure. Multiple observational studies have demonstrated an association between the use of active vitamin D therapy in patients on dialysis and with CKD and improved survival. However, there are also many studies indicating important adverse effects of such treatment. Therefore, large randomized trials are required to analyze whether supplementation of vitamin D may affect outcomes and whether it is safe to be used in CKD patients.

Sleep Apnea and Left Atrial Phasic Function in Heart Failure With Reduced Ejection Fraction.

PubMed

Haruki, Nobuhiko; Tsang, Wendy; Thavendiranathan, Paaladinesh; Woo, Anna; Tomlinson, George; Logan, Alexander G; Bradley, T Douglas; Floras, John S

2016-12-01

The study aim was to determine whether phasic left atrial (LA) function of patients with heart failure with reduced ejection fraction differs between those with obstructive sleep apnea (OSA) and central sleep apnea (CSA). Participation in the Adaptive Servo Ventilation for Therapy of Sleep Apnea in Heart Failure (ADVENT-HF) trial requires 2-dimensional echocardiographic documentation of left ventricular ejection fraction ≤ 45% and a polysomnographic apnea hypopnea index (AHI) ≥ 15 events per hour. Of initial enrollees, we identified 132 patients in sinus rhythm (82 with predominantly OSA and 50 with CSA). To determine LA reservoir (expansion index; EI), conduit (passive emptying index; PEI), and booster function (active emptying index), we blindly quantified maximum and minimum LA volume and LA volume before atrial contraction. Each of EI (P = 0.004), PEI (P < 0.001), and active emptying index (P = 0.045) was less in participants with CSA compared with those with OSA, whereas average left ventricular ejection fraction and LA and left ventricular volumes were similar. Multivariable analysis identified an independent relationship between central AHI and LA EI (P = 0.040) and PEI (P = 0.005). In contrast, the obstructive AHI was unrelated to any LA phasic index, and slopes relating central AHI to EI and PEI differed significantly from corresponding relationships with obstructive AHI (P = 0.018; P = 0.006). In these ADVENT-HF patients with heart failure with reduced ejection fraction, all 3 components of LA phasic function (reservoir, conduit, and contractile) were significantly reduced in those with CSA compared with participants with OSA. The severity of CSA, but not OSA associated inversely and independently with LA reservoir and conduit function. Impaired LA phasic function might be consequent to or could exacerbate CSA. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Haemodynamic and energetic properties of stunned myocardium in rabbit hearts.

PubMed Central

Schipke, J. D.; Korbmacher, B.; Dorszewski, A.; Selcan, G.; Sunderdiek, U.; Arnold, G.

1996-01-01

OBJECTIVE--To amplify the description of myocardial stunning. DESIGN--Control versus 30 min after a 20 min no flow ischaemia. EXPERIMENTAL ANIMALS--15 isolated rabbit hearts perfused with erythrocyte suspension. MAIN OUTCOME MEASURES--Left ventricular systolic function in terms of aortic flow, peak systolic pressure (LVPmax), dP/dtmax, and the end systolic pressure-volume relation (ESPVR); early relaxation from dP/dtmin and rate of left ventricular pressure decay (tau). Passive properties: ventricular and myocardial stiffness. Coronary resistance from coronary blood flow and perfusion pressure. Total myocardial oxygen consumption (MVo2tot). Total mechanical energy via pressure-volume area (PVA). Contractile efficiency (Econ) and MVo2 of the unloaded contracting heart (MVo2unl). External mechanical efficiency (Eext) from stroke work and MVo2tot. RESULTS--Systolic variables in stunned myocardium were significantly decreased (mean (SD)): aortic flow: 38 (13) v 9 (11) ml/min; LVPmax: 112 (19) v 74 (18) mm Hg; dP/dtmax: 1475 (400) v 1075 (275) mm Hg/s. ESPVR was not significantly decreased, at 138 (73) v 125 (58) mm Hg/ml, but the volume axis intercept was shifted rightward: 0.30 (0.37) v 0.65 (0.25) ml. Likewise, early relaxation was impaired: dP/dtmin (-1275 (250) v -975 (250) mm Hg/s) and tau (37 (7) v 46 (10) ms). LVPed was significantly decreased at 19 (12) v 12 (7) mm Hg, and both the ventricular (end diastolic pressure-volume relation) and the myocardial stiffness (constant k) were increased by 75% and 31%, respectively. Coronary resistance increased non-significantly from 0.83 (0.31) to 1.04 (0.41) mm Hg/(ml/min/100 g). Decreases in PVA (570 (280) v 270 (200) mm Hg.ml/100 g), MVo2tot (40 (9) v 34 (8) microliters/beat/100 g), and MVo2unl (26 (9) v 22 (6) microliters/beat/100 g) did not reach significance, in contrast to significant decreases in Econ (31 (18) v 14 (7)%) and Eext (0.75 (0.29) v 0.18 (0.25) arbitrary units). CONCLUSIONS--Ventricular systolic function is decreased after brief episodes of ischaemia. The decrease in diastolic function probably amplifies the systolic deterioration during myocardial stunning. Passive diastolic properties are also changed, shown by increases in both ventricular and myocardial stiffness. The increase in coronary resistance indicates stunning at the vascular level which could limit oxygen supply. With maintained MVo2tot during stunning, external efficiency is decreased. Possible candidates for this metabolic stunning are inadequate excitation-contraction coupling and disturbed O2 utilisation by the contractile apparatus. Images PMID:8624873

Increase in parasympathetic tone by pyridostigmine prevents ventricular dysfunction during the onset of heart failure.

PubMed

Lataro, Renata M; Silva, Carlos A A; Fazan, Rubens; Rossi, Marcos A; Prado, Cibele M; Godinho, Rosely O; Salgado, Helio C

2013-10-15

Heart failure (HF) is characterized by elevated sympathetic activity and reduced parasympathetic control of the heart. Experimental evidence suggests that the increase in parasympathetic function can be a therapeutic alternative to slow HF evolution. The parasympathetic neurotransmission can be improved by acetylcholinesterase inhibition. We investigated the long-term (4 wk) effects of the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance, cardiac remodeling, and cardiac function in the onset of HF following myocardial infarction. Myocardial infarction was elicited in adult male Wistar rats. After 4 wk of pyridostigmine administration, per os, methylatropine and propranolol were used to evaluate the cardiac sympathovagal balance. The tachycardic response caused by methylatropine was considered to be the vagal tone, whereas the bradycardic response caused by propranolol was considered to be the sympathetic tone. In conscious HF rats, pyridostigmine reduced the basal heart rate, increased vagal, and reduced sympathetic control of heart rate. Pyridostigmine reduced the myocyte diameter and collagen density of the surviving left ventricle. Pyridostigmine also increased vascular endothelial growth factor protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac function was assessed by means of the pressure-volume conductance catheter system. HF rats treated with pyridostigmine exhibited a higher stroke volume, ejection fraction, cardiac output, and contractility of the left ventricle. It was demonstrated that the long-term administration of pyridostigmine started right after coronary artery ligation augmented cardiac vagal and reduced sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction during the progression of HF in rats.

Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation.

PubMed

Amino, Mari; Yoshioka, Koichiro; Fujibayashi, Daisuke; Hashida, Tadashi; Furusawa, Yoshiya; Zareba, Wojciech; Ikari, Yuji; Tanaka, Etsuro; Mori, Hidezo; Inokuchi, Sadaki; Kodama, Itsuo; Tanabe, Teruhisa

2010-03-01

A previous study from our laboratory has shown that a single targeted heavy ion irradiation (THIR; 15 Gy) to rabbit hearts increases connexin43 (Cx43) expression for 2 wk in association with an improvement of conduction, a decrease of the spatial inhomogeneity of repolarization, and a reduction of vulnerability to ventricular arrhythmias after myocardial infarction. This study investigated the time- and dose-dependent effects of THIR (5-15 Gy) on Cx43 expression in normal rabbit hearts (n = 45). Five rabbits without THIR were used as controls. A significant upregulation of Cx43 protein and mRNA in the ventricular myocardium was recognized by immunohistochemistry, Western blotting, and real-time PCR from 2 wk up to 1 yr after a single THIR at 15 Gy. THIR > or =10 Gy caused a significant dose-dependent increase of Cx43 protein and mRNA 2 wk after THIR. Anterior, lateral, and posterior free wall of the left ventricle, interventricular septum, and right ventricular free wall were affected similarly by THIR in terms of Cx43 upregulation. The radiation-induced increase of immunolabeled Cx43 was observed not only at the intercalated disk region but also at the lateral surface of ventricular myocytes. The increase of immunoreactive Cx43 protein was predominant in the membrane fraction insoluble in Triton X-100, that is the Cx43 in the sarcolemma. In vivo examinations of the rabbits 1 yr after THIR (15 Gy) revealed no significant changes in ECGs and echocardiograms (left ventricular dimensions, contractility, and diastolic function), indicating no apparent late radiation injury. A single application of THIR causes upregulation and altered cellular distribution of Cx43 in the ventricles lasting for at least 1 yr. This long-lasting remodeling effect on gap junctions may open the pathway to novel therapy against life threatening ventricular arrhythmias in structural heart disease.

Determination of right ventricular ejection fraction in children with cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Piepsz, A.; Ham, H.R.; Millet, E.

1987-01-01

The radionuclide right ventricular ejection fraction (RVEF) determined by means of Krypton-81m represents a simple, noninvasive, and accurate procedure to quantify the right ventricular contractility. This procedure was applied to 25 young patients with cystic fibrosis. The RVEF tended to decrease with the progression of the lung disease, as assessed by the clinical S-K score, the degree of the defects on lung scintigraphy, the PaO/sub 2/, and the lung function tests. However, the decrease of RVEF in patients with marked lung function tests. However, the decrease of RVEF in patients with marked lung involvement was moderate, and terminal lung diseasemore » was sometimes associated with normal right heart contractility.« less

Influence of LVAD function on mechanical unloading and electromechanical delay: a simulation study.

PubMed

Heikhmakhtiar, Aulia Khamas; Ryu, Ah Jin; Shim, Eun Bo; Song, Kwang-Soup; Trayanova, Natalia A; Lim, Ki Moo

2018-05-01

This study hypothesized that a left ventricular assist device (LVAD) shortens the electromechanical delay (EMD) by mechanical unloading. The goal of this study is to examine, by computational modeling, the influence of LVAD on EMD for four heart failure (HF) cases ranging from mild HF to severe HF. We constructed an integrated model of an LVAD-implanted cardiovascular system, then we altered the Ca 2+ transient magnitude, with scaling factors 1, 0.9, 0.8, and 0.7 representing HF1, HF2, HF3, and HF4, respectively, in order of increasing HF severity. The four HF conditions are classified into two groups. Group one is the four HF conditions without LVAD, and group two is the conditions treated with continuous LVAD pump. The single-cell mechanical responses showed that EMD was prolonged with the higher load. The findings indicated that in group one, the HF-induced Ca2 + transient remodeling prolonged the mechanical activation time (MAT) and decreased the contractile tension, which reduced the left ventricle (LV) pressure, and increased the end-diastolic strain. In group two, LVAD shortened MAT of the ventricles. Furthermore, LVAD reduced the contractile tension, and end-diastolic strain, but increased the aortic pressure. The computational study demonstrated that LVAD shortens EMD by mechanical unloading of the ventricle.

Role of left ventricular twist mechanics in cardiomyopathies, dance of the helices

PubMed Central

Kauer, Floris; Geleijnse, Marcel Leonard; van Dalen, Bastiaan Martijn

2015-01-01

Left ventricular twist is an essential part of left ventricular function. Nevertheless, knowledge is limited in “the cardiology community” as it comes to twist mechanics. Fortunately the development of speckle tracking echocardiography, allowing accurate, reproducible and rapid bedside assessment of left ventricular twist, has boosted the interest in this important mechanical aspect of left ventricular deformation. Although the fundamental physiological role of left ventricular twist is undisputable, the clinical relevance of assessment of left ventricular twist in cardiomyopathies still needs to be established. The fact remains; analysis of left ventricular twist mechanics has already provided substantial pathophysiological understanding on a comprehensive variety of cardiomyopathies. It has become clear that increased left ventricular twist in for example hypertrophic cardiomyopathy may be an early sign of subendocardial (microvascular) dysfunction. Furthermore, decreased left ventricular twist may be caused by left ventricular dilatation or an extensive myocardial scar. Finally, the detection of left ventricular rigid body rotation in noncompaction cardiomyopathy may provide an indispensible method to objectively confirm this difficult diagnosis. All this endorses the value of left ventricular twist in the field of cardiomyopathies and may further encourage the implementation of left ventricular twist parameters in the “diagnostic toolbox” for cardiomyopathies. PMID:26322187

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction

PubMed Central

Yoshizumi, Tomo; Zhu, Yang; Jiang, Hongbin; D’Amore, Antonio; Sakaguchi, Hirokazu; Tchao, Jason; Tobita, Kimimasa; Wagner, William R.

2016-01-01

Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes. PMID:26774561

Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction.

PubMed

Yoshizumi, Tomo; Zhu, Yang; Jiang, Hongbin; D'Amore, Antonio; Sakaguchi, Hirokazu; Tchao, Jason; Tobita, Kimimasa; Wagner, William R

2016-03-01

Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

l-Arginine Attenuates Cardiac Dysfunction, But Further Down-Regulates α-Myosin Heavy Chain Expression in Isoproterenol-Induced Cardiomyopathy.

PubMed

Kralova, Eva; Doka, Gabriel; Pivackova, Lenka; Srankova, Jasna; Kuracinova, Kristina; Janega, Pavol; Babal, Pavel; Klimas, Jan; Krenek, Peter

2015-10-01

In view of previously reported increased capacity for nitric oxide production, we suggested that l-arginine (ARG), the nitric oxide synthase (NOS) substrate, supplementation would improve cardiac function in isoproterenol (ISO)-induced heart failure. Male Wistar rats were treated with ISO for 8 days (5 mg/kg/day, i.p.) or vehicle. ARG was given to control (ARG) and ISO-treated (ISO+ARG) rats in water (0.4 g/kg/day). ISO administration was associated with 40% mortality, ventricular hypertrophy, decreased heart rate, left ventricular dysfunction, fibrosis and ECG signs of ischaemia. RT-PCR showed increased mRNA levels of cardiac hypertrophy marker atrial natriuretic peptide, but not BNP, decreased expression of myosin heavy chain isoform MYH6 and unaltered expression of pathological MYH7. ISO increased the protein levels of endothelial nitric oxide synthase, but at the same time it markedly up-regulated mRNA and protein levels of gp91phox, a catalytical subunit of superoxide-producing NADPH oxidase. Fibrosis was markedly increased by ISO. ARG treatment moderately ameliorated left ventricular dysfunction, but was without effect on cardiac hypertrophy and fibrosis. Combination of ISO and ARG led to a decrease in cav-1 expression, a further increase in MYH7 expression and a down-regulation of MYH6 that inversely correlated with gp91phox mRNA levels. Although ARG, at least partially, improved ISO-impaired basal left ventricular systolic function, it failed to reduce cardiac hypertrophy, fibrosis, oxidative stress and mortality. The protection of contractile performance might be related to increased capacity for nitric oxide production and the up-regulation of MYH7 which may compensate for the marked down-regulation of the major MYH6 isoform. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Effects of Frequent Hemodialysis on Ventricular Volumes and Left Ventricular Remodeling

PubMed Central

Greene, Tom; Chertow, Glenn M.; Kliger, Alan S.; Stokes, John B.; Beck, Gerald J.; Daugirdas, John T.; Kotanko, Peter; Larive, Brett; Levin, Nathan W.; Mehta, Ravindra L.; Rocco, Michael; Sanz, Javier; Yang, Phillip C.; Rajagopalan, Sanjay

2013-01-01

Summary Background and objectives Higher left ventricular volume is associated with death in patients with ESRD. This work investigated the effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling. Design, setting, participants, & measurements The Frequent Hemodialysis Network daily trial randomized 245 patients to 12 months of six times per week versus three times per week in-center hemodialysis; the Frequent Hemodialysis Network nocturnal trial randomized 87 patients to 12 months of six times per week nocturnal hemodialysis versus three times per week predominantly home-based hemodialysis. Left and right ventricular end systolic and diastolic volumes, left ventricular mass, and ejection fraction at baseline and end of the study were ascertained by cardiac magnetic resonance imaging. The ratio of left ventricular mass/left ventricular end diastolic volume was used as a surrogate marker of left ventricular remodeling. In each trial, the effect of frequent dialysis on left or right ventricular end diastolic volume was tested between predefined subgroups. Results In the daily trial, frequent hemodialysis resulted in significant reductions in left ventricular end diastolic volume (−11.0% [95% confidence interval, −16.1% to −5.5%]), left ventricular end systolic volume (−14.8% [−22.7% to −6.2%]), right ventricular end diastolic volume (−11.6% [−19.0% to −3.6%]), and a trend for right ventricular end systolic volume (−11.3% [−21.4% to 0.1%]) compared with conventional therapy. The magnitude of reduction in left and right ventricular end diastolic volumes with frequent hemodialysis was accentuated among patients with residual urine output<100 ml/d (P value [interaction]=0.02). In the nocturnal trial, there were no significant changes in left or right ventricular volumes. The frequent dialysis interventions had no substantial effect on the ratio of left ventricular mass/left ventricular end diastolic volume in either trial. Conclusions Frequent in-center hemodialysis reduces left and right ventricular end systolic and diastolic ventricular volumes as well as left ventricular mass, but it does not affect left ventricular remodeling. PMID:23970131

A rabbit model of progressive chronic right ventricular pressure overload.

PubMed

Roldan Ramos, Sara; Pieles, Guido; Hui, Wei; Slorach, Cameron; Redington, Andrew N; Friedberg, Mark K

2018-04-01

Right ventricular (RV) failure from increased pressure loading is a frequent consequence of acquired and congenital heart diseases. However, the mechanisms involved in their pathophysiology are still unclear, and few data exist on RV pressure-loading models and early versus late effects on RV and left ventricular responses. We characterized a rabbit model of chronic RV pressure overload and early-late effects on biventricular function. Twenty-one New Zealand white rabbits were randomized into 3 groups: (i) sham, (ii) pulmonary artery (PA) banding (PAB) for 3 weeks (PAB3W) and (iii) PAB for 6 weeks (PAB6W). Progressive RV pressure overload was created by serial band inflation using an adjustable device. Molecular, echocardiographic and haemodynamic studies were performed. RV pressure overload was achieved with clinical manifestations of RV failure. Heart and liver weights were significantly higher after PAB. PAB-induced echocardiographic ventricular remodelling increased wall thickness and stress and ventricular dilation. Cardiac output (ml/min) (sham 172.4 ± 42.86 vs PAB3W 103.1 ± 23.14 vs PAB6W 144 ± 60.9, P = 0.0027) and systolic and diastolic functions decreased; with increased RV end-systolic and end-diastolic pressures (mmHg) (sham 1.6 ± 0.66 vs PAB3W 3.9 ± 1.8 vs PAB6W 5.2 ± 2.2, P = 0.0103), despite increased contractility [end-systolic pressure-volume relationship (mmHg/ml), sham 3.76 ± 1.76 vs PAB3W 12.21 ± 3.44 vs PAB6W 19.4 ± 6.88, P < 0.0001]. Functional parameters further worsened after PAB6W versus PAB3W. LV contractility increased in both the PAB groups, despite worsening of other invasive measures of systolic and diastolic functions. We describe a novel, unique model of chronic RV pressure overload leading to early biventricular dysfunction and fibrosis with further progression at 6 weeks. These findings can aid in guiding management.

Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montaigne, David; Marechal, Xavier; Baccouch, Riadh

2010-05-01

The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solutionmore » containing 1 muM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt{sub max} of 105 +- 8 mN/s in control hearts vs. 49 +- 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 +- 0.2 in control hearts vs. 2.2 +- 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 +- 1 muM cytochrome c/min/mg in control hearts vs. 14 +- 3 muM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.« less

Low-dose dobutamine gated-SPECT analysis of left ventricular segmental wall thickening in ischemic cardiomyopathy.

PubMed

Candell-Riera, Jaume; Romero-Farina, Guillermo; Milá, Marta; Aguadé-Bruix, Santiago

2008-10-01

The objective of this study was to use low-dose dobutamine (LDD) gated single-photon emission computed tomography (SPECT) to evaluate segmental thickening of the left ventricle (LV) and its relationship with changes in ejection fraction (EF) and ventricular volumes in patients with ischemic cardiomyopathy. This prospective multicenter study involved 89 patients with ischemic cardiomyopathy (i.e., EF < or =40%) who underwent LDD gated-SPECT at rest. The LV was divided into 17 segments and systolic thickening was assessed in a total of 1513 segments during LDD infusion. RESULTS; A significant increase in LVEF (33.2% vs. 30.8%; P< .001) was observed during LDD infusion and occurred at the expense of a reduction in end-systolic volume (130.5 mL vs. 136.4 mL; P=.005). The increase in EF was > or =5% in 33.7% of patients, while the EF decreased by > or =5% in 5.6% of patients. With LDD infusion, both an improvement in > or =3 segments with severely decreased baseline thickening (odds ratio [OR] = 18.3; 95% confidence interval [CI], 5.3-63) and an improvement in > or =10 segments with mild-to-moderate alterations in baseline thickening (OR = 4.53; 95% CI, 1.26-16.16) were associated with a > or =5% increase in LVEF. During the assessment of global left ventricular contractile reserve by LDD gated-SPECT, attention should be paid not only to the behavior of segments with severely decreased baseline thickening, which are generally regarded as indicating viability, but also to segments with mild-to-moderate alterations and to those in which thickening decreases.

Heart Rate Reduction With Ivabradine Protects Against Left Ventricular Remodeling by Attenuating Infarct Expansion and Preserving Remote-Zone Contractile Function and Synchrony in a Mouse Model of Reperfused Myocardial Infarction.

PubMed

O'Connor, Daniel M; Smith, Robert S; Piras, Bryan A; Beyers, Ronald J; Lin, Dan; Hossack, John A; French, Brent A

2016-04-22

Ivabradine selectively inhibits the pacemaker current of the sinoatrial node, slowing heart rate. Few studies have examined the effects of ivabradine on the mechanical properties of the heart after reperfused myocardial infarction (MI). Advances in ultrasound speckle-tracking allow strain analyses to be performed in small-animal models, enabling the assessment of regional mechanical function. After 1 hour of coronary occlusion followed by reperfusion, mice received 10 mg/kg per day of ivabradine dissolved in drinking water (n=10), or were treated as infarcted controls (n=9). Three-dimensional high-frequency echocardiography was performed at baseline and at days 2, 7, 14, and 28 post-MI. Speckle-tracking software was used to calculate intramural longitudinal myocardial strain (Ell) and strain rate. Standard deviation time to peak radial strain (SD Tpeak Err) and temporal uniformity of strain were calculated from short-axis cines acquired in the left ventricular remote zone. Ivabradine reduced heart rate by 8% to 16% over the course of 28 days compared to controls (P<0.001). On day 28 post-MI, the ivabradine group was found to have significantly smaller end-systolic volumes, greater ejection fraction, reduced wall thinning, and greater peak Ell and Ell rate in the remote zone, as well as globally. Temporal uniformity of strain and SD Tpeak Err were significantly smaller in the ivabradine-treated group by day 28 (P<0.05). High-frequency ultrasound speckle-tracking demonstrated decreased left ventricular remodeling and dyssynchrony, as well as improved mechanical performance in remote myocardium after heart rate reduction with ivabradine. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The impact of preload reduction with head-up tilt testing on longitudinal and transverse left ventricular mechanics.

PubMed

Schneider, Caroline; Forsythe, Lynsey; Somauroo, John; George, Keith; Oxborough, David

2018-01-03

Left ventricular (LV) function is dependent on load, intrinsic contractility and relaxation with a variable impact on specific mechanics. Strain (ε) imaging allows the assessment of cardiac function however the direct relationship between volume and strain is currently unknown. The aim of this study was to establish the impact of preload reduction through head-up tilt (HUT) testing on simultaneous left ventricular (LV) longitudinal and transverse function and their respective contribution to volume change. A focused transthoracic echocardiogram was performed on 10 healthy male participants (23 ± 3 years,) in the supine position and following 1 min and 5 min of HUT testing. Raw temporal longitudinal ε (Ls) and transverse ε (Ts) values were exported and divided into 5% increments across the cardiac cycle and corresponding LV volumes were traced at each 5% increment. This provided simultaneous LV longitudinal and transverse ε and volume-loops (deformation-volume analysis - DVA). There was a leftward- shift of the ε -volume loop from supine to 1 min and 5 min of HUT, p<0.001). Moreover, longitudinal shortening was reduced (p<0.001) with a concomitant increase in transverse thickening from supine to 1min, which was further augmented at 5min (p=0.018). Preload reduction occurs within 1 minute of HUT but does not further reduce at 5 minutes. This decline is associated with a decrease in longitudinal ε and concomitant increase in transverse ε. Consequently, augmented transverse relaxation appears to be an important factor in the maintenance of LV filling in the setting of reduced preload. DVA provides information on the relative contribution of mechanics to a change in LV volume and may have a role in the assessment of clinical populations. © 2018 The authors.

Cardiac biomarkers in HIV-exposed uninfected children.

PubMed

Wilkinson, James D; Williams, Paige L; Leister, Erin; Zeldow, Bret; Shearer, William T; Colan, Steven D; Siberry, George K; Dooley, Laurie B; Scott, Gwendolyn B; Rich, Kenneth C; Lipshultz, Steven E

2013-04-24

To evaluate associations of cardiac biomarkers with in-utero antiretroviral drug exposures and cardiac function/structure measured by echocardiograms in HIV-exposed but uninfected (HEU) children. We analyzed the association of three cardiac biomarkers (cardiac troponin T, cTnT; high sensitivity C-reactive protein, hsCRP; and N-terminal pro-brain natriuretic peptide, NT-proBNP) with prenatal antiretroviral drug exposures, maternal-child characteristics, and echocardiographic parameters. Among 338 HEU children (mean age 4.3 years), 51% had at least one elevated cardiac biomarker. Maternal tobacco use was associated with elevated NT-proBNP [adjusted odds ratio (aOR) 2.28, P=0.02]. Maternal alcohol and abacavir use were associated with elevated cTnT levels (aOR 3.56, P=0.01 and aOR 2.33, P=0.04, respectively). Among 94 children with paired echocardiogram-biomarker measurements, cTnT measurements were correlated with increased left-ventricular thickness-to-dimension ratio (r=0.21, P=0.04); and elevated cTnT was associated with higher mean left-ventricular end-diastolic (LVED) posterior wall thickness (P=0.04). hsCRP measurements were negatively correlated with septal thickness (r=-0.22, P=0.03) and elevated hsCRP was associated with lower mean left-ventricular contractility Z-scores (P=0.04). NT-proBNP measurements were correlated with increased LVED dimension (r=0.20, P=0.05) and elevated NT-proBNP was associated with lower mean end-systolic septal thickness (P=0.03). Our findings suggest that cardiac biomarkers may help identify HEU children who require further cardiac evaluation including echocardiography. Potential cardiac effects of prenatal abacavir exposure in this population need further investigation.

Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock.

PubMed

Kumar, Anand; Schupp, Elizabeth; Bunnell, Eugene; Ali, Amjad; Milcarek, Barry; Parrillo, Joseph E

2008-01-01

During septic shock, resistance to the haemodynamic effects of catecholamine vasopressors and inotropes is a well-recognised marker of mortality risk. However, the specific cardiovascular or metabolic response elements that are most closely associated with outcome have not been well defined. The objective of this study was to assess cardiovascular and metabolic responses to dobutamine as correlates of outcome in patients with severe sepsis or septic shock. A prospective, non-randomised, non-blinded interventional study of graded dobutamine challenge (0, 5, 10, and 15 mug/kg/min) in adult patients who had undergone pulmonary artery catheterisation within 48 hours of onset of severe sepsis or septic shock (8 survivors/15 non-survivors) was performed. Radionuclide cineangiography during graded infusion was used to determine biventricular ejection fractions at each increment of dobutamine. In univariate analysis, a variety of cardiovascular or haemodynamic and oxygen transport or metabolic variables (at the point of maximum cardiac index response for a given subject) were associated with survival including: increased stroke volume index (p = 0.0003); right ventricular end-diastolic volume index (p = 0.0047); left ventricular stroke work index (p = 0.0054); oxygen delivery index (p = 0.0084); cardiac index (p = 0.0093); systolic blood pressure/left ventricular end-systolic volume index ratio (p = 0.0188); left ventricular ejection fraction (p = 0.0160); venous oxygen content (p = 0.0208); mixed venous oxygen saturation (p = 0.0234); pulse pressure (p = 0.0403); decreased pulmonary artery diastolic pressure (p = 0.0133); systemic vascular resistance index (p = 0.0154); extraction ratio (p = 0.0160); and pulmonary vascular resistance index (p = 0.0390). Increases of stroke volume index of greater than or less than 8.5 mL/m2 were concordant with survival or death in 21 of 23 cases. Multivariate profile construction showed stroke volume index as the dominant discriminating variable for survival with the systolic blood pressure/left ventricular end-systolic volume index ratio alone among all other variables significantly improving the model. Survivors maintain cardiac responsiveness to catecholamine stimulation during septic shock. Survival from severe sepsis or septic shock is associated with increased cardiac performance and contractility indices during dobutamine infusion. Further studies are required to determine whether these parameters are predictive of outcome in a larger severe sepsis/septic shock population.

Non‐invasive evaluation of the myocardial substrate of cardiac amyloidosis by gadolinium cardiac magnetic resonance

PubMed Central

Perugini, E; Rapezzi, C; Piva, T; Leone, O; Bacchi‐Reggiani, L; Riva, L; Salvi, F; Lovato, L; Branzi, A; Fattori, R

2006-01-01

Objective To investigate the prevalence and distribution of gadolinium (Gd) enhancement at cardiac magnetic resonance (CMR) imaging in patients with cardiac amyloidosis (CA) and to look for associations with clinical, morphological, and functional features. Patients and design 21 patients with definitely diagnosed CA (nine with immunoglobulin light chain amyloidosis and 12 transthyretin related) underwent Gd‐CMR. Results Gd enhancement was detected in 16 of 21 (76%) patients. Sixty six of 357 (18%) segments were enhanced, more often at the mid ventricular level. Transmural extension of enhancement within each patient significantly correlated with left ventricular (LV) end systolic volume (r  =  0.58). The number of enhanced segments correlated with LV end diastolic volume (r  =  0.76), end systolic volume (r  =  0.6), and left atrial size (r  =  0.56). Segments with > 50% extensive transmural enhancement more often were severely hypokinetic or akinetic (p  =  0.001). Patients with > 2 enhanced segments had significantly lower 12 lead QRS voltage and Sokolow‐Lyon index. No relation was apparent with any other clinical, morphological, functional, or histological characteristics. Conclusion Gd enhancement is common but not universally present in CA, probably due to expansion of infiltrated interstitium. The segmental and transmural distribution of the enhancement is highly variable, and mid‐ventricular regions are more often involved. Enhancement appears to be associated with impaired segmental and global contractility and a larger atrium. PMID:15939726

Transmural heterogeneity of cellular level power output is reduced in human heart failure.

PubMed

Haynes, Premi; Nava, Kristofer E; Lawson, Benjamin A; Chung, Charles S; Mitov, Mihail I; Campbell, Stuart G; Stromberg, Arnold J; Sadayappan, Sakthivel; Bonnell, Mark R; Hoopes, Charles W; Campbell, Kenneth S

2014-07-01

Heart failure is associated with pump dysfunction and remodeling but it is not yet known if the condition affects different transmural regions of the heart in the same way. We tested the hypotheses that the left ventricles of non-failing human hearts exhibit transmural heterogeneity of cellular level contractile properties, and that heart failure produces transmural region-specific changes in contractile function. Permeabilized samples were prepared from the sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricular free wall of non-failing (n=6) and failing (n=10) human hearts. Power, an in vitro index of systolic function, was higher in non-failing mid-myocardial samples (0.59±0.06μWmg(-1)) than in samples from the sub-epicardium (p=0.021) and the sub-endocardium (p=0.015). Non-failing mid-myocardial samples also produced more isometric force (14.3±1.33kNm(-2)) than samples from the sub-epicardium (p=0.008) and the sub-endocardium (p=0.026). Heart failure reduced power (p=0.009) and force (p=0.042) but affected the mid-myocardium more than the other transmural regions. Fibrosis increased with heart failure (p=0.021) and mid-myocardial tissue from failing hearts contained more collagen than matched sub-epicardial (p<0.001) and sub-endocardial (p=0.043) samples. Power output was correlated with the relative content of actin and troponin I, and was also statistically linked to the relative content and phosphorylation of desmin and myosin light chain-1. Non-failing human hearts exhibit transmural heterogeneity of contractile properties. In failing organs, region-specific fibrosis produces the greatest contractile deficits in the mid-myocardium. Targeting fibrosis and sarcomeric proteins in the mid-myocardium may be particularly effective therapies for heart failure. Copyright © 2014 Elsevier Ltd. All rights reserved.

A study of ventricular contractility and other parameters possibly related to vasodepressor syncope

NASA Technical Reports Server (NTRS)

Hyatt, K. H.; Sullivan, R. W.; Spears, W. R.; Vetter, W. R.

1973-01-01

The effects of diminished orthostatic and exercise tolerance resulting from prolonged bedrest were studied by noninvasion methods to determine if alterations in myocardial contractility were induced by bedrest. These methods were apexcardiography, systolic time intervals, and echocardiography. It is concluded that bedrest causes detrimental alterations in the contractile state of the myocardium which accounts for the decreases in maximal oxygen uptaken during exercise after bedrest. Tabulated test data are included.

Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression.

PubMed

Knowlton, K U; Baracchini, E; Ross, R S; Harris, A N; Henderson, S A; Evans, S M; Glembotski, C C; Chien, K R

1991-04-25

To study the mechanisms which mediate the transcriptional activation of cardiac genes during alpha adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. alpha 1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with alpha-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that alpha-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate alpha-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during alpha-adrenergic stimulation of neonatal rat ventricular cells.

Cardiac fibroblast GSK-3β regulates ventricular remodeling and dysfunction in ischemic heart

PubMed Central

Lal, Hind; Ahmad, Firdos; Zhou, Jibin; Yu, Justine E.; Vagnozzi, Ronald J.; Guo, Yuanjun; Yu, Daohai; Tsai, Emily J.; Woodgett, James; Gao, Erhe; Force, Thomas

2014-01-01

Background Myocardial infarction-induced remodeling includes chamber dilatation, contractile dysfunction, and fibrosis. Of these, fibrosis is the least understood. Following MI, activated cardiac fibroblasts (CFs) deposit extracellular matrix. Current therapies to prevent fibrosis are inadequate and new molecular targets are needed. Methods and Results Herein we report that GSK-3β is phosphorylated (inhibited) in fibrotic tissues from ischemic human and mouse heart. Using two fibroblast-specific GSK-3β knockout mouse models, we show that deletion of GSK-3β in CFs leads to fibrogenesis, left ventricular dysfunction and excessive scarring in the ischemic heart. Deletion of GSK-3β induces a pro-fibrotic myofibroblast phenotype in isolated CFs, in post-MI hearts, and in MEFs deleted for GSK-3β. Mechanistically, GSK-3β inhibits pro-fibrotic TGF-β1-SMAD-3 signaling via interactions with SMAD-3. Moreover, deletion of GSK-3β resulted in the suppression of SMAD-3 transcriptional activity. This pathway is central to the pathology since a small molecule inhibitor of SMAD-3 largely prevented fibrosis and limited LV remodeling. Conclusion These studies support targeting GSK-3β in myocardial fibrotic disorders and establish critical roles of CFs in remodeling and ventricular dysfunction. PMID:24899689

Functional requirements of a mathematical model of the heart.

PubMed

Palladino, Joseph L; Noordergraaf, Abraham

2009-01-01

Functional descriptions of the heart, especially the left ventricle, are often based on the measured variables pressure and ventricular outflow, embodied as a time-varying elastance. The fundamental difficulty of describing the mechanical properties of the heart with a time-varying elastance function that is set a priori is described. As an alternative, a new functional model of the heart is presented, which characterizes the ventricle's contractile state with parameters, rather than variables. Each chamber is treated as a pressure generator that is time and volume dependent. The heart's complex dynamics develop from a single equation based on the formation and relaxation of crossbridge bonds. This equation permits the calculation of ventricular elastance via E(v) = partial differentialp(v)/ partial differentialV(v). This heart model is defined independently from load properties, and ventricular elastance is dynamic and reflects changing numbers of crossbridge bonds. In this paper, the functionality of this new heart model is presented via computed work loops that demonstrate the Frank-Starling mechanism and the effects of preload, the effects of afterload, inotropic changes, and varied heart rate, as well as the interdependence of these effects. Results suggest the origin of the equivalent of Hill's force-velocity relation in the ventricle.

Integrated quadruple stress echocardiography.

PubMed

Picano, Eugenio; Morrone, Doralisa; Scali, Maria C; Huqi, Alda; Coviello, Katia; Ciampi, Quirino

2018-04-11

Stress Echocardiography (SE) is an established diagnostic technique. For 40 years, the cornerstone of the technique has been the detection of regional wall motion abnormalities (RWMA), due to the underlying physiologically-relevant epicardial coronary artery stenosis. In the last decade, three new parameters (more objective than RWMA) have shown the potential to integrate and comple- ment RWMA: 1- B-lines, also known as ultrasound lung comets, as a marker of extra-vascular lung water, measured using lung ultrasound with the 4-site simplified scan symmetrically of the antero- lateral thorax on the third intercostal space, from mid-axillary to anterior axillary and mid- clavicular line; 2-left ventricular contractile reserve (LVCR), assessed as the peak stress/rest ratio of left ventricular force, also known as elastance (systolic arterial pressure by cuff sphygmomanome- ter/end-systolic volume from 2D echocardiography); 3- coronary flow velocity reserve (CFVR) on left anterior descending coronary artery, calculated as peak stress/rest ratio of diastolic peak flow velocity assessed using pulsed-wave Doppler. The 4 parameters (RWMA, B-lines, LVCR and CFVR) now converge conceptually, logistically, and methodologically in the Integrated Quadruple (IQ)-SE. IQ-SE optimizes the versatility of SE to include in a one-stop shop the core "ABCD" (Asynergy+B-lines+Contractile reserve+Doppler flowmetry) protocol. It allows a synoptic assess- ment of parameters mirroring the epicardial artery stenosis (RWMA), interstitial lung water (B- lines), myocardial function (LVCR) and small coronary vessels (CFVR). Each variable has a clear clinical correlate, different and complementary to all others: RWMA identify an ischemic vs non- ischemic heart; B-lines a wet vs dry lung; LVCR a strong vs weak heart; CFVR a warm vs cold heart. IQ-SE is highly feasible, with minimal increase in the imaging and analysis time, and obvi- ous diagnostic and prognostic impact also beyond coronary artery disease - especially in heart fail- ure. Large scale effectiveness studies with IQ-SE are now under way with the Stress Echo 2020 study, and will provide the necessary evidence base prior to large scale acceptance of the tech- nique.

Pressure overload differentially affects respiratory capacity in interfibrillar and subsarcolemmal mitochondria.

PubMed

Schwarzer, Michael; Schrepper, Andrea; Amorim, Paulo A; Osterholt, Moritz; Doenst, Torsten

2013-02-15

Years ago a debate arose as to whether two functionally different mitochondrial subpopulations, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), exist in heart muscle. Nowadays potential differences are often ignored. Presumably, SSM are providing ATP for basic cell function, whereas IFM provide energy for the contractile apparatus. We speculated that two distinguishable subpopulations exist that are differentially affected by pressure overload. Male Sprague-Dawley rats were subjected to transverse aortic constriction for 20 wk or sham operation. Contractile function was assessed by echocardiography. Heart tissue was analyzed by electron microscopy. Mitochondria were isolated by differential centrifugation, and respiratory capacity was analyzed using a Clark electrode. Pressure overload induced left ventricular hypertrophy with increased posterior wall diameter and impaired contractile function. Mitochondrial state 3 respiration in control was 50% higher in IFM than in SSM. Pressure overload significantly impaired respiratory rates in both IFM and SSM, but in SSM to a lower extent. As a result, there were no differences between SSM and IFM after 20 wk of pressure overload. Pressure overload reduced total citrate synthase activity, suggesting reduced total mitochondrial content. Electron microscopy revealed normal morphology of mitochondria but reduced total mitochondrial volume density. In conclusion, IFM show greater respiratory capacity in the healthy rat heart and a greater depression of respiratory capacity by pressure overload than SSM. The differences in respiratory capacity of cardiac IFM and SSM in healthy hearts are eliminated with pressure overload-induced heart failure. The strong effect of pressure overload on IFM together with the simultaneous appearance of mitochondrial and contractile dysfunction may support the notion of IFM primarily producing ATP for contractile function.

American ginseng acutely regulates contractile function of rat heart.

PubMed

Jiang, Mao; Murias, Juan M; Chrones, Tom; Sims, Stephen M; Lui, Edmund; Noble, Earl G

2014-01-01

Chronic ginseng treatments have been purported to improve cardiac performance. However reports of acute administration of ginseng on cardiovascular function remain controversial and potential mechanisms are not clear. In this study, we examined the effects of acute North American ginseng (Panax quinquefolius) administration on rat cardiac contractile function by using electrocardiogram (ECG), non-invasive blood pressure (BP) measurement, and Langendorff isolated, spontaneously beating, perfused heart measurements (LP). Eight-week old male Sprague-Dawley rats (n = 8 per group) were gavaged with a single dose of water-soluble American ginseng at 300 mg/kg body weight. Heart rate (HR) and BP were measured prior to and at 1 and 24 h after gavaging (ECG and BP). Additional groups were used for each time point for Langendorff measurements. HR was significantly decreased (ECG: 1 h: 6 ± 0.2%, 24 h: 8 ± 0.3%; BP: 1 h: 8.8 ± 0.2%, 24 h: 13 ± 0.4% and LP: 1 h: 22 ± 0.4%, 24 h: 19 ± 0.4%) in rats treated with water-soluble ginseng compared with pre or control measures. An initial marked decrease in left ventricular developed pressure was observed in LP hearts but BP changes were not observed in BP group. A direct inhibitory effect of North American ginseng was observed on cardiac contractile function in LP rats and on fluorescence measurement of intracellular calcium transient in freshly isolated cardiac myocytes when exposed to ginseng (1 and 10 μg/ml). Collectively these data present evidence of depressed cardiac contractile function by acute administration of North American ginseng in rat. This acute reduction in cardiac contractile function appears to be intrinsic to the myocardium.

American ginseng acutely regulates contractile function of rat heart

PubMed Central

Jiang, Mao; Murias, Juan M.; Chrones, Tom; Sims, Stephen M.; Lui, Edmund; Noble, Earl G.

2014-01-01

Chronic ginseng treatments have been purported to improve cardiac performance. However reports of acute administration of ginseng on cardiovascular function remain controversial and potential mechanisms are not clear. In this study, we examined the effects of acute North American ginseng (Panax quinquefolius) administration on rat cardiac contractile function by using electrocardiogram (ECG), non-invasive blood pressure (BP) measurement, and Langendorff isolated, spontaneously beating, perfused heart measurements (LP). Eight-week old male Sprague–Dawley rats (n = 8 per group) were gavaged with a single dose of water-soluble American ginseng at 300 mg/kg body weight. Heart rate (HR) and BP were measured prior to and at 1 and 24 h after gavaging (ECG and BP). Additional groups were used for each time point for Langendorff measurements. HR was significantly decreased (ECG: 1 h: 6 ± 0.2%, 24 h: 8 ± 0.3%; BP: 1 h: 8.8 ± 0.2%, 24 h: 13 ± 0.4% and LP: 1 h: 22 ± 0.4%, 24 h: 19 ± 0.4%) in rats treated with water-soluble ginseng compared with pre or control measures. An initial marked decrease in left ventricular developed pressure was observed in LP hearts but BP changes were not observed in BP group. A direct inhibitory effect of North American ginseng was observed on cardiac contractile function in LP rats and on fluorescence measurement of intracellular calcium transient in freshly isolated cardiac myocytes when exposed to ginseng (1 and 10 μg/ml). Collectively these data present evidence of depressed cardiac contractile function by acute administration of North American ginseng in rat. This acute reduction in cardiac contractile function appears to be intrinsic to the myocardium. PMID:24672484

Myocardial function during bradycardia events in preterm infants.

PubMed

de Waal, Koert; Phad, Nilkant; Collins, Nick; Boyle, Andrew

2016-07-01

Transient bradycardia episodes are common in preterm infants and often secondary to apnea. Decreased ventilation with resultant hypoxemia is believed to be the predominant mechanism. Sudden bradycardias without apnea are also reported, possibly due to vagal stimulation. Point of care ultrasound is used to diagnose and follow cardiovascular complications in preterm infants. Inadvertently, the operator would sometimes capture bradycardia events. This study reports on left ventricular function during such events. We retrospectively reviewed our cardiac ultrasound database for bradycardia events. Apical four or three chamber images before, during and after a bradycardia event were analysed with speckle tracking software which provides systolic and diastolic parameters of myocardial motion, deformation and volume. Over a 2year period, 15 bradycardia events were noted in 14 patients with a median gestational age of 26weeks (range 23 to 29). Heart rate decreased by an average of 43% (171/min to 98/min). Myocardial velocity and longitudinal strain rate during the atrial component of diastole were reduced during bradycardia. Longitudinal strain during systole was increased and radial deformation was unchanged. Ventricular volumes and ejection fraction did not change. Most parameters returned to baseline values after the event. Longitudinal systolic strain rate remained lower and stroke volume was 12% higher compared to baseline. Parameters of systolic contractility and stroke volume were maintained and parameters of atrial contractility were reduced during mild to moderate bradycardia in preterm infants. Bradycardia reduces total cardiac output with a compensatory increase detected following the event. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Coenzyme Q10 protects ischemic myocardium in an open-chest swine model.

PubMed

Atar, D; Mortensen, S A; Flachs, H; Herzog, W R

1993-01-01

Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism.

Cardiac compartment-specific overexpression of a modified retinoic acid receptor produces dilated cardiomyopathy and congestive heart failure in transgenic mice.

PubMed

Colbert, M C; Hall, D G; Kimball, T R; Witt, S A; Lorenz, J N; Kirby, M L; Hewett, T E; Klevitsky, R; Robbins, J

1997-10-15

Retinoids play a critical role in cardiac morphogenesis. To examine the effects of excessive retinoid signaling on myocardial development, transgenic mice that overexpress a constitutively active retinoic acid receptor (RAR) controlled by either the alpha- or beta-myosin heavy chain (MyHC) promoter were generated. Animals carrying the alpha-MyHC-RAR transgene expressed RARs in embryonic atria and in adult atria and ventricles, but developed no signs of either malformations or disease. In contrast, beta-MyHC-RAR animals, where expression was activated in fetal ventricles, developed a dilated cardiomyopathy that varied in severity with transgene copy number. Characteristic postmortem lesions included biventricular chamber dilation and left atrial thrombosis; the incidence and severity of these lesions increased with increasing copy number. Transcript analyses showed that molecular markers of hypertrophy, alpha-skeletal actin, atrial natriuretic factor and beta-MyHC, were upregulated. Cardiac performance of transgenic hearts was evaluated using the isolated perfused working heart model as well as in vivo, by transthoracic M-mode echocardiography. Both analyses showed moderate to severe impairment of left ventricular function and reduced cardiac contractility. Thus, expression of a constitutively active RAR in developing atria and/ or in postnatal ventricles is relatively benign, while ventricular expression during gestation can lead to significant cardiac dysfunction.

Left Ventricular Function in Patients with Pulmonary Arterial Hypertension: The Role of Two-Dimensional Speckle Tracking Strain.

PubMed

de Amorim Corrêa, Ricardo; de Oliveira, Fernanda Brito; Barbosa, Marcia M; Barbosa, Jose Augusto A; Carvalho, Taís Soares; Barreto, Michele Campos; Campos, Frederico Thadeu A F; Nunes, Maria Carmo Pereira

2016-09-01

Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary arterial pressure with abnormal right ventricular (RV) pressure overload that may alter left ventricular (LV) function. The aim of this study was to assess the impact of RV pressure overload on LV function in PAH patients using two-dimensional (2D) speckle tracking strain. The study enrolled 37 group 1 PAH patients and 38 age- and gender-matched healthy controls. LV longitudinal and radial 2D strains were measured with and without including the ventricular septum. Six-minute walk test (6MWT) and brain natriuretic peptide (BNP) levels were also obtained in patients with PAH. The mean age of patients was 46.4 ± 14.8 years, 76% women, and 16 patients (43%) had schistosomiasis. Sixteen patients (43%) were in WHO class III or IV under specific treatment for PAH. The overall 6MWT distance was 441 meters, and the BNP levels were 80 pg/mL. Patients with PAH more commonly presented with LV diastolic dysfunction and impairment of RV function when compared to controls. LV global longitudinal and radial strains were lower in patients than in controls (-17.9 ± 2.8 vs. -20.5 ± 1.9; P < 0.001 and 30.8 ± 10.5 vs. 49.8 ± 15.4; P < 0.001, respectively). After excluding septal values, LV longitudinal and radial strains remained lower in patients than in controls. The independent factors associated with global LV longitudinal strain were LV ejection fraction, RV fractional area change, and tricuspid annular systolic motion. This study showed impaired LV contractility in patients with PAH assessed by speckle tracking strain, irrespective of ventricular septal involvement. Global LV longitudinal strain was associated independently with RV fractional area change and tricuspid annular systolic motion, after adjustment for LV ejection fraction. © 2016, Wiley Periodicals, Inc.

Diastolic heart failure associated with hemangiosarcoma infiltrating left ventricular walls in a dog

PubMed Central

Osuga, Tatsuyuki; Nakamura, Kensuke; Morita, Tomoya; Kagawa, Yumiko; Ohta, Hiroshi; Takiguchi, Mitsuyoshi

2017-01-01

A 9-year-old Shetland sheepdog was diagnosed with cardiogenic pulmonary edema. Echocardiography revealed focally thickened left ventricular free wall and interventricular septum and left atrial dilation. Left ventricular systolic function was preserved. Doppler echocardiography of transmitral flow indicated restrictive left ventricular filling. Cardiac histopathology demonstrated hemangiosarcoma infiltrating the left ventricular walls. PMID:29089652

Diastolic heart failure associated with hemangiosarcoma infiltrating left ventricular walls in a dog.

PubMed

Osuga, Tatsuyuki; Nakamura, Kensuke; Morita, Tomoya; Kagawa, Yumiko; Ohta, Hiroshi; Takiguchi, Mitsuyoshi

2017-11-01

A 9-year-old Shetland sheepdog was diagnosed with cardiogenic pulmonary edema. Echocardiography revealed focally thickened left ventricular free wall and interventricular septum and left atrial dilation. Left ventricular systolic function was preserved. Doppler echocardiography of transmitral flow indicated restrictive left ventricular filling. Cardiac histopathology demonstrated hemangiosarcoma infiltrating the left ventricular walls.

Inappropriate left ventricular mass and poor outcomes in patients with angina pectoris and normal ejection fraction.

PubMed

Huang, Bao-Tao; Peng, Yong; Liu, Wei; Zhang, Chen; Huang, Fang-Yang; Wang, Peng-Ju; Zuo, Zhi-Liang; Liao, Yan-Biao; Chai, Hua; Li, Qiao; Zhao, Zhen-Gang; Luo, Xiao-Lin; Ren, Xin; Huang, Kai-Sen; Meng, Qing-Tao; Chen, Chi; Huang, De-Jia; Chen, Mao

2015-03-01

Although inappropriate left ventricular mass has been associated with clustered cardiac geometric and functional abnormalities, its predictive value in patients with coronary artery disease is still unknown. This study examined the association of inappropriate left ventricular mass with clinical outcomes in patients with angina pectoris and normal ejection fraction. Consecutive patients diagnosed with angina pectoris whose ejection fraction was normal were recruited from 2008 to 2012. Inappropriate left ventricular mass was determined when the ratio of actual left ventricular mass to the predicted one exceeded 150%. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Clinical outcomes between the inappropriate and appropriate left ventricular mass group were compared before and after propensity matching. Of the total of 1515 participants, 18.3% had inappropriate left ventricular mass. Patients with inappropriate left ventricular mass had a higher composite event rate compared with those with appropriate left ventricular mass (11.2 vs. 6.6%, P=0.010). Multivariate Cox regression analyses showed that inappropriate left ventricular mass was an independent risk factor for adverse events (adjusted hazard ratio, 1.59; 95% confidence interval, 1.03-2.45; P=0.035). The worse outcome in patients with inappropriate left ventricular mass was further validated in a propensity matching cohort and patients with the traditional definition of left ventricular hypertrophy. Inappropriate left ventricular mass was associated with an increased risk of adverse events in patients with angina pectoris and normal ejection fraction.

A novel cardiac extracorporeal shock wave for enhancing the efficacy of cell therapy

NASA Astrophysics Data System (ADS)

Khaled, Walaa; Assmus, Birgit; Lutz, Andreas; Walter, Dirk; Leistner, David; Dimmeler, Stefanie; Zeiher, Andreas

2012-11-01

Targeted therapy can maximize therapeutic efficiency and minimize the side effects of drug treatments, especially for cancer and cardiovascular disease. In previous in-vitro experiments, it was shown that shock wave (SW) application can change the permeability of cell membranes for tumor therapy. Similarly, in animal studies, extracorporeal SWs were proven to increase expression of growth and homing factors like SDF-1 and vascular endothelial growth factor (VEGF) within a targeted ischemic tissue. This pretreatment increased the homing and neovascularization following application of bone marrow-derived mononuclear cells (BMC). In a randomized, double blinded, placebo-controlled clinical trial, 103 patients were recruited with stable chronic post-infarction heart failure (CHF). The goal of this work was to demonstrate improved recovery of left ventricular contractile function (LVEF) by combining targeted SW application with subsequent BMC administration. Results showed that the shock wavefacilitated intracoronary BMC administration in patients with chronic post-infarction heart failure is associated with significant persistent improvements in LVEF contractile function, NYHA class, and reduction of major adverse clinical events during extended clinical follow-up. (clinicaltrials.gov: NCT00326989).

Postextrasystolic potentiation and contractile reserve: requirements and restrictions.

PubMed

Lust, R M; Lutherer, L O; Gardner, M E; Cooper, M W

1982-12-01

These studies were conducted to examine the basic characteristics of postextrasystolic potentiation (PESP) and the relationship of loading effects to PESP. Measurements of left ventricular (LV) and aortic pressures, the rate of pressure rise, and echocardiographically determined LV dimensions were made in anesthetized open-chest dogs. The hearts were paced, and timed extrasystoles were introduced that were followed by postextrasystoles (PES). PES's were elicited after an interval equal to either a full compensatory pause or a time when the diastolic properties of the LV could not be distinguished from control (isolength). Potentiation of contraction for the PES's introduced after an isolength pause was dependent on both the heart rate and the extrasystolic interval, whereas the PES's that occurred after a full pause showed no dependence on either of these intervals. PESP elicited during the isolength period was not dependent on either preload and afterload. It is concluded that PESP depends on the combination of heart rate and extrasystolic and postextrasystolic intervals. Further, PESP may be inaccurate in assessing contractile reserve unless the heart rate and extrasystolic interval are known and the PES is introduced after an isolength pause.

Increased coronary blood flow and cardiac contractile efficiency with intraaortic balloon counterpulsation in a porcine model of myocardial ischemia-reperfusion injury.

PubMed

Gelsomino, Sandro; Lucà, Fabiana; Renzulli, Attilio; Rubino, Antonino S; Romano, Salvatore Mario; van der Veen, Frederik H; Carella, Rocco; Maessen, Joseph G; Gensini, Gian Franco; Lorusso, Roberto

2011-01-01

The evaluation of the impact of intraaortic balloon pump (IABP) on postischemic coronary perfusion and myocardial contractile impairment has been so far limited to early reperfusion phase. Therefore, we analyzed the 24-hour effects of IABP on coronary blood flow (CBF) and left ventricular performance in an animal model of acute myocardial ischemia-reperfusion injury. Healthy swine (n = 20) underwent 120-minute ligation of the left anterior descending coronary artery followed by 24 hours of reperfusion. We randomly assigned the animals to have IABP placed in the descending aorta 5 minutes after reperfusion onset (n = 10) or to undergo no implantation (n = 10). We measured CBF, coronary resistance, cardiac cycle efficiency (CCE), and maximal pressure/time ratio before ischemia was induced and at 30 minutes and 1, 6, 12, and 24 hours after reperfusion began. During diastole, CBF was significantly increased in IABP compared with baseline and controls at all time points (all p < 0.001). This was also true during systole in IABP only for the first hour after reperfusion began. Additionally, both CCE and pressure/time ratio were significantly increased in IABP compared with baseline at 30 minutes and 1 hour after reperfusion began (p < 0.001). IABP was associated with enhanced CBF and cardiac efficiency in a model of acute ischemic-reperfusion injury.

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic-Banded Mini-Swine.

PubMed

Hiemstra, Jessica A; Lee, Dong I; Chakir, Khalid; Gutiérrez-Aguilar, Manuel; Marshall, Kurt D; Zgoda, Pamela J; Cruz Rivera, Noelany; Dozier, Daniel G; Ferguson, Brian S; Heublein, Denise M; Burnett, John C; Scherf, Carolin; Ivey, Jan R; Minervini, Gianmaria; McDonald, Kerry S; Baines, Christopher P; Krenz, Maike; Domeier, Timothy L; Emter, Craig A

2016-04-20

Cyclic guanosine monophosphate-protein kinase G-phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl-peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function. We assessed LV hypertrophy and function at the organ and cellular level in aortic-banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end-systolic pressure-volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil-treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening-frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium-retention capacity and Complex II-dependent respiratory control, was present in both HF and tadalafil-treated animals. Both saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin appears superior for treating heart failure with preserved ejection fraction, considering its comprehensive effects on integrated LV systolic and diastolic function. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury

PubMed Central

West, Christopher R; Crawford, Mark A; Poormasjedi-Meibod, Malihe-Sadat; Currie, Katharine D; Fallavollita, Andre; Yuen, Violet; McNeill, John H; Krassioukov, Andrei V

2014-01-01

Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day−1, 5 days week−1 for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFβ1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI. PMID:24535438

Effects of propranolol treatment on left ventricular function and intracellular calcium regulation in rats with postinfarction heart failure

PubMed Central

Litwin, Sheldon E; Katz, Sarah E; Morgan, James P; Douglas, Pamela S

1999-01-01

Chronic treatment with beta-adrenergic blocking agents can improve survival in patients with heart failure. The mechanisms underlying the beneficial effects and whether these effects are generalizable to ischaemic heart failure are unresolved.We performed echocardiographic-Doppler examinations in rats (n=28) 1 and 6 weeks after myocardial infarction (MI) or sham surgery. Rats were randomized to no treatment or propranolol (500 mg/l in drinking water) after the first echocardiogram. Isometric contractions and intracellular Ca transients were recorded simultaneously in noninfarcted left ventricular (LV) papillary muscles.Untreated MI rats had significant LV dilatation (10.6±0.4* vs 8.9±0.3 mm, MI vs control), impaired systolic function (fractional shortening=11±2* vs 38±2%), and a restrictive LV diastolic filling pattern. MI rats receiving propranolol had similar LV chamber sizes (10.6±0.5 mm) and systolic function (13±2%). The propranolol treated animals had higher LV end-diastolic pressures (27±2* vs 20±3 mmHg) and a more restricted LV diastolic filling pattern (increased ratio of early to late filling velocities and more rapid E wave deceleration rate). Contractility of papillary muscles from untreated MI rats was depressed (1.6±0.3 vs 2.4±0.5 g mm−2). In addition, Ca transients were prolonged and the inotropic response to isoproterenol was blunted. Propranolol treatment did not improve force development (1.6±0.3 g mm−2) or the duration of Ca transients during isoproterenol stimulation.Chronic propranolol treatment in rats with postinfarction heart failure did not improve LV remodeling or systolic function. LV diastolic pressures and filling patterns were worsened by propranolol. Treatment also did not produce appreciable improvement in contractility, intracellular Ca regulation or beta-adrenergic responsiveness in the noninfarcted myocardium. PMID:10455325

Effects of intravenous hyperosmotic sodium bicarbonate on arterial and cerebrospinal fluid acid-base status and cardiovascular function in calves with experimentally induced respiratory and strong ion acidosis.

PubMed

Berchtold, Joachim F; Constable, Peter D; Smith, Geoffrey W; Mathur, Sheerin M; Morin, Dawn E; Tranquilli, William J

2005-01-01

The objectives of this study were to determine the effects of hyperosmotic sodium bicarbonate (HSB) administration on arterial and cerebrospinal fluid (CSF) acid-base balance and cardiovascular function in calves with experimentally induced respiratory and strong ion (metabolic) acidosis. Ten healthy male Holstein calves (30-47 kg body weight) were instrumented under halothane anesthesia to permit cardiovascular monitoring and collection of blood samples and CSE Respiratory acidosis was induced by allowing the calves to spontaneously ventilate, and strong ion acidosis was subsequently induced by i.v. administration of L-lactic acid. Calves were then randomly assigned to receive either HSB (8.4% NaHCO3; 5 ml/kg over 5 minutes, i.v.; n=5) or no treatment (controls, n=5) and monitored for 1 hour. Mixed respiratory and strong ion acidosis was accompanied by increased heart rate, cardiac index, mean arterial pressure, cardiac contractility (maximal rate of change of left ventricular pressure), and mean pulmonary artery pressure. Rapid administration of HSB immediately corrected the strong ion acidosis, transiently increased arterial partial pressure of carbon dioxide (P(CO2)), and expanded the plasma volume. The transient increase in arterial P(CO2) did not alter CSF P(CO2) or induce paradoxical CSF acidosis. Compared to untreated control calves, HSB-treated calves had higher cardiac index and contractility and a faster rate of left ventricular relaxation for 1 hour after treatment, indicating that HSB administration improved myocardial systolic function. We conclude that rapid i.v. administration of HSB provided an effective and safe method for treating strong ion acidosis in normovolemic halothane-anesthetized calves with experimentally induced respiratory and strong ion acidosis. Fear of inducing paradoxical CSF acidosis is not a valid reason for withholding HSB administration in calves with mixed respiratory and strong ion acidosis.

Endothelin-1 and ET receptors impair left ventricular function by mediated coronary arteries dysfunction in chronic intermittent hypoxia rats.

PubMed

Wang, Jin-Wei; Li, Ai-Ying; Guo, Qiu-Hong; Guo, Ya-Jing; Weiss, James W; Ji, En-Sheng

2017-01-01

Obstructive sleep apnea (OSA) results in cardiac dysfunction and vascular endothelium injury. Chronic intermittent hypoxia (CIH), the main characteristic of OSAS, is considered to be mainly responsible for cardiovascular system impairment. This study is aimed to evaluate the role of endothelin-1(ET-1) system in coronary injury and cardiac dysfunction in CIH rats. In our study, Sprague-Dawley rats were exposed to CIH (FiO 2 9% for 1.5 min, repeated every 3 min for 8 h/d, 7 days/week for 3 weeks). After 3 weeks, the left ventricular developed pressure (LVDP) and coronary resistance (CR) were measured with the langendorff mode in isolated hearts. Meanwhile, expressions of ET-1 and ET receptors were detected by immunohistochemical and western blot, histological changes were also observed to determine effects of CIH on coronary endothelial cells. Results suggested that decreased LVDP level combined with augmented coronary resistance was exist in CIH rats. CIH could induce endothelial injury and endothelium-dependent vasodilatation dysfunction in the coronary arteries. Furthermore, ET-1 and ET A receptor expressions in coronary vessels were increased after CIH exposure, whereas ET B receptors expression was decreased. Coronary contractile response to ET-1 in both normoxia and CIH rats was inhibited by ET A receptor antagonist BQ123. However, ET B receptor antagonist BQ788 enhanced ET-1-induced contractile in normoxia group, but had no significant effects on CIH group. These results indicate that CIH-induced cardiac dysfunction may be associated with coronary injury. ET-1 plays an important role in coronary pathogenesis of CIH through ET A receptor by mediating a potent vasoconstrictor response. Moreover, decreased ET B receptor expression that leads to endothelium-dependent vasodilatation decline, might be also participated in coronary and cardiac dysfunction. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Coexistence of congenital left ventricular aneurysm and prominent left ventricular trabeculation in a patient with LDB3 mutation: a case report.

PubMed

Shan, Shengshuai; He, Xiaoxiao; He, Lin; Wang, Min; Liu, Chengyun

2017-08-19

The coexistence of congenital left ventricular aneurysm and abnormal cardiac trabeculation with gene mutation has not been reported previously. Here, we report a case of coexisting congenital left ventricular aneurysm and prominent left ventricular trabeculation in a patient with LIM domain binding 3 gene mutation. A 30-year-old Asian man showed paroxysmal sinus tachycardia and Q waves in an electrocardiogram health check. There were no specific findings in physical examinations and serological tests. A coronary-computed tomography angiography check showed normal coronary artery and no coronary stenosis. Both left ventricle contrast echocardiography and cardiac magnetic resonance showed rare patterns of a combination of an apical aneurysm-like out-pouching structure with a wide connection to the left ventricle and prominent left ventricular trabecular meshwork. High-throughput sequencing examinations showed a novel mutation in the LDB3 gene (c.C793>T; p.Arg265Cys). Our finding indicates that the phenotypic expression of two heart conditions, congenital left ventricular aneurysm and prominent left ventricular trabeculation, although rare, can occur simultaneously with LDB3 gene mutation. Congenital left ventricular aneurysm and prominent left ventricular trabeculation may share the same genetic background.

Levosimendan Prevents Pressure-Overload-induced Right Ventricular Failure.

PubMed

Hillgaard, Thomas Krarup; Andersen, Asger; Andersen, Stine; Vildbrad, Mads D; Ringgaard, Steffen; Nielsen, Jan M; Nielsen-Kudsk, Jens E

2016-04-01

We investigated if chronic levosimendan treatment can prevent and revert pressure-overload-induced right ventricular hypertrophy and failure in rats. Right ventricular hypertrophy and failure was induced in Wistar rats by pulmonary trunk banding (PTB). The PTB rats were treated with levosimendan (3 mg·kg·d) 3 days before surgery [n = 10, prevention (PREV)], 3 weeks after surgery [n = 10, reversal (REV)] or vehicle (n = 10, VEH). Sham-operated rats received vehicle (n = 16, SHAM). Right ventricular function was evaluated 7 weeks after surgery by echocardiography, magnetic resonance imaging, pressure-volume relations, gross anatomy, and histology. PTB induced right ventricular hypertrophy and compensated heart failure evident by reduced cardiac index (CI) without extra cardiac signs of heart failure. Levosimendan treatment prevented deterioration of right ventricular function measured by CI and right ventricular ejection fraction (RVEF) (CI: VEH vs. PREV 281 ± 17 vs. 362 ± 34 mL·min·kg, P ≤ 0.05, RVEF: VEH vs. PREV 57 ± 2% vs. 68 ± 3%, P ≤ 0.01) to values similar to SHAM (CI: 345 ± 21 mL·min·kg, RVEF: 71 ± 2%). RV contractility was improved in the REV group measured by preload recruitable stroke work (VEH vs. REV 39 ± 3 vs. 66 ± 10 mmHg P ≤ 0.05). Chronic treatment with levosimendan prevents the development of right ventricular failure and improves contractility in established pressure-overload-induced right ventricular failure.

Importance of the mitral apparatus for left ventricular function: an experimental approach.

PubMed

Gams, E; Hagl, S; Schad, H; Heimisch, W; Mendler, N; Sebening, F

1992-01-01

In an experimental study of 31 anesthetized dogs the importance of the mitral apparatus for the left ventricular function was investigated. During extracorporeal circulation bileaflet mitral valve prostheses were implanted preserving the mitral subvalvular apparatus. Flexible wires were slung around the chordae tendineae and exteriorized through the left ventricular wall to cut the chordae by electrocautery from the outside when the heart was beating again. External and internal left ventricular dimensions were measured by sonomicrometry, left ventricular stroke volume by electromagnetic flowmeters around the ascending aorta, left ventricular end-diastolic volume by dye dilution technique, and left ventricular pressure by catheter tip manometers. Different preload levels were achieved by volume loading with blood transfusion before and after cutting the chordae tendineae. When the chordae had been divided peak systolic left ventricular pressure did not change. Heart rate only increased at the lowest left ventricular end-diastolic pressures of 3-4 mmHg, but remained unchanged at higher preload levels. Cardiac output decreased significantly up to -9% at left ventricular end-diastolic pressures of 5-10 mmHg, while left ventricular dp/dtmax showed a consistent reduction of up to -15% at any preload level. Significant reductions were also seen in systolic shortening in the left ventricular major axis (by external measurements -27%, by internal recording -43%). Left ventricular end-diastolic dimensions increased in the major axis by +2% when recorded externally, by +10% when measured internally. Systolic and diastolic changes in the minor axis were not consistent and different in the external and internal recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

PubMed Central

Wang, Li-li; Miller, Dori; Wanders, Desiree; Nanayakkara, Gayani; Amin, Rajesh; Judd, Robert; Morrison, Edward E; Zhong, Ju-ming

2016-01-01

Aim: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- and 9-weeks following fistula. The protein expression of adiponectin, adiponectin receptors (AdipoR1/R2 and T-cadherin) and AMPK activity were measured using Western blot analyses. Isolated ventricular myocytes were prepared at 12 weeks post-fistula to examine the contractile performance of myocytes and intracellular Ca2+ transient. Results: A-V fistula resulted in significant reductions in serum and myocardial adiponectin levels, myocardial adiponectin receptor (AdipoR1/R2 and T-cadherin) levels, as well as myocardial AMPK activity. Consistent with these changes, the isolated myocytes exhibited significant depression in cell shortening and intracellular Ca2+ transient. Administration of adenoviral adiponectin significantly increased serum adiponectin levels and prevented myocyte contractile dysfunction in fistula rats. Furthermore, pretreatment of isolated myocytes with recombinant adiponectin (2.5 μg/mL) significantly improved their contractile performance in fistula rats, but had no effects in control or adenoviral adiponectin-administered rats. Conclusion: These results demonstrate a positive correlation between adiponectin downregulation and volume overload-induced ventricular remodeling. Adiponectin plays a protective role in volume overload-induced heart failure. PMID:26616727

Growth of left ventricular outflow tract and predictors of future re-intervention after repair for ventricular septal defect and aortic arch obstruction.

PubMed

Jijeh, Abdulraouf; Ismail, Muna; Alhabshan, Fahad

2017-09-01

Ventricular septal defect and aortic arch obstruction are usually associated with a narrow left ventricular outflow tract. The aim of the present study was to analyse the growth and predictors of future obstruction of the left ventricular outflow tract after surgical repair. We carried out a retrospective review of patients who underwent repair for ventricular septal defect and aortic arch obstruction - coarctation or interrupted aortic arch - between July, 2002 and June, 2013. Echocardiographic data were reviewed, and the need for re-intervention was evaluated. A total of 89 patients were included in this study. A significant left ventricular outflow tract growth was noticed after surgical repair. Preoperatively, the mean left ventricular outflow tract Z-score was -1.46±1 (range -5.5 to 1.1) and increased to a mean value of -0.7±1.3 (range -2.7 to 3.2) at last follow-up (p=0.0001), demonstrating relevant growth of the left ventricular outflow tract after repair for ventricular septal defect and aortic arch obstruction. After primary repair, 11 patients (12.3%) required re-intervention with surgical repair for left ventricular outflow tract obstruction after a mean period of 36±21 months. There were no significant differences in age, weight, and indexed aortic valve and left ventricular outflow tract measurements between those who developed obstruction and those who did not. Significant left ventricular outflow tract growth is expected after repair of ventricular septal defect and aortic arch obstruction. Small aortic valve and left ventricular outflow tract at diagnosis are not risk factors to predict the need for surgical re-intervention for left ventricular outflow tract obstruction in future.

Improving pacemaker therapy in congenital heart disease: contractility and resynchronization.

PubMed

Karpawich, Peter P

2015-01-01

Designed as effective therapy for patients with symptomatic bradycardia, implantable cardiac pacemakers initially served to improve symptoms and survival. With initial applications to the elderly and those with severe myocardial disease, extended longevity was not a major concern. However, with design technology advances in leads and generators since the 1980s, pacemaker therapy is now readily applicable to all age patients, including children with congenital heart defects. As a result, emphasis and clinical interests have advanced beyond simply quantity to quality of life. Adverse cardiac effects of pacing from right ventricular apical or epicardial sites with resultant left bundle branch QRS configurations have been recognized. As a result, and with the introduction of newer catheter-delivered pacing leads, more recent studies have focused on alternative or select pacing sites such as septal, outflow tract, and para-bundle of His. This is especially important in dealing with pacemaker therapy among younger patients and those with congenital heart disease, with expected decades of artificial cardiac stimulation, in which adverse myocellular changes secondary to pacing itself have been reported. As a correlate to these alternate or select pacing sites, applications of left ventricular pacing, either via the coronary sinus, intraseptal or epicardial, alone or in combination with right ventricular pacing, have gained interest for patients with heart failure. Although cardiac resynchronization pacing has, to date, had limited clinical applications among patients with congenital heart disease, the few published reports do indicate potential benefits as a bridge to cardiac transplant. Copyright © 2015 Elsevier Inc. All rights reserved.

Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition.

PubMed

Parikh, Victoria Nicole; Liu, Jing; Shang, Ching; Woods, Christopher; Chang, Alex Chia Yu; Zhao, Mingming; Charo, David N; Grunwald, Zachary; Huang, Yong; Seo, Kinya; Tsao, Philip S; Bernstein, Daniel; Ruiz-Lozano, Pilar; Quertermous, Thomas; Ashley, Euan A

2018-05-18

The G protein coupled receptor APJ is a promising therapeutic target for heart failure. Constitutive deletion of APJ in the mouse is protective against the hypertrophy-heart failure transition via elimination of ligand-independent, β-arrestin dependent stretch transduction. However, the cellular origin of this stretch transduction and the details of its interaction with apelin signaling remain unknown. We generated mice with conditional elimination of APJ in the endothelium (APJ endo-/- ) and myocardium (APJ myo-/- ). No baseline difference was observed in LV function in APJ endo-/- , APJ myo-/- or controls (APJ endo+/+ , APJ myo+/+ ). After exposure to transaortic constriction (TAC), APJ endo-/- animals developed left ventricular failure while APJ myo-/- were protected. At the cellular level, carbon fiber stretch of freshly isolated single cardiomyocytes demonstrated decreased contractile response to stretch in APJ -/- cardiomyocytes compared to APJ +/+ cardiomyocytes. Calcium transient did not change with stretch in either APJ -/- or APJ +/+ cardiomyocytes. Application of apelin to APJ +/+ cardiomyocytes resulted in decreased calcium transient. Further, hearts of mice treated with apelin exhibited decreased phosphorylation at Troponin I (cTnI) N-terminal residues (Ser 22,23), consistent with increased calcium sensitivity. These data establish that APJ stretch transduction is mediated specifically by myocardial APJ, that APJ is necessary for stretch-induced increases in contractility, and that apelin opposes APJ's stretch-mediated hypertrophy signaling by lowering calcium transient while maintaining contractility through myofilament calcium sensitization. These findings underscore apelin's unique potential as a therapeutic agent that can simultaneously support cardiac function and protect against the hypertrophy-heart failure transition.

Clinical determinants and consequences of left ventricular hypertrophy.

PubMed

Messerli, F H

1983-09-26

The left ventricle adapts to an increased afterload such as that produced by arterial hypertension with concentric left ventricular hypertrophy. However, this adaptive process can be modified by a variety of physiologic and pathophysiologic states. Progressive aging, black race, and perhaps disorders with an increased sympathetic outflow seem to accelerate left ventricular hypertrophy. Obesity and other high cardiac output states predominantly produce dilatation of the left ventricle, and their combination with arterial hypertension results in eccentric left ventricular hypertrophy. Similarly, endurance exercise increases left ventricular volume more than wall thickness, whereas isometric exercise produces an increase in wall thickness only. The presence or absence of some physiologic and pathogenetic factors has direct implication on the assessment of what constitutes a "normal" left ventricular structure and function. Left ventricular hypertrophy has been shown to increase ventricular ectopic impulse generation and to put patients at a high risk of sudden death. Moreover, the increase in myocardial mass lowers coronary reserve and enhances cardiac oxygen requirements. Thus, the presence of left ventricular hypertrophy has to be considered as an ominous sign rather than as a benign adaptive process.

Basal and β-adrenergic cardiomyocytes contractility dysfunction induced by dietary protein restriction is associated with downregulation of SERCA2a expression and disturbance of endoplasmic reticulum Ca2+ regulation in rats.

PubMed

Penitente, Arlete R; Novaes, Rômulo D; Silva, Marcelo E; Silva, Márcia F; Quintão-Júnior, Judson F; Guatimosim, Silvia; Cruz, Jader S; Chianca, Deoclécio A; Natali, Antônio J; Neves, Clóvis A

2014-01-01

The mechanisms responsible for the cardiac dysfunction associated with dietary protein restriction (PR) are poorly understood. Thus, this study was designed to evaluate the effects of PR on calcium kinetics, basal and β-adrenergic contractility in murine ventricular cardiomyocytes. After breastfeeding male Fisher rats were distributed into a control group (CG, n = 20) and a protein-restricted group (PRG, n = 20), receiving isocaloric diets for 35 days containing 15% and 6% protein, respectively. Biometric and hemodynamic variables were measured. After euthanasia left ventricles (LV) were collected for histopathological evaluation, SERCA2a expression, cardiomyocytes contractility and Ca(2+)sparks analysis. PRG animals showed reduced general growth, increased heart rate and arterial pressure. These animals presented extracellular matrix expansion and disorganization, cardiomyocytes hypotrophy, reduced amplitudes of shortening and maximum velocity of contraction and relaxation at baseline and after β-adrenergic stimulation. Reduced SERCA2a expression as well as higher frequency and lower amplitude of Ca(2+)sparks were observed in PRG cardiomyocytes. The observations reveal that protein restriction induces marked myocardial morphofunctional damage. The pathological changes of cardiomyocyte mechanics suggest the potential involvement of the β-adrenergic system, which is possibly associated with changes in SERCA2a expression and disturbances in Ca(2+) intracellular kinetics. © 2014 S. Karger AG, Basel.

Simultaneous determination of dynamic cardiac metabolism and function using PET/MRI.

PubMed

Barton, Gregory P; Vildberg, Lauren; Goss, Kara; Aggarwal, Niti; Eldridge, Marlowe; McMillan, Alan B

2018-05-01

Cardiac metabolic changes in heart disease precede overt contractile dysfunction. However, metabolism and function are not typically assessed together in clinical practice. The purpose of this study was to develop a cardiac positron emission tomography/magnetic resonance (PET/MR) stress test to assess the dynamic relationship between contractile function and metabolism in a preclinical model. Following an overnight fast, healthy pigs (45-50 kg) were anesthetized and mechanically ventilated. 18 F-fluorodeoxyglucose ( 18 F-FDG) solution was administered intravenously at a constant rate of 0.01 mL/s for 60 minutes. A cardiac PET/MR stress test was performed using normoxic gas (F I O 2  = .209) and hypoxic gas (F I O 2  = .12). Simultaneous cardiac imaging was performed on an integrated 3T PET/MR scanner. Hypoxic stress induced a significant increase in heart rate, cardiac output, left ventricular (LV) ejection fraction (EF), and peak torsion. There was a significant decline in arterial SpO 2 , LV end-diastolic and end-systolic volumes in hypoxia. Increased LV systolic function was coupled with an increase in myocardial FDG uptake (Ki) during hypoxic stress. PET/MR with continuous FDG infusion captures dynamic changes in both cardiac metabolism and contractile function. This technique warrants evaluation in human cardiac disease for assessment of subtle functional and metabolic abnormalities.

The left ventricle as a mechanical engine: from Leonardo da Vinci to the echocardiographic assessment of peak power output-to-left ventricular mass.

PubMed

Dini, Frank L; Guarini, Giacinta; Ballo, Piercarlo; Carluccio, Erberto; Maiello, Maria; Capozza, Paola; Innelli, Pasquale; Rosa, Gian M; Palmiero, Pasquale; Galderisi, Maurizio; Razzolini, Renato; Nodari, Savina

2013-03-01

The interpretation of the heart as a mechanical engine dates back to the teachings of Leonardo da Vinci, who was the first to apply the laws of mechanics to the function of the heart. Similar to any mechanical engine, whose performance is proportional to the power generated with respect to weight, the left ventricle can be viewed as a power generator whose performance can be related to left ventricular mass. Stress echocardiography may provide valuable information on the relationship between cardiac performance and recruited left ventricular mass that may be used in distinguishing between adaptive and maladaptive left ventricular remodeling. Peak power output-to-mass, obtained during exercise or pharmacological stress echocardiography, is a measure that reflects the number of watts that are developed by 100 g of left ventricular mass under maximal stimulation. Power output-to-mass may be calculated as left ventricular power output per 100 g of left ventricular mass: 100× left ventricular power output divided by left ventricular mass (W/100 g). A simplified formula to calculate power output-to-mass is as follows: 0.222 × cardiac output (l/min) × mean blood pressure (mmHg)/left ventricular mass (g). When the integrity of myocardial structure is compromised, a mismatch becomes apparent between maximal cardiac power output and left ventricular mass; when this occurs, a reduction of the peak power output-to-mass index is observed.

Effect of hypokinesia on cardiac contractile function and nervous regulation of the heart

NASA Technical Reports Server (NTRS)

Meyerson, F. Z.; Kapelko, V. I.; Gorina, M. S.; Shchegolkov, A. N.; Larinov, N. P.

1980-01-01

Longterm hypokinesia caused cardiac deadaptation in rabbits, which resulted in the diminishing of the left ventricular rate of contraction and relaxation, joined later by decreased vascular resistance. As a results, the ejection rate as well as stroke volume and cardiac output were normal. The decrease of the relaxation speed was more obvious at a high heart rate and results in shortening of the diastolic pause and diminishing of cardiac output. Hearts of the hypokinetic animals were characterized by normal maximal pressure developed by a unit of muccardial mass aorta clamping, decreased adrenoreactivity, and increased cholinoreactivity. This complex of changes is contrary to changes observed in adaptation to exercise, but is similar to changes observed in compensatory hypertrophy of the heart.

Effect of intra-aortic balloon pump on coronary blood flow during different balloon cycles support: A computer study.

PubMed

Aye, Thin Pa Pa; Htet, Zwe Lin; Singhavilai, Thamvarit; Naiyanetr, Phornphop

2015-01-01

Intra-aortic balloon pump (IABP) has been used in clinical treatment as a mechanical circulatory support device for patients with heart failure. A computer model is used to study the effect on coronary blood flow (CBF) with different balloon cycles under both normal and pathological conditions. The model of cardiovascular and IABP is developed by using MATLAB SIMULINK. The effect on coronary blood flow has been studied under both normal and pathological conditions using different balloon cycles (balloon off; 1:4; 1:2; 1:1). A pathological heart is implemented by reducing the left ventricular contractility. The result of this study shows that the rate of balloon cycles is related to the level of coronary blood flow.

[Usefullness of Beta-blocker for Hemodynamic Changes Induced by Uterotonic Drug in a Patient with Hypertrophic Obstructive Cardiomyopathy Undergoing Elective Cesarean Section].

PubMed

Tsukano, Yuri; Sugita, Michiko; Ikuta, Yoshihiro; Yamamoto, Tatsuo

2015-06-01

Combined spinal-epidural anesthesia (CSEA) was given to a 27-year-old woman with hypertrophic obstructive cardiomyopathy (HOCM) for a selective cesarean section. After the injection of uterotonic drug via uterine muscle and a vein after delivery, the patient developed dyspnea, tachycardia, ST-change on elecrocardiogram and hypotension. It is important in HOCM patients to control heart rate and left ventricular contractile force. We started to infuse beta-blocker (landiolol, 10 μg x kg(-1) x min(-1)) and improved these symptoms of the patient. This case demonstrates that CSEA is safe for HOCM patients and beta-blocker is effective to improve hemodynamic changes induced by uterotonic drug in these patients.

Thyroid-stimulating hormone and adverse left ventricular remodeling following ST-segment elevation myocardial infarction.

PubMed

Reindl, Martin; Feistritzer, Hans-Josef; Reinstadler, Sebastian Johannes; Mueller, Lukas; Tiller, Christina; Brenner, Christoph; Mayr, Agnes; Henninger, Benjamin; Mair, Johannes; Klug, Gert; Metzler, Bernhard

2018-04-01

Adverse left ventricular remodeling is one of the major determinants of heart failure and mortality in patients surviving ST-segment elevation myocardial infarction (STEMI). The hypothalamic-pituitary-thyroid axis is a key cardiovascular regulator; however, the relationship between hypothalamic-pituitary-thyroid status and post-STEMI left ventricular remodeling is unclear. We aimed to investigate the association between thyroid-stimulating hormone concentrations and the development of left ventricular remodeling following reperfused STEMI. In this prospective observational study of 102 consecutive STEMI patients, thyroid-stimulating hormone levels were measured at the first day after infarction and 4 months thereafter. Cardiac magnetic resonance scans were performed within the first week as well as at 4 months follow-up to determine infarct characteristics, myocardial function and as primary endpoint left ventricular remodeling, defined as a 20% or greater increase in left ventricular end-diastolic volume. Patients with left ventricular remodeling ( n=15, 15%) showed significantly lower concentrations of baseline (1.20 [0.92-1.91] vs. 1.73 [1.30-2.60] mU/l; P=0.02) and follow-up (1.11 [0.86-1.28] vs. 1.51 [1.15-2.02] mU/l; P=0.002) thyroid-stimulating hormone. The association between baseline thyroid-stimulating hormone and left ventricular remodeling remained significant after adjustment for major clinical (peak high-sensitivity cardiac troponin T and C-reactive protein, heart rate; odds ratio (OR) 5.33, 95% confidence interval (CI) 1.52-18.63; P=0.01) and cardiac magnetic resonance predictors of left ventricular remodeling (infarct size, microvascular obstruction, ejection fraction; OR 4.59, 95% CI 1.36-15.55; P=0.01). Furthermore, chronic thyroid-stimulating hormone was related to left ventricular remodeling independently of chronic left ventricular remodeling correlates (infarct size, ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume; OR 9.22, 95% CI 1.69-50.22; P=0.01). Baseline and chronic thyroid-stimulating hormone concentrations following STEMI were independently associated with left ventricular remodeling, proposing a novel pathophysiological axis in the development of post-STEMI left ventricular remodeling.

Presence of reduced regional left ventricular function even in the absence of left ventricular wall scar tissue in the long term after repair of an anomalous left coronary artery from the pulmonary artery.

PubMed

Nordmeyer, Sarah; Schmitt, Boris; Nasseri, Boris; Alexi-Meskishvili, Vladimir; Kuehne, Titus; Berger, Felix; Nordmeyer, Johannes

2018-02-01

We sought to assess left ventricular regional function in patients with and without left ventricular wall scar tissue in the long term after repair of an anomalous origin of the left coronary artery from the pulmonary artery. A total of 20 patients aged 12.8±7.4 years were assessed 10 (0.5-17) years after the repair of an anomalous origin of the left coronary artery from the pulmonary artery; of them, 10 (50%) patients showed left ventricular wall scar tissue on current cardiac MRI. Left ventricular regional function was assessed by two-dimensional speckle-tracking echocardiography in 10 patients with scar tissue and 10 patients without scar tissue and in 10 age-matched controls. In patients with scar tissue, MRI-derived left ventricular ejection fraction was significantly reduced compared with that in patients without scar tissue (51 versus 61%, p<0.05), and echocardiography-derived longitudinal strain was significantly reduced in five of six left ventricular areas compared with that in healthy controls (average relative reduction, 46%; p<0.05). In patients without scar tissue, longitudinal strain was significantly reduced in two of six left ventricular areas (average relative reduction, 23%; p<0.05) and circumferential strain was reduced in one of six left ventricular areas (relative reduction, 56%; p<0.05) compared with that in healthy controls. Regional left ventricular function is reduced even in patients without left ventricular wall scar tissue late after successful repair of an anomalous origin of the left coronary artery from the pulmonary artery. This highlights the need for meticulous lifelong follow-up in all patients with a repaired anomalous origin of the left coronary artery from the pulmonary artery.

Dynamic radionuclide determination of regional left ventricular wall motion using a new digital imaging device

NASA Technical Reports Server (NTRS)

Steele, P.; Kirch, D.

1975-01-01

In 47 men with arteriographically defined coronary artery disease comparative studies of left ventricular ejection fraction and segmental wall motion were made with radionuclide data obtained from the image intensifier camera computer system and with contrast cineventriculography. The radionuclide data was digitized and the images corresponding to left ventricular end-diastole and end-systole were identified from the left ventricular time-activity curve. The left ventricular end-diastolic and end-systolic images were subtracted to form a silhouette difference image which described wall motion of the anterior and inferior left ventricular segments. The image intensifier camera allows manipulation of dynamically acquired radionuclide data because of the high count rate and consequently improved resolution of the left ventricular image.

Central-Approach Surgical Repair of Coarctation of the Aorta with a Back-up Left Ventricular Assist Device for an Infant Presenting with Severe Left Ventricular Dysfunction.

PubMed

Kim, Tae Hoon; Shin, Yu Rim; Kim, Young Sam; Kim, Do Jung; Kim, Hyohyun; Shin, Hong Ju; Htut, Aung Thein; Park, Han Ki

2015-12-01

A two-month-old infant presented with coarctation of the aorta, severe left ventricular dysfunction, and moderate to severe mitral regurgitation. Through median sternotomy, the aortic arch was repaired under cardiopulmonary bypass and regional cerebral perfusion. The patient was postoperatively supported with a left ventricular assist device for five days. Left ventricular function gradually improved, eventually recovering with the concomitant regression of mitral regurgitation. Prompt surgical repair of coarctation of the aorta is indicated for patients with severe left ventricular dysfunction. A central approach for surgical repair with a back-up left ventricular assist device is a safe and effective treatment strategy for these patients.

Patterns of left ventricular remodeling among patients with essential and secondary hypertension.

PubMed

Radulescu, Dan; Stoicescu, Laurentiu; Buzdugan, Elena; Donca, Valer

2013-12-01

High blood pressure causes left ventricular hypertrophy, which is a negative prognostic factor among hypertensive patients. To assess left ventricular geometric remodeling patterns in patients with essential hypertension or with hypertension secondary to parenchymal renal disease. We analyzed data from echocardiograms performed in 250 patients with essential hypertension (150 females) and 100 patients with secondary hypertension (60 females). The interventricular septum and the left ventricular posterior wall thickness were measured in the parasternal long-axis. Left ventricular mass was calculated using the Devereaux formula. The most common remodeling type in females and males with essential hypertension were eccentric and concentric left ventricular hypertrophy (cLVH), respectively. Among patients with secondary arterial hypertension, cLVH was most commonly observed in both genders. The prevalence of left ventricular hypertrophy was higher among patients with secondary hypertension. The left ventricular mass index and the relative left ventricular wall thickness were higher in males and also in the secondary hypertension group. Age, blood pressure values and the duration of hypertension, influenced remodeling patterns. We documented a higher prevalence of LVH among patients with secondary hypertension. The type of ventricular remodeling depends on gender, age, type of hypertension, blood pressure values and the duration of hypertension.

Noninvasive evaluation of left ventricular elastance according to pressure-volume curves modeling in arterial hypertension.

PubMed

Bonnet, Benjamin; Jourdan, Franck; du Cailar, Guilhem; Fesler, Pierre

2017-08-01

End-systolic left ventricular (LV) elastance ( E es ) has been previously calculated and validated invasively using LV pressure-volume (P-V) loops. Noninvasive methods have been proposed, but clinical application remains complex. The aims of the present study were to 1 ) estimate E es according to modeling of the LV P-V curve during ejection ("ejection P-V curve" method) and validate our method with existing published LV P-V loop data and 2 ) test the clinical applicability of noninvasively detecting a difference in E es between normotensive and hypertensive subjects. On the basis of the ejection P-V curve and a linear relationship between elastance and time during ejection, we used a nonlinear least-squares method to fit the pressure waveform. We then computed the slope and intercept of time-varying elastance as well as the volume intercept (V 0 ). As a validation, 22 P-V loops obtained from previous invasive studies were digitized and analyzed using the ejection P-V curve method. To test clinical applicability, ejection P-V curves were obtained from 33 hypertensive subjects and 32 normotensive subjects with carotid tonometry and real-time three-dimensional echocardiography during the same procedure. A good univariate relationship ( r 2  = 0.92, P < 0.005) and good limits of agreement were found between the invasive calculation of E es and our new proposed ejection P-V curve method. In hypertensive patients, an increase in arterial elastance ( E a ) was compensated by a parallel increase in E es without change in E a / E es In addition, the clinical reproducibility of our method was similar to that of another noninvasive method. In conclusion, E es and V 0 can be estimated noninvasively from modeling of the P-V curve during ejection. This approach was found to be reproducible and sensitive enough to detect an expected increase in LV contractility in hypertensive patients. Because of its noninvasive nature, this methodology may have clinical implications in various disease states. NEW & NOTEWORTHY The use of real-time three-dimensional echocardiography-derived left ventricular volumes in conjunction with carotid tonometry was found to be reproducible and sensitive enough to detect expected differences in left ventricular elastance in arterial hypertension. Because of its noninvasive nature, this methodology may have clinical implications in various disease states. Copyright © 2017 the American Physiological Society.

Validation of an in vitro contractility assay using canine ventricular myocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harmer, A.R., E-mail: alex.harmer@astrazeneca.com; Abi-Gerges, N.; Morton, M.J.

Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscopemore » at ∼ 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ► Cardiac contractility is an important physiological function of the heart. ► Assessment of contractility is a logical part of pre-clinical drug safety testing. ► There are limited validated assays that predict effects of compounds on contractility. ► Using dog myocytes, we have developed an in vitro cardiac contractility assay. ► The assay predicted the in vivo contractility with a good level of accuracy.« less

Injectable Microsphere Gel Progressively Improves Global Ventricular Function, Regional Contractile Strain, and Mitral Regurgitation after Myocardial Infarction

PubMed Central

McGarvey, Jeremy R; Kondo, Norihiro; Witschey, Walter RT; Takebe, Manabu; Aoki, Chikashi; Burdick, Jason A.; Spinale, Francis G; Gorman, Joseph H; Pilla, James J; Gorman, Robert C

2014-01-01

Background There is continued need for therapies which reverse or abate the remodeling process following myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. Methods Twenty five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into four groups: one week treatment, one week control, four week treatment, and four week control. Following infarction, animals received either twenty 150μl calcium hydroxyapatite gel or saline injections within the infarct. At their respective timepoints, echocardiograms, cardiac MRI, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. Results Global and regional LV function were depressed in all infarcted subjects at one week compared to healthy controls. By four weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared to infarcted controls (EF 48.5±1.9% vs. 38.0±1.7%, p<0.01). Similarly, regional borderzone radial contractile strain (16.3±1.5% vs. 11.2±1.5%, p=0.04), MR grade (0.4±0.2 vs. 1.2±0.2, p=0.04), and infarct thickness (7.8±0.5mm vs. 4.5±0.2mm, p<0.01) were improved at this timepoint in the treatment group compared to infarct controls. Conclusions Calcium hydroxyapatite injection following MI progressively improves global LV function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is viable alternative in the current management of heart failure. PMID:25524397

Beta1-adrenoceptor antagonist, metoprolol attenuates cardiac myocyte Ca2+ handling dysfunction in rats with pulmonary artery hypertension.

PubMed

Fowler, Ewan D; Drinkhill, Mark J; Norman, Ruth; Pervolaraki, Eleftheria; Stones, Rachel; Steer, Emma; Benoist, David; Steele, Derek S; Calaghan, Sarah C; White, Ed

2018-07-01

Right heart failure is the major cause of death in Pulmonary Artery Hypertension (PAH) patients but is not a current, specific therapeutic target. Pre-clinical studies have shown that adrenoceptor blockade can improve cardiac function but the mechanisms of action within right ventricular (RV) myocytes are unknown. We tested whether the β 1 -adrenoceptor blocker metoprolol could improve RV myocyte function in an animal model of PAH, by attenuating adverse excitation-contraction coupling remodeling. PAH with RV failure was induced in rats by monocrotaline injection. When PAH was established, animals were given 10 mg/kg/day metoprolol (MCT + BB) or vehicle (MCT). The median time to the onset of heart failure signs was delayed from 23 days (MCT), to 31 days (MCT + BB). At 23 ± 1 days post-injection, MCT + BB showed improved in vivo cardiac function, measured by echocardiography. RV hypertrophy was reduced despite persistent elevated afterload. RV myocyte contractility during field stimulation was improved at higher pacing frequencies in MCT + BB. Preserved t-tubule structure, more uniform evoked Ca 2+ release, increased SERCA2a expression and faster ventricular repolarization (measured in vivo by telemetry) may account for the improved contractile function. Sarcoplasmic reticulum Ca 2+ overload was prevented in MCT + BB myocytes resulting in fewer spontaneous Ca 2+ waves, with a lower pro-arrhythmic potential. Our novel finding of attenuation of defects in excitation contraction coupling by β 1 -adrenoceptor blockade with delays in the onset of HF, identifies the RV as a promising therapeutic target in PAH. Moreover, our data suggest existing therapies for left ventricular failure may also be beneficial in PAH induced RV failure. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Value of right ventricular mapping in patients with postinfarction ventricular tachycardia.

PubMed

Yokokawa, Miki; Good, Eric; Crawford, Thomas; Chugh, Aman; Pelosi, Frank; Latchamsetty, Rakesh; Oral, Hakan; Morady, Fred; Bogun, Frank

2012-06-01

Postinfarction ventricular tachycardia (VT) typically involves the left ventricular endocardium. Right ventricular involvement in the arrhythmogenic substrate of postinfarction VT is considered unusual. To assess the role of right ventricular mapping and ablation in patients with prior septal myocardial infarction. From among 37 consecutive patients with recurrent postinfarction VT, 18 patients with evidence of left ventricular septal involvement of myocardial infarction were identified; these patients were the subjects of this report. In these 18 patients, 166 VTs (cycle length 372 ± 117 ms) were induced. Right ventricular voltage mapping was performed in all 18 patients with left ventricular septal myocardial infarction. Right ventricular voltage mapping showed areas of low voltage in 11 patients; pace mapping from these areas revealed matching pace maps for 17 VTs, and radiofrequency ablation from the right ventricular endocardium but not the left ventricular endocardium eliminated 14 of 17 VTs. VTs with critical components in the right ventricle had a left bundle branch block morphology that had similar characteristics as left bundle branch block VTs with critical areas involving the left ventricular septum. Patients with right ventricular VT breakthrough sites had a lower ejection fraction than did patients without VT breaking out on the right ventricular septum (18% ± 5% vs 33% ± 15%; P = .01). Right ventricular mapping and ablation may be necessary in order to eliminate all inducible VTs in patients with postinfarction VT. More than half the patients with septal myocardial infarction have right ventricular septal areas that are critical for postinfarction VT and that cannot be eliminated by left ventricular ablation alone. Copyright © 2012 Heart Rhythm Society. All rights reserved.

Experimental study of quantitative assessment of left ventricular mass with contrast enhanced real-time three-dimensional echocardiography.

PubMed

Zhuang, Lei; Wang, Xin-Fang; Xie, Ming-Xing; Chen, Li-Xin; Fei, Hong-Wen; Yang, Ying; Wang, Jing; Huang, Run-Qing; Chen, Ou-Di; Wang, Liang-Yu

2004-01-01

To evaluate the feasibility and accuracy of measurement of left ventricular mass with intravenous contrast enhanced real-time three-dimensional (RT3D) echocardiography in the experimental setting. RT3D echocardiography was performed in 13 open-chest mongrel dogs before and after intravenous infusion of a perfluorocarbon contrast agent. Left ventricular myocardium volume was measured according to the apical four-plane method provided by TomTec 4D cardio-View RT1.0 software, then the left ventricular mass was calculated as the myocardial volume multiplied by the relative density of myocardium. Correlative analysis and paired t-test were performed between left ventricular mass obtained from RT3D echocardiography and the anatomic measurements. Anatomic measurement of total left ventricular mass was 55.6 +/- 9.3 g, whereas RT3D echocardiographic calculation of left ventricular mass before and after intravenous perfluorocarbon contrast agent was 57.5 +/- 11.4 and 55.5 +/- 9.3 g, respectively. A significant correlation was observed between the RT3D echocardiographic estimates of total left ventricular mass and the corresponding anatomic measurements (r = 0.95). A strong correlation was found between RT3D echocardiographic estimates of left ventricular mass with perfluorocarbon contrast and the anatomic results (r = 0.99). Analysis of intraobserver and interobserver variability showed strong indexes of agreement in the measurement of left ventricular mass with pre and post-contrast RT3D echocardiography. Measurements of left ventricular mass derived from RT3D echocardiography with and without intravenous contrast showed a significant correlation with the anatomic results. Contrast enhanced RT3D echocardiography permitted better visualization of the endocardial border, which would provide a more accurate and reliable means of determining left ventricular myocardial mass in the experimental setting.

Is Doppler tissue velocity during early left ventricular filling preload independent?

NASA Technical Reports Server (NTRS)

Yalcin, F.; Kaftan, A.; Muderrisoglu, H.; Korkmaz, M. E.; Flachskampf, F.; Garcia, M.; Thomas, J. D.

2002-01-01

BACKGROUND: Transmitral Doppler flow indices are used to evaluate diastolic function. Recently, velocities measured by Doppler tissue imaging have been used as an index of left ventricular relaxation. OBJECTIVE: To determine whether Doppler tissue velocities are influenced by alterations in preload. METHODS: Left ventricular preload was altered in 17 patients (all men, mean (SD) age, 49 (8) years) during echocardiographic measurements of left ventricular end diastolic volume, maximum left atrial area, peak early Doppler filling velocity, and left ventricular myocardial velocities during early filling. Preload altering manoeuvres included Trendelenberg (stage 1), reverse Trendelenberg (stage 2), and amyl nitrate (stage 3). Systolic blood pressure was measured at each stage. RESULTS: In comparison with baseline, left ventricular end diastolic volume (p = 0.001), left atrial area (p = 0.003), peak early mitral Doppler filling velocity (p = 0.01), and systolic blood pressures (p = 0.001) were all changed by preload altering manoeuvres. Only left ventricular myocardial velocity during early filling remained unchanged by these manoeuvres. CONCLUSIONS: In contrast to standard transmitral Doppler filling indices, Doppler tissue early diastolic velocities are not significantly affected by physiological manoeuvres that alter preload. Thus Doppler tissue velocities during early left ventricular diastole may provide a better index of diastolic function in cardiac patients by providing a preload independent assessment of left ventricular filling.

Right ventricular contractile reserve in mitral stenosis: implications on hemodynamic burden and clinical outcome.

PubMed

Sade, Leyla Elif; Ozin, Bülent; Ulus, Taner; Açikel, Sadik; Pirat, Bahar; Bilgi, Muhammed; Uluçam, Melek; Müderrisoğlu, Haldun

2009-06-26

We investigated whether isovolumic acceleration (IVA) under inotropic stimulation as a means of right ventricular (RV) contractile reserve, is a surrogate for hemodynamic burden and has prognostic value in patients with mitral stenosis (MS). Thirty-one pure MS patients and 20 controls underwent cardiac catheterization, exercise test, and dobutamine stress echocardiography. RV fractional area change (FAC), +dP/dt/P(max), RV tissue Doppler indices (isovolumic contraction [IVC] and systolic [S] velocity, and IVA) were measured. Patients were followed-up for the occurrence of cardiac adverse events. Inotropic modulation unmasked statistically significant differences regarding magnitude of changes in IVA, IVC, S, and +dP/dt/P(max), but not RV FAC. Inability to increase IVA more than 6.5 m/s(2) was the only independent determinant of pulmonary capillary wedge pressure >or=18 mm Hg (P=.004). Although MS severity did not predict the RV contractile reserve and pulmonary artery pressure (PAP) behavior during inotropic stimulation, the RV contractile reserve was related to the degree of systolic PAP. IVA increases of <3.4 m/s(2) had 86% sensitivity and 75% specificity to predict unfavorable outcomes during long-term follow-up (20+/-8 months). RV contractile reserve provides complementary data to the hemodynamic significance of MS severity, may contribute to clinical decision making, and be of prognostic value in these patients.

Diastolic function of the nonfilling human left ventricle.

PubMed

Paulus, W J; Vantrimpont, P J; Rousseau, M F

1992-12-01

To investigate an early-diastolic left ventricular suction effect in humans, tip-micromanometer left ventricular pressure recordings were obtained in patients with mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon, which fits tightly in the mitral orifice. When mitral inflow was impeded in anesthetized dogs, left ventricular pressure decayed to a negative asymptote value. This negative asymptote value was consistent with an early diastolic suction effect. Tip-micromanometer left ventricular pressure recordings were obtained in 23 patients with symptomatic mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon. The left ventricular diastolic asymptote pressure (P(asy)) was determined in 47 nonfilling beats with a sufficiently long (greater than 200 ms) diastolic time interval (that is, the interval from minimal first derivative of left ventricular pressure to left ventricular end-diastolic pressure) and equaled 2 +/- 3 mm Hg for beats with normal intraventricular conduction and 3 +/- 2 mm Hg for beats with aberrant intraventricular conduction. Left ventricular angiography was performed in five patients during the first inflation of the Inoue balloon at the time of complete balloon expansion. Left ventricular end-diastolic volume of the nonfilling beats averaged 38 +/- 14 ml and was comparable to the left ventricular end-systolic volume (39 +/- 19 ml) measured during baseline angiography before mitral valvuloplasty. Time constants of left ventricular pressure decay were calculated on 21 nonfilling beats with a diastolic time interval greater than 200 ms, normal intraventricular conduction and peak left ventricular pressure greater than 50 mm Hg. Time constants (T0 and TBF) derived from an exponential curve fit with zero asymptote pressure and with a best-fit asymptote pressure were compared with a time constant (T(asy)) derived from an exponential curve fit with the measured diastolic left ventricular asymptote pressure. The value for T(asy) (37 +/- 9 ms) was significantly smaller than that for TBF (68 +/- 28 ms, p less than 0.001) and the value for the measured diastolic left ventricular asymptote pressure (2 +/- 4 mm Hg) was significantly larger than that for the best-fit asymptote pressure (-9 +/- 11 mm Hg, p less than 0.001). T0 (44 +/- 20 ms) was significantly (p less than 0.01) different from TBF but not from T(asy). During balloon inflation of a self-positioning Inoue balloon, left ventricular pressure decayed continuously toward a positive asymptote value and left ventricular cavity volume was comparable to the left ventricular end-systolic volume of filling beats. In these nonfilling beats, the best-fit asymptote pressure was unrelated to the measured asymptote pressure and T0 was a better measure of T(asy) than was TBF. Reduced internal myocardial restoring forces, caused by different extracellular matrix of the human heart, reduced external myocardial restoring forces caused by low coronary perfusion pressure during the balloon inflation and inward motion of the balloon-occluded mitral valve into the left ventricular cavity could explain the failure to observe significant diastolic left ventricular suction in the human heart.

Sustained IGF-1 Secretion by Adipose-Derived Stem Cells Improves Infarcted Heart Function.

PubMed

Bagno, Luiza L; Carvalho, Deivid; Mesquita, Fernanda; Louzada, Ruy A; Andrade, Bruno; Kasai-Brunswick, Taís H; Lago, Vivian M; Suhet, Grazielle; Cipitelli, Debora; Werneck-de-Castro, João Pedro; Campos-de-Carvalho, Antonio C

2016-01-01

The mechanism by which stem cell-based therapy improves heart function is still unknown, but paracrine mechanisms seem to be involved. Adipose-derived stem cells (ADSCs) secrete several factors, including insulin-like growth factor-1 (IGF-1), which may contribute to myocardial regeneration. Our aim was to investigate whether the overexpression of IGF-1 in ADSCs (IGF-1-ADSCs) improves treatment of chronically infarcted rat hearts. ADSCs were transduced with a lentiviral vector to induce IGF-1 overexpression. IGF-1-ADSCs transcribe100- to 200-fold more IGF-1 mRNA levels compared to nontransduced ADSCs. IGF-1 transduction did not alter ADSC immunophenotypic characteristics even under hypoxic conditions. However, IGF-1-ADSCs proliferate at higher rates and release greater amounts of growth factors such as IGF-1, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) under normoxic and hypoxic conditions. Importantly, IGF-1 secreted by IGF-1-ADSCs is functional given that Akt-1 phosphorylation was remarkably induced in neonatal cardiomyocytes cocultured with IGF-1-ADSCs, and this increase was prevented with phosphatidylinositol 3-kinase (PI3K) inhibitor treatment. Next, we tested IGF-1-ADSCs in a rat myocardial infarction (MI) model. MI was performed by coronary ligation, and 4 weeks after MI, animals received intramyocardial injections of either ADSCs (n = 7), IGF-1-ADSCs (n = 7), or vehicle (n = 7) into the infarcted border zone. Left ventricular function was evaluated by echocardiography before and after 6 weeks of treatment, and left ventricular hemodynamics were assessed 7 weeks after cell injection. Notably, IGF-1-ADSCs improved left ventricular ejection fraction and cardiac contractility index, but did not reduce scar size when compared to the ADSC-treated group. In summary, transplantation of ADSCs transduced with IGF-1 is a superior therapeutic approach to treat MI compared to nontransduced ADSCs, suggesting that gene and cell therapy may bring additional benefits to the treatment of MI.

The impact of preload reduction with head-up tilt testing on longitudinal and transverse left ventricular mechanics: a study utilizing deformation volume analysis

PubMed Central

Schneider, Caroline; Forsythe, Lynsey; Somauroo, John; George, Keith

2018-01-01

Background Left ventricular (LV) function is dependent on load, intrinsic contractility and relaxation with a variable impact on specific mechanics. Strain (ε) imaging allows the assessment of cardiac function; however, the direct relationship between volume and strain is currently unknown. The aim of this study was to establish the impact of preload reduction through head-up tilt (HUT) testing on simultaneous left ventricular (LV) longitudinal and transverse function and their respective contribution to volume change. Methods A focused transthoracic echocardiogram was performed on 10 healthy male participants (23 ± 3 years) in the supine position and following 1 min and 5 min of HUT testing. Raw temporal longitudinal ε (Ls) and transverse ε (Ts) values were exported and divided into 5% increments across the cardiac cycle and corresponding LV volumes were traced at each 5% increment. This provided simultaneous LV longitudinal and transverse ε and volume loops (deformation volume analysis – DVA). Results There was a leftward shift of the ε-volume loop from supine to 1 min and 5 min of HUT (P < 0.001). Moreover, longitudinal shortening was reduced (P < 0.001) with a concomitant increase in transverse thickening from supine to 1 min, which was further augmented at 5 min (P = 0.018). Conclusions Preload reduction occurs within 1 min of HUT but does not further reduce at 5 min. This decline is associated with a decrease in longitudinal ε and concomitant increase in transverse ε. Consequently, augmented transverse relaxation appears to be an important factor in the maintenance of LV filling in the setting of reduced preload. DVA provides information on the relative contribution of mechanics to a change in LV volume and may have a role in the assessment of clinical populations. PMID:29339401

The impact of preload reduction with head-up tilt testing on longitudinal and transverse left ventricular mechanics: a study utilizing deformation volume analysis.

PubMed

Schneider, Caroline; Forsythe, Lynsey; Somauroo, John; George, Keith; Oxborough, David

2018-03-01

Left ventricular (LV) function is dependent on load, intrinsic contractility and relaxation with a variable impact on specific mechanics. Strain (ε) imaging allows the assessment of cardiac function; however, the direct relationship between volume and strain is currently unknown. The aim of this study was to establish the impact of preload reduction through head-up tilt (HUT) testing on simultaneous left ventricular (LV) longitudinal and transverse function and their respective contribution to volume change. A focused transthoracic echocardiogram was performed on 10 healthy male participants (23 ± 3 years) in the supine position and following 1 min and 5 min of HUT testing. Raw temporal longitudinal ε (Ls) and transverse ε (Ts) values were exported and divided into 5% increments across the cardiac cycle and corresponding LV volumes were traced at each 5% increment. This provided simultaneous LV longitudinal and transverse ε and volume loops (deformation volume analysis - DVA). There was a leftward shift of the ε-volume loop from supine to 1 min and 5 min of HUT ( P  < 0.001). Moreover, longitudinal shortening was reduced ( P  < 0.001) with a concomitant increase in transverse thickening from supine to 1 min, which was further augmented at 5 min ( P  = 0.018). Preload reduction occurs within 1 min of HUT but does not further reduce at 5 min. This decline is associated with a decrease in longitudinal ε and concomitant increase in transverse ε. Consequently, augmented transverse relaxation appears to be an important factor in the maintenance of LV filling in the setting of reduced preload. DVA provides information on the relative contribution of mechanics to a change in LV volume and may have a role in the assessment of clinical populations. © 2018 The authors.

Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model

PubMed Central

Huang, Chun-kai; Chen, Bi-yi; Guo, Ang; Chen, Rong; Zhu, Yan-qi; Kutschke, William; Hong, Jiang; Song, Long-sheng

2016-01-01

Aim: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule (T-tubule) remodeling in left ventricular (LV) failure and thereby providing the therapeutic benefits. Methods: A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding (TAB). One day after TAB, the mice received sildenafil (100 mg·kg−1·d−1, sc) or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results: TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy (R2=0.74, P<0.01) and global LV function (R2=0.47, P<0.01). Conclusion: Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure. PMID:26972492

When withdrawal of life-sustaining care does more than allow death to take its course: the dilemma of left ventricular assist devices.

PubMed

Bramstedt, K A; Wenger, N S

2001-05-01

Left ventricular assist devices (LVADs) are a relatively new technology that is increasingly used to preserve cardiac function. These devices work by a mechanism that may complicate ethical decision-making for patients who subsequently lose decision-making capacity and are no longer considered transplant candidates. Using a clinical case from our medical center, we explored the complex ethical issues associated with the discontinuation of LVAD therapy by discussing how this device is distinct from the withdrawal of other treatments. While halting an implanted LVAD may permit a patient to die, the deactivated device itself may contribute to patient death due to the potential for blood backflow and pooling, as well as the disruption of heart contractility. Inadequate informed consent and failure to appoint a surrogate decision-maker in advance of the implant procedure resulted in a complex ethical dilemma for the patient's family and the medical team. Clinicians and families must consider the benefits and burdens of LVAD therapy as they do when considering removal of other life-sustaining treatment. The informed consent process associated with LVADs as bridging technology should include extensive consideration of the purpose of the device, future circumstances in which it may be halted, and how such situations would be recognized and handled. Appointment of a surrogate decision-maker before the surgical procedure is essential.

Decreased left ventricular torsion in patients with isolated mitral stenosis.

PubMed

Kirilmaz, B; Asgun, F; Saygi, S; Ercan, E

2015-02-01

Left ventricular (LV) torsion is a sensitive indicator of myocardial contractility and cardiac structure, and has recently been recognized as a sensitive indicator of cardiac performance. The aim of our study was to assess the effect of isolated mitral stenosis on LV torsion. We enrolled 19 patients with isolated mitral stenosis and 19 age- and gender-matched healthy subjects in the study. All patients had a normal sinus rhythm. All study subjects underwent two-dimensional echocardiography. Basal and apical LV rotations and LV torsion were evaluated using speckle-tracking echocardiography. Demographic characteristics, basic echocardiographic measures of LV ejection fraction, LV wall thickness, and LV mass index were similar between the two groups. The degrees of LV torsion (11.3 ± 4.7, 15.4 ± 4.9°, p=0.014) and LV basal rotation (- 3.7 ± 1.9, - 6.5 ± 2.1°, p< 0.001) were significantly decreased in the mitral stenosis group. There was a moderate positive correlation between mitral valve area and LV torsion (r=0.531, p=0.019). We showed significant reductions in LV torsion and LV basal rotation in patients with mitral valve stenosis. Structural and anatomical changes occurring during the progression of mitral stenosis may be responsible for these impaired movements.

High Spatial Resolution Multi-Organ Finite Element Modeling of Ventricular-Arterial Coupling

PubMed Central

Shavik, Sheikh Mohammad; Jiang, Zhenxiang; Baek, Seungik; Lee, Lik Chuan

2018-01-01

While it has long been recognized that bi-directional interaction between the heart and the vasculature plays a critical role in the proper functioning of the cardiovascular system, a comprehensive study of this interaction has largely been hampered by a lack of modeling framework capable of simultaneously accommodating high-resolution models of the heart and vasculature. Here, we address this issue and present a computational modeling framework that couples finite element (FE) models of the left ventricle (LV) and aorta to elucidate ventricular—arterial coupling in the systemic circulation. We show in a baseline simulation that the framework predictions of (1) LV pressure—volume loop, (2) aorta pressure—diameter relationship, (3) pressure—waveforms of the aorta, LV, and left atrium (LA) over the cardiac cycle are consistent with the physiological measurements found in healthy human. To develop insights of ventricular-arterial interactions, the framework was then used to simulate how alterations in the geometrical or, material parameter(s) of the aorta affect the LV and vice versa. We show that changing the geometry and microstructure of the aorta model in the framework led to changes in the functional behaviors of both LV and aorta that are consistent with experimental observations. On the other hand, changing contractility and passive stiffness of the LV model in the framework also produced changes in both the LV and aorta functional behaviors that are consistent with physiology principles. PMID:29551977

Load dependence of left ventricular contraction and relaxation. Effects of caffeine.

PubMed

Leite-Moreira, A F; Correia-Pinto, J; Gillebert, T C

1999-08-01

Load dependence of left ventricular (LV) contraction and relaxation was investigated at baseline and after alteration of intracellular calcium handling by caffeine. Afterload was increased by aortic clamp occlusions (n = 281) in anesthetized open-chest dogs (n = 7). Control and first heartbeat after the intervention were considered for analysis. Caffeine (50 mg/kg, iv) had no inotropic effect. The systolic LV pressure (LVP), developed in response to aortic occlusion, decreased as ejection proceeded and this pressure generating capacity was not affected by caffeine. Late-systolic aortic occlusions induced premature onset and accelerated rate of initial LVP fall at baseline and similarly after caffeine. Graded diastolic aortic occlusions induced systolic LVP elevations of various magnitudes. Smaller LVP elevations prolonged ejection and accelerated LVP fall, while larger elevations had opposite effects. The transition from acceleration to deceleration was observed at 83.1 +/- 1.1% of peak isovolumetric LVP at baseline and at lower loads, at 77.6 +/- 1.2%, after caffeine (p < 0.01). Isovolumetric heartbeats prolonged the time constant tau by 238 +/- 70% at baseline and only by 155 +/- 44% after caffeine (p < 0.01). The relaxation-systolic pressure relation, which describes afterload dependence of relaxation, was also modified by caffeine. Caffeine affected LV relaxation without altering contractility. As a consequence contraction-relaxation coupling was modified by caffeine. These results might help to understand load dependence of relaxation in conditions where intracellular calcium handling is altered.

Cardiac compartment-specific overexpression of a modified retinoic acid receptor produces dilated cardiomyopathy and congestive heart failure in transgenic mice.

PubMed Central

Colbert, M C; Hall, D G; Kimball, T R; Witt, S A; Lorenz, J N; Kirby, M L; Hewett, T E; Klevitsky, R; Robbins, J

1997-01-01

Retinoids play a critical role in cardiac morphogenesis. To examine the effects of excessive retinoid signaling on myocardial development, transgenic mice that overexpress a constitutively active retinoic acid receptor (RAR) controlled by either the alpha- or beta-myosin heavy chain (MyHC) promoter were generated. Animals carrying the alpha-MyHC-RAR transgene expressed RARs in embryonic atria and in adult atria and ventricles, but developed no signs of either malformations or disease. In contrast, beta-MyHC-RAR animals, where expression was activated in fetal ventricles, developed a dilated cardiomyopathy that varied in severity with transgene copy number. Characteristic postmortem lesions included biventricular chamber dilation and left atrial thrombosis; the incidence and severity of these lesions increased with increasing copy number. Transcript analyses showed that molecular markers of hypertrophy, alpha-skeletal actin, atrial natriuretic factor and beta-MyHC, were upregulated. Cardiac performance of transgenic hearts was evaluated using the isolated perfused working heart model as well as in vivo, by transthoracic M-mode echocardiography. Both analyses showed moderate to severe impairment of left ventricular function and reduced cardiac contractility. Thus, expression of a constitutively active RAR in developing atria and/ or in postnatal ventricles is relatively benign, while ventricular expression during gestation can lead to significant cardiac dysfunction. PMID:9329959

Giant and thrombosed left ventricular aneurysm

PubMed Central

de Agustin, Jose Alberto; de Diego, Jose Juan Gomez; Marcos-Alberca, Pedro; Rodrigo, Jose Luis; Almeria, Carlos; Mahia, Patricia; Luaces, Maria; Garcia-Fernandez, Miguel Angel; Macaya, Carlos; de Isla, Leopoldo Perez

2015-01-01

Left ventricular aneurysms are a frequent complication of acute extensive myocardial infarction and are most commonly located at the ventricular apex. A timely diagnosis is vital due to the serious complications that can occur, including heart failure, thromboembolism, or tachyarrhythmias. We report the case of a 78-year-old male with history of previous anterior myocardial infarction and currently under evaluation by chronic heart failure. Transthoracic echocardiogram revealed a huge thrombosed and calcified anteroapical left ventricular aneurysm. Coronary angiography demonstrated that the left anterior descending artery was chronically occluded, and revealed a big and spherical mass with calcified borders in the left hemithorax. Left ventriculogram confirmed that this spherical mass was a giant calcified left ventricular aneurysm, causing very severe left ventricular systolic dysfunction. The patient underwent cardioverter-defibrillator implantation for primary prevention. PMID:26225205

Analysis of left ventricular mass in untreated men and in men treated with agalsidase-β: data from the Fabry Registry.

PubMed

Germain, Dominique P; Weidemann, Frank; Abiose, Ademola; Patel, Manesh R; Cizmarik, Marta; Cole, J Alexander; Beitner-Johnson, Dana; Benistan, Karelle; Cabrera, Gustavo; Charrow, Joel; Kantola, Ilkka; Linhart, Ales; Nicholls, Kathy; Niemann, Markus; Scott, C Ronald; Sims, Katherine; Waldek, Stephen; Warnock, David G; Strotmann, Jörg

2013-12-01

The aim of this study was to evaluate the progression of left ventricular hypertrophy in untreated men with Fabry disease and to assess the effects of agalsidase-β (recombinant human α-galactosidase A) on left ventricular hypertrophy. Longitudinal Fabry Registry data were analyzed from 115 men treated with agalsidase-β (1 mg/kg/2 weeks) and 48 untreated men. Measurements included baseline left-ventricular mass and at least one additional left-ventricular mass assessment over ≥ 2 years. Patients were grouped into quartiles, based on left-ventricular mass slopes. Multivariate logistic regression analyses identified factors associated with left ventricular hypertrophy progression. For men in whom treatment was initiated at the age of 18 to <30 years, mean left ventricular mass slope was -3.6 g/year (n = 31) compared with +9.5 g/year in untreated men of that age (n = 15) (P < 0.0001). Untreated men had a 3.4-fold higher risk of having faster increases in left-ventricular mass compared with treated men (odds ratio: 3.43; 95% confidence interval: 1.05-11.22; P = 0.0415). A baseline age of ≥ 40 years was also associated with left--ventricular hypertrophy progression (odds ratio: 5.03; 95% confidence interval: 1.03-24.49; P = 0.0457) compared with men younger than 30 years. Agalsidase-β treatment for ≥2 years may improve or stabilize left-ventricular mass in men with Fabry disease. Further investigations may determine whether early intervention and stabilization of LVM are correlated with clinical outcomes.

Increased Efferent Cardiac Sympathetic Nerve Activity and Defective Intrinsic Heart Rate Regulation in Type 2 Diabetes.

PubMed

Thaung, H P Aye; Baldi, J Chris; Wang, Heng-Yu; Hughes, Gillian; Cook, Rosalind F; Bussey, Carol T; Sheard, Phil W; Bahn, Andrew; Jones, Peter P; Schwenke, Daryl O; Lamberts, Regis R

2015-08-01

Elevated sympathetic nerve activity (SNA) coupled with dysregulated β-adrenoceptor (β-AR) signaling is postulated as a major driving force for cardiac dysfunction in patients with type 2 diabetes; however, cardiac SNA has never been assessed directly in diabetes. Our aim was to measure the sympathetic input to and the β-AR responsiveness of the heart in the type 2 diabetic heart. In vivo recording of SNA of the left efferent cardiac sympathetic branch of the stellate ganglion in Zucker diabetic fatty rats revealed an elevated resting cardiac SNA and doubled firing rate compared with nondiabetic rats. Ex vivo, in isolated denervated hearts, the intrinsic heart rate was markedly reduced. Contractile and relaxation responses to β-AR stimulation with dobutamine were compromised in externally paced diabetic hearts, but not in diabetic hearts allowed to regulate their own heart rate. Protein levels of left ventricular β1-AR and Gs (guanine nucleotide binding protein stimulatory) were reduced, whereas left ventricular and right atrial β2-AR and Gi (guanine nucleotide binding protein inhibitory regulatory) levels were increased. The elevated resting cardiac SNA in type 2 diabetes, combined with the reduced cardiac β-AR responsiveness, suggests that the maintenance of normal cardiovascular function requires elevated cardiac sympathetic input to compensate for changes in the intrinsic properties of the diabetic heart. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Myocardial Adeno-Associated Virus Serotype 6–βARKct Gene Therapy Improves Cardiac Function and Normalizes the Neurohormonal Axis in Chronic Heart Failure

PubMed Central

Rengo, Giuseppe; Lymperopoulos, Anastasios; Zincarelli, Carmela; Donniacuo, Maria; Soltys, Stephen; Rabinowitz, Joseph E.; Koch, Walter J.

2009-01-01

Background The upregulation of G protein–coupled receptor kinase 2 in failing myocardium appears to contribute to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function. The peptide βARKct, which can inhibit the activation of G protein–coupled receptor kinase 2 and improve βAR signaling, has been shown in transgenic models and short-term gene transfer experiments to rescue heart failure (HF). This study was designed to evaluate long-term βARKct expression in HF with the use of stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). Methods and Results In HF rats, we delivered βARKct or green fluorescent protein as a control via AAV6-mediated direct intramyocardial injection. We also treated groups with concurrent administration of the β-blocker metoprolol. We found robust and long-term transgene expression in the left ventricle at least 12 weeks after delivery. βARKct significantly improved cardiac contractility and reversed left ventricular remodeling, which was accompanied by a normalization of the neurohormonal (catecholamines and aldosterone) status of the chronic HF animals, including normalization of cardiac βAR signaling. Addition of metoprolol neither enhanced nor decreased βARKct-mediated beneficial effects, although metoprolol alone, despite not improving contractility, prevented further deterioration of the left ventricle. Conclusions Long-term cardiac AAV6-βARKct gene therapy in HF results in sustained improvement of global cardiac function and reversal of remodeling at least in part as a result of a normalization of the neurohormonal signaling axis. In addition, βARKct alone improves outcomes more than a β-blocker alone, whereas both treatments are compatible. These findings show that βARKct gene therapy can be of long-term therapeutic value in HF. PMID:19103992

Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity.

PubMed

Bakkehaug, Jens Petter; Kildal, Anders Benjamin; Engstad, Erik Torgersen; Boardman, Neoma; Næsheim, Torvind; Rønning, Leif; Aasum, Ellen; Larsen, Terje Steinar; Myrmel, Truls; How, Ole-Jakob

2015-07-01

Omecamtiv mecarbil (OM) is a novel inotropic agent that prolongs systolic ejection time and increases ejection fraction through myosin ATPase activation. We hypothesized that a potentially favorable energetic effect of unloading the left ventricle, and thus reduction of wall stress, could be counteracted by the prolonged contraction time and ATP-consumption. Postischemic left ventricular dysfunction was created by repetitive left coronary occlusions in 7 pigs (7 healthy pigs also included). In both groups, systolic ejection time and ejection fraction increased after OM (0.75 mg/kg loading for 10 minutes, followed by 0.5 mg/kg/min continuous infusion). Cardiac efficiency was assessed by relating myocardial oxygen consumption to the cardiac work indices, stroke work, and pressure-volume area. To circumvent potential neurohumoral reflexes, cardiac efficiency was additionally assessed in ex vivo mouse hearts and isolated myocardial mitochondria. OM impaired cardiac efficiency; there was a 31% and 23% increase in unloaded myocardial oxygen consumption in healthy and postischemic pigs, respectively. Also, the oxygen cost of the contractile function was increased by 63% and 46% in healthy and postischemic pigs, respectively. The increased unloaded myocardial oxygen consumption was confirmed in OM-treated mouse hearts and explained by an increased basal metabolic rate. Adding the myosin ATPase inhibitor, 2,3-butanedione monoxide abolished all surplus myocardial oxygen consumption in the OM-treated hearts. Omecamtiv mecarbil, in a clinically relevant model, led to a significant myocardial oxygen wastage related to both the contractile and noncontractile function. This was mediated by that OM induces a continuous activation in resting myosin ATPase. © 2015 American Heart Association, Inc.

Left Atrial Remodeling and Atrioventricular Coupling in a Canine Model of Early Heart Failure With Preserved Ejection Fraction

PubMed Central

Zakeri, Rosita; Moulay, Gilles; Chai, Qiang; Ogut, Ozgur; Hussain, Saad; Takahama, Hiroyuki; Lu, Tong; Wang, Xiao-Li; Linke, Wolfgang A.; Lee, Hon-Chi; Redfield, Margaret M.

2016-01-01

Background Left atrial (LA) compliance and contractility influence left ventricular (LV) stroke volume. We hypothesized that diminished LA compliance and contractile function occur early during development of heart failure with preserved ejection fraction (HFpEF) and impair overall cardiac performance. Method and Results Cardiac magnetic resonance imaging, echocardiography, LV and LA pressure-volume studies, and tissue analyses were performed in a model of early HFpEF (elderly dogs, renal wrap-induced hypertension, exogenous aldosterone; n=9) and young control dogs (sham surgery; n=13). Early HFpEF was associated with LA enlargement, cardiomyocyte hypertrophy and enhanced LA contractile function (median active emptying fraction 16% [95% CI 13–24] vs 12[10–14]%, p=0.008; end-systolic pressure-volume relationship slope 2.4[1.9–3.2]mmHg/mL HFpEF vs 1.5[1.2–2.2]mmHg/mL controls, p=0.01). However, atrioventricular coupling was impaired and the curvilinear LA end-reservoir pressure-volume relationship was shifted upward/leftward in HFpEF (LA stiffness constant, βLA, 0.16[0.11–0.18]mmHg/mL vs 0.06[0.04–0.10]mmHg/mL controls, p=0.002) indicating reduced LA compliance. Impaired atrioventricular coupling and lower LA compliance correlated with lower LV stroke volume. Total fibrosis and titin isoform composition were similar between groups, however titin was hyperphosphorylated in HFpEF and correlated with βLA. LA microvascular reactivity was diminished in HFpEF versus controls. LA microvascular density tended to be lower in HFpEF and inversely correlated with βLA. Conclusions In early-stage hypertensive HFpEF, LA cardiomyocyte hypertrophy, titin hyperphosphorylation and microvascular dysfunction occur in association with increased systolic and diastolic LA chamber stiffness, impaired atrioventricular coupling and decreased LV stroke volume. These data indicate that maladaptive LA remodeling occurs early during HFpEF development, supporting a concept of global myocardial remodeling. PMID:27758811

Differences in Contractile Function of Myofibrils within Human Embryonic Stem Cell-Derived Cardiomyocytes vs. Adult Ventricular Myofibrils Are Related to Distinct Sarcomeric Protein Isoforms

PubMed Central

Iorga, Bogdan; Schwanke, Kristin; Weber, Natalie; Wendland, Meike; Greten, Stephan; Piep, Birgit; dos Remedios, Cristobal G.; Martin, Ulrich; Zweigerdt, Robert; Kraft, Theresia; Brenner, Bernhard

2018-01-01

Characterizing the contractile function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is key for advancing their utility for cellular disease models, promoting cell based heart repair, or developing novel pharmacological interventions targeting cardiac diseases. The aim of the present study was to understand whether steady-state and kinetic force parameters of β-myosin heavy chain (βMyHC) isoform-expressing myofibrils within human embryonic stem cell-derived cardiomyocytes (hESC-CMs) differentiated in vitro resemble those of human ventricular myofibrils (hvMFs) isolated from adult donor hearts. Contractile parameters were determined using the same micromechanical method and experimental conditions for both types of myofibrils. We identified isoforms and phosphorylation of main sarcomeric proteins involved in the modulation of force generation of both, chemically demembranated hESC-CMs (d-hESC-CMs) and hvMFs. Our results indicate that at saturating Ca2+ concentration, both human-derived contractile systems developed forces with similar rate constants (0.66 and 0.68 s−1), reaching maximum isometric force that was significantly smaller for d-hESC-CMs (42 kPa) than for hvMFs (94 kPa). At submaximal Ca2+-activation, where intact cardiomyocytes normally operate, contractile parameters of d-hESC-CMs and hvMFs exhibited differences. Ca2+ sensitivity of force was higher for d-hESC-CMs (pCa50 = 6.04) than for hvMFs (pCa50 = 5.80). At half-maximum activation, the rate constant for force redevelopment was significantly faster for d-hESC-CMs (0.51 s−1) than for hvMFs (0.28 s−1). During myofibril relaxation, kinetics of the slow force decay phase were significantly faster for d-hESC-CMs (0.26 s−1) than for hvMFs (0.21 s−1), while kinetics of the fast force decay were similar and ~20x faster. Protein analysis revealed that hESC-CMs had essentially no cardiac troponin-I, and partially non-ventricular isoforms of some other sarcomeric proteins, explaining the functional discrepancies. The sarcomeric protein isoform pattern of hESC-CMs had features of human cardiomyocytes at an early developmental stage. The study indicates that morphological and ultrastructural maturation of βMyHC isoform-expressing hESC-CMs is not necessarily accompanied by ventricular-like expression of all sarcomeric proteins. Our data suggest that hPSC-CMs could provide useful tools for investigating inherited cardiac diseases affecting contractile function during early developmental stages. PMID:29403388

Gene Therapy With Angiotensin-(1-9) Preserves Left Ventricular Systolic Function After Myocardial Infarction.

PubMed

Fattah, Caroline; Nather, Katrin; McCarroll, Charlotte S; Hortigon-Vinagre, Maria P; Zamora, Victor; Flores-Munoz, Monica; McArthur, Lisa; Zentilin, Lorena; Giacca, Mauro; Touyz, Rhian M; Smith, Godfrey L; Loughrey, Christopher M; Nicklin, Stuart A

2016-12-20

Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin-angiotensin-aldosterone system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic mini-pump. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). The authors evaluated effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post-infarction. C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular pressure volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation/contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff-perfused whole-heart model. Gene delivery of Ang-(1-9) reduced sudden cardiac death post-MI. Pressure volume measurements revealed complete restoration of end-systolic pressure, ejection fraction, end-systolic volume, and the end-diastolic pressure volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism. Our novel findings showed that Ang-(1-9) gene therapy preserved left ventricular systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) directly affected cardiomyocyte calcium handling through a protein kinase A-dependent mechanism. These data emphasized Ang-(1-9) gene therapy as a potential new strategy in the context of MI. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Contractile reserve and intracellular calcium regulation in mouse myocytes from normal and hypertrophied failing hearts

NASA Technical Reports Server (NTRS)

Ito, K.; Yan, X.; Tajima, M.; Su, Z.; Barry, W. H.; Lorell, B. H.; Schneider, M. (Principal Investigator)

2000-01-01

Mouse myocyte contractility and the changes induced by pressure overload are not fully understood. We studied contractile reserve in isolated left ventricular myocytes from mice with ascending aortic stenosis (AS) during compensatory hypertrophy (4-week AS) and the later stage of early failure (7-week AS) and from control mice. Myocyte contraction and [Ca(2+)](i) transients with fluo-3 were measured simultaneously. At baseline (0.5 Hz, 1.5 mmol/L [Ca(2+)](o), 25 degrees C), the amplitude of myocyte shortening and peak-systolic [Ca(2+)](i) in 7-week AS were not different from those of controls, whereas contraction, relaxation, and the decline of [Ca(2+)](i) transients were slower. In response to the challenge of high [Ca(2+)](o), fractional cell shortening was severely depressed with reduced peak-systolic [Ca(2+)](i) in 7-week AS compared with controls. In response to rapid pacing stimulation, cell shortening and peak-systolic [Ca(2+)](i) increased in controls, but this response was depressed in 7-week AS. In contrast, the responses to both challenge with high [Ca(2+)](o) and rapid pacing in 4-week AS were similar to those of controls. Although protein levels of Na(+)-Ca(2+) exchanger were increased in both 4-week and 7-week AS, the ratio of SR Ca(2+)-ATPase to phospholamban protein levels was depressed in 7-week AS compared with controls but not in 4-week AS. This was associated with an impaired capacity to increase sarcoplasmic reticulum Ca(2+) load during high work states in 7-week AS myocytes. In hypertrophied failing mouse myocytes, depressed contractile reserve is related to an impaired augmentation of systolic [Ca(2+)](i) and SR Ca(2+) load and simulates findings in human failing myocytes.

Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography: a comparison with contrast-enhanced magnetic resonance imaging.

PubMed

Nelson, Charles; McCrohon, Jane; Khafagi, Frederick; Rose, Stephen; Leano, Rodel; Marwick, Thomas H

2004-04-07

We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, <25%, 26% to 50%, 51% to 75%, and >75% of the wall thickness replaced by scar. As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (<25% TES), >50% were viable by SPECT. Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar.

Postoperative B-Type Natriuretic Peptide as Predictor for Postoperative Outcomes in Patients Implanted With Left Ventricular Assist Devices.

PubMed

Yost, Gardner; Bhat, Geetha; Pappas, Patroklos; Tatooles, Antone

2018-04-18

Brain natriuretic peptide (BNP) is a cardiac neurohormone known to correlate with left ventricular (LV) dilation, decreased contractility, and increased stiffness. Consequently, BNP has been used as a prognostic tool to assess the degree of LV unloading for patients supported by continuous-flow LV assist devices (LVADs). We assessed the prognostic value of changes in BNP in the 2 weeks after LVAD implantation. This retrospective study analyzed laboratory findings and outcomes of 189 LVAD patients. Patients were separated into two groups based on whether serum BNP levels had improved from preoperative levels by postoperative day 14. Group 1 had improvement in BNP levels, whereas group 2 had no improvement or worsening in BNP. There were no significant differences between the groups in age, gender, race, body mass index, or comorbidities. Group 1 had preoperative BNP 1,125 ± 1,078.3 pg/dl and postoperative BNP 440.2 ± 267.7 pg/dl (ΔBNP = -693.09 ± 942.4 pg/dl), whereas group 2 had preoperative BNP 346.0 ± 309.1 pg/dl and postoperative BNP 631.57 ± 483.4 pg/dl (ΔBNP = 289.32 ± 329.7 pg/dl). Postoperative survival in group 2 was significantly worse than in group 1. Rates of right ventricular failure (RVF) were significantly higher in group 2 (group 1: 39%, group 2: 52.7%; p = 0.01). In most patients implanted with a LVAD, BNP improves significantly in the postoperative period as the LV is unloaded. Our results indicate that lack of improvement in postoperative BNP is associated with longer length of stay, increased rates of RVF, and is an independent risk factor for reduced postoperative survival.

Association between left ventricular mechanics and diffuse myocardial fibrosis in patients with repaired Tetralogy of Fallot: a cross-sectional study.

PubMed

Haggerty, Christopher M; Suever, Jonathan D; Pulenthiran, Arichanah; Mejia-Spiegeler, Abba; Wehner, Gregory J; Jing, Linyuan; Charnigo, Richard J; Fornwalt, Brandon K; Fogel, Mark A

2017-12-11

Patients with repaired tetralogy of Fallot (TOF) have progressive, adverse biventricular remodeling, leading to abnormal contractile mechanics. Defining the mechanisms underlying this dysfunction, such as diffuse myocardial fibrosis, may provide insights into poor long-term outcomes. We hypothesized that left ventricular (LV) diffuse fibrosis is related to impaired LV mechanics. Patients with TOF were evaluated with cardiac magnetic resonance in which modified Look-Locker (MOLLI) T1-mapping and spiral cine Displacement encoding (DENSE) sequences were acquired at three LV short-axis positions. Linear mixed modeling was used to define the association between regional LV mechanics from DENSE based on regional T1-derived diffuse fibrosis measures, such as extracellular volume fraction (ECV). Forty patients (26 ± 11 years) were included. LV ECV was generally within normal range (0.24 ± 0.05). For LV mechanics, peak circumferential strains (-15 ± 3%) and dyssynchrony indices (16 ± 8 ms) were moderately impaired, while peak radial strains (29 ± 8%) were generally normal. After adjusting for patient age, sex, and regional LV differences, ECV was associated with log-adjusted LV dyssynchrony index (β = 0.67) and peak LV radial strain (β = -0.36), but not LV circumferential strain. Moreover, post-contrast T1 was associated with log-adjusted LV diastolic circumferential strain rate (β = 0.37). We observed several moderate associations between measures of fibrosis and impaired mechanics, particularly the LV dyssynchrony index and peak radial strain. Diffuse fibrosis may therefore be a causal factor in some ventricular dysfunction in TOF.

Echocardiographic left ventricular masses in distance runners and weight lifters

NASA Technical Reports Server (NTRS)

Longhurst, J. C.; Gonyea, W. J.; Mitchell, J. H.; Kelly, A. R.

1980-01-01

The relationships of different forms of exercise training to left ventricular mass and body mass are investigated by echocardiographic studies of weight lifters, long-distance runners, and comparatively sized untrained control subjects. Left ventricular mass determinations by the Penn convention reveal increased absolute left ventricular masses in long-distance runners and competitive weight lifters with respect to controls matched for age, body weight, and body surface area, and a significant correlation between ventricular mass and lean body mass. When normalized to lean body mass, the ventricular masses of distance runners are found to be significantly higher than those of the other groups, suggesting that dynamic training elevates left ventricular mass compared to static training and no training, while static training increases ventricular mass only to the extent that lean body mass is increased.

Frequent premature atrial contractions impair left atrial contractile function and promote adverse left atrial remodeling.

PubMed

John, Anub G; Hirsch, Glenn A; Stoddard, Marcus F

2018-06-10

This study assessed if frequent premature atrial contractions (PACs) were associated with decreased left atrial (LA) strain and adverse remodeling. Left atrial dysfunction and enlargement increases risk of stroke. If frequent PACs cause LA dysfunction and remodeling, PAC suppressive therapy may be beneficial. Inclusion criteria were age ≥18 years and sinus rhythm. Exclusion criteria were atrial fibrillation or any etiology for LA enlargement. Hundred and thirty-two patients with frequent PACs (≥100/24 hours) by Holter were matched to controls. Speckle tracking strain of the left atrium was performed from the 4-chamber view. Strain measurements were LA peak contractile, reservoir and conduit strain and strain rates. In the frequent PAC vs control group, PACs were more frequent (1959 ± 3796 vs 28 ± 25/24 hours, P < .0001). LA peak contractile strain was reduced in the group with frequent PACs vs controls (-7.85 ± 4.12% vs -9.33 ± 4.45%, P = .006). LA peak late negative contractile strain rate was less negative in the frequent PAC vs control group (-0.63 ± 0.27 s -1 vs -0.69 ± 0.32 s -1 , P = .051). LA reservoir and conduit strain and strain rates did not differ. LA volume index (LAVI) was larger in the frequent PAC vs control group (26.6 ± 7.8 vs 24.6 ± 8.8 mL/m 2 , P < .05). Frequent PACs were an independent predictor of reduced LA peak contractile strain and reduced LA peak late negative contractile strain rate. Patients with frequent PACs have reduced LA peak contractile strain and strain rates and larger LAVI compared to controls. Frequent PACs are an independent predictor of reduced LA peak contractile strain and strain rate. These findings support the hypothesis that frequent PACs impair LA contractile function and promote adverse LA remodeling. © 2018 Wiley Periodicals, Inc.

Transesophageal Echocardiography, 3-Dimensional and Speckle Tracking Together as Sensitive Markers for Early Outcome in Patients With Left Ventricular Dysfunction Undergoing Cardiac Surgery.

PubMed

Kumar, Alok; Puri, Goverdhan Dutt; Bahl, Ajay

2017-10-01

Speckle tracking, when combined with 3-dimensional (3D) left ventricular ejection fraction, might prove to be a more sensitive marker for postoperative ventricular dysfunction. This study investigated early outcomes in a cohort of patients with left ventricular dysfunction undergoing cardiac surgery. Prospective, blinded, observational study. University hospital; single institution. The study comprised 73 adult patients with left ventricular ejection fraction <50% undergoing cardiac surgery using cardiopulmonary bypass. Routine transesophageal echocardiography before and after bypass. Global longitudinal strain using speckle tracking and 3D left ventricular ejection fraction were computed using transesophageal echocardiography. Mean prebypass global longitudinal strain and 3D left ventricle ejection fraction were significantly lower in patients with postoperative low-cardiac-output syndrome compared with patients who did not develop low cardiac output (global longitudinal strain -7.5% v -10.7% and 3D left ventricular ejection fraction 29% v 39%, respectively; p < 0.0001). The cut-off value of global longitudinal strain predicting postoperative low-cardiac-output syndrome was -6%, with 95% sensitivity and 68% specificity; and 3D left ventricular ejection fraction was 19% with 98% sensitivity and 81% specificity. Preoperative left ventricular global longitudinal strain (-6%) and 3D left ventricular ejection fraction (19%) together could act as predictor of postoperative low-cardiac-output states with high sensitivity (99.9%) in patients undergoing cardiac surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of training nurses to perform semi-automated three-dimensional left ventricular ejection fraction using a customised workstation-based training protocol.

PubMed

Guppy-Coles, Kristyan B; Prasad, Sandhir B; Smith, Kym C; Hillier, Samuel; Lo, Ada; Atherton, John J

2015-06-01

We aimed to determine the feasibility of training cardiac nurses to evaluate left ventricular function utilising a semi-automated, workstation-based protocol on three dimensional echocardiography images. Assessment of left ventricular function by nurses is an attractive concept. Recent developments in three dimensional echocardiography coupled with border detection assistance have reduced inter- and intra-observer variability and analysis time. This could allow abbreviated training of nurses to assess cardiac function. A comparative, diagnostic accuracy study evaluating left ventricular ejection fraction assessment utilising a semi-automated, workstation-based protocol performed by echocardiography-naïve nurses on previously acquired three dimensional echocardiography images. Nine cardiac nurses underwent two brief lectures about cardiac anatomy, physiology and three dimensional left ventricular ejection fraction assessment, before a hands-on demonstration in 20 cases. We then selected 50 cases from our three dimensional echocardiography library based on optimal image quality with a broad range of left ventricular ejection fractions, which was quantified by two experienced sonographers and the average used as the comparator for the nurses. Nurses independently measured three dimensional left ventricular ejection fraction using the Auto lvq package with semi-automated border detection. The left ventricular ejection fraction range was 25-72% (70% with a left ventricular ejection fraction <55%). All nurses showed excellent agreement with the sonographers. Minimal intra-observer variability was noted on both short-term (same day) and long-term (>2 weeks later) retest. It is feasible to train nurses to measure left ventricular ejection fraction utilising a semi-automated, workstation-based protocol on previously acquired three dimensional echocardiography images. Further study is needed to determine the feasibility of training nurses to acquire three dimensional echocardiography images on real-world patients to measure left ventricular ejection fraction. Nurse-performed evaluation of left ventricular function could facilitate the broader application of echocardiography to allow cost-effective screening and monitoring for left ventricular dysfunction in high-risk populations. © 2014 John Wiley & Sons Ltd.

Management of severe ischemic cardiomyopathy: left ventricular assist device as destination therapy versus conventional bypass and mitral valve surgery.

PubMed

Maltais, Simon; Tchantchaleishvili, Vahtang; Schaff, Hartzell V; Daly, Richard C; Suri, Rakesh M; Dearani, Joseph A; Topilsky, Yan; Stulak, John M; Joyce, Lyle D; Park, Soon J

2014-04-01

Patients with severe ischemic cardiomyopathy (left ventricular ejection fraction <25%) and severe ischemic mitral regurgitation have a poor survival with medical therapy alone. Left ventricular assist device as destination therapy is reserved for patients who are too high risk for conventional surgery. We evaluated our outcomes with conventional surgery within this population and the comparative effectiveness of these 2 therapies. We identified patients who underwent conventional surgery or left ventricular assist device as destination therapy for severe ischemic cardiomyopathy (left ventricular ejection fraction <25%) and severe mitral regurgitation. The era for conventional surgery spanned from 1993 to 2009 and from 2007 to 2011 for left ventricular assist device as destination therapy. We compared baseline patient characteristics and outcomes in terms of end-organ function and survival. A total of 88 patients were identified; 55 patients underwent conventional surgery (63%), and 33 patients (37%) received a left ventricular assist device as destination therapy. Patients who received left ventricular assist device as destination therapy had the increased prevalence of renal failure, inotrope dependency, and intra-aortic balloon support. Patients undergoing conventional surgery required longer ventilatory support, and patients receiving a left ventricular assist device required more reoperation for bleeding. Mortality rates were similar between the 2 groups at 30 days (7% in the conventional surgery group vs 3% in the left ventricular assist device as destination therapy group, P = .65) and at 1 year (22% in the conventional surgery group vs 15% in the left ventricular assist device as destination therapy group, P = .58). There was a trend toward improved survival in patients receiving a left ventricular assist device compared with the propensity-matched groups at 1 year (94% vs 71%, P = .171). The operative mortality and early survival after conventional surgery seem to be acceptable. For inoperable or prohibitive-risk patients, left ventricular assist device as destination therapy can be offered with similar outcomes. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

A left ventricular epicardial to right ventricular endocardial dominant frequency gradient exists in human ventricular fibrillation.

PubMed

Torres, Jose Luis; Shah, Bindi K; Greenberg, Richard M; Deger, Florin Titus; Gerstenfeld, Edward P

2010-10-01

We hypothesized that in patients with left ventricular dysfunction undergoing implant of a biventricular ICD, the local dominant frequency during early induced ventricular fibrillation would be higher at an epicardial left ventricular position compared to an endocardial right ventricular position. Patients undergoing implant of a biventricular ICD were studied. During ventricular fibrillation induction, bipolar electrograms were recorded from leads at an epicardial left ventricular position and an endocardial right ventricular position. Overlapping 2-s fast Fourier transforms were obtained for 6 s of ventricular fibrillation. The dominant frequency and organizational index were compared. Thirty-four patients (20 men, age 64 ± 11 years) underwent 57 inductions of ventricular fibrillation. Eighteen patients had non-ischemic dilated cardiomyopathy and 16 had ischemic dilated cardiomyopathy. The dominant frequency was higher at a lateral epicardial left ventricular position than an apical endocardial right ventricular position in 18 patients with non-ischemic dilated cardiomyopathy (LV epicardial 5.34 ± 0.37 Hz, RV endocardial 5.09 ± 0.41 Hz, p < 0.001), but not in 16 patients with ischemic dilated cardiomyopathy (LV epicardial 4.99 ± 0.57 Hz, RV epicardial 4.87 ± 0.65 Hz, p = 0.094). In patients with non-ischemic dilated cardiomyopathy, there is a dominant frequency gradient during early ventricular fibrillation induced at ICD testing from the lateral left ventricular epicardium to the apical right ventricular endocardium.

Ductal stenting retrains the left ventricle in transposition of great arteries with intact ventricular septum.

PubMed

Sivakumar, Kothandam; Francis, Edwin; Krishnan, Prasad; Shahani, Jagdish

2006-11-01

In late presenters with transposition of the great arteries, intact ventricular septum, and regressing left ventricle, left ventricular retraining by pulmonary artery banding and aortopulmonary shunt is characterized by a stormy postoperative course and high costs. Ductal stenting in the cardiac catheterization laboratory is conceptualized to retrain the left ventricle with less morbidity. Recanalization and transcatheter stenting of patent ductus arteriosus was performed in patients with transposition to induce pressure and volume overload to the regressing left ventricle. Serial echocardiographic monitoring of left ventricular shape, mass, free wall thickness, and volumes was done, and once the left ventricle was adequately prepared, an arterial switch was performed. The ductal stent was removed and the remaining surgical steps were similar to a 1-stage arterial switch operation. Postoperative course, need for inotropic agents, and left ventricular function were monitored. Ductal stenting in 2 patients aged 3 months resulted in improvement of indexed left ventricular mass from 18.9 to 108.5 g/m2, left ventricular free wall thickness from 2.5 to 4.8 mm, and indexed left ventricular volumes from 7.6 to 29.5 mL/m2 within 3 weeks. Both patients underwent arterial switch (bypass times 125 and 158 minutes) uneventfully, needed inotropic agents and ventilatory support for 3 days, and were discharged in 8 and 10 days. Ductal stenting is a less morbid method of left ventricular retraining in transposition of the great arteries with regressed left ventricle. Its major advantages lie in avoiding pulmonary artery distortion and neoaortic valve regurgitation resulting from banding and also in avoiding thoracotomy.

A large left ventricular thrombus.

PubMed

Patanè, Salvatore; Marte, Filippo

2009-06-26

The discovery of a left ventricular mass obliges the clinician to perform a differential diagnosis including tumour or lipoma versus thrombus and its assessment presents important clinical implications. Dilated cardiomyopathy has been associated with left ventricular thrombosis which leads to substantial morbidity and mortality as a site for peripheral emboli. There are some studies on patients with dilated cardiomyopathy showing altered hemostasis and platelet behavior despite sinus rhythm. An increased incidence of thromboembolism is also well recognized in patients with left ventricular systolic dysfunction complicating history of myocardial infarction. Clinical dilemmas in treating left ventricular thrombus have been described too. We present a case of a large mobile left ventricular thrombus in a 71-year-old Italian man with dilated cardiomyopathy and history of myocardial infarction.

Left ventricular function before and after kidney transplantation.

PubMed

Omran, Mohammad T; Khakpour, Somayeh; Oliaie, Farshid

2009-06-01

To evaluate left ventricular function by echocardiography before and after kidney transplantation (KT). This analytical study included 50 patients that had successful KT in Shahid Beheshti Hospital, Babol, Iran from October 2005 to December 2007. The echocardiography study was performed by one cardiologist before and at least 3 months after KT. Data were analyzed by SPSS, and a p<0.05 was considered statistically significant. The mean age of patients was 33.94 +/- 11.66 years, 66% were male and 56% less than 45 years old. The ejection fraction and stroke volume after KT increased, however, the left ventricular end diastolic volume, left ventricular end systolic volume, left ventricular end systolic dimension, and left ventricular end diastolic diameter decreased. In patients with end stage renal disease, successful kidney transplantation could improve the function of the left ventricle.

Does quantitative left ventricular regional wall motion change after fibrous tissue resection in endomyocardial fibrosis?

PubMed

Salemi, Vera Maria Cury; Fernandes, Fabio; Sirvente, Raquel; Nastari, Luciano; Rosa, Leonardo Vieira; Ferreira, Cristiano A; Pena, José Luiz Barros; Picard, Michael H; Mady, Charles

2009-01-01

We compared left ventricular regional wall motion, the global left ventricular ejection fraction, and the New York Heart Association functional class pre- and postoperatively. Endomyocardial fibrosis is characterized by fibrous tissue deposition in the endomyocardium of the apex and/or inflow tract of one or both ventricles. Although left ventricular global systolic function is preserved, patients exhibit wall motion abnormalities in the apical and inferoapical regions. Fibrous tissue resection in New York Heart Association FC III and IV endomyocardial fibrosis patients has been shown to decrease morbidity and mortality. We prospectively studied 30 patients (20 female, 30+/-10 years) before and 5+/-8 months after surgery. The left ventricular ejection fraction was determined using the area-length method. Regional left ventricular motion was measured by the centerline method. Five left ventricular segments were analyzed pre- and postoperatively. Abnormality was expressed in units of standard deviation from the mean motion in a normal reference population. Left ventricular wall motion in the five regions did not differ between pre- and postoperative measurements. Additionally, the left ventricular ejection fraction did not change after surgery (0.45+/-0.13% x 0.43+/-0.12% pre- and postoperatively, respectively). The New York Heart Association functional class improved to class I in 40% and class II in 43% of patients postoperatively (p<0.05). Although endomyocardial fibrosis patients have improved clinical symptoms after surgery, the global left ventricular ejection fraction and regional wall motion in these patients do not change. This finding suggests that other explanations, such as improvements in diastolic function, may be operational.

Diagnostic electrocardiographic dyad criteria of emphysema in left ventricular hypertrophy

PubMed Central

Lanjewar, Swapnil S; Chhabra, Lovely; Chaubey, Vinod K; Joshi, Saurabh; Kulkarni, Ganesh; Kothagundla, Chandrasekhar; Kaul, Sudesh; Spodick, David H

2013-01-01

Background The electrocardiographic diagnostic dyad of emphysema, namely a combination of the frontal vertical P-vector and a narrow QRS duration, can serve as a quasidiagnostic marker for emphysema, with specificity close to 100%. We postulated that the presence of left ventricular hypertrophy in emphysema may affect the sensitivity of this electrocardiographic criterion given that left ventricular hypertrophy generates prominent left ventricular forces and may increase the QRS duration. Methods We reviewed the electrocardiograms and echocardiograms for 73 patients with emphysema. The patients were divided into two groups based on the presence or absence of echocardiographic evidence of left ventricular hypertrophy. The P-vector, QRS duration, and forced expiratory volume in one second (FEV1) were computed and compared between the two subgroups. Results There was no statistically significant difference in qualitative lung function (FEV1) between the subgroups. There was no statistically significant difference in mean P-vector between the subgroups. The mean QRS duration was significantly longer in patients with left ventricular hypertrophy as compared with those without left ventricular hypertrophy. Conclusion The presence of left ventricular hypertrophy may not affect the sensitivity of the P-vector verticalization when used as a lone criterion for diagnosing emphysema. However, the presence of left ventricular hypertrophy may significantly reduce the sensitivity of the electrocardiographic diagnostic dyad in emphysema, as it causes a widening of the QRS duration. PMID:24293995

Diagnostic electrocardiographic dyad criteria of emphysema in left ventricular hypertrophy.

PubMed

Lanjewar, Swapnil S; Chhabra, Lovely; Chaubey, Vinod K; Joshi, Saurabh; Kulkarni, Ganesh; Kothagundla, Chandrasekhar; Kaul, Sudesh; Spodick, David H

2013-01-01

The electrocardiographic diagnostic dyad of emphysema, namely a combination of the frontal vertical P-vector and a narrow QRS duration, can serve as a quasidiagnostic marker for emphysema, with specificity close to 100%. We postulated that the presence of left ventricular hypertrophy in emphysema may affect the sensitivity of this electrocardiographic criterion given that left ventricular hypertrophy generates prominent left ventricular forces and may increase the QRS duration. We reviewed the electrocardiograms and echocardiograms for 73 patients with emphysema. The patients were divided into two groups based on the presence or absence of echocardiographic evidence of left ventricular hypertrophy. The P-vector, QRS duration, and forced expiratory volume in one second (FEV1) were computed and compared between the two subgroups. There was no statistically significant difference in qualitative lung function (FEV1) between the subgroups. There was no statistically significant difference in mean P-vector between the subgroups. The mean QRS duration was significantly longer in patients with left ventricular hypertrophy as compared with those without left ventricular hypertrophy. The presence of left ventricular hypertrophy may not affect the sensitivity of the P-vector verticalization when used as a lone criterion for diagnosing emphysema. However, the presence of left ventricular hypertrophy may significantly reduce the sensitivity of the electrocardiographic diagnostic dyad in emphysema, as it causes a widening of the QRS duration.

Right Ventricular Dysfunction in Chronic Lung Disease

PubMed Central

Kolb, Todd M.; Hassoun, Paul M.

2012-01-01

Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

Epinephrine and left atrial and left ventricular diastolic function decrease in normal subjects.

PubMed

Fuenmayor, Abdel J; Solórzano, Moisés I; Gómez, Luisangelly

2016-10-01

We assessed the effect of epinephrine over left atrial and left ventricular diastolic function in subjects without structural heart disease. Twenty-seven, 34.6±17.2year-old patients without structural heart disease were included. Intravenous epinephrine (50 to 100ng/kg/min) was infused. Left atrial and ventricular functions were evaluated by means of echocardiography before and during the epinephrine infusion. No complications were observed. Significant increases in heart rate and systolic blood pressure were recorded. Both left atrial (minimal and maximal) volumes increased but increase in the minimal volume was more pronounced, and the ejection fraction diminished. Left atrial expansion index decreased and the fraction of left ventricular inflow volume resulting from atrial contraction increased. Two patients displayed abnormal left ventricular diastolic function. During epinephrine infusion, E/A and e' decreased, and isovolumetric relaxation time increased. In this group of young adults without structural heart disease, epinephrine infusion was safe, did not produce any complications, and induced a small but significant decrease in left atrial function and left ventricular diastolic function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Long-term effects of hydroxychloroquine on metabolism of serum lipids and left ventricular structure and function in patients of systemic lupus erythematosus].

PubMed

Meng, Juan; Lu, Yuewu; Dong, Xin; Liu, Hongyan

2014-04-08

To observe the long-term effects of hydroxychloroquine treatment on blood lipids and left ventricular function of systemic lupus erythematosus (SLE) patients. A total of 72 SLE patients were randomly divided into 2 groups of hydroxychloroquine treatment (n = 36) and non-hydroxychloroquine (n = 36). The serum level of lipids, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), fractional shortening rate (FS), left ventricular ejection fraction (LVEF) and E/A ratio were measured before, 6 month, 12 month and 2 years after treatment. After long-term use of hydroxychloroquine, there were statistically differences in the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). And LVEDD, LVWPT and E/A were statistically different (P < 0.05) before and after hydroxychloroquine dosing. The long-term use of hydroxychloroquine may improve lipid metabolism and left ventricular function in SLE patients.

Cardiac structure and function, and ventricular-arterial interaction 11 years following a pregnancy with preeclampsia.

PubMed

Al-Nashi, Maha; Eriksson, Maria J; Östlund, Eva; Bremme, Katarina; Kahan, Thomas

2016-04-01

Preeclampsia (PE) is associated with acute left ventricular dysfunction. Whether these changes eventually resolve remains unclear. This study assessed left and right ventricular structure and function, and ventricular-arterial interaction in 15 women 11 years after a pregnancy with PE and 16 matched control subjects with a normal pregnancy. We found normal left and right ventricular dimensions, systolic function, and global left ventricular strain, with no differences between the groups. In addition, indices of diastolic function, left and right atrial size, and amino-terminal pro-brain natriuretic peptide were normal and did not differ between the groups. Women with a previous PE had impaired night/day ratios for systolic and diastolic ambulatory blood pressure. However, indices of aortic stiffness or ventricular-arterial coupling did not differ between the groups. In conclusion, we could not demonstrate remaining alterations in systolic or diastolic left or right ventricular function, or in ventricular-arterial interaction in women 11 years after PE. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Measurement of left ventricular mass in vivo using gated nuclear magnetic resonance imaging.

PubMed

Florentine, M S; Grosskreutz, C L; Chang, W; Hartnett, J A; Dunn, V D; Ehrhardt, J C; Fleagle, S R; Collins, S M; Marcus, M L; Skorton, D J

1986-07-01

Alterations of left ventricular mass occur in a variety of congenital and acquired heart diseases. In vivo determination of left ventricular mass, using several different techniques, has been previously reported. Problems inherent in some previous methods include the use of ionizing radiation, complicated geometric assumptions and invasive techniques. We tested the ability of gated nuclear magnetic resonance imaging to determine in vivo left ventricular mass in animals. By studying both dogs (n = 9) and cats (n = 2) of various sizes, a broad range of left ventricular mass (7 to 133 g) was examined. With a 0.5 tesla superconducting nuclear magnetic resonance imaging system the left ventricle was imaged in the transaxial plane and multiple adjacent 10 mm thick slices were obtained. Endocardial and epicardial edges were manually traced in each computer-displayed image. The wall area of each image was determined by computer and the areas were summed and multiplied by the slice thickness and the specific gravity of muscle, providing calculated left ventricular mass. Calculated left ventricular mass was compared with actual postmortem left ventricular mass using linear regression analysis. An excellent relation between calculated and actual mass was found (r = 0.95; SEE = 13.1 g; regression equation: magnetic resonance mass = 0.95 X actual mass + 14.8 g). Intraobserver and interobserver reproducibility were also excellent (r = 0.99). Thus, gated nuclear magnetic resonance imaging can accurately determine in vivo left ventricular mass in anesthetized animals.

High-Intensity Interval Training for Severe Left Ventricular Dysfunction Treated with Left Ventricular Assist Device.

PubMed

Ugata, Yusuke; Wada, Hiroshi; Sakakura, Kenichi; Ibe, Tatsuro; Ito, Miyuki; Ikeda, Nahoko; Fujita, Hideo; Momomura, Shin-Ichi

2018-01-27

Aerobic training based on anaerobic threshold (AT) is well-known to improve cardiac function, exercise capacity, and long-term outcomes of patients with heart failure. Recent reports suggested that high-intensity interval training (HIIT) for patients with cardiovascular disease may improve cardiopulmonary exercise capacity. We present a 61-year-old male patient of severe left ventricular dysfunction with left ventricular assisted device (LVAD). Following HIIT for 8 weeks, exercise capacity and muscle strength have improved without worsening left ventricular function. Our case showed the possibility that HIIT was feasible and effective even in patients with LVAD.

Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension

PubMed Central

Spranger, Marty D.; Kaur, Jasdeep; Sala-Mercado, Javier A.; Krishnan, Abhinav C.; Abu-Hamdah, Rania; Alvarez, Alberto; Machado, Tiago M.; Augustyniak, Robert A.

2017-01-01

Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise likely occurs via the action of and interaction among activation of skeletal muscle afferents, central command, and resetting of the arterial baroreflex. As SNA is heightened even at rest in subjects with hypertension (HTN), we tested whether HTN causes exaggerated coronary vasoconstriction in canines during mild treadmill exercise with muscle metaboreflex activation (MMA; elicited by reducing hindlimb blood flow by ~60%) thereby limiting increases in CBF and ventricular performance. Experiments were repeated after α1-adrenergic blockade (prazosin; 75 µg/kg) and in the same animals following induction of HTN (modified Goldblatt 2K1C model). HTN increased mean arterial pressure from 97.1 ± 2.6 to 132.1 ± 5.6 mmHg at rest and MMA-induced increases in CBF, left ventricular dP/dtmax, and cardiac output were markedly reduced to only 32 ± 13, 26 ± 11, and 28 ± 12% of the changes observed in control. In HTN, α1-adrenergic blockade restored the coronary vasodilation and increased in ventricular function to the levels observed when normotensive. We conclude that exaggerated MMA-induced increases in SNA functionally vasoconstrict the coronary vasculature impairing increases in CBF, which limits oxygen delivery and ventricular performance in HTN. NEW & NOTEWORTHY We found that metaboreflex-induced increases in coronary blood flow and ventricular contractility are attenuated in hypertension. α1-Adrenergic blockade restored these parameters toward normal levels. These findings indicate that the primary mechanism mediating impaired metaboreflex-induced increases in ventricular function in hypertension is accentuated coronary vasoconstriction. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/metaboreflex-induced-functional-coronary-vasoconstriction/. PMID:27769997

Right ventricular dysfunction affects survival after surgical left ventricular restoration.

PubMed

Couperus, Lotte E; Delgado, Victoria; Palmen, Meindert; van Vessem, Marieke E; Braun, Jerry; Fiocco, Marta; Tops, Laurens F; Verwey, Harriëtte F; Klautz, Robert J M; Schalij, Martin J; Beeres, Saskia L M A

2017-04-01

Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P < .01 per additional impaired parameter). Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Effects of adaptive servo-ventilation therapy on cardiac function and remodeling in patients with chronic heart failure (SAVIOR-C): study protocol for a randomized controlled trial.

PubMed

Seino, Yoshihiko; Momomura, Shin-Ichi; Kihara, Yasuki; Adachi, Hitoshi; Yasumura, Yoshio; Yokoyama, Hiroyuki

2015-01-16

Adaptive servo-ventilation (ASV) therapy, which is a form of noninvasive positive pressure ventilation therapy and uses an innovative ventilator that has simple operability and provides good patient adherence, potentially has therapeutic benefits-suppression of the deterioration and progression of chronic heart failure (CHF) and a reduction in the number of repeated hospitalizations. Therefore, ASV therapy draws attention as a novel, noninvasive nonpharmacotherapy for patients with CHF owing to its hemodynamics-improving effect, and it is currently being accepted in real-world clinical settings in Japan. However, clinical evidence sufficient for treatment recommendation is lacking because a multicenter, randomized, controlled study of ASV therapy has never been conducted. The present study is a confirmatory, prospective, multicenter, collaborative, open-label, blinded-endpoint, parallel-group, randomized, controlled study. At 40 medical institutions in Japan, 200 Japanese outpatients with mild to severe CHF (age: ≥ 20 years; New York Heart Association classification: greater than or equal to class II) will be randomly assigned to either of the following two study groups: the ASV group, in which 100 outpatients undergo guideline-directed medical therapy and ASV therapy for 24 weeks; and the control group, in which 100 outpatients undergo only guideline-directed medical therapy for 24 weeks. The objective of the present study is to confirm whether the ASV group is superior to the control group concerning the improvement of left ventricular contractility and remodeling, both assessed by two-dimensional echocardiography. Furthermore, the present study will also secondarily examine the effects of ASV therapy on the prognosis and quality of life of patients with CHF. ASV therapy using the device has the potential to provide therapeutic benefits based on its simple operability and good patient adherence and possesses the potential to improve left ventricular contractility and remodeling. Therefore, the present study is expected to afford more solid scientific evidence regarding ASV therapy as a novel, noninvasive, nonpharmacological, in-home, long-term ventilation therapy for patients with mild to severe CHF. UMIN identifier: UMIN000006549 , registered on 17 October, 2011.

Microtubule Actin Cross-Linking Factor 1 Regulates Cardiomyocyte Microtubule Distribution and Adaptation to Hemodynamic Overload

PubMed Central

Kwak, Dongmin; Wang, Huan; Liu, Xiaoyu; Hu, Xinli; Bache, Robert J.; Chen, Yingjie

2013-01-01

Aberrant cardiomyocyte microtubule growth is a feature of pressure overload induced cardiac hypertrophy believed to contribute to left ventricular (LV) dysfunction. Microtubule Actin Cross-linking Factor 1 (MACF1/Acf7) is a 600 kd spectraplakin that stabilizes and guides microtubule growth along actin filaments. MACF1 is expressed in the heart, but its impact on cardiac microtubules, and how this influences cardiac structure, function, and adaptation to hemodynamic overload is unknown. Here we used inducible cardiac-specific MACF1 knockout mice (MACF1 KO) to determine the impact of MACF1 on cardiac microtubules and adaptation to pressure overload (transverse aortic constriction (TAC).In adult mouse hearts, MACF1 expression was low under basal conditions, but increased significantly in response to TAC. While MACF1 KO had no observable effect on heart size or function under basal conditions, MACF1 KO exacerbated TAC induced LV hypertrophy, LV dilation and contractile dysfunction. Interestingly, subcellular fractionation of ventricular lysates revealed that MACF1 KO altered microtubule distribution in response to TAC, so that more tubulin was associated with the cell membrane fraction. Moreover, TAC induced microtubule redistribution into this cell membrane fraction in both WT and MACF1 KO mice correlated strikingly with the level of contractile dysfunction (r2 = 0.786, p<.001). MACF1 disruption also resulted in reduction of membrane caveolin 3 levels, and increased levels of membrane PKCα and β1 integrin after TAC, suggesting MACF1 function is important for spatial regulation of several physiologically relevant signaling proteins during hypertrophy. Together, these data identify for the first time, a role for MACF1 in cardiomyocyte microtubule distribution and in adaptation to hemodynamic overload. PMID:24086300

Microtubule Actin Cross-linking Factor 1 regulates cardiomyocyte microtubule distribution and adaptation to hemodynamic overload.

PubMed

Fassett, John T; Xu, Xin; Kwak, Dongmin; Wang, Huan; Liu, Xiaoyu; Hu, Xinli; Bache, Robert J; Chen, Yingjie

2013-01-01

Aberrant cardiomyocyte microtubule growth is a feature of pressure overload induced cardiac hypertrophy believed to contribute to left ventricular (LV) dysfunction. Microtubule Actin Cross-linking Factor 1 (MACF1/Acf7) is a 600 kd spectraplakin that stabilizes and guides microtubule growth along actin filaments. MACF1 is expressed in the heart, but its impact on cardiac microtubules, and how this influences cardiac structure, function, and adaptation to hemodynamic overload is unknown. Here we used inducible cardiac-specific MACF1 knockout mice (MACF1 KO) to determine the impact of MACF1 on cardiac microtubules and adaptation to pressure overload (transverse aortic constriction (TAC).In adult mouse hearts, MACF1 expression was low under basal conditions, but increased significantly in response to TAC. While MACF1 KO had no observable effect on heart size or function under basal conditions, MACF1 KO exacerbated TAC induced LV hypertrophy, LV dilation and contractile dysfunction. Interestingly, subcellular fractionation of ventricular lysates revealed that MACF1 KO altered microtubule distribution in response to TAC, so that more tubulin was associated with the cell membrane fraction. Moreover, TAC induced microtubule redistribution into this cell membrane fraction in both WT and MACF1 KO mice correlated strikingly with the level of contractile dysfunction (r(2) = 0.786, p<.001). MACF1 disruption also resulted in reduction of membrane caveolin 3 levels, and increased levels of membrane PKCα and β1 integrin after TAC, suggesting MACF1 function is important for spatial regulation of several physiologically relevant signaling proteins during hypertrophy. Together, these data identify for the first time, a role for MACF1 in cardiomyocyte microtubule distribution and in adaptation to hemodynamic overload.

Radionuclide evaluation of left ventricular function with nonimaging probes.

PubMed

Wexler, J P; Blaufox, M D

1979-10-01

Portable nonimaging probes have been developed that can evaluate left ventricular function using radionuclide techniques. Two modes of data acquisition are possible with these probe systems, first-pass and gated. Precordial radiocardiograms obtained after a bolus injection can be used to determine cardiac output, pulmonary transit time, pulmonary blood volume, left ventricle ejection fraction, and left-to-right shunts. Gated techniques can be used to determine left ventricular ejection fraction and sytolic time intervals. Probe-determined indices of left ventricular function agree excellently with comparable measurements determined by conventional camera-computer methods as well as by invasive techniques. These have begun to be used in a preliminary manner in a variety of clinical problems associated with left ventricular dysfunction. This review discusses the types of probe systems available, the methods used in positioning them, and details the specifics of their data acquisition and processing capacity. The major criticisms of probe methods are that they are nonimaging and that they measure global rather than regional left ventricular function. In spite of these criticisms, probe systems, because of their portability, high sensitivity, and relatively low cost are useful supplements to conventional camera-computer systems for the measurement of parameters of left ventricular performance using radionuclide techniques.

Maternal obesity, gestational weight gain and childhood cardiac outcomes: role of childhood body mass index.

PubMed

Toemen, L; Gishti, O; van Osch-Gevers, L; Steegers, E A P; Helbing, W A; Felix, J F; Reiss, I K M; Duijts, L; Gaillard, R; Jaddoe, V W V

2016-07-01

Maternal obesity may affect cardiovascular outcomes in the offspring. We examined the associations of maternal prepregnancy body mass index and gestational weight gain with childhood cardiac outcomes and explored whether these associations were explained by parental characteristics, infant characteristics or childhood body mass index. In a population-based prospective cohort study among 4852 parents and their children, we obtained maternal weight before pregnancy and in early, mid- and late pregnancy. At age 6 years, we measured aortic root diameter (cm) and left ventricular dimensions. We calculated left ventricular mass (g), left ventricular mass index (g m(-2.7)), relative wall thickness ((2 × left ventricular posterior wall thickness)/left ventricular diameter), fractional shorting (%), eccentric left ventricular hypertrophy and concentric remodeling. A one standard deviation score (SDS) higher maternal prepregnancy body mass index was associated with higher left ventricular mass (0.10 SDS (95% confidence interval (CI) 0.08, 0.13)), left ventricular mass index (0.06 SDS (95% CI 0.03, 0.09)) and aortic root diameter (0.09 SDS (95% CI 0.06, 0.12)), but not with relative wall thickness or fractional shortening. A one SDS higher maternal prepregnancy body mass index was associated with an increased risk of eccentric left ventricular hypertrophy (odds ratio 1.21 (95% CI 1.03, 1.41)), but not of concentric remodeling. When analyzing the effects of maternal weight in different periods simultaneously, only maternal prepregnancy weight and early pregnancy weight were associated with left ventricular mass, left ventricular mass index and aortic root diameter (P-values<0.05), independent of weight in other pregnancy periods. All observed associations were independent of parental and infant characteristics, but attenuated to non-significance after adjustment for childhood body mass index. Maternal prepregnancy body mass index and weight gain in early pregnancy are both associated with offspring cardiac structure in childhood, but these associations seem to be fully explained by childhood body mass index.

Additional mechanism for left ventricular dysfunction: chronic pulmonary regurgitation decreases left ventricular preload in patients with tetralogy of Fallot.

PubMed

Ylitalo, Pekka; Jokinen, Eero; Lauerma, Kirsi; Holmström, Miia; Pitkänen-Argillander, Olli M

2018-02-01

Right ventricular dysfunction in patients with tetralogy of Fallot and significant pulmonary regurgitation may lead to systolic dysfunction of the left ventricle due to altered ventricular interaction. We were interested in determining whether chronic pulmonary regurgitation affects the preload of the left ventricle. In addition, we wanted to study whether severe chronic pulmonary regurgitation would alter the preload of the left ventricle when compared with patients having preserved pulmonary valve annulus. The study group comprised 38 patients with tetralogy of Fallot who underwent surgical repair between 1990 and 2003. Transannular patching was required in 21 patients to reconstruct the right ventricular outflow tract. Altogether, 48 age- and gender-matched healthy volunteers were recruited. Cardiac MRI was performed on all study patients to assess the atrial and ventricular volumes and function. Severe pulmonary regurgitation (>30 ml/m2) was present in 13 patients, of whom 11 had a transannular patch, but only two had a preserved pulmonary valve annulus. The ventricular preload volumes from both atria were significantly reduced in patients with severe pulmonary regurgitation, and left ventricular stroke volumes (44.1±4.7 versus 58.9±10.7 ml/m2; p<0.0001) were smaller compared with that in patients with pulmonary regurgitation <30 ml/m2 or in controls. In patients with tetralogy of Fallot, severe pulmonary regurgitation has a significant effect on volume flow through the left atrium. Reduction in left ventricular preload volume may be an additional factor contributing to left ventricular dysfunction.

The effect of postoperative medical treatment on left ventricular mass regression after aortic valve replacement.

PubMed

Helder, Meghana R K; Ugur, Murat; Bavaria, Joseph E; Kshettry, Vibhu R; Groh, Mark A; Petracek, Michael R; Jones, Kent W; Suri, Rakesh M; Schaff, Hartzell V

2015-03-01

The study objective was to analyze factors associated with left ventricular mass regression in patients undergoing aortic valve replacement with a newer bioprosthesis, the Trifecta valve pericardial bioprosthesis (St Jude Medical Inc, St Paul, Minn). A total of 444 patients underwent aortic valve replacement with the Trifecta bioprosthesis from 2007 to 2009 at 6 US institutions. The clinical and echocardiographic data of 200 of these patients who had left ventricular hypertrophy and follow-up studies 1 year postoperatively were reviewed and compared to analyze factors affecting left ventricular mass regression. Mean (standard deviation) age of the 200 study patients was 73 (9) years, 66% were men, and 92% had pure or predominant aortic valve stenosis. Complete left ventricular mass regression was observed in 102 patients (51%) by 1 year postoperatively. In univariate analysis, male sex, implantation of larger valves, larger left ventricular end-diastolic volume, and beta-blocker or calcium-channel blocker treatment at dismissal were significantly associated with complete mass regression. In the multivariate model, odds ratios (95% confidence intervals) indicated that male sex (3.38 [1.39-8.26]) and beta-blocker or calcium-channel blocker treatment at dismissal (3.41 [1.40-8.34]) were associated with increased probability of complete left ventricular mass regression. Patients with higher preoperative systolic blood pressure were less likely to have complete left ventricular mass regression (0.98 [0.97-0.99]). Among patients with left ventricular hypertrophy, postoperative treatment with beta-blockers or calcium-channel blockers may enhance mass regression. This highlights the need for close medical follow-up after operation. Labeled valve size was not predictive of left ventricular mass regression. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Itraconazole decreases left ventricular contractility in isolated rabbit heart: Mechanism of action

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, Yusheng, E-mail: yqu@amgen.com; Fang, Mei; Gao, BaoXi

Itraconazole (ITZ) is an approved antifungal agent that carries a “black box warning” in its label regarding a risk of negative cardiac inotropy based on clinical findings. Since the mechanism of the negative inotropic effect is unknown, we performed a variety of preclinical and mechanistic studies to explore the pharmacological profile of ITZ and understand the negative inotropic mechanism. ITZ was evaluated in: (1) an isolated rabbit heart (IRH) preparation using Langendorff retrograde perfusion; (2) ion channel studies; (3) a rat heart mitochondrial function profiling screen; (4) a mitochondrial membrane potential (MMP) assay; (5) in vitro pharmacology profiling assays (148more » receptors, ion channels, transporters, and enzymes); and (6) a kinase selectivity panel (451 kinases). In the IRH, ITZ decreased cardiac contractility (> 30%) at 0.3 μM, with increasing effect at higher concentrations, which indicated a direct negative inotropic effect upon the heart. It also decreased heart rate and coronary flow (≥ 1 μM) and prolonged PR/QRS intervals (3 μM). In mechanistic studies, ITZ inhibited the cardiac NaV channel (IC{sub 50}: 4.2 μM) and was devoid of any functional inhibitory effect at the remaining pharmacological targets. Lastly, ITZ did not affect MMP, nor interfere with mitochondrial enzymes or processes involved with fuel substrate utilization or energy formation. Overall, the cardiovascular and mechanistic data suggest that ITZ-induced negative inotropy is a direct effect on the heart, in addition, the potential involvement of mitochondria function and L-type Ca{sup 2+} channels are eliminated. The exact mechanism underlying the negative inotropy is uncertain, and requires further study. - Highlights: ► Effect of itraconazole (ITZ) was assessed in the isolated rabbit heart (IRH) assay. ► ITZ decreased ventricular contractility in IRH, indicating a direct effect. ► IC{sub 50} of ITZ on L-type I{sub Ca} was greater than 30 μM, on I{sub Na} was 4.2 μM. ► ITZ had minimal effects on mitochondrial functions. ► ITZ had minimal hits in pharmacology profiling and kinase selectivity panel.« less

Left dominant arrhythmogenic cardiomyopathy: a morbid association of ventricular arrhythmias and unexplained infero-lateral T-wave inversion.

PubMed

Protonotarios, Alexandros; Patrianakos, Alexandros; Spanoudaki, Elpida; Kochiadakis, Georgios; Michalodimitrakis, Emmanouel; Vardas, Panagiotis

2013-01-01

Left-dominant arrhythmogenic cardiomyopathy is a subtype of arrhythmogenic right ventricular cardiomyopathy characterized by early predominant left ventricular involvement. Α 34-year-old man presented with palpitations and a history of frequent ventricular extrasystoles of both LBBB and RBBB configuration. Cardiac workup revealed repolarization abnormalities at infero-lateral leads in the absence of diagnostic structural/functional alterations or obstructive coronary artery disease. Six months later he died suddenly. Histopathology was diagnostic for arrhythmogenic right ventricular cardiomyopathy affecting predominantly the left ventricle at subepicardial/midwall myocardial layers. Thus, ventricular arrhythmias accompanied by unexplained infero-lateral T-wave inversion should warn of a possible morbid association underlying left-dominant arrhythmogenic cardiomyopathy. Copyright © 2013 Elsevier Inc. All rights reserved.

Can the epirubicin cardiotoxicity in cancer patients be prevented by angiotensin converting enzyme inhibitors?

PubMed

Radulescu, D; Buzdugan, E; Ciuleanu, T E; Todor, N; Stoicescu, L

2013-01-01

The aim of this study was to assess whether treatment with angiotensin converting enzyme inhibitors (ACEI) can prevent the alteration of left ventricular systolic and diastolic performance in cancer patients treated with different chemotherapy regimens containing epirubicin. In this prospective study , 68 patients with different malignant tumors treated with epirubicin and perindopril in different chemotherapy protocols (study group), and a gender- and age-matched group of 68 patients with different malignant tumors treated with epirubicin without perindopril in different chemotherapy protocols (control group), were assessed by Doppler echocardiography. Left ventricular systolic function was assessed by measuring left ventricular ejection fraction (EF). Left ventricular diastolic function was assessed by Doppler ultrasound by evaluating the transmitral flow. We also assessed the QTc on the 12 lead electrocardiograms. At the end of chemotherapy the left ventricular systolic function was less altered in the study group compared to the control group and was superior in the study group (epirubicin+ACEI) compared to the control group (epirubicin alone). We documented a significantly deteriorated left ventricular diastolic function in both groups at the completion of chemotherapy. QTc time in both arms was also significantly prolonged. In the present echo-Doppler study we documented a preserved left ventricular systolic performance in patients with various malignancies treated with epirubicin plus perindopril. Although co-treatment with ACEI prevented the alteration of systolic performance, it failed to prevent the deterioration of the left ventricular diastolic performance impairment due to poor left ventricular compliance.

Evaluation of left ventricular performance during supine exercise by transoesophageal M-mode echocardiography in normal subjects.

PubMed Central

Matsumoto, M; Hanrath, P; Kremer, P; Tams, C; Langenstein, B A; Schlüter, M; Weiter, R; Bleifeld, W

1982-01-01

In order to evaluate left ventricular function during dynamic exercise transoesophageal M-mode recordings of the left ventricle were carried out with a newly developed transducer gastroscope system. Twelve healthy subjects performed a graded supine bicycle exercise test. Stable and good quality images of the left ventricle at rest and during exercise at different steps up to a maximum workload of 100 watts were obtained in all patients. Isotonic maximum exercise resulted in a significant increase in fractional shortening of the left ventricle, peak shortening rate, and peak lengthening rate of the left ventricular minor axis. Left ventricular end-diastolic dimension decreased significantly. With increasing workload the pressure rate product increased significantly. It is concluded that transoesophageal M-mode echocardiography is a useful method of evaluating left ventricular performance during dynamic exercise. Images PMID:7082515

[Effects of genistein on contractility of isolated right ventricular muscles in guinea pig].

PubMed

Wu, Jin-xia; Li, Hong-fang; Liu, Chong-bin; Tian, Zhi-feng

2008-11-01

To study the effect of genistein (GEN) on contractility of isolated right ventricular muscles in guinea pig and its mechanisms. Isolated guinea pig ventricular muscles were suspended in organ baths containing K-H solution.After an equilibration period, the effect of GEN on contraction of myocardium was observed. GEN and isoprenaline hydrochloride had the positive inotropic effects on contractity of myocardium. Meanwhile, the effect of GEN (1-100 micromol x L(-1)) was in dose-dependent manner. Propranolol (1 micromol x L(-1)) and verapamil hydrochloride (0.5 micromol x L(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride (1 micromol x L(-1)), but did not change the effect of GEN (50 micromol x L(-1)). Further more, the enhancement of the contraction induced by elevation of extracellular Ca2+ concentration in ventricular muscles had no change after pretreatment with GEN (1.10 micromol x L(-1)). In addition,the positive inotropic effect of GEN was inhibited partially by tamoxifen (1 micromol x L(-1)) and SQ22536 (1 micromol x L(-1)), also, could be attenuated by bpV (1 micromol x L(-1)). GEN has the positive inotropic effect on guinea pig ventricular muscles, which is not related to the activation of beta adrenoceptor, Ca2+ channel on cell membrane,but may involve in cAMP of intracellular signal transduction and tyrosine kinase pathway.

Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output

PubMed Central

Gresham, Kenneth S.; Mamidi, Ranganath; Li, Jiayang; Kwak, Hyerin

2017-01-01

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/dtmax and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca2+ activation compared with SAL-treated mice but unaltered myofilament Ca2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output. NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress. PMID:27909224

Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output.

PubMed

Gresham, Kenneth S; Mamidi, Ranganath; Li, Jiayang; Kwak, Hyerin; Stelzer, Julian E

2017-03-01

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/d t max and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca 2+ activation compared with SAL-treated mice but unaltered myofilament Ca 2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output. NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress. Copyright © 2017 the American Physiological Society.

Change of heart dimensions and function during pregnancy in goats.

PubMed

Szaluś-Jordanow, Olga; Czopowicz, Michał; Witkowski, Lucjan; Moroz, Agata; Mickiewicz, Marcin; Frymus, Tadeusz; Markowska-Daniel, Iwona; Bagnicka, Emilia; Kaba, Jarosław

2018-03-08

The study aimed to evaluate the effect of pregnancy on heart diameters and function in goats. Transthoracic echocardiography of 12 female dairy goats of two Polish regional breeds was performed. A Mindray M7 diagnostic ultrasound system with Phased Array transducer was used. Simultaneously, electrocardiography was recorded. All animals were examined four times - at mating season, at the end of the first trimester, at the end of the second trimester and just before kidding. Eleven measurements were taken each time: aortic and left atrial diameter (AoD and LAD), right and left ventricular internal diameter in diastole (RVIDd and LVIDd), left ventricular internal diameter in systole (LVIDs), inter-ventricular septum thickness in diastole and systole (IVSd and IVSd) and left ventricular posterior wall in diastole and systole (LVPWd and LVPWs), maximum left and right ventricular outflow tract velocity (RVOT Vmax and LVOT Vmax). Nine consecutive measurements were derived: the ratio of the left atrial diameter to the aortic diameter (AoD/LAD), left ventricular fractional shortening (FS%), left ventricular ejection fraction (EF%), maximum outflow tract pressure gradients (RVOT PGmax and LVOT PGmax), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV), stroke volume (SV) and cardiac output (CO). HR, LAD, LVPWs, IVSs increased significantly in the first trimester. AoD and RVIDd were significantly higher around parturition. LVIDd, FS%, EF%, SV and CO rose both in the first and third trimester. No measurement decreased during pregnancy. The study confirms that pregnancy causes changes in the heart size and functioning. Copyright © 2018. Published by Elsevier Ltd.

Remote magnetic navigation to map and ablate left coronary cusp ventricular tachycardia.

PubMed

Burkhardt, J David; Saliba, Walid I; Schweikert, Robert A; Cummings, Jennifer; Natale, Andrea

2006-10-01

Premature ventricular contractions (PVCs) and ventricular tachycardia may arise from the coronary cusps. Navigation, mapping, and ablation in the coronary cusps can be challenging. Remote magnetic navigation may offer an alternative to conventional manually operated catheters. We report a case of left coronary cusp ventricular tachycardia ablation using remote magnetic navigation. Right ventricular outflow tract and coronary cusp mapping, and ablation of the left coronary cusp using a remote magnetic navigation and three-dimensional (3-D) mapping system was performed in a 28-year-old male with frequent, symptomatic PVCs and ventricular tachycardia. Successful ablation of left coronary cusp ventricular tachycardia was performed using remote magnetic navigation. Remote magnetic navigation may be used to map and ablate PVCs and ventricular tachycardia originating from the coronary cusps.

[Left ventricular dysfunction measured in diabetic patients with chronic renal failure on continuous ambulatory peritoneal dialysis].

PubMed

Díaz-Arrieta, Gustavo; Mendoza-Hernández, María Elsa; Pacheco-Aranda, Erika; Rivas-Duro, Miguel; Robles-Parra, Héctor Manuel; Espinosa-Vázquez, Raúl Arturo; Hernández-Cabrera, Jorge

2010-01-01

In diabetic patients with chronic renal failure (CRF) treated with dialysis, the diastolic and systolic left ventricular dysfunction is frequent. The aim was to assess by echocardiography the prevalence of diastolic and systolic ventricular dysfunction in diabetic patients with CRF treated with continuous ambulatory peritoneal dialysis (CAPD). Sixty diabetic patients with CRF in CAPD were studied. The mean age was 54.5 +/- 12 years (27-78 years). The left ventricular filling pattern (LVFP) as a diastolic function parameter and left ventricular ejection fraction (LVEF) as a systolic function parameter were measured by transthoracic echocardiography. Descriptive statistical analysis was used. 27 (45 %) patients were women and 33 (55 %) were men. In 55 (91.7 %) left ventricular concentric hypertrophy was observed. Fifty-two patients (86.7 %) showed LVFP type I; three (5 %) had the type II; two (3.3 %) showed pseudonormal pattern and three (5 %) had a normal LVFP. The LVEF was 0.63 +/- 0.09 (CI = 0.41-0.82). Forty nine (81.7 %) patients had LVEF equal or greater than 0.55. The prevalence of diastolic left ventricular dysfunction was 95 % and the prevalence of systolic left ventricular dysfunction was 18.3%.

Magnetic resonance imaging during untreated ventricular fibrillation reveals prompt right ventricular overdistention without left ventricular volume loss.

PubMed

Berg, Robert A; Sorrell, Vincent L; Kern, Karl B; Hilwig, Ronald W; Altbach, Maria I; Hayes, Melinda M; Bates, Kathryn A; Ewy, Gordon A

2005-03-08

Most out-of-hospital ventricular fibrillation (VF) is prolonged (>5 minutes), and defibrillation from prolonged VF typically results in asystole or pulseless electrical activity. Recent visual epicardial observations in an open-chest, open-pericardium model of swine VF indicate that blood flows from the high-pressure arterial system to the lower-pressure venous system during untreated VF, thereby overdistending the right ventricle and apparently decreasing left ventricular size. Therefore, inadequate left ventricular stroke volume after defibrillation from prolonged VF has been postulated as a major contributor to the development of pulseless rhythms. Ventricular dimensions were determined by MRI for 30 minutes of untreated VF in a closed-chest, closed-pericardium model in 6 swine. Within 1 minute of untreated VF, mean right ventricular volume increased by 29% but did not increase thereafter. During the first 5 minutes of untreated VF, mean left ventricular volume increased by 34%. Between 20 and 30 minutes of VF, stone heart occurred as manifested by dramatic thickening of the myocardium and concomitant substantial decreases in left ventricular volume. In this closed-chest swine model of VF, substantial right ventricular volume changes occurred early and did not result in smaller left ventricular volumes. The changes in ventricular volumes before the late development of stone heart do not explain why defibrillation from brief duration VF (<5 minutes) typically results in a pulsatile rhythm with return of spontaneous circulation, whereas defibrillation from prolonged VF (5 to 15 minutes) does not.

Hemodynamics on abrupt stoppage of centrifugal pumps during left ventricular assist.

PubMed

Kono, S; Nishimura, K; Nishina, T; Akamatsu, T; Komeda, M

2000-01-01

A magnetically suspended centrifugal pump (MSCP), developed for long-term ventricular assist, is reliable and durable because it has no shaft or seal. However, with nonvalve pumps such as a MSCP, regurgitation occurs when they accidentally stop without cannula clamping. We investigated the hemodynamics during temporary stoppage of a MSCP being used as a left ventricular assist system (LVAS), comparing two inflow cannulation sites. In four sheep (weight, 35-45 kg), microspheres were injected into the left main coronary artery to induce heart failure. An outflow cannula was sutured onto the descending aorta, and two inflow cannulae were inserted into the left atrium and the left ventricle. The MSCP was stopped with both the left ventricular cannula and left atrial cannula clamped, and the hemodynamics and P-V loops were recorded. Each cannula was then unclamped in order, and similar parameters were recorded. LVEDP increased at unclamping of the left ventricular cannula (ULVC), and rose further at unclamping of the left atrial cannula (ULAC). Aortic pressure did not change at ULVC, but decreased at ULAC. The effective systemic flow that subtracted the regurgitant flow through the MSCP from left ventricular output was half at ULVC and almost 0 at ULAC. When stopping centrifugal pumps without circuit clamping, hemodynamic deterioration is less at ULVC than at ULAC. This finding suggests that left ventricular inflow cannulation is recommended to allow more time in emergency situations.

Nonlinear isochrones in murine left ventricular pressure-volume loops: how well does the time-varying elastance concept hold?

PubMed

Claessens, T E; Georgakopoulos, D; Afanasyeva, M; Vermeersch, S J; Millar, H D; Stergiopulos, N; Westerhof, N; Verdonck, P R; Segers, P

2006-04-01

The linear time-varying elastance theory is frequently used to describe the change in ventricular stiffness during the cardiac cycle. The concept assumes that all isochrones (i.e., curves that connect pressure-volume data occurring at the same time) are linear and have a common volume intercept. Of specific interest is the steepest isochrone, the end-systolic pressure-volume relationship (ESPVR), of which the slope serves as an index for cardiac contractile function. Pressure-volume measurements, achieved with a combined pressure-conductance catheter in the left ventricle of 13 open-chest anesthetized mice, showed a marked curvilinearity of the isochrones. We therefore analyzed the shape of the isochrones by using six regression algorithms (two linear, two quadratic, and two logarithmic, each with a fixed or time-varying intercept) and discussed the consequences for the elastance concept. Our main observations were 1) the volume intercept varies considerably with time; 2) isochrones are equally well described by using quadratic or logarithmic regression; 3) linear regression with a fixed intercept shows poor correlation (R(2) < 0.75) during isovolumic relaxation and early filling; and 4) logarithmic regression is superior in estimating the fixed volume intercept of the ESPVR. In conclusion, the linear time-varying elastance fails to provide a sufficiently robust model to account for changes in pressure and volume during the cardiac cycle in the mouse ventricle. A new framework accounting for the nonlinear shape of the isochrones needs to be developed.

Computational medical imaging and hemodynamics framework for functional analysis and assessment of cardiovascular structures.

PubMed

Wong, Kelvin K L; Wang, Defeng; Ko, Jacky K L; Mazumdar, Jagannath; Le, Thu-Thao; Ghista, Dhanjoo

2017-03-21

Cardiac dysfunction constitutes common cardiovascular health issues in the society, and has been an investigation topic of strong focus by researchers in the medical imaging community. Diagnostic modalities based on echocardiography, magnetic resonance imaging, chest radiography and computed tomography are common techniques that provide cardiovascular structural information to diagnose heart defects. However, functional information of cardiovascular flow, which can in fact be used to support the diagnosis of many cardiovascular diseases with a myriad of hemodynamics performance indicators, remains unexplored to its full potential. Some of these indicators constitute important cardiac functional parameters affecting the cardiovascular abnormalities. With the advancement of computer technology that facilitates high speed computational fluid dynamics, the realization of a support diagnostic platform of hemodynamics quantification and analysis can be achieved. This article reviews the state-of-the-art medical imaging and high fidelity multi-physics computational analyses that together enable reconstruction of cardiovascular structures and hemodynamic flow patterns within them, such as of the left ventricle (LV) and carotid bifurcations. The combined medical imaging and hemodynamic analysis enables us to study the mechanisms of cardiovascular disease-causing dysfunctions, such as how (1) cardiomyopathy causes left ventricular remodeling and loss of contractility leading to heart failure, and (2) modeling of LV construction and simulation of intra-LV hemodynamics can enable us to determine the optimum procedure of surgical ventriculation to restore its contractility and health This combined medical imaging and hemodynamics framework can potentially extend medical knowledge of cardiovascular defects and associated hemodynamic behavior and their surgical restoration, by means of an integrated medical image diagnostics and hemodynamic performance analysis framework.

[The importance of bisoprolol in prevention of heart left ventricular hypertrophy in patients with long term L-thyroxin suppressive therapy, after the operation of differentiated thyroid carcinoma].

PubMed

Matuszewska, Gabriela; Marek, Bogdan; Kajdaniuk, Dariusz; Przywara-Chowaniec, Brygida; Jarzab, Jerzy; Jarzab, Barbara

2007-01-01

Patients with differentiated thyroid carcinoma have to undergo radical surgical treatment, which includes total thyreoidectomy, radioiodine therapy and a life-time suppressive therapy with L-thyroxine. The aim of this study was a prospective evaluation of left ventricular hypertrophy during L suppressive-thyroxine treatment in patients treated for differentiated thyroid carcinoma. The examined group comprised 50 patients with differentiated thyroid carcinoma, treated by total thyroidectomy and 131I therapy. Echocardiographic measurements were needed for estimation of left ventricular mass and its index, according to recommendations of American Echocardiography Society. During two-years long suppressive therapy we observed a significant rise in left ventricular mass. In woman group left ventricular mass was increased from 168+/-39 g to 204+/-45 g (p<0.001) and in men from 205+/-60 to 320+/-21 g. Likewise, left ventricular mass index was increased in women group from 96+/-18 g/m(2) to 116+/-25 g/m(2) (p<0.001) and in men group from 107+/-37 g/m(2) to 158+/-28 g/m(2). Simultaneous treatment with bisoprolol caused a regression of left myocardial hypertrophy. Already after 6 months of simultaneous treatment with L-thyroxin and bisoprolol, for left ventricular mass was reduced to normal: in woman 165+/-35 g, and in men to 178+/-38 g. Analogous results were obtained left ventricular mass index. After 6 months it was reduced to 94+/-12 g/m(2) in woman and in men to 132+/-32 g/m(2). 1. In differentiated thyroid cancer patients, treated postoperatively with L-thyroxine suppressive therapy, left ventricular hypertrophy is observed already during the first year of suppressive therapy and progresses during the next year of treatment. 2 Addition of a beta-adrenergic antagonist to suppressive doses of L-thyroxine causes a regression of left ventricular hypertrophy, thus, beta-adrenergic antagonists should be administered in this group of patients.

The Role of CMR in Cardiomyopathies

PubMed Central

Kramer, Christopher M.

2015-01-01

Cardiac magnetic resonance imaging (CMR) has made major inroads in the new millenium in the diagnosis and assessment of prognosis for patients with cardiomyopathies. Imaging of left and right ventricular structure and function and tissue characterization with late gadolinium enhancement (LGE) as well as T1 and T2 mapping enable accurate diagnosis of the underlying etiology. In the setting of coronary artery disease, either transmurality of LGE or contractile reserve in response to dobutamine can assess the likelihood of recovery of function after revascularization. The presence of scar reduces the likelihood of response to medical therapy and to cardiac resynchronization therapy in heart failure. The presence and extent of LGE relate to overall cardiovascular outcome in cardiomyopathies. An emerging major role for CMR in cardiomyopathies is to identify myocardial scar for diagnostic and prognostic purposes. PMID:26033902

Left ventricular dimensions, systolic functions, and mass in term neonates with symmetric and asymmetric intrauterine growth restriction.

PubMed

Cinar, Bahar; Sert, Ahmet; Gokmen, Zeynel; Aypar, Ebru; Aslan, Eyup; Odabas, Dursun

2015-02-01

Previous studies have demonstrated structural changes in the heart and cardiac dysfunction in foetuses with intrauterine growth restriction. There are no available data that evaluated left ventricular dimensions and mass in neonates with symmetric and asymmetric intrauterine growth restriction. Therefore, we aimed to evaluate left ventricular dimensions, systolic functions, and mass in neonates with symmetric and asymmetric intrauterine growth restriction. We also assessed associated maternal risk factors, and compared results with healthy appropriate for gestational age neonates. In all, 62 asymmetric intrauterine growth restriction neonates, 39 symmetric intrauterine growth restriction neonates, and 50 healthy appropriate for gestational age neonates were evaluated by transthoracic echocardiography. The asymmetric intrauterine growth restriction group had significantly lower left ventricular end-systolic and end-diastolic diameters and posterior wall diameter in systole and diastole than the control group. The symmetric intrauterine growth restriction group had significantly lower left ventricular end-diastolic diameter than the control group. All left ventricular dimensions were lower in the asymmetric intrauterine growth restriction neonates compared with symmetric intrauterine growth restriction neonates (p>0.05), but not statistically significant except left ventricular posterior wall diameter in diastole (3.08±0.83 mm versus 3.54 ±0.72 mm) (p<0.05). Both symmetric and asymmetric intrauterine growth restriction groups had significantly lower relative posterior wall thickness (0.54±0.19 versus 0.48±0.13 versus 0.8±0.12), left ventricular mass (9.8±4.3 g versus 8.9±3.4 g versus 22.2±5.7 g), and left ventricular mass index (63.6±29.1 g/m2 versus 54.5±24.4 g/m2 versus 109±28.8 g/m2) when compared with the control group. Our study has demonstrated that although neonates with both symmetric and asymmetric intrauterine growth restriction had lower left ventricular dimensions, relative posterior wall thickness, left ventricular mass, and mass index when compared with appropriate for gestational age neonates, left ventricular systolic functions were found to be preserved. In our study, low socio-economic level, short maternal stature, and low maternal weight were found to be risk factors to develop intrauterine growth restriction. To our knowledge, our study is the first to evaluate left ventricular dimensions, wall thicknesses, mass, and systolic functions in neonates with intrauterine growth restriction and compare results with respect to asymmetric or symmetric subgroups.

Right Ventricular Outflow Tract Tachycardia with Structural Abnormalities of the Right Ventricle and Left Ventricular Diverticulum.

PubMed

Martini, Bortolo; Trevisi, Nicola; Martini, Nicolò; Zhang, Li

2015-01-01

A 43-year-old woman presented to the emergency room with a sustained ventricular tachycardia (VT). ECG showed a QRS in left bundle branch block morphology with inferior axis. Echocardiography, ventricular angiography, and cardiac magnetic resonance imaging (CMRI) revealed a normal right ventricle and a left ventricular diverticulum. Electrophysiology studies with epicardial voltage mapping identified a large fibrotic area in the inferolateral layer of the right ventricular wall and a small area of fibrotic tissue at the anterior right ventricular outflow tract. VT ablation was successfully performed with combined epicardial and endocardial approaches.

Right Ventricular Outflow Tract Tachycardia with Structural Abnormalities of the Right Ventricle and Left Ventricular Diverticulum

PubMed Central

Martini, Bortolo; Trevisi, Nicola; Martini, Nicolò; Zhang, Li

2015-01-01

A 43-year-old woman presented to the emergency room with a sustained ventricular tachycardia (VT). ECG showed a QRS in left bundle branch block morphology with inferior axis. Echocardiography, ventricular angiography, and cardiac magnetic resonance imaging (CMRI) revealed a normal right ventricle and a left ventricular diverticulum. Electrophysiology studies with epicardial voltage mapping identified a large fibrotic area in the inferolateral layer of the right ventricular wall and a small area of fibrotic tissue at the anterior right ventricular outflow tract. VT ablation was successfully performed with combined epicardial and endocardial approaches. PMID:26509086

Creation of a genetic calcium channel blocker by targeted gem gene transfer in the heart.

PubMed

Murata, Mitsushige; Cingolani, Eugenio; McDonald, Amy D; Donahue, J Kevin; Marbán, Eduardo

2004-08-20

Calcium channel blockers are among the most commonly used therapeutic drugs. Nevertheless, the utility of calcium channel blockers for heart disease is limited because of the potent vasodilatory effect that causes hypotension, and other side effects attributable to blockade of noncardiac channels. Therefore, focal calcium channel blockade by gene transfer is highly desirable. With a view to creating a focally applicable genetic calcium channel blocker, we overexpressed the ras-related small G-protein Gem in the heart by somatic gene transfer. Adenovirus-mediated delivery of Gem markedly decreased L-type calcium current density in ventricular myocytes, resulting in the abbreviation of action potential duration. Furthermore, transduction of Gem resulted in a significant shortening of the electrocardiographic QTc interval and reduction of left ventricular systolic function. Focal delivery of Gem to the atrioventricular (AV) node significantly slowed AV nodal conduction (prolongation of PR and AH intervals), which was effective in the reduction of heart rate during atrial fibrillation. Thus, these results indicate that gene transfer of Gem functions as a genetic calcium channel blocker, the local application of which can effectively modulate cardiac electrical and contractile function.

Osmolality- and Na+ -dependent effects of hyperosmotic NaCl solution on contractile activity and Ca2+ cycling in rat ventricular myocytes.

PubMed

Ricardo, Rafael A; Bassani, Rosana A; Bassani, José W M

2008-01-01

Hypertonic NaCl solutions have been used for small-volume resuscitation from hypovolemic shock. We sought to identify osmolality- and Na(+)-dependent components of the effects of the hyperosmotic NaCl solution (85 mOsm/kg increment) on contraction and cytosolic Ca(2+) concentration ([Ca(2+)](i)) in isolated rat ventricular myocytes. The biphasic change in contraction and Ca(2+) transient amplitude (decrease followed by recovery) was accompanied by qualitatively similar changes in sarcoplasmic reticulum (SR) Ca(2+) content and fractional release and was mimicked by isosmotic, equimolar increase in extracellular [Na(+)] ([Na(+)](o)). Raising osmolality with sucrose, however, augmented systolic [Ca(2+)](i) monotonically without change in SR parameters and markedly decreased contraction amplitude and diastolic cell length. Functional SR inhibition with thapsigargin abolished hyperosmolality effects on [Ca(2+)](i). After 15-min perfusion, both hyperosmotic solutions slowed mechanical relaxation during twitches and [Ca(2+)](i) decline during caffeine-evoked transients, raised diastolic and systolic [Ca(2+)](i), and depressed systolic contractile activity. These effects were greater with sucrose solution, and were not observed after isosmotic [Na(+)](o) increase. We conclude that under the present experimental conditions, transmembrane Na(+) redistribution apparently plays an important role in determining changes in SR Ca(2+) mobilization, which markedly affect contractile response to hyperosmotic NaCl solutions and attenuate the osmotically induced depression of contractile activity.

Dynamic left ventricular dyssynchrony and severe mitral regurgitation caused by exercise: should we go beyond the guidelines?

PubMed

Laflamme, Emilie; Philippon, François; O'Connor, Kim; Sarrazin, Jean-François; Auffret, Vincent; Chauvette, Vincent; Dubois, Michelle; Voisine, Pierre; Bergeron, Sébastien; Sénéchal, Mario

2018-01-01

Guidelines for cardiac resynchronization therapy (CRT) have been established, but there may be a subgroup of patients not identified in these guidelines who may benefit from this therapy. We report a patient with a dynamic left ventricular dyssynchrony and severe mitral regurgitation caused by exercise successfully treated with CRT. Exercise testing should be considered in patients with left ventricular ejection fraction <35% and QRS <130 ms with severe heart failure symptoms that are unexplained by rest echocardiography evaluation in order to rule out ischemia and/or dynamic left ventricular dyssynchrony. In the presence of exercise-induced left ventricular bundle branch block, the implantation of CRT should be contemplated.

Effects of pimobendan for mitral valve regurgitation in dogs.

PubMed

Kanno, Nobuyuki; Kuse, Hiroshi; Kawasaki, Masaya; Hara, Akashi; Kano, Rui; Sasaki, Yoshihide

2007-04-01

Pimobendan has a dual mechanism of action: it increases myocardial contractility by increasing calcium sensitization to troponin C and it promotes vasodilation by inhibiting PDEIII. This study examined the effects of pimobendan on cardiac function, hemodynamics, and neurohormonal factors in dogs with mild mitral regurgitation (MR). The dogs were given 0.25 mg/kg of pimobendan orally every 12 hr for 4 weeks. With pimobendan, the heart rate and stroke volume did not change, but the systolic blood pressure gradually decreased and the degree of mitral valve regurgitation tended to decrease. Renal blood flow was significantly increased and the glomerular filtration rate was slightly increased at 2 and 4 weeks. Furthermore, over the 4-week period, the plasma norepinephrine concentration decreased significantly, the systolic index increased slightly, the left atrial diameter and the left ventricular diameters decreased significantly, and the heart size improved. Given these results, pimobendan appears to be useful for treating MR in dogs. However, further long-term studies of pimobendan involving a larger number of dogs with mild and moderate MR are needed to establish the safety of pimobendan and document improvements in quality of life.

Intraspecific individual variation of temperature tolerance associated with oxygen demand in the European sea bass (Dicentrarchus labrax)

PubMed Central

Ozolina, Karlina; Shiels, Holly A; Ollivier, Hélène; Claireaux, Guy

2016-01-01

Abstract The European sea bass (Dicentrarchus labrax) is an economically important fish native to the Mediterranean and Northern Atlantic. Its complex life cycle involves many migrations through temperature gradients that affect the energetic demands of swimming. Previous studies have shown large intraspecific variation in swimming performance and temperature tolerance, which could include deleterious and advantageous traits under the evolutionary pressure of climate change. However, little is known of the underlying determinants of this individual variation. We investigated individual variation in temperature tolerance in 30 sea bass by exposing them to a warm temperature challenge test. The eight most temperature-tolerant and eight most temperature-sensitive fish were then studied further to determine maximal swimming speed (UCAT), aerobic scope and post-exercise oxygen consumption. Finally, ventricular contractility in each group was determined using isometric muscle preparations. The temperature-tolerant fish showed lower resting oxygen consumption rates, possessed larger hearts and initially recovered from exhaustive exercise faster than the temperature-sensitive fish. Thus, whole-animal temperature tolerance was associated with important performance traits. However, the temperature-tolerant fish also demonstrated poorer maximal swimming capacity (i.e. lower UCAT) than their temperature-sensitive counterparts, which may indicate a trade-off between temperature tolerance and swimming performance. Interestingly, the larger relative ventricular mass of the temperature-tolerant fish did not equate to greater ventricular contractility, suggesting that larger stroke volumes, rather than greater contractile strength, may be associated with thermal tolerance in this species. PMID:27382468

Intraspecific individual variation of temperature tolerance associated with oxygen demand in the European sea bass (Dicentrarchus labrax).

PubMed

Ozolina, Karlina; Shiels, Holly A; Ollivier, Hélène; Claireaux, Guy

2016-01-01

The European sea bass (Dicentrarchus labrax) is an economically important fish native to the Mediterranean and Northern Atlantic. Its complex life cycle involves many migrations through temperature gradients that affect the energetic demands of swimming. Previous studies have shown large intraspecific variation in swimming performance and temperature tolerance, which could include deleterious and advantageous traits under the evolutionary pressure of climate change. However, little is known of the underlying determinants of this individual variation. We investigated individual variation in temperature tolerance in 30 sea bass by exposing them to a warm temperature challenge test. The eight most temperature-tolerant and eight most temperature-sensitive fish were then studied further to determine maximal swimming speed (U CAT), aerobic scope and post-exercise oxygen consumption. Finally, ventricular contractility in each group was determined using isometric muscle preparations. The temperature-tolerant fish showed lower resting oxygen consumption rates, possessed larger hearts and initially recovered from exhaustive exercise faster than the temperature-sensitive fish. Thus, whole-animal temperature tolerance was associated with important performance traits. However, the temperature-tolerant fish also demonstrated poorer maximal swimming capacity (i.e. lower U CAT) than their temperature-sensitive counterparts, which may indicate a trade-off between temperature tolerance and swimming performance. Interestingly, the larger relative ventricular mass of the temperature-tolerant fish did not equate to greater ventricular contractility, suggesting that larger stroke volumes, rather than greater contractile strength, may be associated with thermal tolerance in this species.

Decompression of Left Ventricle During Venoarterial Extracorporeal Membrane Oxygenation Support as a Step to Transplant.

PubMed

Gültekin, Bahadır; Ersoy, Özgür; Akkaya, İlknur; Kayıpmaz, Çağrı; Pirat, Araş; Sezgin, Atilla

2016-11-01

Left ventricular distention can be recognized during the use of venoarterial extracorporeal membrane oxygenation as a key complication. Left ventricular decompression may decrease pulmonary pressure, minimize ventricular distention, and allow myocardial recovery. We applied venoarterial extracorporeal membrane oxygenation to 4 patients while on a wait list for cardiac transplant. Two patients with severe heart failure developed high end-diastolic pressures leading to left ventricular distention. We used atrial venting methods to decrease the pressure. Here, we discussed the strategies to manage ventricular distention by conservative, interventional, and surgical means.

Relationship of central and peripheral blood pressure to left ventricular mass in hypertensive patients.

PubMed

Pérez-Lahiguera, Francisco J; Rodilla, Enrique; Costa, Jose A; Gonzalez, Carmen; Martín, Joaquin; Pascual, Jose M

2012-12-01

The purpose of the present study was to assess the relationship of central and peripheral blood pressure to left ventricular mass. Cross-sectional study that included 392 never treated hypertensive individuals. Measurement of office, 24-h ambulatory, and central blood pressure (obtained using applanation tonometry) and determination of left ventricular mass by echocardiography were performed in all patients. In a multiple regression analysis, with adjustment for age, gender and metabolic syndrome, 24-h blood pressure was more closely related to ventricular mass than the respective office and central blood pressures. Systolic blood pressures always exhibited a higher correlation than diastolic blood pressures in all 3 determinations. The correlation between left ventricular mass index and 24-h systolic blood pressure was higher than that of office (P<.002) or central systolic blood pressures (P<.002). Changes in 24-h systolic blood pressure caused the greatest variations in left ventricular mass index (P<.001). In our population of untreated middle-aged hypertensive patients, left ventricular mass index is more closely related to 24-h ambulatory blood pressure than to office or central blood pressure. Central blood pressure does not enable us to better identify patients with left ventricular hypertrophy. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Orthotopic heart transplant versus left ventricular assist device: A national comparison of cost and survival

PubMed Central

Mulloy, Daniel P.; Bhamidipati, Castigliano M.; Stone, Matthew L.; Ailawadi, Gorav; Kron, Irving L.; Kern, John A.

2012-01-01

Objectives Orthotopic heart transplantation is the standard of care for end-stage heart disease. Left ventricular assist device implantation offers an alternative treatment approach. Left ventricular assist device practice has changed dramatically since the 2008 Food and Drug Administration approval of the HeartMate II (Thoratec, Pleasanton, Calif), but at what societal cost? The present study examined the cost and efficacy of both treatments over time. Methods All patients who underwent either orthotopic heart transplantation (n = 9369) or placement of an implantable left ventricular assist device (n = 6414) from 2005 to 2009 in the Nationwide Inpatient Sample were selected. The trends in treatment use, mortality, and cost were analyzed. Results The incidence of orthotopic heart transplantation increased marginally within a 5-year period. In contrast, the annual left ventricular assist device implantation rates nearly tripled. In-hospital mortality from left ventricular assist device implantation decreased precipitously, from 42% to 17%. In-hospital mortality for orthotopic heart transplantation remained relatively stable (range, 3.8%–6.5%). The mean cost per patient increased for both orthotopic heart transplantation and left ventricular assist device placement (40% and 17%, respectively). With the observed increase in both device usage and cost per patient, the cumulative Left ventricular assist device cost increased 232% within 5 years (from $143 million to $479 million). By 2009, Medicare and Medicaid were the primary payers for nearly one half of all patients (orthotopic heart transplantation, 45%; left ventricular assist device, 51%). Conclusions Since Food and Drug Administration approval of the HeartMate II, mortality after left ventricular assist device implantation has decreased rapidly, yet has remained greater than that after orthotopic heart transplantation. The left ventricular assist device costs have continued to increase and have been significantly greater than those for orthotopic heart transplantation. Because of the evolving healthcare economics climate, with increasing emphasis on the costs and comparative effectiveness, a concerted effort at LVAD cost containment and judicious usage is essential to preserve the viability of this invaluable treatment. PMID:23246055

Purinergic modulation of adult guinea pig cardiomyocytes in long term cultures and co-cultures with extracardiac or intrinsic cardiac neurones.

PubMed

Horackova, M; Huang, M H; Armour, J A

1994-05-01

To determine the capacity of ATP to modify cardiomyocytes directly or indirectly via peripheral autonomic neurones, the effects of various purinergic agents were studied on long term cultures of adult guinea pig ventricular myocytes and their co-cultures with extracardiac (stellate ganglion) or intrinsic cardiac neurones. Ventricular myocytes and cardiac neurones were enzymatically dissociated and plated together or alone (myocytes only). Myocyte cultures were used for experiments after three to six weeks. The electrical and contractile properties of cultured myocytes and myocyte-neuronal networks were investigated. The spontaneous beating frequency of ventricular myocytes co-cultured with stellate ganglion neurones increased by approximately 140% (p < 0.001) following superfusion with 10(-5) M ATP. This effect was not modified significantly by tetrodotoxin or by beta adrenoceptor blockade (10(-5) M timolol), but was eliminated following application of the P2 antagonist suramin (10(-5) M). Basal spontaneous contractile rate was reduced by approximately 86% (p < 0.001) in the presence of suramin, indicating the existence of tonically active purinergic synaptic mechanisms in stellate ganglion neurone-myocyte cocultures. Suramin did not significantly affect non-innervated myocyte cultures. ATP increased myocyte contractile rate in intrinsic cardiac neurone-myocyte co-cultures by approximately 40% (p < 0.01) under control conditions, but when beta adrenergic receptors of tetrodotoxin sensitive neural responses were blocked, ATP induced greater augmentation (> 100%). In contrast, ATP induced much smaller effects in non-innervated myocyte cultures (approximately 26%, p < 0.01). Analogues of AT) showed the following order of potency: ATP > UTP > MSATP > beta gamma ATP > alpha beta ATP. Adenosine (10(-4) M) attenuated the beating frequency of myocytes in both types of co-culture, while not significantly affecting non-innervated myocyte cultures. The experimental model used in this study showed that extrinsic and intrinsic cardiac neurones which possess P2 receptors can greatly enhance cardiac myocyte contractile rate when activated by ATP. Since adenosine reduced contractile rate in both types of co-cultures while not affecting non-innervated myocytes, it is concluded that some of these neurones possess P1 receptors.

Mechanism of reduction of mitral regurgitation with vasodilator therapy.

PubMed

Yoran, C; Yellin, E L; Becker, R M; Gabbay, S; Frater, R W; Sonnenblick, E H

1979-04-01

Acute mitral regurgitation was produced in six open chest dogs by excising a portion of the anterior valve leaflet. Electromagnetic flow probes were placed in the left atrium around the mitral anulus and in the ascending aorta to determine phasic left ventricular filling volume, regurgitant volume and stroke volume. The systolic pressure gradient was calculated from simultaneously measured high fidelity left atrial and left ventricular pressures. The effective mitral regurgitant orifice area was calculated from Gorlin's hydraulic equation. Infusion of nitroprusside resulted in a significant reduction in mitral regurgitation. No significant change occurred in the systolic pressure gradient between the left ventricle and the left atrium because both peak left ventricular pressure and left atrial pressure were reduced. The reduction of mitral regurgitation was largely due to reduction in the size of the mitral regurgitant orifice. Reduction of ventricular volume rather than the traditional concept of reduction of impedance of left ventricular ejection may explain the effects of vasodilators in reducing mitral regurgitation.

Finite element stress analysis of the human left ventricle whose irregular shape is developed from single plane cineangiocardiogram

NASA Technical Reports Server (NTRS)

Ghista, D. N.; Hamid, M. S.

1977-01-01

The three-dimensional left ventricular chamber geometrical model is developed from single plane cineangiocardiogram. This left ventricular model is loaded by an internal pressure monitored by cardiac catheterization. The resulting stresses in the left ventricular model chamber's wall are determined by computerized finite element procedure. For the discretization of this left ventricular model structure, a 20-node, isoparametric finite element is employed. The analysis and formulation of the computerised procedure is presented in the paper, along with the detailed algorithms and computer programs. The procedure is applied to determine the stresses in a left ventricle at an instant, during systole. Next, a portion (represented by a finite element) of this left ventricular chamber is simulated as being infarcted by making its active-state modulus value equal to its passive-state value; the neighbouring elements are shown to relieve the 'infarcted' element of stress by themselves taking on more stress.

Robotic assisted excision of a left ventricular myxoma.

PubMed

Hassan, Mohammed; Smith, J Michael

2012-01-01

We present a rare case of left ventricular myxoma discovered incidentally in an asymptomatic 16-year old male. The patient underwent the appropriate work-up and a robotic-assisted excision of the mass. The patient had an uneventful recovery and was discharged home at postoperative day 3. To our knowledge, this is the first case of robotic-assisted left ventricular myxoma excision in the literature. Robotic-assisted surgery of left ventricular myxomas is a safe and feasible method of excision.

Papillary Muscle Repositioning as a Subvalvular Apparatus Preservation Technique in Mitral Stenosis Patients with Normal Left Ventricular Systolic Function

PubMed Central

Lafci, Gokhan; Cagli, Kerim; Korkmaz, Kemal; Turak, Osman; Uzun, Alper; Yalcinkaya, Adnan; Diken, Adem; Gunertem, Eren; Cagli, Kumral

2014-01-01

Subvalvular apparatus preservation is an important concept in mitral valve replacement (MVR) surgery that is performed to remedy mitral regurgitation. In this study, we sought to determine the effects of papillary muscle repositioning (PMR) on clinical outcomes and echocardiographic left ventricular function in rheumatic mitral stenosis patients who had normal left ventricular systolic function. We prospectively assigned 115 patients who were scheduled for MVR surgery with mechanical prosthesis to either PMR or MVR-only groups. Functional class and echocardiographic variables were evaluated at baseline and at early and late postoperative follow-up examinations. All values were compared between the 2 groups. The PMR group consisted of 48 patients and the MVR-only group of 67 patients. The 2 groups’ baseline characteristics and surgery-related factors (including perioperative mortality) were similar. During the 18-month follow-up, all echocardiographic variables showed a consistent improvement in the PMR group; the mean left ventricular ejection fraction deteriorated significantly in the MVR-only group. Comparison during follow-up of the magnitude of longitudinal changes revealed that decreases in left ventricular end-diastolic and end-systolic diameters and in left ventricular sphericity indices, and increases in left ventricular ejection fractions, were significantly higher in the PMR group than in the MVR-only group. This study suggests that, in patients with rheumatic mitral stenosis and preserved left ventricular systolic function, the addition of papillary muscle repositioning to valve replacement with a mechanical prosthesis improves left ventricular dimensions, ejection fraction, and sphericity index at the 18-month follow-up with no substantial undesirable effect on the surgery-related factors. PMID:24512397

Autoantibodies against β1 receptor and AT1 receptor in type 2 diabetes patients with left ventricular dilatation.

PubMed

Zhao, Linshuang; Xu, Chunyan; Xu, Jinling

2014-01-01

To explore the relationship between the autoantibodies against the β1 and AT1 receptors and left ventricular dilatation in patients with type 2 diabetes (T2DM). The autoantibodies against the β1 and angiotensin II type 1 (AT1) receptors of T2DM patients with and without hypertension were screened by ELISA. Multiple logistic regression was used to analyze the risk factors for left ventricular dilatation. The reversing effect of left ventricular dilatation was evaluated after receptor blocker treatment. The positive rates of autoantibodies against the β1 and AT1 receptors (43.0 and 44.1%, respectively) in T2DM patients with hypertension were significantly higher than those in normotensive patients (16.0 and 10.4%, respectively; all p < 0.01). Furthermore, among T2DM patients with hypertension, the positive rates (61.4 and 64.9%, respectively) in patients with left ventricular dilatation were remarkably higher than those with normal left ventricular dimensions (34.4 and 36.1%, respectively; all p < 0.01). The presence of β1 receptor antibody and AT1 receptor antibody were risk factors for left ventricular dilatation (p < 0.05). The curative effect of metoprolol tartrate and valsartan in reversing left ventricular hypertrophy in the group positive for autoantibodies was much better than in the negative group. The findings show that autoantibodies against the β1 and AT1 receptors may play a role in predicting left ventricular dilatation in T2DM patients in combination with hypertension. Metoprolol tartrate and valsartan are effective and safe in the treatment of these patients. © 2014 S. Karger AG, Basel.

Growth of left ventricular mass with military basic training in army recruits.

PubMed

Batterham, Alan M; George, Keith P; Birch, Karen M; Pennell, Dudley J; Myerson, Saul G

2011-07-01

Exercise-induced left ventricular hypertrophy is well documented, but whether this occurs merely in line with concomitant increases in lean body mass is unclear. Our aim was to model the extent of left ventricular hypertrophy associated with increased lean body mass attributable to an exercise training program. Cardiac and whole-body magnetic resonance imaging was performed before and after a 10-wk intensive British Army basic training program in a sample of 116 healthy Caucasian males (aged 17-28 yr). The within-subjects repeated-measures allometric relationship between lean body mass and left ventricular mass was modeled to allow the proper normalization of changes in left ventricular mass for attendant changes in lean body mass. To linearize the general allometric model (Y=aXb), data were log-transformed before analysis; the resulting effects were therefore expressed as percent changes. We quantified the probability that the true population increase in normalized left ventricular mass was greater than a predefined minimum important difference of 0.2 SD, assigning a probabilistic descriptive anchor for magnitude-based inference. The absolute increase in left ventricular mass was 4.8% (90% confidence interval=3.5%-6%), whereas lean body mass increased by 2.6% (2.1%-3.0%). The change in left ventricular mass adjusted for the change in lean body mass was 3.5% (1.9%-5.1%), equivalent to an increase of 0.25 SD (0.14-0.37). The probability that this effect size was greater than or equal to our predefined minimum important change of 0.2 SD was 0.78-likely to be important. After correction for allometric growth rates, left ventricular hypertrophy and lean body mass changes do not occur at the same magnitude in response to chronic exercise.

Different effects of prolonged exercise on the right and left ventricles.

PubMed

Douglas, P S; O'Toole, M L; Hiller, W D; Reichek, N

1990-01-01

To examine the functional consequences of the greater increase in right ventricular work with exercise, the effects of prolonged exercise on the right and left heart chambers were compared in 41 athletes before, at the finish (13 min) and after recovery (28 h) from the Hawaii Ironman Triathlon (3.9 km swim, 180.2 km bike ride, 42.2 km run). Two-dimensional and Doppler echocardiograms were analyzed for left and right atrial and ventricular areas at end-diastole and end-systole, right and left ventricular inflow velocities and mitral and tricuspid regurgitation. After exercise, left ventricular and left and right atrial sizes were reduced, whereas right ventricular size increased (diastole: 21.4 to 24.2 cm2; systole: 15.8 to 18.2 cm2; p less than 0.01). The emptying fraction of all chambers was unchanged. Left but not right ventricular inflow showed an increase in peak velocity of rapid filling, whereas both atrial systolic velocities increased (26 to 38 cm/s tricuspid; 38 to 54 cm/s mitral; both p less than 0.01). Overall, the right ventricular early to atrial velocity ratio was reduced after exercise (1.56 to 1.17; p less than 0.05) and the left ventricular pattern was unchanged. The prevalence of tricuspid regurgitation was statistically unchanged (86% to 52%), although that of mitral regurgitation was greatly reduced (76% to 0%). Changes in all variables returned toward prerace values during recovery. Thus, in highly trained athletes, prolonged exercise causes differing responses of the right and left ventricles. These differences may be due to changes in right ventricular function, shape or compliance.

Left ventricular assist devices as destination therapy: a new look at survival.

PubMed

Park, Soon J; Tector, Alfred; Piccioni, William; Raines, Edward; Gelijns, Annetine; Moskowitz, Alan; Rose, Eric; Holman, William; Furukawa, Satoshi; Frazier, O Howard; Dembitsky, Walter

2005-01-01

The REMATCH trial compared the use of left ventricular assist devices with optimal medical management for patients with end-stage heart failure. When the trial met its primary end point criteria in July 2001, left ventricular assist device therapy was shown to significantly improve survival and quality of life. With extended follow-up, 2 critical questions emerge: (1) Did these benefits persist, and (2) did outcomes improve over the course of the trial, given the evolving nature of the technology? We analyzed survival in this randomized trial by using the product-limit method of Kaplan and Meier. Changes in the benefits of therapy were analyzed by examining the effect of the enrollment period. The survival rates for patients receiving left ventricular assist devices (n = 68) versus patients receiving optimal medical management (n = 61) were 52% versus 28% at 1 year and 29% versus 13% at 2 years ( P = .008, log-rank test). As of July 2003, 11 patients were alive on left ventricular assist device support out of a total 16 survivors (including 3 patients receiving optimal medical management who crossed over to left ventricular assist device therapy). There was a significant improvement in survival for left ventricular assist device-supported patients who enrolled during the second half of the trial compared with the first half ( P = .03). The Minnesota Living with Heart Failure scores improved significantly over the course of the trial. The extended follow-up confirms the initial observation that left ventricular assist device therapy renders significant survival and quality-of-life benefits compared with optimal medical management for patients with end-stage heart failure. Furthermore, we observed an improvement in the survival of patients receiving left ventricular assist devices over the course of the trial, suggesting the effect of greater clinical experience.

Long-term results after left ventricular aneurysmectomy.

PubMed Central

Otterstad, J E; Christensen, O; Levorstad, K; Nitter-Hauge, S

1981-01-01

Twenty-six patients (21 men and five women) with a mean age of 54.8 years have been reinvestigated nine to 62 months (mean 29.7) after left ventricular aneurysmectomy. Preoperatively left ventricular angiography disclosed an anterior aneurysm in all cases, which was large in 15 (57%) and small to medium in 11 (42%). At follow-up a large residual aneurysm was found in five (19%), a small to medium one in 13 (50%), and akinesia without aneurysm in eight (31%). The sum of ST elevation (sigma ST) in praecordial leads in the electrocardiogram was reduced from a mean value of 11.2 mm to 7.7 mm. In no patient did ST segments return to normal after operation. Preoperatively, mean sigma ST was identical in patients with large and with small to medium aneurysms. At reinvestigation mean sigma ST was identical in patients with large and with small to medium residual aneurysms as well as in patients with akinesia. Left ventricular end-diastolic pressure before angiography was reduced from a mean value of 21.5 mm to 15.1 mmHg and after angiography from 26.7 mm to 21.1 mmHg. Progression of coronary artery stenoses was a characteristic finding in patients whose left ventricular end-diastolic pressures did not return to normal. These patients had a longer follow-up time than those with no progression of coronary disease, who all showed an improvement in left ventricular end-diastolic pressure. Six patients who had coronary bypass grafting performed had unchanged left ventricular end-diastolic pressures at follow-up. The results indicate that progression of coronary artery disease may be responsible for an eventual further deterioration in left ventricular function after aneurysmectomy. Additional bypass grafting did not result in improved left ventricular function. PMID:6971647

Propofol administration to the fetal-maternal unit reduces cardiac oxidative stress in preterm lambs subjected to prenatal asphyxia and cardiac arrest.

PubMed

Seehase, Matthias; Houthuizen, Patrick; Collins, Jennifer J P; Zimmermann, Luc J; Kramer, Boris W

2016-05-01

Little is known about the effects of propofol on oxidative stress and its effect on key structures of the contractile apparatus as the myosin light chain 2 (MLC2) and the p38MAPK survival pathway in the preterm heart. We hypothesized that propofol administration could attenuate the hypoxic myocardial injury after birth asphyxia. Pregnant ewes were randomized to receive either propofol or isoflurane anesthesia. A total of 44 late-preterm lambs were subjected to in utero umbilical cord occlusion (UCO), resulting in asphyxia and cardiac arrest, or sham treatment. After emergency cesarean delivery, each fetus was resuscitated, mechanically ventilated, and supported under anesthesia for 8 h using the same anesthetic as the one received by its mother. At 8 h after UCO, occurrence of reactive oxygen species and activation of inducible nitric oxide synthase in the heart were lower in association with propofol anesthesia than with isoflurane. This was accompanied by less degradation of MLC2 but higher p38MAPK level and in echocardiography with a trend toward a higher median left ventricular fractional shortening. The use of propofol resulted in less oxidative stress and was associated with less cytoskeletal damage of the contractile apparatus than the use of isoflurane anesthesia.

Experimental myocardial infarction

PubMed Central

Kumar, Raj; Joison, Julio; Gilmour, David P.; Molokhia, Farouk A.; Pegg, C. A. S.; Hood, William B.

1971-01-01

The hemodynamic effects of tachycardia induced by atrial pacing were investigated in left ventricular failure of acute and healing experimental myocardial infarction in 20 intact, conscious dogs. Myocardial infarction was produced by gradual inflation of a balloon cuff device implanted around the left anterior descending coronary artery 10-15 days prior to the study. 1 hr after acute myocardial infarction, atrial pacing at a rate of 180 beats/min decreased left ventricular end-diastolic pressure from 19 to 8 mm Hg and left atrial pressure from 17 to 12 mm Hg, without change in cardiac output. In the healing phase of myocardial infarction 1 wk later, atrial pacing decreased left ventricular end-diastolic pressure from 17 to 9 mm Hg and increased the cardiac output by 37%. This was accompanied by evidence of peripheral vasodilation. In two dogs with healing anterior wall myocardial infarction, left ventricular failure was enhanced by partial occlusion of the circumflex coronary artery. Both the dogs developed pulmonary edema. Pacing improved left ventricular performance and relieved pulmonary edema in both animals. In six animals propranolol was given after acute infarction, and left ventricular function deteriorated further. However the pacing-induced augmentation of cardiac function was unaltered and, hence, is not mediated by sympathetics. The results show that the spontaneous heart rate in left ventricular failure of experimental canine myocardial infarction may be less than optimal and that maximal cardiac function may be achieved at higher heart rates. Images PMID:4395910

Percutaneous Repair of Postoperative Mitral Regurgitation After Left Ventricular Assist Device Implant.

PubMed

Cork, David P; Adamson, Robert; Gollapudi, Raghava; Dembitsky, Walter; Jaski, Brian

2018-02-01

Mitral regurgitation commonly improves after implantation of a left ventricular assist device without concomitant valvular repair owing to the mechanical unloading of the left ventricle. However, the development (or persistence) of significant mitral regurgitation after implantation of a left ventricular assist device is associated with adverse clinical events. We present a case of a left ventricular assist device patient who successfully underwent a percutaneous MitraClip procedure for repair of persistent late postoperative mitral insufficiency with demonstrable clinical and hemodynamic improvement. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Changes of myocardial lipidomics profiling in a rat model of diabetic cardiomyopathy using UPLC/Q-TOF/MS analysis.

PubMed

Dong, Shifen; Zhang, Rong; Liang, Yaoyue; Shi, Jiachen; Li, Jiajia; Shang, Fei; Mao, Xuezhou; Sun, Jianning

2017-01-01

Diabetic cardiomyopathy (DCM) is a serious cardiac dysfunction induced by changes in the structure and contractility of the myocardium that are initiated in part by alterations in energy substrates. The underlying mechanisms of DCM are still under controversial. The observation of lipids, especially lipidomics profiling, can provide an insight into the know the biomarkers of DCM. The aim of our research was to detect changes of myocardial lipidomics profiling in a rat model of diabetic cardiomyopathy. Diabetic cardiomyopathy was induced by feeding a high-sucrose/fat diet (HSFD) for 28 weeks and streptozotocin (30 mg/kg, intraperitoneally). The ultra-high-performance liquid chromatography (UPLC) coupled to quadruple time-of flight (QTOF) mass spectrometer was used to acquire and analyze the lipidomics profiling of myocardial tissue. Meanwhile, parameters of cardiac function were collected using cardiac catheterization, and the cardiac index was calculated, and fasting blood glucose and lipid levels were measured by an ultraviolet spectrophotometric method. We detected 3023 positive ion peaks and 300 negative ion peaks. Levels of phosphatidylcholine (PC) (22:6/18:2), PC (22:6/18:1), PC (20:4/16:1), PC (16:1/18:3), phosphatidylethanolamine (PE) (20:4/18:2), and PE (20:4/16:0) were down-regulated, and PC (20:2/18:2), PC (18:0/16:0), and PC (20:4/18:0) were up-regulated in DCM model rats, when compared with control rats. Cardiac functions signed as values of left ventricular systolic pressure, maximal uprising velocity of left ventricular pressure and maximal decreasing velocity of left ventricular pressure were injured by 21-44%, and the cardiac index was increased by 25%, and fasting blood glucose and lipids were increased by 34-368%. Meanwhile, the cardiac lipid-related biomarkers have significant correlation with changes of cardiac function and cardiac index. UPLC/Q-TOF/MS analysis data suggested changes of some potential lipid biomarkers in the development of cardiac dysfunction and hypertrophy of diabetic cardiomyopathy, which may serve as potential important targets for clinical diagnosis and therapeutic intervention of DCM in the future.

Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model.

PubMed

Dash, Rajesh; Kim, Paul J; Matsuura, Yuka; Ikeno, Fumiaki; Metzler, Scott; Huang, Ngan F; Lyons, Jennifer K; Nguyen, Patricia K; Ge, Xiaohu; Foo, Cheryl Wong Po; McConnell, Michael V; Wu, Joseph C; Yeung, Alan C; Harnish, Phillip; Yang, Phillip C

2015-07-27

The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts. Twelve adult swine underwent ischemia-reperfusion injury. Digital subtraction of MEMRI-negative myocardium (intrainfarct region) from delayed gadolinium enhancement MRI-positive myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI demonstrated an increased PIR viability signal compared with control. Direct PIR viability remained higher in hAMSC-treated hearts for >6 weeks. Increased PIR viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and hAMSC engraftment, as confirmed by immunocytochemistry. Increased MEMRI and positron emission tomography reporter gene signal in the intrainfarct region and the PIR correlated with sustained functional augmentation (global and regional) within the hAMSC group (mean change, left ventricular ejection fraction: hAMSC 85±60%, control 8±10%; P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume increase: hAMSC 24±8%, control 110±30%; P<0.05). The positron emission tomography reporter gene signal of hAMSC engraftment correlates with the improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real-time method of tracking PIR viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Left ventricular hypertrophy as protective factor after bypass grafting.

PubMed

Iannuzzi, Gian Luca; Maniscalco, Mauro; Elia, Andrea; Scognamiglio, Anna; Furgi, Giuseppe; Rengo, Franco

2018-05-01

Left ventricular hypertrophy (LVH) is a well established cardiovascular risk factor, accounting for an increase in cardiovascular morbid-mortality, although how much the magnitude and the kind of LVH could affect cardiovascular outcomes is in large part unknown. We speculate that mild LVH in absence of left ventricular (LV) chamber dilation, could play a protective role towards functional capacity, clinical outcome, cardiovascular and total morbi-mortality in conditions in which LV systolic function is generally reduced. Accordingly to many epidemiological observations, the availability of extra-quote of systolic function could lead to a significative improvement in the final outcome of some kinds of heart patients, as those undergoing bypass-grafting, where the stress for heart and cardiovascular system is always high. We suppose that the functional reserve available for patients with LVH could make the difference with respect to other patients undergoing myocardial revascularization. Similarly, the availability of a contractile reserve warranted by LVH could ensure a little gain in the outcome for patients after other major cardiovascular events (such as myocardial infarction or other heart surgery as surgical valve replacement). However, our hypothesis only involves mild LVH without LV chamber dilation, that is the initial stage of "non-dilated concentric" LVH and "non-dilated eccentric" LVH according to the new four-tiered classification of LVH based on relative wall thickness and LV dilation. Support for our hypothesis derives from the well-known protective role of systolic function that is a major factor in almost all cardiovascular diseases, where LV ejection fraction (LVEF) has shown to significantly improve quality of life, as well as morbidity and mortality. The knowledge that mild LVH in absence of LV chamber dilation is not as harmful in such conditions as believed at present could make avoidable some drugs prescription in some stages of the disease. Furthermore, it may allow a better evaluation of the risk profile of patients with LVH undergoing some cardiovascular major events like bypass grafting, myocardial infarction or surgical heart valve replacement. Copyright © 2018 Elsevier Ltd. All rights reserved.

Left Ventricular Architecture, Long-Term Reverse Remodeling, and Clinical Outcome in Mild Heart Failure With Cardiac Resynchronization: Results From the REVERSE Trial.

PubMed

St John Sutton, Martin; Linde, Cecilia; Gold, Michael R; Abraham, William T; Ghio, Stefano; Cerkvenik, Jeffrey; Daubert, Jean-Claude

2017-03-01

This study sought to determine the effects of abnormal left ventricular (LV) architecture on cardiac remodeling and clinical outcomes in mild heart failure (HF). Cardiac resynchronization therapy (CRT) is an established treatment for HF that improves survival in part by favorably remodeling LV architecture. LV shape is a dynamic component of LV architecture on which contractile function depends. Transthoracic 2-dimensional echocardiography was used to quantify changes in LV architecture over 5 years of follow-up of patients with mild HF from the REVERSE study. REVERSE was a prospective study of patients with large hearts (LV end-diastolic dimension ≥55 mm), LV ejection fraction <40%, and QRS duration >120 ms randomly assigned to CRT-ON (n = 419) and CRT-OFF (n = 191). CRT-OFF patients were excluded from this analysis. LV dimensions, volumes, mass index, and LV ejection fraction were calculated. LV architecture was assessed using the sphericity index, as follows: (LV end-diastolic volume)/(4/3 × π × r 3 ) × 100%. LV architecture improved over time and demonstrated significant associations between LV shape, age, sex, and echocardiography metrics. Changes in LV architecture were strongly correlated with changes in LV end-systolic volume index and LV end-diastolic volume index (both p < 0.0001). Sphericity index emerged as a predictor of death and HF hospitalization in spite of the low adverse event rate. A decrease in LV end-systolic volume index >15% occurred in more than two-thirds of patients, which indicates considerable reverse remodeling. We demonstrated that change in LV architecture in patients with mild HF with CRT is associated with structural and functional remodeling. Mean LV filling pressure was elevated, and the inability to lower it was an additional predictor of HF hospitalization or death. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Annular subvalvular left ventricular aneurysm in Bahia, Brazil.

PubMed Central

Guimarães, A C; Filho, A S; Esteves, J P; Abreu, W N; Vinhaes, L A; de Almeida Souza, J A; Machado, A

1976-01-01

Two cases of left ventricular aneurysm, a 16-year-old black boy and a 23-year-old white girl, from Bahia, Brazil, are presented. In both patients there was enlargement of the cardiac silhouette and a prominent bulge of the left inferior border. On the right oblique view a ring of calcium at the ventricular opening of the aneurysms was visualized. A left ventriculogram showed a huge aneurysm in the first case and a bulge on the lateral wall of the left ventricle in the other. Cardiac catheterization showed a rise in left and right ventricular end-diastolic pressures and in the mean pulmonary artery pressure. In the first case the contour of the right ventricular pressure curve showed a restrictive pattern. The similarities of these aneurysms with the annular submitral type described in young black Africans are stressed. Images PMID:973882

Annular subvalvular left ventricular aneurysm in Bahia, Brazil.

PubMed

Guimarães, A C; Filho, A S; Esteves, J P; Abreu, W N; Vinhaes, L A; de Almeida Souza, J A; Machado, A

1976-10-01

Two cases of left ventricular aneurysm, a 16-year-old black boy and a 23-year-old white girl, from Bahia, Brazil, are presented. In both patients there was enlargement of the cardiac silhouette and a prominent bulge of the left inferior border. On the right oblique view a ring of calcium at the ventricular opening of the aneurysms was visualized. A left ventriculogram showed a huge aneurysm in the first case and a bulge on the lateral wall of the left ventricle in the other. Cardiac catheterization showed a rise in left and right ventricular end-diastolic pressures and in the mean pulmonary artery pressure. In the first case the contour of the right ventricular pressure curve showed a restrictive pattern. The similarities of these aneurysms with the annular submitral type described in young black Africans are stressed.

Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction.

PubMed

Bybee, Kevin A; Kara, Tomas; Prasad, Abhiram; Lerman, Amir; Barsness, Greg W; Wright, R Scott; Rihal, Charanjit S

2004-12-07

The transient left ventricular apical ballooning syndrome, also known as takotsubo cardiomyopathy, is characterized by transient wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. In this paper, we review case series that report on patients with the transient left ventricular apical ballooning syndrome to better characterize patients presenting with the syndrome. We identified 7 case series that reported on at least 5 consecutive patients with the transient left ventricular apical ballooning syndrome. The syndrome more often affects postmenopausal women (82% to 100%) (mean age, 62 to 75 years). Patients commonly present with ST-segment elevation in the precordial leads, chest pain, relatively minor elevation of cardiac enzyme and biomarker levels, and transient apical systolic left ventricular dysfunction despite the absence of obstructive epicardial coronary disease. An episode of emotional or physiologic stress frequently precedes presentation with the syndrome. The in-hospital mortality rate seems to be low, as does the risk for recurrence.

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction

PubMed Central

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

Objective: To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. Background: QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. Material and methods: We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X2 test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. Results: QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function, (Chi-square: 16.77, P<0.0001). A prolonged QTc dispersion, was found in 40.6% of patients, in diabetic group with subclinical left ventricular diastolic dysfunction vs. 20% of patients in diabetic group with normal left ventricular diastolic function Chi-square: 14.11, P<0.0002). A prolonged dispersion of Tpeak-Tend interval was found in 24% of patients in diabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function (Chi-square: 12.00, P<0.005). Females in diabetic group with subclinical left ventricular diastolic dysfunction in comparison with males in diabetic group with subclinical left ventricular diastolic dysfunction, have a significantly prolonged: mean QTc max. interval (23.3% vs. 10%, Chisquare: 12.0, P<0.005), mean QTc dispersion (27.3% vs. 13.3%, Chi-square: 10.24, P<0.001), mean Tpeak-Tend interval (10% vs. 3.3%, Chi-square: 5.77, P<0.01), mean Tpek-Tend dispersion (16.6% vs. 6.6%, Chi-square: 8.39, P<0.003). Conclusion: The present study has shown that influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization. PMID:26550530

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction.

PubMed

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X(2) test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function, (Chi-square: 16.77, P<0.0001). A prolonged QTc dispersion, was found in 40.6% of patients, in diabetic group with subclinical left ventricular diastolic dysfunction vs. 20% of patients in diabetic group with normal left ventricular diastolic function Chi-square: 14.11, P<0.0002). A prolonged dispersion of Tpeak-Tend interval was found in 24% of patients in diabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function (Chi-square: 12.00, P<0.005). Females in diabetic group with subclinical left ventricular diastolic dysfunction in comparison with males in diabetic group with subclinical left ventricular diastolic dysfunction, have a significantly prolonged: mean QTc max. interval (23.3% vs. 10%, Chisquare: 12.0, P<0.005), mean QTc dispersion (27.3% vs. 13.3%, Chi-square: 10.24, P<0.001), mean Tpeak-Tend interval (10% vs. 3.3%, Chi-square: 5.77, P<0.01), mean Tpek-Tend dispersion (16.6% vs. 6.6%, Chi-square: 8.39, P<0.003). The present study has shown that influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization.

Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction

PubMed Central

Russell, Richard O.; Rackley, Charles E.; Pombo, Jaoquin; Hunt, David; Potanin, Constantine; Dodge, Harold T.

1970-01-01

Left ventricular performance in 19 patients with acute myocardial infarction has been evaluated by measuring left ventricular response in terms of cardiac output, stroke volume, work, and power to progressive elevation of filling pressure accomplished by progressive expansion of blood volume with rapid infusion of low molecular weight dextran. Such infusion can elevate the cardiac output, stroke volume, work, and power and thus delineate the function of the left ventricle by Frank-Starling function curves. Left ventricular filling pressure in the range of 20-24 mm Hg was associated with the peak of the curves and when the filling pressure exceeded this range, the curves became flattened or decreased. An increase in cardiac output could be maintained for 4 or more hr. Patients with a flattened function curve had a high mortality in the ensuing 8 wk. The function curve showed improvement in myocardial function during the early convalescence. When left ventricular filling pressure is monitored directly or as pulmonary artery end-diastolic pressure, low molecular weight dextran provides a method for assessment of left ventricular function. Images PMID:5431663

The left ventricle in aortic stenosis--imaging assessment and clinical implications.

PubMed

Călin, Andreea; Roşca, Monica; Beladan, Carmen Cristiana; Enache, Roxana; Mateescu, Anca Doina; Ginghină, Carmen; Popescu, Bogdan Alexandru

2015-04-29

Aortic stenosis has an increasing prevalence in the context of aging population. In these patients non-invasive imaging allows not only the grading of valve stenosis severity, but also the assessment of left ventricular function. These two goals play a key role in clinical decision-making. Although left ventricular ejection fraction is currently the only left ventricular function parameter that guides intervention, current imaging techniques are able to detect early changes in LV structure and function even in asymptomatic patients with significant aortic stenosis and preserved ejection fraction. Moreover, new imaging parameters emerged as predictors of disease progression in patients with aortic stenosis. Although proper standardization and confirmatory data from large prospective studies are needed, these novel parameters have the potential of becoming useful tools in guiding intervention in asymptomatic patients with aortic stenosis and stratify risk in symptomatic patients undergoing aortic valve replacement.This review focuses on the mechanisms of transition from compensatory left ventricular hypertrophy to left ventricular dysfunction and heart failure in aortic stenosis and the role of non-invasive imaging assessment of the left ventricular geometry and function in these patients.

Three-dimensional echocardiographic measurements using automated quantification software for big data processing.

PubMed

Feng, Cheng; Chen, Lixin; Li, Jian; Wang, Jiangtao; Dong, Fajin; Xu, Jinfeng

2017-01-01

To compare a full-automated software to quantify 3D transthoracic echocardiography namely, 3DE-HM (three-dimensional echocardiography HeartModel, Philips Healthcare) with the traditional manual quantitative method (3DE-manual) for assessing volumes of left atrial and ventricular volumes, and left ventricular ejection fraction (LVEF). 3D full volume images acquired from 156 subjects were collected and divided into 3 groups, which include 70 normal control cases (Group A), 17 patients with left ventricular remodeling after acute myocardial infarction (AMI) (Group B), and 69 patients with left atrial remodeling secondary to hypertension (Group C). The 3DE-HM method was used to quantify left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial end-systolic volume (LAESV), and left ventricular ejection fraction (LVEF), respectively. The results were compared with those obtained with the 3DE-manual method for correlation and consistency analyses. The reproducibility of the 3DE-HM method was also evaluated. There was a high correlation between LVEDV, LVESV, LAESV and LVEF values obtained with the 3DE-HM method and those obtained using the 3DE-manual method (r = 0.72 to 0.97). The correlation was strongest for Group B, patients with left ventricular remodeling post-AMI also demonstrated the greatest degree of morphologic changes. There was a significant difference in all parameters measured with the 3DE-HM method in different groups (P < 0.05). The difference in the measurements of LVEDV and LVESV between the two methods was greatest in patients in Group B compared with patients with hypertension-induced left ventricular remodeling (Group C) and in normal controls (Group A) (P < 0.05). Lastly, the difference in the measurement of LAESV between the two methods was greater in patients with hypertension-induced left ventricular remodeling (Group C) than that in the control group (Group A) (P < 0.05). The post-processing time of the 3DE-HM data was significantly shorter than that using the 3DE-manual method (P < 0.05). There was no significant variability in repeated measurements at different time points using the 3DE-HM method either between subjects in different groups or within the same subject. 3DE-HM is a quick and feasible method for left ventricular quantification and is clinically applicable for evaluating patients with left atrial and left ventricular remodeling.

Left ventricular mass, blood pressure, and lowered cognitive performance in the Framingham offspring.

PubMed

Elias, Merrill F; Sullivan, Lisa M; Elias, Penelope K; D'Agostino, Ralph B; Wolf, Philip A; Seshadri, Sudha; Au, Rhoda; Benjamin, Emelia J; Vasan, Ramachandran S

2007-03-01

The purpose of this study was to determine whether echocardiographic left ventricular mass is related to cognitive performance beyond casual blood pressure adjusting for the influence of other vascular risk factors. We used multivariable regression analyses to relate left ventricular mass assessed at a routine examination (1995-1998) to measures of cognitive ability obtained routinely (1998-2001) in 1673 Framingham Offspring Study participants (56% women; mean age: 57 years) free from stroke, transient ischemic attack, and dementia. We adjusted for the following covariates hierarchically: (1) age, education, sex, body weight, height, interval between left ventricular mass measurement and neuropsychological testing (basic model); (2) basic model+blood pressure+treatment for hypertension; and (3) basic model+blood pressure+treatment for hypertension+vascular risk factors and prevalent cardiovascular disease. For the basic model, left ventricular mass was inversely associated with abstract reasoning (similarities), visual-spatial memory and organization, and verbal memory. For the basic model+blood pressure+treatment for hypertension, left ventricular mass was inversely associated with similarities and visual-spatial memory and organization. For the basic+blood pressure+treatment for hypertension+risk factors+cardiovascular disease model, no significant associations were observed. Echocardiographic left ventricular mass is associated with cognitive performance beyond casual and time-averaged systolic blood pressure, but this association is attenuated and rendered nonsignificant with additional adjustment for cardiovascular risk factors and cardiovascular disease, thus suggesting that these variables play an important role in mediating the association between left ventricular mass and cognition.

N-terminal pro B-type natriuretic peptide predicts mortality in patients with left ventricular hypertrophy.

PubMed

Garcia, Santiago; Akbar, Muhammad S; Ali, Syed S; Kamdar, Forum; Tsai, Michael Y; Duprez, Daniel A

2010-09-03

Left ventricular hypertrophy adversely affects outcomes in patients with hypertension. Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) adds incremental prognostic information in patients with hypertension and left ventricular hypertrophy (LVH) is not well established. We aimed to study the prognostic value of NT-proBNP in hypertensive patients with LVH. Echocardiography was performed in 232 patients (mean age 61±15, 102 males, 130 females) for the diagnosis of left ventricular hypertrophy. Left ventricular mass was measured according to The American Society of Echocardiography guidelines. A blood sample was taken for NT-proBNP determination. NT-proBNP levels were analyzed in quartiles after log transformation. Long term survival was established by review of electronic medical records. Arterial hypertension was present in 130 patients (56%) and left ventricular hypertrophy was present in 105 patients (45%). In patients with left ventricular hypertrophy, NT-proBNP levels predicted long term survival (Chi-square=10, p=0.01). After adjusting by age, presence of coronary artery disease, ejection fraction, diabetes status, and hypertension; patients in highest NT pro-BNP quartile were twice as likely to die when compared to patients in the lowest NT-ptoBNP quartile (OR=2.2, 95% CI=1.0-4.6, p=0.03). NT-proBNP is an independent predictor of survival in patients with hypertension and increased left ventricular mass. Copyright © 2009 Elsevier B.V. All rights reserved.

Metaiodobenzylguanidine (/sup 131/I) scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabinovitch, M.A.; Rose, C.P.; Rouleau, J.L.

1987-12-01

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine (/sup 131/I) to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine (/sup 131/I) and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4more » hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine (/sup 131/I) scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine (/sup 123/I) scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.« less

Effect of left ventricular diastolic dysfunction on left atrial appendage function and thrombotic potential in nonvalvular atrial fibrillation.

PubMed

Demirçelik, Muhammed Bora; Çetin, Mustafa; Çiçekcioğlu, Hülya; Uçar, Özgül; Duran, Mustafa

2014-05-01

We aimed to investigate effects of left ventricular diastolic dysfunction on left atrial appendage functions, spontaneous echo contrast and thrombus formation in patients with nonvalvular atrial fibrillation. In 58 patients with chronic nonvalvular atrial fibrilation and preserved left ventricular systolic function, left atrial appendage functions, left atrial spontaneous echo contrast grading and left ventricular diastolic functions were evaluated using transthoracic and transoesophageal echocardiogram. Patients divided in two groups: Group D (n=30): Patients with diastolic dysfunction, Group N (n=28): Patients without diastolic dysfunction. Categorical variables in two groups were evaluated with Pearson's chi-square or Fisher's exact test. The significance of the lineer correlation between the degree of spontaneous echo contrast (SEC) and clinical measurements was evaluated with Spearman's correlation analysis. Peak pulmonary vein D velocity of the Group D was significantly higher than the Group N (p=0.006). However, left atrial appendage emptying velocity, left atrial appendage lateral wall velocity, peak pulmonary vein S, pulmonary vein S/D ratio were found to be significantly lower in Group D (p=0.028, p<0.001, p<0.001; p<0.001). Statistically significant negative correlation was found between SEC in left atrium and left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities respectively (r=-0.438, r=-0.328, r=-0.233, r=-0.447). Left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities were significantly lower in SEC 2-3-4 than SEC 1 (p=0.003, p=0.029, p<0.001, p=0.002). In patients with nonvalvular atrial fibrillation and preserved left ventricular ejection fraction, left atrial appendage functions are decreased in patients with left ventricular diastolic dysfunction. Left ventricular diastolic dysfunction may constitute a potential risk for formation of thrombus and stroke.

Minimally invasive surgical implantation of left ventricular epicardial leads for ventricular resynchronization using video-assisted thoracoscopy.

PubMed

Fernández, Angel L; García-Bengochea, José B; Ledo, Ramiro; Vega, Marino; Amaro, Antonio; Alvarez, Julián; Rubio, José; Sierra, Juan; Sánchez, Daniel

2004-04-01

Cardiac resynchronization via left ventricular or biventricular pacing is an option for selected patients with ventricular systolic dysfunction and widened QRS complex. Stimulation through a coronary vein is the technique of choice for left ventricular pacing, but this approach results in a failure rate of approximately 8%. We describe our initial experience with minimally invasive surgical implantation of left ventricular epicardial leads using video-assisted thoracoscopy. A total of 14 patients with congestive heart failure, NYHA functional class 3.2 (0.6) and mean ejection fraction 22.9 (6.8)% were included in this study. Left bundle branch block, QRS complex >140 ms and abnormal septal motion were observed in all cases. Epicardial leads were implanted on the left ventricular free wall under general anesthesia using video-assisted thoracoscopic surgery. Lead implantation was successful in 13 patients. Conversion to a small thoracotomy was necessary in one patient. All patients were extubated in the operating room. None of the patients died during their hospital stay. Follow-up showed reversal of ventricular asynchrony and significant improvement in ejection fraction and functional class. Minimally invasive surgery for ventricular resynchronization using video-assisted thoracoscopy in selected patients is a safe procedure that makes it possible to choose the best site for lead implantation and provides adequate short- and medium-term stimulation.

Platelet counts on admission affect coronary flow, myocardial perfusion and left ventricular systolic function after primary percutaneous coronary intervention.

PubMed

Sharif, Dawod; Abu-Salem, Mira; Sharif-Rasslan, Amal; Rosenschein, Uri

2017-10-01

Patients with acute ST-elevation myocardial infarction (STEMI) and increased platelet count treated by fibrinolysis have worse outcomes. The aim of this study was to test the hypothesis that platelet blood count at admission in patients with acute STEMI treated by primary percutaneous coronary intervention affects coronary flow, myocardial perfusion and recovery of left ventricular systolic function. A total of 174 patients presenting with acute anterior STEMI and treated with primary percutaneous coronary intervention were included and divided into subgroups of admission platelet blood count of <200 K, 200-300 K, 300-400 K and >400 K. Evaluation of coronary artery flow and myocardial blush grade was performed according to the TIMI criteria. Electrocardiographic ST elevation resolution post-primary percutaneous coronary intervention was evaluated. Doppler echocardiographic evaluation of left anterior descending coronary artery velocities early and late after primary percutaneous coronary intervention and assessment of left ventricular ejection fraction and wall motion score index (WMSI) of left ventricular and left anterior descending coronary artery territory were performed. Post-primary percutaneous coronary intervention TIMI, myocardial blush grade and ST elevation resolution were similar in all groups. Patients with platelet counts <200 K had higher peak diastolic left anterior descending coronary artery velocity both early and late after primary percutaneous coronary intervention, and higher prevalence of left anterior descending coronary artery velocity deceleration time exceeding 600 ms, (45.5% vs. 40%, P<0.05). Patients with platelet counts >400 K presented with worse left ventricular ejection fraction, left ventricular WMSI and left anterior descending coronary artery WMSI, and before discharge this subgroup had worse left ventricular WMSI and left anterior descending coronary artery WMSI, P<0.01. Patients with anterior STEMI treated by primary percutaneous coronary intervention with lower admission platelet count had higher left anterior descending coronary artery diastolic velocities, better myocardial perfusion with more patients having left anterior descending coronary artery-descending coronary artery velocity deceleration time >600 ms. Patients with higher platelet counts had lower left ventricular systolic function both at admission and before discharge.

Investigating the Role of Interventricular Interdependence in Development of Right Heart Dysfunction During LVAD Support: A Patient-Specific Methods-Based Approach.

PubMed

Sack, Kevin L; Dabiri, Yaghoub; Franz, Thomas; Solomon, Scott D; Burkhoff, Daniel; Guccione, Julius M

2018-01-01

Predictive computation models offer the potential to uncover the mechanisms of treatments whose actions cannot be easily determined by experimental or imaging techniques. This is particularly relevant for investigating left ventricular mechanical assistance, a therapy for end-stage heart failure, which is increasingly used as more than just a bridge-to-transplant therapy. The high incidence of right ventricular failure following left ventricular assistance reflects an undesired consequence of treatment, which has been hypothesized to be related to the mechanical interdependence between the two ventricles. To investigate the implication of this interdependence specifically in the setting of left ventricular assistance device (LVAD) support, we introduce a patient-specific finite-element model of dilated chronic heart failure. The model geometry and material parameters were calibrated using patient-specific clinical data, producing a mechanical surrogate of the failing in vivo heart that models its dynamic strain and stress throughout the cardiac cycle. The model of the heart was coupled to lumped-parameter circulatory systems to simulate realistic ventricular loading conditions. Finally, the impact of ventricular assistance was investigated by incorporating a pump with pressure-flow characteristics of an LVAD (HeartMate II™ operating between 8 and 12 k RPM) in parallel to the left ventricle. This allowed us to investigate the mechanical impact of acute left ventricular assistance at multiple operating-speeds on right ventricular mechanics and septal wall motion. Our findings show that left ventricular assistance reduces myofiber stress in the left ventricle and, to a lesser extent, right ventricle free wall, while increasing leftward septal-shift with increased operating-speeds. These effects were achieved with secondary, potentially negative effects on the interventricular septum which showed that support from LVADs, introduces unnatural bending of the septum and with it, increased localized stress regions. Left ventricular assistance unloads the left ventricle significantly and shifts the right ventricular pressure-volume-loop toward larger volumes and higher pressures; a consequence of left-to-right ventricular interactions and a leftward septal shift. The methods and results described in the present study are a meaningful advancement of computational efforts to investigate heart-failure therapies in silico and illustrate the potential of computational models to aid understanding of complex mechanical and hemodynamic effects of new therapies.

Ethical challenges with the left ventricular assist device as a destination therapy

PubMed Central

Rizzieri, Aaron G; Verheijde, Joseph L; Rady, Mohamed Y; McGregor, Joan L

2008-01-01

The left ventricular assist device was originally designed to be surgically implanted as a bridge to transplantation for patients with chronic end-stage heart failure. On the basis of the REMATCH trial, the US Food and Drug Administration and the US Centers for Medicare & Medicaid Services approved permanent implantation of the left ventricular assist device as a destination therapy in Medicare beneficiaries who are not candidates for heart transplantation. The use of the left ventricular assist device as a destination therapy raises certain ethical challenges. Left ventricular assist devices can prolong the survival of average recipients compared with optimal medical management of chronic end-stage heart failure. However, the overall quality of life can be adversely affected in some recipients because of serious infections, neurologic complications, and device malfunction. Left ventricular assist devices alter end-of-life trajectories. The caregivers of recipients may experience significant burden (e.g., poor physical health, depression, anxiety, and posttraumatic stress disorder) from destination therapy with left ventricular assist devices. There are also social and financial ramifications for recipients and their families. We advocate early utilization of a palliative care approach and outline prerequisite conditions so that consenting for the use of a left ventricular assist device as a destination therapy is a well informed process. These conditions include: (1) direct participation of a multidisciplinary care team, including palliative care specialists, (2) a concise plan of care for anticipated device-related complications, (3) careful surveillance and counseling for caregiver burden, (4) advance-care planning for anticipated end-of-life trajectories and timing of device deactivation, and (5) a plan to address the long-term financial burden on patients, families, and caregivers. Short-term mechanical circulatory devices (e.g. percutaneous cardiopulmonary bypass, percutaneous ventricular assist devices, etc.) can be initiated in emergency situations as a bridge to permanent implantation of ventricular assist devices in chronic end-stage heart failure. In the absence of first-person (patient) consent, presumed consent or surrogate consent should be used cautiously for the initiation of short-term mechanical circulatory devices in emergency situations as a bridge to permanent implantation of left ventricular assist devices. Future clinical studies of destination therapy with left ventricular assist devices should include measures of recipients' quality of end-of-life care and caregivers' burden. PMID:18694496

Bacopa monnieri extract increases rat coronary flow and protects against myocardial ischemia/reperfusion injury.

PubMed

Srimachai, Sirintorn; Devaux, Sylvie; Demougeot, Celine; Kumphune, Sarawut; Ullrich, Nina D; Niggli, Ernst; Ingkaninan, Kornkanok; Kamkaew, Natakorn; Scholfield, C Norman; Tapechum, Sompol; Chootip, Krongkarn

2017-02-20

This study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points. In normal isolated rat hearts, coronary flow, left ventricular developed pressure, heart rate, and functional recovery were measured using the Langendorff preparation. Hearts were perfused with either (i) Krebs-Henseleit (normal) solution, (control), or with 30, 100 μg/ml B. monnieri ethanolic extract (30 min), or (ii) with normal solution or extract for 10 min preceding no-perfusion ischemia (30 min) followed by reperfusion (30 min) with normal solution. Infarct volumes were measured by triphenyltetrazolium staining. L-type Ca 2+ -currents (I Ca, L ) were measured by whole-cell patching in HL-1 cells, a mouse atrial cardiomyocyte cell line. Cytotoxicity of B. monnieri was assessed in rat isolated ventricular myocytes by trypan blue exclusion. In normally perfused hearts, B. monnieri increased coronary flow by 63 ± 13% (30 μg/ml) and 216 ± 21% (100 μg/ml), compared to control (5 ± 3%) (n = 8-10, p < 0.001). B. monnieri treatment preceding ischemia/reperfusion improved left ventricular developed pressure by 84 ± 10% (30 μg/ml), 82 ± 10% (100 μg/ml) and 52 ± 6% (control) compared to pre- ischemia/reperfusion. Similarly, functional recovery showed a sustained increase. Moreover, B. monnieri (100 μg/ml) reduced the percentage of infarct size from 51 ± 2% (control) to 25 ± 2% (n = 6-8, p < 0.0001). B. monnieri (100 μg/ml) reduced I Ca, L by 63 ± 4% in HL-1 cells. Ventricular myocyte survival decreased at higher concentrations (50-1000 μg/ml) B. monnieri. B. monnieri improves myocardial function following ischemia/reperfusion injury through recovery of coronary blood flow, contractile force and decrease in infarct size. Thus this may lead to a novel cardioprotectant strategy.

Structural Adaptation

ERIC Educational Resources Information Center

Crowley, Julianne; Titmus, Morgan

2016-01-01

This article explores an alternative conception held by high school and first-year university biology students regarding the structure of the left and right ventricles of the heart and the significance of the left ventricular wall being thicker than the right. The left ventricular wall of the heart is thicker than the right ventricular wall due to…

Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis.

PubMed

Patel, Keval; Griffing, George T; Hauptman, Paul J; Stolker, Joshua M

2016-04-01

Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy.

Diastolic dysfunction in hypertension.

PubMed

Nazário Leão, R; Marques da Silva, P

Hypertension and coronary heart disease, often coexisting, are the most common risk factors for heart failure. The progression of hypertensive heart disease involves myocardial fibrosis and alterations in the left ventricular geometry that precede the functional change, initially asymptomatic. The left ventricular diastolic dysfunction is part of this continuum being defined by the presence of left ventricular diastolic dysfunction without signs or symptoms of heart failure or poor left ventricular systolic function. It is highly prevalent in hypertensive patients and is associated with increased cardiovascular morbidity and mortality. Despite its growing importance in clinical practice it remains poorly understood. This review aims to present the epidemiological fundamentals and the latest developments in the pathophysiology, diagnosis and treatment of left ventricular diastolic dysfunction. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy.

PubMed

Liu, Dan; Hu, Kai; Nordbeck, Peter; Ertl, Georg; Störk, Stefan; Weidemann, Frank

2016-05-10

Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull's eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull's eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull's eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull's eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy.

[Echocardiographic characteristics of the left heart ventricle in people with different somatotypes].

PubMed

Seebaluck, Sh; Babaev, M V; Kondrashev, A V

2003-01-01

The objective of this study was to analyze echocardiographic parameters in 143 healthy individuals aged 18-21 years with different somatotypes. The evaluation of somatotype was performed using the the method of R.N. Dorokhov and V.G. Petrukhin (1989). During the echocardiography, left ventricular wall thickness, internal diameter and myocardial mass were measured. The investigation showed marked sex- and somatotype-related differences in left ventricular parameters. The correlations between the studied left ventricular parameters and body mass, length and surface area were demonstrated. The optimal method of the indexation of left ventricular myocardial mass as related to (body length)3, is described.

Echocardiographic features of impaired left ventricular diastolic function in Chagas's heart disease.

PubMed Central

Combellas, I; Puigbo, J J; Acquatella, H; Tortoledo, F; Gomez, J R

1985-01-01

To study left ventricular diastolic function in Chagas's disease, simultaneous echocardiograms, phonocardiograms, and apexcardiograms were recorded in 20 asymptomatic patients with positive Chagas's serology and no signs of heart disease (group 1), 12 with Chagas's heart disease and symptoms of ventricular arrhythmia but no heart failure (group 2), 20 normal subjects (group 3), and 12 patients with left ventricular hypertrophy (group 4). The recordings were digitised to determine left ventricular isovolumic relaxation time and the rate and duration of left ventricular cavity dimension increase and wall thinning. In groups 1 and 2 (a) aortic valve closure (A2) and mitral valve opening were significantly delayed relative to minimum dimension and were associated with prolonged isovolumic relaxation, (b) left ventricular cavity size was abnormally increased during isovolumic relaxation and abnormally reduced during isovolumic contraction, and (c) peak rate of posterior wall thinning and dimension increase were significantly reduced and duration of posterior wall thinning was significantly prolonged; both of these abnormalities occurred at the onset of diastolic filling. These abnormalities were more pronounced in group 2 and were accompanied by an increase in the height of the apexcardiogram "a" wave, an indication of pronounced atrial systole secondary to end diastolic filling impairment due to reduced left ventricular distensibility. Group 4, which had an established pattern of diastolic abnormalities, showed changes similar to those in group 2; however, the delay in aortic valve closure (A2) and in mitral valve opening and the degree of dimension change were greater in the latter group. Thus early isovolumic relaxation and left ventricular abnormalities were pronounced in the patients with Chagas's heart disease and may precede systolic compromise, which may become apparent in later stages of the disease. The digitised method is valuable in the early detection of myocardial damage. Images PMID:3155954

Left ventricular dysfunction after closure of large patent ductus arteriosus.

PubMed

Galal, M Omar; Amin, Mohamed; Hussein, Arif; Kouatli, Amjad; Al-Ata, Jameel; Jamjoom, Ahmed

2005-03-01

Changes in left ventricular dimensions and performance were studied in 43 patients after transcatheter occlusion or surgical ligation of patent ductus arteriosus. The patients were assigned to 2 groups based on their ductal diameter: >/= 3.1 mm to group A (n = 27) and

Mitral regurgitation: anatomy is destiny.

PubMed

Athanasuleas, Constantine L; Stanley, Alfred W H; Buckberg, Gerald D

2018-04-26

Mitral regurgitation (MR) occurs when any of the valve and ventricular mitral apparatus components are disturbed. As MR progresses, left ventricular remodelling occurs, ultimately causing heart failure when the enlarging left ventricle (LV) loses its conical shape and becomes globular. Heart failure and lethal ventricular arrhythmias may develop if the left ventricular end-systolic volume index exceeds 55 ml/m2. These adverse changes persist despite satisfactory correction of the annular component of MR. Our goal was to describe this process and summarize evolving interventions that reduce the volume of the left ventricle and rebuild its elliptical shape. This 'valve/ventricle' approach addresses the spherical ventricular culprit and offsets the limits of treating MR by correcting only its annular component.

Comparison of speckle-tracking echocardiography with invasive hemodynamics for the detection of characteristic cardiac dysfunction in type-1 and type-2 diabetic rat models.

PubMed

Mátyás, Csaba; Kovács, Attila; Németh, Balázs Tamás; Oláh, Attila; Braun, Szilveszter; Tokodi, Márton; Barta, Bálint András; Benke, Kálmán; Ruppert, Mihály; Lakatos, Bálint Károly; Merkely, Béla; Radovits, Tamás

2018-01-16

Measurement of systolic and diastolic function in animal models is challenging by conventional non-invasive methods. Therefore, we aimed at comparing speckle-tracking echocardiography (STE)-derived parameters to the indices of left ventricular (LV) pressure-volume (PV) analysis to detect cardiac dysfunction in rat models of type-1 (T1DM) and type-2 (T2DM) diabetes mellitus. Rat models of T1DM (induced by 60 mg/kg streptozotocin, n = 8) and T2DM (32-week-old Zucker Diabetic Fatty rats, n = 7) and corresponding control animals (n = 5 and n = 8, respectively) were compared. Echocardiography and LV PV analysis were performed. LV short-axis recordings were used for STE analysis. Global circumferential strain, peak strain rate values in systole (SrS), isovolumic relaxation (SrIVR) and early diastole (SrE) were measured. LV contractility, active relaxation and stiffness were measured by PV analysis. In T1DM, contractility and active relaxation were deteriorated to a greater extent compared to T2DM. In contrast, diastolic stiffness was impaired in T2DM. Correspondingly, STE described more severe systolic dysfunction in T1DM. Among diastolic STE parameters, SrIVR was more decreased in T1DM, however, SrE was more reduced in T2DM. In T1DM, SrS correlated with contractility, SrIVR with active relaxation, while in T2DM SrE was related to cardiac stiffness, cardiomyocyte diameter and fibrosis. Strain and strain rate parameters can be valuable and feasible measures to describe the dynamic changes in contractility, active relaxation and LV stiffness in animal models of T1DM and T2DM. STE corresponds to PV analysis and also correlates with markers of histological myocardial remodeling.

Glucose-6-phosphate dehydrogenase and NADPH redox regulates cardiac myocyte L-type calcium channel activity and myocardial contractile function.

PubMed

Rawat, Dhwajbahadur K; Hecker, Peter; Watanabe, Makino; Chettimada, Sukrutha; Levy, Richard J; Okada, Takao; Edwards, John G; Gupte, Sachin A

2012-01-01

We recently demonstrated that a 17-ketosteroid, epiandrosterone, attenuates L-type Ca(2+) currents (I(Ca-L)) in cardiac myocytes and inhibits myocardial contractility. Because 17-ketosteroids are known to inhibit glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, and to reduce intracellular NADPH levels, we hypothesized that inhibition of G6PD could be a novel signaling mechanism which inhibit I(Ca-L) and, therefore, cardiac contractile function. We tested this idea by examining myocardial function in isolated hearts and Ca(2+) channel activity in isolated cardiac myocytes. Myocardial function was tested in Langendorff perfused hearts and I(Ca-L) were recorded in the whole-cell patch configuration by applying double pulses from a holding potential of -80 mV and then normalized to the peak amplitudes of control currents. 6-Aminonicotinamide, a competitive inhibitor of G6PD, increased pCO(2) and decreased pH. Additionally, 6-aminonicotinamide inhibited G6PD activity, reduced NADPH levels, attenuated peak I(Ca-L) amplitudes, and decreased left ventricular developed pressure and ±dp/dt. Finally, dialyzing NADPH into cells from the patch pipette solution attenuated the suppression of I(Ca-L) by 6-aminonicotinamide. Likewise, in G6PD-deficient mice, G6PD insufficiency in the heart decreased GSH-to-GSSG ratio, superoxide, cholesterol and acetyl CoA. In these mice, M-mode echocardiographic findings showed increased diastolic volume and end-diastolic diameter without changes in the fraction shortening. Taken together, these findings suggest that inhibiting G6PD activity and reducing NADPH levels alters metabolism and leads to inhibition of L-type Ca(2+) channel activity. Notably, this pathway may be involved in modulating myocardial contractility under physiological and pathophysiological conditions during which the pentose phosphate pathway-derived NADPH redox is modulated (e.g., ischemia-reperfusion and heart failure).

Vascular dilation, tachycardia, and increased inotropy occur sequentially with increasing epinephrine dose rate, plasma and myocardial concentrations, and cAMP

PubMed Central

Maslov, Mikhail Y.; Wei, Abraham E.; Pezone, Matthew J.; Edelman, Elazer R.; Lovich, Mark A.

2015-01-01

Background While epinephrine infusion is widely used in critical care for inotropic support, there is no direct method to detect the onset and measure the magnitude of this response. We hypothesized that surrogate measurements, such as heart rate and vascular tone, may indicate if the plasma and tissue concentrations of epinephrine and cAMP are in a range sufficient to increase myocardial contractility. Methods Cardiovascular responses to epinephrine infusion (0.05–0.5 mcg·kg−1·min−1) were measured in rats using arterial and left ventricular catheters. Epinephrine and cAMP levels were measured using ELISA techniques. Results The lowest dose of epinephrine infusion (0.05 mcg·kg−1·min−1) did not raise plasma epinephrine level and did not lead to cardiovascular response. Incremental increase in epinephrine infusion (0.1 mcg·kg−1·min−1) elevated plasma but not myocardial epinephrine levels, providing vascular, but not cardiac effects. Further increase in the infusion rate (0.2 mcg·kg−1·min−1) raised myocardial tissue epinephrine levels sufficient to increase heart rate but not contractility. Inotropic and lusitropic effects were significant at the infusion rate of 0.3 mcg·kg−1·min−1. Correlation of plasma epinephrine to hemodynamic parameters suggest that as plasma concentration increases, systemic vascular resistance falls (EC50=47 pg/ml), then HR increases (ED50=168 pg/ml), followed by a rise in contractility and lusitropy (ED50=346 pg/ml and ED50=324 pg/ml accordingly). Conclusions The dose response of epinephrine is distinct for vascular tone, HR and contractility. The need for higher doses to see cardiac effects is likely due to the threshold for drug accumulation in tissue. Successful inotropic support with epinephrine cannot be achieved unless the infusion is sufficient to raise the heart rate. PMID:25790776

Right and Left Ventricular Function and Mass in Male Elite Master Athletes: A Controlled Contrast-Enhanced Cardiovascular Magnetic Resonance Study.

PubMed

Bohm, Philipp; Schneider, Günther; Linneweber, Lutz; Rentzsch, Axel; Krämer, Nadine; Abdul-Khaliq, Hashim; Kindermann, Wilfried; Meyer, Tim; Scharhag, Jürgen

2016-05-17

It is under debate whether the cumulative effects of intensive endurance exercise induce chronic cardiac damage, mainly involving the right heart. The aim of this study was to examine the cardiac structure and function in long-term elite master endurance athletes with special focus on the right ventricle by contrast-enhanced cardiovascular magnetic resonance. Thirty-three healthy white competitive elite male master endurance athletes (age range, 30-60 years) with a training history of 29±8 years, and 33 white control subjects pair-matched for age, height, and weight underwent cardiopulmonary exercise testing, echocardiography including tissue-Doppler imaging and speckle tracking, and cardiovascular magnetic resonance. Indexed left ventricular mass and right ventricular mass (left ventricular mass/body surface area, 96±13 and 62±10 g/m(2); P<0.001; right ventricular mass/body surface area, 36±7 and 24±5 g/m(2); P<0.001) and indexed left ventricular end-diastolic volume and right ventricular end-diastolic volume (left ventricular end-diastolic volume/body surface area, 104±13 and 69±18 mL/m(2); P<0.001; right ventricular end-diastolic volume/body surface area, 110±22 and 66±16 mL/m(2); P<0.001) were significantly increased in athletes in comparison with control subjects. Right ventricular ejection fraction did not differ between athletes and control subjects (52±8 and 54±6%; P=0.26). Pathological late enhancement was detected in 1 athlete. No correlations were found for left ventricular and right ventricular volumes and ejection fraction with N-terminal pro-brain natriuretic peptide, and high-sensitive troponin was negative in all subjects. Based on our results, chronic right ventricular damage in elite endurance master athletes with lifelong high training volumes seems to be unlikely. Thus, the hypothesis of an exercise-induced arrhythmogenic right ventricular cardiomyopathy has to be questioned. © 2016 American Heart Association, Inc.

Left ventricular pressure and volume data acquisition and analysis using LabVIEW.

PubMed

Cassidy, S C; Teitel, D F

1997-03-01

To automate analysis of left ventricular pressure-volume data, we used LabVIEW to create applications that digitize and display data recorded from conductance and manometric catheters. Applications separate data into cardiac cycles, calculate parallel conductance, and calculate indices of left ventricular function, including end-systolic elastance, preload-recruitable stroke work, stroke volume, ejection fraction, stroke work, maximum and minimum derivative of ventricular pressure, heart rate, indices of relaxation, peak filling rate, and ventricular chamber stiffness. Pressure-volume loops can be graphically displayed. These analyses are exported to a text-file. These applications have simplified and automated the process of evaluating ventricular function.

Echocardiographic diagnosis of left ventricular-right atrial communication (Gerbode-type defect) in an adult with chronic renal failure: a case report.

PubMed

Eroglu, Serpil; Sade, Elif; Bozbas, Huseyin; Pirat, Bahar; Yildirir, Aylin; Muderrisoglu, Haldun

2008-03-01

Left ventricular-right atrial communication, known as a Gerbode-type defect, is a rare form of ventricular septal defect. It is usually congenital, but rarely acquired. Clinical presentation is associated with the volume of the shunt. Transthoracic echocardiography is the most useful diagnostic method. We present a 63-year-old man with chronic renal failure and left ventricular-right atrial shunt.

High Serum Phosphorus Level Is Associated with Left Ventricular Diastolic Dysfunction in Peritoneal Dialysis Patients.

PubMed

Ye, Min; Tian, Na; Liu, Yanqiu; Li, Wei; Lin, Hong; Fan, Rui; Li, Cuiling; Liu, Donghong; Yao, Fengjuan

We initiated this study to explore the relationships of serum phosphorus level with left ventricular ultrasound features and diastolic function in peritoneal dialysis (PD) patients. 174 patients with end-stage renal disease (ESRD) receiving PD were enrolled in this retrospective observational study. Conventional echocardiography examination and tissue Doppler imaging (TDI) were performed in each patient. Clinical information and laboratory data were also collected. Analyses of echocardiographic features were performed according to phosphorus quartiles groups. And multivariate regression models were used to determine the association between serum phosphorus and Left ventricular diastolic dysfunction (LVDD). With the increase of serum phosphorus levels, patients on PD showed an increased tissue Doppler-derived E/e' ratio of lateral wall (P < 0.001), indicating a deterioration of left ventricular diastolic function. Steady growths of left atrium and left ventricular diameters as well as increase of left ventricular muscle mass were also observed across the increasing quartiles of phosphorus, while left ventricular ejection fraction remained normal. In a multivariate analysis, the regression coefficient for E/e' ratio in the highest phosphorus quartile was almost threefold higher relative to those in the lowest quartile group. And compared with patients in the lowest phosphorus quartile (<1.34 mmol/L) those in the highest phosphorus quartile (>1.95 mmol/L) had a more than fivefold increased odds of E/e' ratio >15. Our study showed an early impairment of left ventricular diastolic function in peritoneal dialysis patients. High serum phosphorus level was independently associated with greater risk of LVDD in these patients. Whether serum phosphorus will be a useful target for prevention or improvement of LVDD remains to be proved by further studies.

Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology.

PubMed

Vonk-Noordegraaf, Anton; Haddad, François; Chin, Kelly M; Forfia, Paul R; Kawut, Steven M; Lumens, Joost; Naeije, Robert; Newman, John; Oudiz, Ronald J; Provencher, Steve; Torbicki, Adam; Voelkel, Norbert F; Hassoun, Paul M

2013-12-24

Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Abnormal cardiac response to exercise in a murine model of familial hypertrophic cardiomyopathy.

PubMed

Nguyen, Lan; Chung, Jessica; Lam, Lien; Tsoutsman, Tatiana; Semsarian, Christopher

2007-07-10

Clinical outcome in familial hypertrophic cardiomyopathy (FHC) may be influenced by modifying factors such as exercise. Transgenic mice which overexpress the human disease-causing cTnI gene mutation, Gly203Ser (designated cTnI-G203S), develop all the characteristic phenotypic features of FHC. To study the modifying effect of exercise in early disease, mice underwent swimming exercise at an early age prior to the development of the FHC phenotype. In non-transgenic and cTnI-wt mice, swimming resulted in a significant increase in left ventricular wall thickness and contractility on echocardiography, consistent with a physiological hypertrophic response to exercise. In contrast, cTnI-G203S mice showed no increase in these parameters, indicating an abnormal response to exercise. The lack of a physiological response to exercise may indicate an important novel mechanistic insight into the role of exercise in triggering adverse events in FHC.

Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

PubMed Central

Elnakish, Mohammad T.; Ahmed, Amany A. E.; Mohler, Peter J.; Janssen, Paul M. L.

2015-01-01

Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models. PMID:26146529

Cardiovascular responses of women to lower body negative pressure

NASA Technical Reports Server (NTRS)

Frey, M. A. B.; Mathes, K. L.; Hoffler, G. W.

1986-01-01

The effects of lower body negative pressure (LBNP) on the cardiovascular response of 20 women between 23-43 years are evaluated. Calf circumference and cardiovascular data were recorded for women in the follicular and luteal phases of the menstrual cycle at -30, -40, and -50 mm Hg LBNP. The data reveal that the two menstrual phases did not cause differences in the way women respond to LBNP. It is observed that during LBNP calf circumference is enlarged; transthoracic impedance, and heart rate are increased; stroke volume, left ventricular ejection time, the Heather Index of contractility and systolic pressure, and cardiac output are reduced; and total peripheral resistance is elevated. The experimental data are compared to Montgomery et al. (1979). It is noted that the response of women to -50 mm Hg LBNP is similar to that of men; however, women adapt to stresses on the cardiovascular system with greater heart rate adjustments.

Physiological pump loading of isolated cardiac muscle.

PubMed

Paulus, W J; Claes, V A; Brutsaert, D L

1976-05-01

Cat papillary muscles were subjected to a continuously changing load, resulting from an analysis of the left ventricle as a muscle pump system. The papillary muscle was assumed to be part of a circumferential bundle of muscle fibers of a simplified ejecting ventricle. The load included the pressure--stress relationship of this ventricle and the peripheral vascular load with its inertial, resistive and capacitive components. When this loading function was imposed on a shortening muscle through an electronic feedback circuit, the time course of force development and the velocity versus force plots closely resembled data obtained in the intact heart. Analysis of mechanical work (delta 1 X f) and power (V X f) and their respective time course permitted distinction between changes of contractile performance due to (1) positive or negative inotropic interventions, (2) altered hypothetical ventricular dimensions and changed preload, and (3) the long-term load-dependent memory of cardiac muscle.

Development of a pump flow estimator for rotary blood pumps to enhance monitoring of ventricular function.

PubMed

Granegger, Marcus; Moscato, Francesco; Casas, Fernando; Wieselthaler, Georg; Schima, Heinrich

2012-08-01

Estimation of instantaneous flow in rotary blood pumps (RBPs) is important for monitoring the interaction between heart and pump and eventually the ventricular function. Our group has reported an algorithm to derive ventricular contractility based on the maximum time derivative (dQ/dt(max) as a substitute for ventricular dP/dt(max) ) and pulsatility of measured flow signals. However, in RBPs used clinically, flow is estimated with a bandwidth too low to determine dQ/dt(max) in the case of improving heart function. The aim of this study was to develop a flow estimator for a centrifugal pump with bandwidth sufficient to provide noninvasive cardiac diagnostics. The new estimator is based on both static and dynamic properties of the brushless DC motor. An in vitro setup was employed to identify the performance of pump and motor up to 20 Hz. The algorithm was validated using physiological ventricular and arterial pressure waveforms in a mock loop which simulated different contractilities (dP/dt(max) 600 to 2300 mm Hg/s), pump speeds (2 to 4 krpm), and fluid viscosities (2 to 4 mPa·s). The mathematically estimated pump flow data were then compared to the datasets measured in the mock loop for different variable combinations (flow ranging from 2.5 to 7 L/min, pulsatility from 3.5 to 6 L/min, dQ/dt(max) from 15 to 60 L/min/s). Transfer function analysis showed that the developed algorithm could estimate the flow waveform with a bandwidth up to 15 Hz (±2 dB). The mean difference between the estimated and measured average flows was +0.06 ± 0.31 L/min and for the flow pulsatilities -0.27 ± 0.2 L/min. Detection of dQ/dt(max) was possible up to a dP/dt(max) level of 2300 mm Hg/s. In conclusion, a flow estimator with sufficient frequency bandwidth and accuracy to allow determination of changes in ventricular contractility even in the case of improving heart function was developed. © 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Integration of mechanical, structural and electrical imaging to understand response to cardiac resynchronization therapy.

PubMed

Silva, Etelvino; Bijnens, Bart; Berruezo, Antonio; Mont, Lluis; Doltra, Adelina; Andreu, David; Brugada, Josep; Sitges, Marta

2014-10-01

There is extensive controversy exists on whether cardiac resynchronization therapy corrects electrical or mechanical asynchrony. The aim of this study was to determine if there is a correlation between electrical and mechanical sequences and if myocardial scar has any relevant impact. Six patients with normal left ventricular function and 12 patients with left ventricular dysfunction and left bundle branch block, treated with cardiac resynchronization therapy, were studied. Real-time three-dimensional echocardiography and electroanatomical mapping were performed in all patients and, where applicable, before and after therapy. Magnetic resonance was performed for evaluation of myocardial scar. Images were postprocessed and mechanical and electrical activation sequences were defined and time differences between the first and last ventricular segment to be activated were determined. Response to therapy was defined as a reduction in left ventricular end-systolic volume ≥ 15% after 12 months of follow-up. Good correlation between electrical and mechanical timings was found in patients with normal left ventricular function (r(2) = 0.88; P = .005) but not in those with left ventricular dysfunction (r(2) = 0.02; P = not significant). After therapy, both timings and sequences were modified and improved, except in those with myocardial scar. Despite a close electromechanical relationship in normal left ventricular function, there is no significant correlation in patients with dysfunction. Although resynchronization therapy improves this correlation, the changes in electrical activation may not yield similar changes in left ventricular mechanics particularly depending on the underlying myocardial substrate. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Dynamic Changes of QRS Morphology of Premature Ventricular Contractions During Ablation in the Right Ventricular Outflow Tract: A Case Report.

PubMed

Yue-Chun, Li; Jia-Feng, Lin; Jia-Xuan, Lin

2015-10-01

Electrocardiographic characteristics can be useful in differentiating between right ventricular outflow tract (RVOT) and aortic sinus cusp (ASC) ventricular arrhythmias. Ventricular arrhythmias originating from ASC, however, show preferential conduction to RVOT that may render the algorithms of electrocardiographic characteristics less reliable. Even though there are few reports describing ventricular arrhythmias with ASC origins and endocardial breakout sites of RVOT, progressive dynamic changes in QRS morphology of the ventricular arrhythmias during ablation obtained were rare.This case report describes a patient with symptomatic premature ventricular contractions of left ASC origin presenting an electrocardiogram (ECG) characteristic of right ventricular outflow tract before ablation. Pacing at right ventricular outflow tract reproduced an excellent pace map. When radiofrequency catheter ablation was applied to the right ventricular outflow tract, the QRS morphology of premature ventricular contractions progressively changed from ECG characteristics of right ventricular outflow tract origin to ECG characteristics of left ASC origin.Successful radiofrequency catheter ablation was achieved at the site of the earliest ventricular activation in the left ASC. The distance between the successful ablation site of the left ASC and the site with an excellent pace map of the RVOT was 20 mm.The ndings could be strong evidence for a preferential conduction via the myocardial bers from the ASC origin to the breakout site in the right ventricular outflow tract. This case demonstrates that ventricular arrhythmias with a single origin and exit shift may exhibit QRS morphology changes.

Matrix elasticity regulates the optimal cardiac myocyte shape for contractility

PubMed Central

McCain, Megan L.; Yuan, Hongyan; Pasqualini, Francesco S.; Campbell, Patrick H.

2014-01-01

Concentric hypertrophy is characterized by ventricular wall thickening, fibrosis, and decreased myocyte length-to-width aspect ratio. Ventricular thickening is considered compensatory because it reduces wall stress, but the functional consequences of cell shape remodeling in this pathological setting are unknown. We hypothesized that decreases in myocyte aspect ratio allow myocytes to maximize contractility when the extracellular matrix becomes stiffer due to conditions such as fibrosis. To test this, we engineered neonatal rat ventricular myocytes into rectangles mimicking the 2-D profiles of healthy and hypertrophied myocytes on hydrogels with moderate (13 kPa) and high (90 kPa) elastic moduli. Actin alignment was unaffected by matrix elasticity, but sarcomere content was typically higher on stiff gels. Microtubule polymerization was higher on stiff gels, implying increased intracellular elastic modulus. On moderate gels, myocytes with moderate aspect ratios (∼7:1) generated the most peak systolic work compared with other cell shapes. However, on stiffer gels, low aspect ratios (∼2:1) generated the most peak systolic work. To compare the relative contributions of intracellular vs. extracellular elasticity to contractility, we developed an analytical model and used our experimental data to fit unknown parameters. Our model predicted that matrix elasticity dominates over intracellular elasticity, suggesting that the extracellular matrix may potentially be a more effective therapeutic target than microtubules. Our data and model suggest that myocytes with lower aspect ratios have a functional advantage when the elasticity of the extracellular matrix decreases due to conditions such as fibrosis, highlighting the role of the extracellular matrix in cardiac disease. PMID:24682394

Congenital left ventricular outpouchings: a systematic review of 839 cases and introduction of a novel classification after two centuries.

PubMed

Malakan Rad, Elaheh; Awad, Sawsan; Hijazi, Ziyad M

2014-01-01

Congenital left ventricular outpouchings (LVOs) are reported under five overlapping and poorly defined terms including left ventricular accessory chamber, left ventricular aneurysm (LVA), left ventricular diverticulum (LVD), double-chambered LV, and accessory left ventricle. Diagnostic criteria are frequently mixed and not mutually exclusive. They convey no information regarding treatment strategy and prognosis. The aim of this systematic review is to provide a clear and inclusive classification, with therapeutic and prognostic implications, for congenital LVOs. We performed three separate sets of search on three subjects including "congenital left ventricular outpouchings," "important and simply measurable markers of left ventricular function," and "relationship of mechanics of intraventricular blood flow and optimal vortex formation in left ventricle and elliptical geometry of LV." We enrolled case series, review articles, and case reports with literature review. All types of acquired LVO's were excluded. We studied the abstracts of all searched articles. We focused on diagnostic criteria and patients' outcome. To examine the validity and reliability of the novel classification, fifteen previous studies were revisited using the novel classification. A total of 20 papers from 11 countries fulfilled our inclusion criteria. The age of patients ranged from prenatal age to geriatric age range. Diagnostic criteria were clearly stated only for two of the above five terms (i.e., congenital LVA and congenital LVD). Cases with mixed diagnostic criteria were frequent.Elliptical geometry of left ventricle was found to have significant impact on effective blood flow mechanics in LV. A simple inclusive classification for congenital LVOs, with therapeutic and prognostic implications, was introduced. The cornerstone of this classification is elliptical LV geometry. Large-type IIc LVO have dismal prognosis, if left untreated. LVO type I and small LVO type IIa have the best prognosis. © 2014 Wiley Periodicals, Inc.

Right ventricular stress-induced perfusion defects and late gadolinium enhancement in coronary artery disease.

PubMed

Milks, Michael Wesley; Upadhya, Bharathi; Hall, Michael E; Vasu, Sujethra; Hundley, William Gregory; Stacey, Richard Brandon

2015-01-01

The assessment of right ventricular (RV) perfusion defects has remained challenging during vasodilator stress perfusion with cardiovascular magnetic resonance (CMR). The significance of RV signal abnormalities during vasodilator stress perfusion and late gadolinium-enhanced CMR is yet uncertain. Among 61 individuals who underwent adenosine CMR stress testing before cardiac catheterization, we assessed the severity of coronary artery stenoses, mortality, the presence of stress and rest perfusion defects, as well as the presence of late gadolinium enhancement (LGE). Right ventricular stress-induced perfusion defects were positively associated with left anterior descending artery and proximal right coronary artery stenoses but were negatively associated with left circumflex artery stenoses. The presence of RVLGE was associated with mortality, but 77% of those with RVLGE also had left ventricular LGE. Proximal right coronary artery and left anterior descending artery stenoses are positively associated, whereas left circumflex artery stenoses are negatively associated with RV stress-induced perfusion defects. Right ventricular LGE was associated with mortality, but further study is needed to determine whether this is independent of left ventricular LGE.

Association between central sleep apnea and left ventricular structure: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Javaheri, Sogol; Sharma, Ravi K; Bluemke, David A; Redline, Susan

2017-08-01

We assessed whether the presence of central sleep apnea is associated with adverse left ventricular structural changes. We analysed 1412 participants from the Multi-Ethnic Study of Atherosclerosis who underwent both overnight polysomnography and cardiac magnetic resonance imaging. Subjects had been recruited 10 years earlier when free of cardiovascular disease. Our main exposure is the presence of central sleep apnea as defined by central apnea-hypopnea index = 5 or the presence of Cheyne-Stokes breathing. Outcome variables were left ventricular mass/height, left ventricular ejection fraction, and left ventricular mass/volume ratio. Multivariate linear regression models adjusted for age, gender, race, waist circumference, tobacco use, hypertension, and the obstructive apnea-hypopnea index were fit for the outcomes. Of the 1412 participants, 27 (2%) individuals had central sleep apnea. After adjusting for covariates, the presence of central sleep apnea was significantly associated with elevated left ventricular mass/volume ratio (β = 0.11 ± 0.04 g mL -1 , P = 0.0071), an adverse cardiac finding signifying concentric remodelling. © 2017 European Sleep Research Society.

[Blood pressure variability and left ventricular hypertrophy in arterial hypertension].

PubMed

Amodeo, C; Martins, S M; Silva Júnior, O; Barros, L M; Batlouni, M; Sousa, J E

1993-05-01

To evaluate the left ventricular hypertrophy correlation with blood pressure variability during day and night time as well as throughout the 24h period. Fifteen patients with mild to moderate essential hypertension underwent to bi-dimensional echocardiographic study and to 24h ambulatory blood pressure monitorization. Left ventricular mass was calculated according to previous validated formulas. The standard deviation of the mean blood pressures during day-time, night-time and 24h period was taken as blood pressure variability indices. The mean age of the group was 42 years old; 9 patients were male and all were white. This study showed that only the systolic and diastolic blood pressure variability during the 24h period correlated significantly with left ventricular mass, (r = 0.53 and p < 0.05; r = 0.58 and p < 0.05 respectively). There was no significant correlation of the day-time and night-time pressures variability with left ventricular mass. The systolic and diastolic blood pressure variability during the 24h period may be one of the many determinants of left ventricular hypertrophy in patients with mild to moderate hypertension.

Surgical myocardial revascularization in patients with reduced systolic left ventricular function.

PubMed

Bruno, Piergiorgio; Iafrancesco, Mauro; Massetti, Massimo

2018-04-20

Surgical myocardial revascularization in patients with reduced left ventricular function has been a matter of debate for decades. Recently published 10-years extension follow-up of the STICH trial have conclusively demonstrated benefit of surgical myocardial revascularization in patients with significant coronary artery disease and low left ventricular ejection fraction. However, selection of patients for surgery remains challenging as well as decision to perform percutaneous rather than surgical revascularization in this class of patients. New evidence helped to clarify the role of preoperative patients' characteristics as risk factors for surgery and to identify those patients who may benefit the most from surgery. Focus of this review is to review epidemiology, aetiology and pathophysiology of coronary artery disease in patients with reduced left ventricular function, role of viability and results of observational and investigational studies on revascularization in patients with reduced left ventricular function with a particular emphasis on relative indication of coronary artery bypass grafting and percutaneous coronary intervention and the surgical implications of development of ischemic mitral regurgitation or ischemic left ventricular aneurysm.

A novel combination technique of cold crystalloid perfusion but not cold storage facilitates transplantation of canine hearts donated after circulatory death.

PubMed

Rosenfeldt, Franklin; Ou, Ruchong; Salamonsen, Robert; Marasco, Silvana; Zimmet, Adam; Byrne, Joshua; Cosic, Filip; Saxena, Pankaj; Esmore, Donald

2016-11-01

Donation after circulatory death (DCD) represents a potential new source of hearts to increase the donor pool. We showed previously that DCD hearts in Greyhound dogs could be resuscitated and preserved by continuous cold crystalloid perfusion but not by cold static storage and could demonstrate excellent contractile and metabolic function on an in vitro system. In the current study, we demonstrate that resuscitated DCD hearts are transplantable. Donor Greyhound dogs (n = 12) were divided into perfusion (n = 8) and cold static storage (n = 4) groups. General anesthesia was induced and ventilation ceased for 30 minutes to achieve circulatory death. Donor cardiectomy was performed, and for 4 hours the heart was preserved by controlled reperfusion, followed by continuous cold perfusion with an oxygenated crystalloid perfusate or by static cold storage, after which orthotopic heart transplantation was performed. Recovery was assessed over 4 hours by hemodynamic monitoring. During cold perfusion, hearts showed continuous oxygen consumption and low lactate levels, indicating aerobic metabolism. The 8 dogs in the perfusion group were weaned off bypass, and 4 hours after bypass produced cardiac output of 4.73 ± 0.51 liters/min, left ventricular power of 7.63 ± 1.32 J/s, right ventricular power of 1.40 ± 0.43 J/s, and left ventricular fractional area shortening of 39.1% ± 5.2%, all comparable to pre-transplant values. In the cold storage group, 3 of 4 animals could not be weaned from cardiopulmonary bypass, and the fourth exhibited low-level function. Cold crystalloid perfusion, but not cold static storage, can resuscitate and preserve the DCD donor heart in a canine model of heart transplantation, thus rendering it transplantable. Controlled reperfusion and cold crystalloid perfusion have potential for clinical application in DCD transplantation. Copyright © 2016. Published by Elsevier Inc.

Pulsatile operation of a continuous-flow right ventricular assist device (RVAD) to improve vascular pulsatility

PubMed Central

Ng, Boon C.; Timms, Daniel; Cohn, William E.

2018-01-01

Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction. In addition, the performance of the speed modulation strategy has been assessed under different cardiovascular states, including variation in ventricular contractility and pulmonary arterial compliance. Our results indicated that the proposed pulse profile with optimised parameters (Apulse = 10000 rpm and ωmin = 3000 rpm) was able to generate pulmonary arterial pulse pressure within the physiological range (9–15 mmHg) while avoiding undesirable pump backflow under both co- and counter-pulsation modes. As compared to co-pulsation, stroke work was reduced by over 44% under counter-pulsation, suggesting that mechanical workload of the right ventricle can be efficiently mitigated through counter-pulsing the pump speed. Furthermore, our results showed that improved ventricular contractility could potentially lead to higher risk of ventricular suction and pump backflow, while stiffening of the pulmonary artery resulted in increased pulse pressure. In conclusion, the proposed speed modulation strategy produces pulsatile hemodynamics, which is more physiologic than continuous blood flow. The findings also provide valuable insight into the interaction between RVAD speed modulation and the pulmonary circulation under various cardiovascular states. PMID:29677212

Three-dimensional Speckle Tracking Echocardiography in Light Chain Cardiac Amyloidosis: Examination of Left and Right Ventricular Myocardial Mechanics Parameters.

PubMed

Urbano-Moral, Jose Angel; Gangadharamurthy, Dakshin; Comenzo, Raymond L; Pandian, Natesa G; Patel, Ayan R

2015-08-01

The study of myocardial mechanics has a potential role in the detection of cardiac involvement in patients with amyloidosis. This study aimed to characterize 3-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics in light chain amyloidosis and examine their relationship with brain natriuretic peptide. In patients with light chain amyloidosis, left ventricular longitudinal and circumferential strain (n=40), and right ventricular longitudinal strain and radial displacement (n=26) were obtained by 3-dimensional-speckle tracking echocardiography. Brain natriuretic peptide levels were determined. All myocardial mechanics measurements showed differences when compared by brain natriuretic peptide level tertiles. Left and right ventricular longitudinal strain were highly correlated (r=0.95, P<.001). Left ventricular longitudinal and circumferential strain were reduced in patients with cardiac involvement (-9±4 vs -16±2; P<.001, and -24±6 vs -29±4; P=.01, respectively), with the most prominent impairment at the basal segments. Right ventricular longitudinal strain and radial displacement were diminished in patients with cardiac involvement (-9±3 vs -17±3; P<.001, and 2.7±0.8 vs 3.8±0.3; P=.002). On multivariate analysis, left ventricular longitudinal strain was associated with the presence of cardiac involvement (odds ratio = 1.6; 95% confidence interval, 1.04 to 2.37; P=.03) independent of the presence of brain natriuretic peptide and troponin I criteria for cardiac amyloidosis. Three-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics are increasingly altered as brain natriuretic peptide increases in light chain amyloidosis. There appears to be a strong association between left ventricular longitudinal strain and cardiac involvement, beyond biomarkers such as brain natriuretic peptide and troponin I. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Electrophysiological and mechanical effects of caffeic acid phenethyl ester, a novel cardioprotective agent with antiarrhythmic activity, in guinea-pig heart.

PubMed

Chang, Gwo-Jyh; Chang, Chi-Jen; Chen, Wei-Jan; Yeh, Yung-Hsin; Lee, Hsiao-Yu

2013-02-28

Caffeic acid phenethyl ester (CAPE) is an active component of propolis that exhibits cardioprotective and antiarrhythmic effects. The detailed mechanisms underlying these effects, however, are not entirely understood. The aim of this study was to elucidate the electromechanical effects of CAPE in guinea-pig cardiac preparations. Intracardiac electrograms, left ventricular (LV) pressure, and the anti-arrhythmic efficacy were determined using isolated hearts. Action potentials of papillary muscles were assessed with microelectrodes, Ca(2+) transients were measured by fluorescence, and ion fluxes were measured by patch-clamp techniques. In a perfused heart model, CAPE prolonged the atrio-ventricular conduction interval, the Wenckebach cycle length, and the refractory periods of the AV node and His-Purkinje system, while shortening the QT interval. CAPE reduced the occurrence of reperfusion-induced ventricular fibrillation and decreased LV pressure in isolated hearts. In papillary muscles, CAPE shortened the action potential duration and reduced both the maximum upstroke velocity and contractile force. In fura-2-loaded single ventricular myocytes, CAPE decreased cell shortening and the Ca(2+) transient amplitude. Patch-clamp experiments revealed that CAPE produced a use-dependent decrease in L-type Ca(2+) current (ICa,L) (IC50=1.1 μM) and Na(+) current (INa) (IC50=0.43 μM), caused a negative-shift of the voltage-dependent inactivation and a delay of recovery from inactivation. CAPE decreased the delayed outward K(+) current (IK) slightly, without affecting the inward rectifier K(+) current (IK1). These results suggest that the preferential inhibition of Ca(2+) inward and Na(+) inward currents by CAPE may induce major electromechanical alterations in guinea-pig cardiac preparations, which may underlie its antiarrhythmic action. Copyright © 2013 Elsevier B.V. All rights reserved.

[Evaluation of left ventricular diastolic function in canine acute myocardial ischemia using velocity vector imaging and quantitative tissue velocity imaging].

PubMed

Zhang, Chuan; Zha, Dao-Gang; DU, Rong-Sheng; Hu, Feng; Li, Sheng-Hui; Wu, Xiao-Yuan; Liu, Yi-Li

2009-07-01

To assess the value of velocity vector imaging (VVI) and quantitative tissue velocity imaging (QTVI) in assessing left ventricular diastolic function of the dogs with acute myocardial ischemia. Six healthy mongrel dogs were subjected to ligation of the left circumflex artery or left anterior descending artery to induce coronary artery stenosis of varying degrees. The mean peak diastolic velocity (Em) of the ventricular walls around the mitral annulus was recorded with VVI or QTVI in the coronary blood flow. The left ventricular end diastolic pressure (LVEDP) was measured with pigtail catheter in the left ventricle. As the coronary blood flow decreased, LVEDP was gradually increased, and Em measured by VVI or QTVI were also gradually decreased. A good linear correlation was shown between Em measured by VVI or QTVI and LVEDP (r=-0.834, P<0.001, and r=-0.68, P<0.001, respectively). A significant difference was observed in the correlation coefficient between VVI and QTVI (Z=2.625, P=0.0087). VVI and QTVI both provide good noninvasive means for measuring left ventricular diastolic function. VVI, a new echocardiographic modality without angular dependence, is better than QTVI in evaluating left ventricular diastolic function.

Cardioprotective effects of amlodipine on ischemia and reperfusion in two experimental models.

PubMed

Hoff, P T; Tamura, Y; Lucchesi, B R

1990-11-20

The cardioprotective effect of amlodipine, a long-acting dihydropyridine derivative, was studied in 2 experimental models of ischemia and reperfusion. Isolated and blood-perfused feline hearts were made globally ischemic for 60 minutes and then reperfused for 60 minutes. Alterations of left ventricular developed pressure and compliance were monitored in both amlodipine-treated hearts and saline-treated control animals. Changes in perfusion pressure indicated that amlodipine significantly reduced myocardial oxygen consumption and coronary vascular resistance. Furthermore, a progressive increase in resting left ventricular diastolic pressure indicated that amlodipine, administered before the onset of global ischemia, attenuated the development of ischemic contracture. Return of contractile function 60 minutes after reperfusion and maintenance of tissue concentrations of electrolytes were significantly better in the amlodipine-treated group than in the control animals. In intact canine hearts, regional myocardial ischemia was induced for 90 minutes, followed by 6 hours of reperfusion. Although the hemodynamic variables and the size of the region of risk did not differ significantly between treated animals and control animals, the infarct size was significantly smaller in the amlodipine-treated group than in the control animals, and a gradual reduction in coronary blood flow was observed in the control group that was prevented in the amlodipine group. A comparison of these findings with those observed with oxygen radical scavengers also is discussed. A detailed report of these studies was published in The American Journal of Cardiology (1989;64:101I-116I). This review is included here to maintain continuity of the symposium for the convenience of the reader.

Assessment of regional systolic and diastolic myocardial function using tissue Doppler and strain imaging in dogs with dilated cardiomyopathy.

PubMed

Chetboul, Valérie; Gouni, Vassiliki; Sampedrano, Carolina Carlos; Tissier, Renaud; Serres, François; Pouchelon, Jean-Louis

2007-01-01

Tissue Doppler Imaging (TDI) or strain (St) imaging could provide sensitive indices for early detection and treatment follow-up of canine dilated cardiomyopathy (DCM). Analysis of TDI and St features in dogs with overt DCM is a prerequisite before using these new criteria in prospective screenings of predisposed families or in clinical trials. Radial and longitudinal right and left myocardial motion, assessed by TDI and St variables, is altered in dogs with DCM. Case records for 26 dogs; 14 with DCM and 12 healthy controls of comparable age and weight were reviewed. A retrospective analysis was conducted of conventional echocardiography, 2-dimensional color TDI, and St imaging data. The DCM group was characterized by decreases in radial and longitudinal systolic velocity gradients of the left ventricular free wall (LVFW), radial and longitudinal absolute values of peak systolic St of the LVFW, and longitudinal systolic right ventricular (RV) velocities (all P < .001 versus control) associated with longitudinal postsystolic contraction waves in 7/14 dogs. Early diastolic LVFW velocities also were decreased for longitudinal (P < .01) and radial (P < .05) motions. All radial LVFW, longitudinal basal LVFW, and RV systolic velocities were negatively correlated with heart rate (P < .01). LV contractility along both the short and long axes is impaired in dogs with spontaneous DCM, as is systolic RV and diastolic LVFW function. These myocardial alterations are associated with an inverse force-frequency relationship. Studies now are needed to determine the comparative sensitivity of TDI and St variables for the early detection of canine DCM.

Ultrastructural changes in cardiac myocytes from Boxer dogs with arrhythmogenic right ventricular cardiomyopathy

PubMed Central

Oxford, Eva M.; Danko, Charles G.; Kornreich, Bruce G.; Maass, Karen; Hemsley, Shari A.; Raskolnikov, Dima; Fox, Philip R.; Delmar, Mario; Moïse, N. Sydney

2011-01-01

Objectives We sought to quantify the number and length of desmosomes, gap junctions, and adherens junctions in arrhythmogenic right ventricular cardiomyopathy (ARVC) and non-ARVC dogs, and to determine if ultrastructural changes existed. Animals Hearts from 8 boxer dogs afflicted with histopathologically confirmed ARVC and 6 dogs without ARVC were studied. Methods Quantitative transmission electron microscopy (TEM) and Western blot semi-quantification of α-actinin were used to study the intercalated disc and sarcomere of the right and left ventricles. Results When ARVC dogs were compared to non-ARVC dogs reductions in the number of desmosomes (P = 0.04), adherens junctions (P = 0.04) and gap junctions (P = 0.02) were found. The number of gap junctions (P = 0.04) and adherens junctions (P = 0.04) also were reduced in the left ventricle, while the number of desmosomes was not (P = 0.88). A decrease in the length of desmosomal complexes within LV samples (P=0.04) was found. These findings suggested disruption of proteins providing attachment of the cytoskeleton to the intercalated disc. Immunoblotting did not demonstrate a quantitative reduction in the amount of α-actinin in ARVC afflicted samples. All boxers with ARVC demonstrated the presence of electron dense material originating from the Z band and extending into the sarcomere, apparently at the expense of the cytoskeletal structure. Conclusions These results emphasize the importance of structural integrity of the intercalated disc in the pathogenesis of ARVC. In addition, observed abnormalities in sarcomeric structure suggest a novel link between ARVC and the actin-myosin contractile apparatus. PMID:21636338

Myocyte repolarization modulates myocardial function in aging dogs

PubMed Central

Sorrentino, Andrea; Signore, Sergio; Borghetti, Giulia; Meo, Marianna; Cannata, Antonio; Zhou, Yu; Wybieralska, Ewa; Luciani, Marco; Kannappan, Ramaswamy; Zhang, Eric; Matsuda, Alex; Webster, Andrew; Cimini, Maria; Kertowidjojo, Elizabeth; D'Alessandro, David A.; Wunimenghe, Oriyanhan; Michler, Robert E.; Royer, Christopher; Goichberg, Polina; Leri, Annarosa; Barrett, Edward G.; Anversa, Piero; Hintze, Thomas H.

2016-01-01

Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions. PMID:26801307

Cardiovascular magnetic resonance of cardiac function and myocardial mass in preterm infants: a preliminary study of the impact of patent ductus arteriosus

PubMed Central

2014-01-01

Background Many pathologies seen in the preterm population are associated with abnormal blood supply, yet robust evaluation of preterm cardiac function is scarce and consequently normative ranges in this population are limited. The aim of this study was to quantify and validate left ventricular dimension and function in preterm infants using cardiovascular magnetic resonance (CMR). An initial investigation of the impact of the common congenital defect patent ductus arteriosus (PDA) was then carried out. Methods Steady State Free Procession short axis stacks were acquired. Normative ranges of left ventricular end diastolic volume (EDV), stroke volume (SV), left ventricular output (LVO), ejection fraction (EF), left ventricular (LV) mass, wall thickness and fractional thickening were determined in “healthy” (control) neonates. Left ventricular parameters were then investigated in PDA infants. Unpaired student t-tests compared the 2 groups. Multiple linear regression analysis assessed impact of shunt volume in PDA infants, p-value ≤ 0.05 being significant. Results 29 control infants median (range) corrected gestational age at scan 34+6(31+1-39+3) weeks were scanned. EDV, SV, LVO, LV mass normalized by weight and EF were shown to decrease with increasing corrected gestational age (cGA) in controls. In 16 PDA infants (cGA 30+3(27+3-36+1) weeks) left ventricular dimension and output were significantly increased, yet there was no significant difference in ejection fraction and fractional thickening between the two groups. A significant association between shunt volume and increased left ventricular mass correcting for postnatal age and corrected gestational age existed. Conclusion CMR assessment of left ventricular function has been validated in neonates, providing more robust normative ranges of left ventricular dimension and function in this population. Initial investigation of PDA infants would suggest that function is relatively maintained. PMID:25160730

Left ventricular hypertrophy diagnosed after a stroke: a case report.

PubMed

Umeojiako, Wilfred Ifeanyi; Kanyal, Ritesh

2018-03-22

Stroke is a recognized clinical course of hypertrophic cardiomyopathy. This interesting case showed notable difference on the electrocardiogram of a patient 4 months prior to suffering a stroke and 10 days after suffering a stroke. The pre-stroke electrocardiogram showed atrial fibrillation with a narrow QRS complex, while the post-stroke electrocardiogram showed marked left ventricular hypertrophy. Left ventricular hypertrophy was diagnosed using the Sokolow-Lyon indices. The development of left ventricular hypertrophy a few days after suffering a stroke has not previously been reported. An 83-year-old white British woman with a background history of permanent atrial fibrillation, hypertension, and previous stroke attended the emergency department with a 2-day history of exertional dyspnea, and chest tightness. On examination, she had bibasal crepitations with a systolic murmur loudest at the apex. In-patient investigations include an electrocardiogram, blood tests, chest X-ray, contrast echocardiogram, coronary angiogram, and cardiovascular magnetic resonance imaging. An electrocardiogram showed atrial fibrillation, with inferolateral T wave inversion, and left ventricular hypertrophy. A chest X-ray showed features consistent with pulmonary edema. A contrast echocardiogram showed marked hypertrophy of the mid to apical left ventricle, appearance consistent with apical hypertrophic cardiomyopathy. Coronary angiography showed eccentric shelf-type plaque with non-flow-limiting stenosis in the left coronary artery main stem. Cardiovascular magnetic resonance imaging reported findings highly suggestive of apical hypertrophic cardiomyopathy. Our patient was treated and discharged on rivaroxaban, bisoprolol, and atorvastatin with a follow-up in the cardiomyopathy outpatient clinic. Electrocardiogram diagnosis of left ventricular hypertrophy led to the diagnosis of apical hypertrophic cardiomyopathy in this patient. Left ventricular hypertrophy was only evident a few days after our patient suffered a stroke. The underlying mechanisms responsible for this remain unclear. Furthermore, differential diagnosis of hypertrophic cardiomyopathy should be considered in people with electrocardiogram criteria for left ventricular hypertrophy. Cardiovascular magnetic resonance imaging is an important diagnostic tool in identifying causes of left ventricular hypertrophy. Family screening should be recommended in patients with new diagnosis of hypertrophic cardiomyopathy.

Large right ventricular sinusoids in an infant with aorta-left ventricular tunnel and proximal right coronary artery atresia.

PubMed

Chen, Peter C; Spinner, Joseph A; Heinle, Jeffrey S

2018-07-01

We report a 1-month-old infant diagnosed with an aorta-left ventricular tunnel, ventricular septal defect, and right coronary atresia with right ventricular sinusoids. The patient's anatomy and physiology did not indicate right-ventricular-dependent coronary circulation, and therefore right ventricular decompression could be performed without compromising coronary perfusion during surgical correction. A detailed understanding of the coronary anatomy is critical in managing this defect when coronary anomalies are present.

Lower risk of postinfarct rupture in mouse heart overexpressing beta 2-adrenergic receptors: importance of collagen content.

PubMed

Gao, Xiao-Ming; Dilley, Rodney J; Samuel, Chrishan S; Percy, Elodie; Fullerton, Meryl J; Dart, Anthony M; Du, Xiao-Jun

2002-10-01

This paper addresses whether the enhanced left ventricular (LV) contractility and heart rate, seen in transgenic mice overexpressing beta -adrenergic receptor in the heart, might raise the incidence of LV rupture after myocardial infarct. Transgenic and wild-type mice underwent left coronary artery occlusion. Postinfarct deaths that occurred 1-7 days after surgery were analyzed. Hemodynamics, morphologic parameters, and collagen content in the LV were determined. A significantly lower incidence of LV rupture was observed in transgenic than in wild-type mice 3-5 days after myocardial infarct (2.5 versus 19.7%, p < 0.05), despite a similar infarct size between the two groups and better hemodynamic function in transgenic mouse hearts. Morphologic analysis showed a more severe infarct expansion in wild-type versus transgenic mice or in mice dying of rupture versus those that died of acute heart failure. Collagen content was higher in the LV of sham-operated transgenic than wild-type mice (p < 0.01) with both type I and type III collagen elevated. Such difference in collagen content between transgenic and wild-type mice was maintained in noninfarcted and infarcted LV. In conclusion, transgenic mice overexpressing beta -adrenergic receptor had a lower risk of cardiac rupture during the acute phase after infarction despite the markedly enhanced LV contractility and heart rate. As a hyperdynamic function due to beta-adrenergic activation would likely increase the risk of cardiac rupture and infarct expansion, the lack of rupture in this transgenic mouse model suggests that the interstitial collagen level is a more important factor than functional status in the pathogenesis of rupture and infarct expansion.

Cardiovascular simulator improvement: pressure versus volume loop assessment.

PubMed

Fonseca, Jeison; Andrade, Aron; Nicolosi, Denys E C; Biscegli, José F; Leme, Juliana; Legendre, Daniel; Bock, Eduardo; Lucchi, Julio Cesar

2011-05-01

This article presents improvement on a physical cardiovascular simulator (PCS) system. Intraventricular pressure versus intraventricular volume (PxV) loop was obtained to evaluate performance of a pulsatile chamber mimicking the human left ventricle. PxV loop shows heart contractility and is normally used to evaluate heart performance. In many heart diseases, the stroke volume decreases because of low heart contractility. This pathological situation must be simulated by the PCS in order to evaluate the assistance provided by a ventricular assist device (VAD). The PCS system is automatically controlled by a computer and is an auxiliary tool for VAD control strategies development. This PCS system is according to a Windkessel model where lumped parameters are used for cardiovascular system analysis. Peripheral resistance, arteries compliance, and fluid inertance are simulated. The simulator has an actuator with a roller screw and brushless direct current motor, and the stroke volume is regulated by the actuator displacement. Internal pressure and volume measurements are monitored to obtain the PxV loop. Left chamber internal pressure is directly obtained by pressure transducer; however, internal volume has been obtained indirectly by using a linear variable differential transformer, which senses the diaphragm displacement. Correlations between the internal volume and diaphragm position are made. LabVIEW integrates these signals and shows the pressure versus internal volume loop. The results that have been obtained from the PCS system show PxV loops at different ventricle elastances, making possible the simulation of pathological situations. A preliminary test with a pulsatile VAD attached to PCS system was made. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Functional and structural regeneration in the axolotl heart (Ambystoma mexicanum) after partial ventricular amputation.

PubMed

Cano-Martínez, Agustina; Vargas-González, Alvaro; Guarner-Lans, Verónica; Prado-Zayago, Esteban; León-Oleda, Martha; Nieto-Lima, Betzabé

2010-01-01

"In the present study we evaluated the effect of partial ventricular amputation (PVA) in the heart of the adult urodele amphibian (Ambystoma mexicanum) in vivo on spontaneous heart contractile activity recorded in vitro in association to the structural recovery at one, five, 30 and 90 days after injury. One day after PVA, ventricular-tension (VT) (16 ± 3%), atrium-tension (AT) (46 ± 4%) and heart rate (HR) (58+10%) resulted lower in comparison to control hearts. On days five, 30 and 90 after damage, values achieved a 61 ± 5, 93 ± 3, and 98 ± 5% (VT), 60 ± 4, 96 ± 3 and 99 ± 5% (AT) and 74 ± 5, 84 ± 10 and 95 ± 10% (HR) of the control values, respectively. Associated to contractile activity recovery we corroborated a gradual tissue restoration by cardiomyocyte proliferation. Our results represent the first quantitative evidence about the recovery of heart of A. mexicanum restores its functional capacity concomitantly to the structural recovery of the myocardium by proliferation of cardiomyocytes after PVA. These properties make the heart of A. mexicanum a potential model to study the mechanisms underlying heart regeneration in adult vertebrates in vivo.

Regression equations for calculation of z scores for echocardiographic measurements of left heart structures in healthy Han Chinese children.

PubMed

Wang, Shan-Shan; Hong, Wen-Jing; Zhang, Yu-Qi; Chen, Shu-Bao; Huang, Guo-Ying; Zhang, Hong-Yan; Chen, Li-Jun; Wu, Lan-Ping; Shen, Rong; Liu, Yi-Qing; Zhu, Jun-Xue

2018-06-01

Clinical decision making in children with heart disease relies on detailed measurements of cardiac structures using two-dimensional and M-mode echocardiography. However, no echocardiographic reference values are available for the Chinese children. We aimed to establish z-score regression equations for left heart structures in a population-based cohort of healthy Chinese Han children. Echocardiography was performed in 545 children with a normal heart. The dimensions of the aortic valve annulus (AVA), aortic sinuses of Valsalva (ASV), sinotubular junction (STJ), ascending aorta (AAO), left atrium (LA), mitral valve annulus (MVA), interventricular septal end-diastolic thickness (IVSd), interventricular septal end-systolic thickness (IVSs), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), left ventricular posterior wall end-diastolic thickness (LVPWd), left ventricular posterior wall end-systolic thickness (LVPWs) were measured. Regression analyses were conducted to relate the measurements of left heart structures to body surface area (BSA). Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were calculated. Several models were used, and the adjusted R2 values were compared for each model. AVA, ASV, STJ, AAO, LA, MVA, IVSd, IVSs, LVIDd, LVIDs, LVPWd, and LVPWs had a cubic relationship with BSA. LVEF and LVFS fell within a narrow range. Our results provide reference values for z scores and regression equations for left heart structures in Han Chinese children. These data may help make a quick and accurate judgment of the routine clinical measurement of left heart structures in children with heart disease. © 2018 Wiley Periodicals, Inc.

[Rare cause of heart failure in an elderly woman in Djibouti: left ventricular non compaction].

PubMed

Massoure, P L; Lamblin, G; Bertani, A; Eve, O; Kaiser, E

2011-10-01

The purpose of this report is to describe the first case of left ventricular non compaction diagnosed in Djibouti. The patient was a 74-year-old Djiboutian woman with symptomatic heart failure. Echocardiography is the key tool for assessment of left ventricular non compaction. This rare cardiomyopathy is probably underdiagnosed in Africa.

Wolff-Parkinson-White syndrome type B and left bundle-branch block: electrophysiologic and radionuclide study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rakovec, P.; Kranjec, I.; Fettich, J.J.

1985-01-01

Coinciding left bundle-branch block and Wolff-Parkinson-White syndrome type B, a very rare electrocardiographic occurrence, was found in a patient with dilated cardiomyopathy. Electrophysiologic study revealed eccentric retrograde atrial activation during ventricular pacing, suggesting right-sided accessory pathway. At programmed atrial pacing, effective refractory period of the accessory pathway was 310 ms; at shorter pacing coupling intervals, normal atrioventricular conduction with left bundle-branch block was seen. Left bundle-branch block was seen also with His bundle pacing. Radionuclide phase imaging demonstrated right ventricular phase advance and left ventricular phase delay; both right and left ventricular phase images revealed broad phase distribution histograms. Combinedmore » electrophysiologic and radionuclide investigations are useful to disclose complex conduction abnormalities and their mechanical correlates.« less

Left ventricular oxygen extraction during submaximal and maximal exertion in ponies.

PubMed Central

Manohar, M

1988-01-01

1. Left ventricular (LV) myocardial O2 extraction was studied in five healthy ponies which had catheters implanted in the great cardiac vein and main pulmonary artery 15-30 days before the study. The abdominal aorta was percutaneously catheterized to sample arterial blood. 2. In addition, phasic LV and aortic pressures, LV dP/dtmax and rate-pressure product were also studied; dP/dtmax is the maximal rate of rise of the left ventricular pressure during the isovolumic phase, and is considered an index of myocardial contractility. Measurements were made at rest (control) and during adenosine infusion (3 mumol kg-1 min-1) at rest, moderate exercise (heart rate 169 +/- 10 beats min-1), heavy exercise (heart rate 198 +/- 7 beats min-1), maximal exercise (heart rate 232 +/- 7 beats min-1), and adenosine infusion (3 mumol kg-1 min-1) during maximal exercise (heart rate 230 +/- 6 beats min-1). 3. In resting ponies, LV arterial to coronary venous O2 content difference (delta LVa-v O2) was 8.9 +/- 0.5 ml dl-1 and O2 extraction was 59.9 +/- 2.2%. Adenosine infusion at rest decreased delta LVa-v O2 and O2 extraction precipitously (2.6 ml dl-1 and 14.3 +/- 1.7%, respectively), thereby indicating superfluous LV myocardial perfusion. 4. Moderate, heavy and maximal exercise increased delta LVa-v O2 to 185, 194 and 218% of its control value and O2 extraction rose to 71 +/- 2, 75 +/- 1.5 and 78 +/- 0.9%, respectively. The widening of the delta LVa-v O2 gradient was due to the increased arterial O2 content during exercise. 5. Combining these observations with equine myocardial perfusion, the LV O2 consumption was calculated to be 7.8, 47.9 and 103.6 ml min-1 100 g-1 at rest, moderate and maximal exercise. In order to achieve the 13.4-fold increase in LV O2 consumption, the LV perfusion rose only 6-fold; the rest being met by widening the delta LVa-v O2. 6. Adenosine infusion during maximal exercise decreased delta LVa-v O2 and O2 extraction (10.7 +/- 1 ml dl-1 and 45%, respectively; P less than 0.0001). This indicated that coronary vasodilator capacity was not being completely expended in maximally exercising ponies. It is concluded that coronary circulation is unlikely to be a limiting factor to further exertion in ponies. Organ/tissue perfusion studies in exercising ponies have demonstrated that of all working muscles, the left ventricular (LV) myocardium received the highest level of blood flow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3150987

Masked hypertension and cardiac remodeling in middle-aged endurance athletes.

PubMed

Trachsel, Lukas D; Carlen, Frederik; Brugger, Nicolas; Seiler, Christian; Wilhelm, Matthias

2015-06-01

Extensive endurance training and arterial hypertension are established risk factors for atrial fibrillation. We aimed to assess the proportion of masked hypertension in endurance athletes and the impact on cardiac remodeling, mechanics, and supraventricular tachycardias (SVT). Male participants of a 10-mile race were recruited and included if office blood pressure was normal (<140/90 mmHg). Athletes were stratified into a masked hypertension and normotension group by ambulatory blood pressure. Primary endpoint was diastolic function, expressed as peak early diastolic mitral annulus velocity (E'). Left ventricular global strain, left ventricular mass/volume ratio, left atrial volume index, signal-averaged P-wave duration (SAPWD), and SVT during 24-h Holter monitoring were recorded. From 108 runners recruited, 87 were included in the final analysis. Thirty-three (38%) had masked hypertension. The mean age was 42 ± 8 years. Groups did not differ with respect to age, body composition, cumulative training hours, and 10-mile race time. Athletes with masked hypertension had a lower E' and a higher left ventricular mass/volume ratio. Left ventricular global strain, left atrial volume index, SAPWD, and SVT showed no significant differences between the groups. In multiple linear regression analysis, masked hypertension was independently associated with E' (beta = -0.270, P = 0.004) and left ventricular mass/volume ratio (beta = 0.206, P = 0.049). Cumulative training hours was the only independent predictor for left atrial volume index (beta = 0.474, P < 0.001) and SAPWD (beta = 0.481, P < 0.001). In our study, a relevant proportion of middle-aged athletes had masked hypertension, associated with a lower diastolic function and a higher left ventricular mass/volume ratio, but unrelated to left ventricular systolic function, atrial remodeling, or SVT.

Mechanisms of decreased left ventricular preload during continuous positive pressure ventilation in ARDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhainaut, J.F.; Devaux, J.Y.; Monsallier, J.F.

1986-07-01

Continuous positive pressure ventilation is associated with a reduction in left ventricular preload and cardiac output, but the mechanisms responsible are controversial. The decrease in left ventricular preload may result exclusively from a decreased systemic venous return due to increased pleural pressure, or from an additional effect such as decreased left ventricular compliance. To determine the mechanisms responsible, we studied the changes in cardiac output induced by continuous positive pressure ventilation in eight patients with the adult respiratory distress syndrome. We measured cardiac output by thermodilution, and biventricular ejection fraction by equilibrium gated blood pool scintigraphy. Biventricular end-diastolic volumes weremore » then calculated by dividing stroke volume by ejection fraction. As positive end-expiratory pressure increased from 0 to 20 cm H/sub 2/O, stroke volume and biventricular end-diastolic volumes fell about 25 percent, and biventricular ejection fraction remained unchanged. At 20 cm H/sub 2/O positive end-expiratory pressure, volume expansion for normalizing cardiac output restored biventricular end-diastolic volumes without markedly changing biventricular end-diastolic transmural pressures. The primary cause of the reduction in left ventricular preload with continuous positive pressure ventilation appears to be a fall in venous return and hence in right ventricular stroke volume, without evidence of change in left ventricular diastolic compliance.« less

Relationship Between 24-Hour Ambulatory Central Systolic Blood Pressure and Left Ventricular Mass: A Prospective Multicenter Study.

PubMed

Weber, Thomas; Wassertheurer, Siegfried; Schmidt-Trucksäss, Arno; Rodilla, Enrique; Ablasser, Cornelia; Jankowski, Piotr; Lorenza Muiesan, Maria; Giannattasio, Cristina; Mang, Claudia; Wilkinson, Ian; Kellermair, Jörg; Hametner, Bernhard; Pascual, Jose Maria; Zweiker, Robert; Czarnecka, Danuta; Paini, Anna; Salvetti, Massimo; Maloberti, Alessandro; McEniery, Carmel

2017-12-01

We investigated the relationship between left ventricular mass and brachial office as well as brachial and central ambulatory systolic blood pressure in 7 European centers. Central systolic pressure was measured with a validated oscillometric device, using a transfer function, and mean/diastolic pressure calibration. M-mode images were obtained by echocardiography, and left ventricular mass was determined by one single reader blinded to blood pressure. We studied 289 participants (137 women) free from antihypertensive drugs (mean age: 50.8 years). Mean office blood pressure was 145/88 mm Hg and mean brachial and central ambulatory systolic pressures were 127 and 128 mm Hg, respectively. Mean left ventricular mass was 93.3 kg/m 2 , and 25.6% had left ventricular hypertrophy. The correlation coefficient between left ventricular mass and brachial office, brachial ambulatory, and central ambulatory systolic pressure was 0.29, 0.41, and 0.47, respectively ( P =0.003 for comparison between brachial office and central ambulatory systolic pressure and 0.32 for comparison between brachial and central ambulatory systolic pressure). The results were consistent for men and women, and young and old participants. The areas under the curve for prediction of left ventricular hypertrophy were 0.618, 0.635, and 0.666 for brachial office, brachial, and central ambulatory systolic pressure, respectively ( P =0.03 for comparison between brachial and central ambulatory systolic pressure). In younger participants, central ambulatory systolic pressure was superior to both other measurements. Central ambulatory systolic pressure, measured with an oscillometric cuff, shows a strong trend toward a closer association with left ventricular mass and hypertrophy than brachial office/ambulatory systolic pressure. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01278732. © 2017 American Heart Association, Inc.

Racial/Ethnic Differences in Left Ventricular Structure and Function in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort.

PubMed

Ahmad, Faraz S; Cai, Xuan; Kunkel, Katherine; Ricardo, Ana C; Lash, James P; Raj, Dominic S; He, Jiang; Anderson, Amanda H; Budoff, Matthew J; Wright Nunes, Julie A; Roy, Jason; Wright, Jackson T; Go, Alan S; St John Sutton, Martin G; Kusek, John W; Isakova, Tamara; Wolf, Myles; Keane, Martin G

2017-08-01

Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) and it is especially common among Blacks. Left ventricular hypertrophy (LVH) is an important subclinical marker of CVD, but there are limited data on racial variation in left ventricular structure and function among persons with CKD. In a cross-sectional analysis of the Chronic Renal Insufficiency Cohort Study, we compared the prevalence of different types of left ventricular remodeling (concentric hypertrophy, eccentric hypertrophy, and concentric remodeling) by race/ethnicity. We used multinomial logistic regression to test whether race/ethnicity associated with different types of left ventricular remodeling independently of potential confounding factors. We identified 1,164 non-Hispanic Black and 1,155 non-Hispanic White participants who completed Year 1 visits with echocardiograms that had sufficient data to categorize left ventricular geometry type. Compared to non-Hispanic Whites, non-Hispanic Blacks had higher mean left ventricular mass index (54.7 ± 14.6 vs. 47.4 ± 12.2 g/m2.7; P < 0.0001) and prevalence of concentric LVH (45.8% vs. 24.9%). In addition to higher systolic blood pressure and treatment with >3 antihypertensive medications, Black race/ethnicity was independently associated with higher odds of concentric LVH compared to White race/ethnicity (odds ratio: 2.73; 95% confidence interval: 2.02, 3.69). In a large, diverse cohort with CKD, we found significant differences in left ventricular mass and hypertrophic morphology between non-Hispanic Blacks and Whites. Future studies will evaluate whether higher prevalence of LVH contribute to racial/ethnic disparities in cardiovascular outcomes among CKD patients. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Serum Bilirubin Concentration is Associated with Left Ventricular Remodeling in Patients with Type 2 Diabetes Mellitus: A Cohort Study.

PubMed

Inoue, Tomoaki; Sonoda, Noriyuki; Hiramatsu, Shinsuke; Kimura, Shinichiro; Ogawa, Yoshihiro; Inoguchi, Toyoshi

2018-02-01

Previous studies have shown that serum bilirubin concentration is inversely associated with the risk of cardiovascular disease. The relationship between serum bilirubin concentration and left ventricular geometry, however, has not been investigated in patients with diabetes mellitus. In this cohort study, 158 asymptomatic patients with type 2 diabetes mellitus without overt heart disease were enrolled. Left ventricular structure and function were assessed using echocardiography. Serum bilirubin concentration, glycemic control, lipid profile, and other clinical characteristics were evaluated, and their association with left ventricular geometry was determined. Patients with New York Heart Association Functional Classification greater than I, left ventricular ejection fraction less than 50%, history of coronary artery disease, severe valvulopathy, chronic atrial fibrillation, or creatinine clearance less than 30 ml/min, and those receiving insulin treatment, were excluded. Univariate analyses showed that relative wall thickness (RWT) was significantly correlated with diastolic blood pressure (P = 0.003), HbA1c (P = 0.024), total cholesterol (P = 0.043), urinary albumin (P = 0.023), and serum bilirubin concentration (P = 0.009). There was no association between left ventricular mass index and serum bilirubin concentration. Multivariate linear regression analysis showed that log RWT was positively correlated with diastolic blood pressure (P = 0.010) and that log RWT was inversely correlated with log bilirubin (P = 0.003). In addition, the patients with bilirubin less than 0.8 mg/dl had a higher prevalence of concentric left ventricular remodeling compared with those with bilirubin 0.8 mg/dl or more. Our study shows that the serum bilirubin concentration may be associated with the progression of concentric left ventricular remodeling in patients with type 2 diabetes mellitus.

Left ventricular mass of persistent masked hypertension in Hong Kong Chinese adolescents: a 4-year follow-up study.

PubMed

Yam, Man-Ching; So, Hung-Kwan; Kwok, Sit-Yee; Lo, Fung-Cheung; Mok, Chi-Fung; Leung, Chuk-Kwan; Yip, Wai-Kwok; Sung, Yn-Tz

2018-06-01

In our previous study, the prevalence of childhood masked hypertension was 11%. This study aims to assess the left ventricular mass index of persistent masked hypertension and determine the factors of elevated left ventricular mass index in Hong Kong Chinese adolescents from a community cohort. Community prospective cohort study, follow-up of a case-control study in community. Patients with masked hypertension at baseline were invited to recheck ambulatory blood pressure for the persistence of masked hypertension. A total of 144 out of 165 patients with masked hypertension in the 2011/2012 ambulatory blood pressure survey consented to participate in the study. In all, 48 patients were found to have persistent masked hypertension by ambulatory blood pressure rechecking and were matched with normotensive controls by sex, age, and body height. The left ventricular mass (117.3±39.9 g versus 87.0±28.2 g versus 102.0±28.2 g) and left ventricular mass index (30.1±8.4 g/m2.7 versus 23.9±6.3 g/m2.7 versus 25.1±5.7 g/m2.7) were significantly higher in the persistent masked hypertension group (p<0.0001) compared with the patients without persistent masked hypertension and controls. In multivariate linear regression analysis, left ventricular mass index was found to be higher in male gender (β=4.874, p<0.0001) and the patients with persistent masked hypertension (β=2.796, p=0.003). In addition, left ventricular mass index was positively associated with body mass index z-score (β=3.045, p<0.0001) and low-density lipoprotein cholesterol concentration (β=1.634, p=0.015). Persistent masked hypertension in adolescents is associated with elevated left ventricular mass index.

Effects of 4 month exercise on left ventricular remodeling and autonomic nervous system in hypertensive patients.

PubMed

Zheng, Huan; Xie, Nanzi; Xu, Huifeng; Huang, Junling; Xie, Xiaoyun; Luo, Ming

2016-03-01

We sought to investigate effects of supervised exercise training on left ventricular remodeling, left ventricular function and autonomic nervous system of hypertensive patients without medication. Fifty borderline and mildly hypertensive patients were enrolled and randomly divided into 2 groups (25 in each). Exercise group received a 4 months' exercise program, prescribed according to their first cardiopulmonary exercise tests, while the control group received routine dietary recommendation. All patients underwent noradrenalin assay, cardiopulmonary exercise tests and echocardiographic studies at enrollment and 4 month follow-up. At baseline no statistically difference between the two groups were observed in clinical characteristics, echographic variants or cardiopulmonary test index. Four months later, exercise group showed higher values of VO2peak, Powermax (max workload), AT (anaerobic threshold), VO2AT (VO2 at anaerobic threshold), tAT (time from beginning to anaerobic threshold) and heart rate recovery compared to the control group (P<0.05). Additionally, systolic/diastolic blood pressure decreased significantly in the exercise group compared to the control group (P<0.05). Moreover, there was significant reduction in left ventricular mass index in the exercise group (P<0.01), and there was also an inverse correlation between changes in left ventricular mass index and heart rate recovery (r=-0.52, P<0.01). Four-month exercise training in borderline and mildly hypertensive patients not only decreased their blood pressure levels, but also induced an improvement of exercise capability, left ventricular remodeling and heart rate recovery. Heart rate recovery improvement was significantly associated with decrease of left ventricular mass index, which indicated that favorable adjustment in autonomic nervous system of exercise training might be an important pathway to reverse left ventricular remodeling.

Screening for Fabry disease in left ventricular hypertrophy: documentation of a novel mutation.

PubMed

Baptista, Ana; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio

2015-08-01

Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test - [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5).

Transesophageal Echocardiography-Guided Epicardial Left Ventricular Lead Placement by Video-Assisted Thoracoscopic Surgery in Nonresponders to Biventricular Pacing and Previous Chest Surgery.

PubMed

Schroeder, Carsten; Chung, Jane M; Mackall, Judith A; Cakulev, Ivan T; Patel, Aaron; Patel, Sunny J; Hoit, Brian D; Sahadevan, Jayakumar

2018-06-14

The aim of the study was to study the feasibility, safety, and efficacy of transesophageal echocardiography-guided intraoperative left ventricular lead placement via a video-assisted thoracoscopic surgery approach in patients with failed conventional biventricular pacing. Twelve patients who could not have the left ventricular lead placed conventionally underwent epicardial left ventricular lead placement by video-assisted thoracoscopic surgery. Eight patients had previous chest surgery (66%). Operative positioning was a modified far lateral supine exposure with 30-degree bed tilt, allowing for groin and sternal access. To determine the optimal left ventricular location for lead placement, the left ventricular surface was divided arbitrarily into nine segments. These segments were transpericardially paced using a hand-held malleable pacing probe identifying the optimal site verified by transesophageal echocardiography. The pacing leads were screwed into position via a limited pericardiotomy. The video-assisted thoracoscopic surgery approach was successful in all patients. Biventricular pacing was achieved in all patients and all reported symptomatic benefit with reduction in New York Heart Association class from III to I-II (P = 0.016). Baseline ejection fraction was 23 ± 3%; within 1-year follow-up, the ejection fraction increased to 32 ± 10% (P = 0.05). The mean follow-up was 566 days. The median length of hospital stay was 7 days with chest tube removal between postoperative days 2 and 5. In patients who are nonresponders to conventional biventricular pacing, intraoperative left ventricular lead placement using anatomical and functional characteristics via a video-assisted thoracoscopic surgery approach is effective in improving heart failure symptoms. This optimized left ventricular lead placement is feasible and safe. Previous chest surgery is no longer an exclusion criterion for a video-assisted thoracoscopic surgery approach.

Acute right ventricular dysfunction: real-time management with echocardiography.

PubMed

Krishnan, Sundar; Schmidt, Gregory A

2015-03-01

In critically ill patients, the right ventricle is susceptible to dysfunction due to increased afterload, decreased contractility, or alterations in preload. With the increased use of point-of-care ultrasonography and a decline in the use of pulmonary artery catheters, echocardiography can be the ideal tool for evaluation and to guide hemodynamic and respiratory therapy. We review the epidemiology of right ventricular failure in critically ill patients; echocardiographic parameters for evaluating the right ventricle; and the impact of mechanical ventilation, fluid therapy, and vasoactive infusions on the right ventricle. Finally, we summarize the principles of management in the context of right ventricular dysfunction and provide recommendations for echocardiography-guided management.

Improvement of Aging-Associated Cardiovascular Dysfunction by the Orally Administered Copper(II)-Aspirinate Complex

PubMed Central

Gerö, Domokos; Lin, Li-ni; Loganathan, Sivakkanan; Hoppe-Tichy, Torsten; Szabó, Csaba; Karck, Matthias; Sakurai, Hiromu; Szabó, Gábor

2008-01-01

Abstract Background Aging-associated nitro-oxidative stress causes tissue injury and activates proinflammatory pathways that play an important role in the pathogenesis of aging-associated cardiovascular dysfunction. It has been recently reported, that the copper(II)–aspirinate complex (CuAsp) exerts not only the well-known anti-inflammatory and platelet antiaggregating effects of aspirin, but, due to its superoxide dismutase mimetic activity, it acts as a potent antioxidant as well. In this study we investigated the effects of CuAsp on aging-associated myocardial and endothelial dysfunction. Methods and Results Aging and young rats were treated for 3 weeks with vehicle, or with CuAsp (200 mg/kg per day per os). Left ventricular pressure–volume relations were measured by using a microtip pressure–volume conductance catheter, and indexes of contractility (e.g., slope of end-systolic pressure–volume relationships [ESPVR] [Ees], and dP/dtmax – end-diastolic volume [EDV]) were calculated. In organ bath experiments for isometric tension with isolated aortic rings, endothelium-dependent and -independent vasorelaxation were investigated by using acetylcholine and sodium nitroprusside. When compared to the young controls, aging rats showed impaired left ventricular contractility (Ees, 0.51 ± 0.04 vs. 2.16 ± 0.28 mmHg/μL; dP/dtmax – EDV, 10.71 ± 2.02 vs. 37.23 ± 4.18 mmHg/sec per μL; p < 0.05) and a marked endothelial dysfunction (maximal relaxation to acetylcholine: 66.66 ± 1.30 vs. 87.09 ± 1.35%; p < 0.05). Treatment with CuAsp resulted in reduced nitro-oxidative stress, improved cardiac function (Ees, 1.21 ± 0.17 vs. 0.51 ± 0.04 mmHg/μL; dP/dtmax – EDV, 23.40 ± 3.34 vs. 10.71 ± 2.02 mmHg/sec per μL; p < 0.05) and higher vasorelaxation to acetylcholine in aging animals (94.83 ± 0.73 vs. 66.66 ± 1.30%; p < 0.05). The treatment did not influence the cardiovascular functions of young rats. Conclusions Our results demonstrate that oxidative stress and inflammatory pathways contribute to the pathogenesis of cardiovascular dysfunction in the aging organism, which can be reversed by CuAsp. PMID:18922047

Altered myofilament structure and function in dogs with Duchenne muscular dystrophy cardiomyopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ait Mou, Younss; Lacampagne, Alain; Irving, Thomas

Aim Duchenne Muscular Dystrophy (DMD) is associated with progressive depressed left ventricular (LV) function. However, DMD effects on myofilament structure and function are poorly understood. Golden Retriever Muscular Dystrophy (GRMD) is a dog model of DMD recapitulating the human form of DMD. Objective The objective of this study is to evaluate myofilament structure and function alterations in GRMD model with spontaneous cardiac failure. Methods and results We have employed synchrotron X-rays diffraction to evaluate myofilament lattice spacing at various sarcomere lengths (SL) on permeabilized LV myocardium. We found a negative correlation between SL and lattice spacing in both sub-epicardium (EPI)more » and sub-endocardium (ENDO) LV layers in control dog hearts. In the ENDO of GRMD hearts this correlation is steeper due to higher lattice spacing at short SL (1.9 μm). Furthermore, cross-bridge cycling indexed by the kinetics of tension redevelopment (ktr) was faster in ENDO GRMD myofilaments at short SL. We measured post-translational modifications of key regulatory contractile proteins. S-glutathionylation of cardiac Myosin Binding Protein-C (cMyBP-C) was unchanged and PKA dependent phosphorylation of the cMyBP-C was significantly reduced in GRMD ENDO tissue and more modestly in EPI tissue. Conclusions We found a gradient of contractility in control dogs' myocardium that spreads across the LV wall, negatively correlated with myofilament lattice spacing. Chronic stress induced by dystrophin deficiency leads to heart failure that is tightly associated with regional structural changes indexed by increased myofilament lattice spacing, reduced phosphorylation of regulatory proteins and altered myofilament contractile properties in GRMD dogs.« less

A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation.

PubMed

Toepfer, Christopher N; Sikkel, Markus B; Caorsi, Valentina; Vydyanath, Anupama; Torre, Iratxe; Copeland, O'Neal; Lyon, Alexander R; Marston, Steven B; Luther, Pradeep K; Macleod, Kenneth T; West, Timothy G; Ferenczi, Michael A

2016-08-01

Myocardial remodeling in response to chronic myocardial infarction (CMI) progresses through two phases, hypertrophic "compensation" and congestive "decompensation." Nothing is known about the ability of uninfarcted myocardium to produce force, velocity, and power during these clinical phases, even though adaptation in these regions likely drives progression of compensation. We hypothesized that enhanced cross-bridge-level contractility underlies mechanical compensation and is controlled in part by changes in the phosphorylation states of myosin regulatory proteins. We induced CMI in rats by left anterior descending coronary artery ligation. We then measured mechanical performance in permeabilized ventricular trabecula taken distant from the infarct zone and assayed myosin regulatory protein phosphorylation in each individual trabecula. During full activation, the compensated myocardium produced twice as much power and 31% greater isometric force compared with noninfarcted controls. Isometric force during submaximal activations was raised >2.4-fold, while power was 2-fold greater. Electron and confocal microscopy demonstrated that these mechanical changes were not a result of increased density of contractile protein and therefore not an effect of tissue hypertrophy. Hence, sarcomere-level contractile adaptations are key determinants of enhanced trabecular mechanics and of the overall cardiac compensatory response. Phosphorylation of myosin regulatory light chain (RLC) increased and remained elevated post-MI, while phosphorylation of myosin binding protein-C (MyBP-C) was initially depressed but then increased as the hearts became decompensated. These sensitivities to CMI are in accordance with phosphorylation-dependent regulatory roles for RLC and MyBP-C in crossbridge function and with compensatory adaptation in force and power that we observed in post-CMI trabeculae. Copyright © 2016 the American Physiological Society.

Geraniol blocks calcium and potassium channels in the mammalian myocardium: useful effects to treat arrhythmias.

PubMed

de Menezes-Filho, José Evaldo Rodrigues; Gondim, Antônio Nei Santana; Cruz, Jader Santos; de Souza, Américo Azevedo; Santos, José Nilson Andrade Dos; Conde-Garcia, Eduardo Antônio; de Sousa, Damião Pergentino; Santos, Michel Santana; de Oliveira, Evaleide Diniz; de Vasconcelos, Carla Maria Lins

2014-12-01

Geraniol is a monoterpene present in several essential oils, and it is known to have a plethora of pharmacological activities. In this study, we explored the contractile and electrophysiological properties of geraniol and its antiarrhythmic effects in the heart. The geraniol effects on atrial contractility, L-type Ca(2+) current, K(+) currents, action potential (AP) parameters, ECG profile and on the arrhythmia induced by ouabain were evaluated. In the atrium, geraniol reduced the contractile force (~98%, EC = 1,510 ± 160 μM) and diminished the positive inotropism of CaCl2 and BAY K8644. In cardiomyocytes, the IC a,L was reduced by 50.7% (n = 5) after perfusion with 300 μM geraniol. Moreover, geraniol prolonged the AP duration (APD) measured at 50% (n = 5) after repolarization, without changing the resting potential. The increased APD could be attributed to the blockade of the transient outward K(+) current (Ito ) (59.7%, n = 4), the non-inactivation K(+) current (Iss ) (39.2%, n = 4) and the inward rectifier K(+) current (IK 1 ) (33.7%, n = 4). In isolated hearts, geraniol increased PRi and QTi without affecting the QRS complex (n = 6), and it reduced both the left ventricular pressure (83%) and heart rate (16.5%). Geraniol delayed the time to onset of ouabain-induced arrhythmias by 128%, preventing 30% of the increase in resting tension (n = 6). Geraniol exerts its negative inotropic and chronotropic responses in the heart by decreasing both L-type Ca(2+) and voltage-gated K(+) currents, ultimately acting against ouabain-induced arrhythmias. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

NASA Technical Reports Server (NTRS)

Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

1997-01-01

We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

Serca2a and Na{sup +}/Ca{sup 2+} exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nascimento, Andrews Marques do; Lima, Ewelyne Mira

Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Main methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20 mg/kg/week for 4 weeks); and NDE (trained and treated). The haemodynamic parameters (+ dP/dt{sub max}, − dP/dt{sub min} and Tau) were assessed in the leftmore » ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. Results: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na{sup +}/Ca{sup 2+} exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Conclusion: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. - Highlights: • ND and resistive exercise enhanced the cardiac function and increased expression of cytosolic calcium regulatory components.« less

Relationship between right and left ventricular function in candidates for implantable cardioverter defibrillator with low left ventricular ejection fraction.

PubMed

Jimenez-Juan, Laura; Karur, Gauri R; Connelly, Kim A; Deva, Djeven; Yan, Raymond T; Wald, Rachel M; Singh, Sheldon; Leung, General; Oikonomou, Anastasia; Dorian, Paul; Angaran, Paul; Yan, Andrew T

2017-04-01

Indications for the primary prevention of sudden death using an implantable cardioverter defibrillator (ICD) are based predominantly on left ventricular ejection fraction (LVEF). However, right ventricular ejection fraction (RVEF) is also a known prognostic factor in a variety of structural heart diseases that predispose to sudden cardiac death. We sought to investigate the relationship between right and left ventricular parameters (function and volume) measured by cardiovascular magnetic resonance (CMR) among a broad spectrum of patients considered for an ICD. In this retrospective, single tertiary-care center study, consecutive patients considered for ICD implantation who were referred for LVEF assessment by CMR were included. Right and left ventricular function and volumes were measured. In total, 102 patients (age 62±14 years; 23% women) had a mean LVEF of 28±11% and RVEF of 44±12%. The left ventricular and right ventricular end diastolic volume index was 140±42 mL/m 2 and 81±27 mL/m 2 , respectively. Eighty-six (84%) patients had a LVEF <35%, and 63 (62%) patients had right ventricular systolic dysfunction. Although there was a significant and moderate correlation between LVEF and RVEF ( r =0.40, p <0.001), 32 of 86 patients (37%) with LVEF <35% had preserved RVEF, while 9 of 16 patients (56%) with LVEF ≥35% had right ventricular systolic dysfunction (Kappa=0.041). Among patients being considered for an ICD, there is a positive but moderate correlation between LVEF and RVEF. A considerable proportion of patients who qualify for an ICD based on low LVEF have preserved RVEF, and vice versa.

Congenital left ventricular aneurysms and diverticula: an entity in search of an identity

PubMed Central

Ohlow, Marc-Alexander

2017-01-01

Congenital left ventricular aneurysm or diverticulum are rare cardiac malformations described in 809 cases since the first description in 1816, being associated with other cardiac, vascular or thoraco-abdominal abnormalities in about 70%. It appears to be a developmental anomaly, starting in the 4th embryonic week. In an experimental study, targeted knockdown of cardiac troponin T in the chick was performed at day 3, after the heart tube has formed. Morpholino treatment of gene TNNT2 at this stage led to the development of left ventricular diverticula (LVD) in the primitive left ventricular wall. Diagnosis of left ventricular aneurysms (LVA)/LVD can be made after exclusion of coronary artery disease, local or systemic inflammation or traumatic causes as well as cardiomyopathies. Clinically, most of LVA and LVD are asymptomatic or may cause systemic embolization, congestive heart failure, valvular regurgitation, ventricular wall rupture, ventricular tachycardia or sudden cardiac death. Diagnosis is established by imaging studies (echocardiography, magnetic resonance imaging or left ventricular angiography) visualizing the structural changes and accompanying abnormalities. Mode of treatment has to be individually tailored and depends on clinical presentation, accompanying abnormalities and possible complications, options include surgical resection (especially in symptomatic patients), anticoagulation after systemic embolization, radiofrequency ablation or implantation of an implantable cardioverter defibrillator (ICD) in case of symptomatic ventricular tachycardias, and occasionally combined with class I- or III-antiarrhythmic drugs. Cardiac death occurs usually in childhood, is significantly more frequent in LVA patients and caused by congestive heart failure in most of the cases, whereas patients diagnosed with LVD died more frequently from rupture of the LVD. PMID:29581714

Congenital left ventricular aneurysms and diverticula: an entity in search of an identity.

PubMed

Ohlow, Marc-Alexander

2017-12-01

Congenital left ventricular aneurysm or diverticulum are rare cardiac malformations described in 809 cases since the first description in 1816, being associated with other cardiac, vascular or thoraco-abdominal abnormalities in about 70%. It appears to be a developmental anomaly, starting in the 4 th embryonic week. In an experimental study, targeted knockdown of cardiac troponin T in the chick was performed at day 3, after the heart tube has formed. Morpholino treatment of gene TNNT2 at this stage led to the development of left ventricular diverticula (LVD) in the primitive left ventricular wall. Diagnosis of left ventricular aneurysms (LVA)/LVD can be made after exclusion of coronary artery disease, local or systemic inflammation or traumatic causes as well as cardiomyopathies. Clinically, most of LVA and LVD are asymptomatic or may cause systemic embolization, congestive heart failure, valvular regurgitation, ventricular wall rupture, ventricular tachycardia or sudden cardiac death. Diagnosis is established by imaging studies (echocardiography, magnetic resonance imaging or left ventricular angiography) visualizing the structural changes and accompanying abnormalities. Mode of treatment has to be individually tailored and depends on clinical presentation, accompanying abnormalities and possible complications, options include surgical resection (especially in symptomatic patients), anticoagulation after systemic embolization, radiofrequency ablation or implantation of an implantable cardioverter defibrillator (ICD) in case of symptomatic ventricular tachycardias, and occasionally combined with class I- or III-antiarrhythmic drugs. Cardiac death occurs usually in childhood, is significantly more frequent in LVA patients and caused by congestive heart failure in most of the cases, whereas patients diagnosed with LVD died more frequently from rupture of the LVD.

Mathematical modeling physiological effects of the overexpression of β2-adrenoceptors in mouse ventricular myocytes.

PubMed

Rozier, Kelvin; Bondarenko, Vladimir E

2018-03-01

Transgenic (TG) mice overexpressing β 2 -adrenergic receptors (β 2 -ARs) demonstrate enhanced myocardial function, which manifests in increased basal adenylyl cyclase activity, enhanced atrial contractility, and increased left ventricular function in vivo. To gain insights into the mechanisms of these effects, we developed a comprehensive mathematical model of the mouse ventricular myocyte overexpressing β 2 -ARs. We found that most of the β 2 -ARs are active in control conditions in TG mice. The simulations describe the dynamics of major signaling molecules in different subcellular compartments, increased basal adenylyl cyclase activity, modifications of action potential shape and duration, and the effects on L-type Ca 2+ current and intracellular Ca 2+ concentration ([Ca 2+ ] i ) transients upon stimulation of β 2 -ARs in control, after the application of pertussis toxin, upon stimulation with a specific β 2 -AR agonist zinterol, and upon stimulation with zinterol in the presence of pertussis toxin. The model also describes the effects of the β 2 -AR inverse agonist ICI-118,551 on adenylyl cyclase activity, action potential, and [Ca 2+ ] i transients. The simulation results were compared with experimental data obtained in ventricular myocytes from TG mice overexpressing β 2 -ARs and with simulation data on wild-type mice. In conclusion, a new comprehensive mathematical model was developed that describes multiple experimental data on TG mice overexpressing β 2 -ARs and can be used to test numerous hypotheses. As an example, using the developed model, we proved the hypothesis of the major contribution of L-type Ca 2+ current to the changes in the action potential and [Ca 2+ ] i transient upon stimulation of β 2 -ARs with zinterol. NEW & NOTEWORTHY We developed a new mathematical model for transgenic mouse ventricular myocytes overexpressing β 2 -adrenoceptors that describes the experimental findings in transgenic mice. The model reveals mechanisms of the differential effects of stimulation of β 2 -adrenoceptors in wild-type and transgenic mice overexpressing β 2 -adrenoceptors.

Surgical approach to left ventricular inflow obstruction due to dilated coronary sinus.

PubMed

Vargas, Florentino J; Rozenbaum, Jorge; Lopez, Ricardo; Granja, Miguel; De Dios, Ana; Zarlenga, Beatriz; Flores, Enrique; Fischman, Enrique; Kreutzer, Eduardo

2006-07-01

Left superior vena cava draining to a dilated coronary sinus can cause left ventricular inflow obstruction. Our purpose is to report 4 severely ill patients with this malformation who were operated upon and in whom repair was accomplished using an original surgical approach. An operative procedure was designed, which included complete resection of the wall of the coronary sinus along its entire extension in the left atrium; division of the left superior vena cava; and establishment of the left superior vena cava-right atrial continuity by a wide left superior vena cava-right atrial appendage anastomosis. The series included 1 patient with interrupted inferior vena cava-hemiazygous continuation to left superior vena cava. There were no deaths. Absence of residual left ventricular inflow obstruction was demonstrated at follow-up in all cases, together with an unobstructed left superior vena cava-right atrial appendage-right atrial connection. A predictable relief of the left ventricular inflow obstruction, together with preservation of an adequate drainage for the systemic venous return, were both achieved with this repair.

Biventricular and atrial diastolic function assessment using conventional echocardiography and tissue-Doppler imaging in adults with Marfan syndrome.

PubMed

Kiotsekoglou, Anatoli; Moggridge, James C; Bijnens, Bart H; Kapetanakis, Venediktos; Alpendurada, Francisco; Mullen, Michael J; Saha, Samir; Nassiri, Dariush K; Camm, John; Sutherland, George R; Child, Anne H

2009-12-01

Previous studies provided evidence about left ventricular systolic and diastolic dysfunction in adults with Marfan syndrome (MFS). However, in the literature, data on right ventricular and bi-atrial diastolic function are limited. We aimed to investigate whether, in the absence of significant valvular disease, diastolic dysfunction is present not only in both ventricles but also in the atrial cavities. Seventy-two adult unoperated MFS patients and 73 controls without significant differences in age, sex, and body surface area from the patient group were studied using two-dimensional, pulsed, and colour-Doppler and tissue-Doppler imaging (TDI). Biventricular early filling measurements were significantly decreased in MFS patients when compared with controls (P < 0.001). Pulsed TDI early filling measurements obtained from five mitral annular regions and over the lateral tricuspid valve corner were significantly reduced in the patient group (P < 0.001). Indices reflecting atrial function at the reservoir, conduit and contractile phases were also significantly decreased in MFS patients (P < 0.001). This study demonstrated significant biventricular diastolic and biatrial systolic and diastolic dysfunction in MFS patients. Our findings suggest that MFS affects diastolic function independently. Diastolic abnormalities could be attributed to fibrillin-1 deficiency and dysregulation of transforming growth factor-beta activity in the cardiac extracellular matrix.

Animal Models of Congenital Cardiomyopathies Associated With Mutations in Z-Line Proteins.

PubMed

Bang, Marie-Louise

2017-01-01

The cardiac Z-line at the boundary between sarcomeres is a multiprotein complex connecting the contractile apparatus with the cytoskeleton and the extracellular matrix. The Z-line is important for efficient force generation and transmission as well as the maintenance of structural stability and integrity. Furthermore, it is a nodal point for intracellular signaling, in particular mechanosensing and mechanotransduction. Mutations in various genes encoding Z-line proteins have been associated with different cardiomyopathies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, and left ventricular noncompaction, and mutations even within the same gene can cause widely different pathologies. Animal models have contributed to a great advancement in the understanding of the physiological function of Z-line proteins and the pathways leading from mutations in Z-line proteins to cardiomyopathy, although genotype-phenotype prediction remains a great challenge. This review presents an overview of the currently available animal models for Z-line and Z-line associated proteins involved in human cardiomyopathies with special emphasis on knock-in and transgenic mouse models recapitulating the clinical phenotypes of human cardiomyopathy patients carrying mutations in Z-line proteins. Pros and cons of mouse models will be discussed and a future outlook will be given. J. Cell. Physiol. 232: 38-52, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

(-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

PubMed

Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan

2016-09-01

A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

[Surgical treatment of congenital obstruction of the left ventricular outflow tract].

PubMed

Biocina, B; Sutlić, Z; Husedinović, I; Letica, D; Sokolić, J

1993-01-01

This report presents the classification and all types of left ventricular outflow tract obstructions. The possibilities of operative therapies are surveyed as well. Results of surgical treatment in 34 patients with obstruction to left ventricular outflow are shown. The majority of patients underwent operation under extracorporeal circulation (84.4%), while the rest were operated by means of the inflow occlusion technique (14.7%). The obtained results were compared with those from the literature. The importance of echocardiographic evaluation of location of the left ventricular outflow tract obstruction and the appropriate choice of a surgical technique according to the patient's age are emphasized.

[Geographical distribution of left ventricular Tei index based on principal component analysis].

PubMed

Xu, Jinhui; Ge, Miao; He, Jinwei; Xue, Ranyin; Yang, Shaofang; Jiang, Jilin

2014-11-01

To provide a scientific standard of left ventricular Tei index for healthy people from various region of China, and to lay a reliable foundation for the evaluation of left ventricular diastolic and systolic function. The correlation and principal component analysis were used to explore the left ventricular Tei index, which based on the data of 3 562 samples from 50 regions of China by means of literature retrieval. Th e nine geographical factors were longitude(X₁), latitude(X₂), altitude(X₃), annual sunshine hours (X₄), the annual average temperature (X₅), annual average relative humidity (X₆), annual precipitation (X₇), annual temperature range (X₈) and annual average wind speed (X₉). ArcGIS soft ware was applied to calculate the spatial distribution regularities of left ventricular Tei index. There is a significant correlation between the healthy people's left ventricular Tei index and geographical factors, and the correlation coefficients were -0.107 (r₁), -0.301 (r₂), -0.029 (r₃), -0.277 (r₄), -0.256(r₅), -0.289(r₆), -0.320(r₇), -0.310 (r₈) and -0.117 (r₉), respectively. A linear equation between the Tei index and the geographical factor was obtained by regression analysis based on the three extracting principal components. The geographical distribution tendency chart for healthy people's left Tei index was fitted out by the ArcGIS spatial interpolation analysis. The geographical distribution for left ventricular Tei index in China follows certain pattern. The reference value in North is higher than that in South, while the value in East is higher than that in West.

Left ventricular diastolic dysfunction without left ventricular hypertrophy in obese children and adolescents: a Tissue Doppler Imaging and Cardiac Troponin I Study.

PubMed

El Saiedi, Sonia A; Mira, Marwa F; Sharaf, Sahar A; Al Musaddar, Maysoun M; El Kaffas, Rania M H; AbdelMassih, Antoine F; Barsoum, Ihab H Y

2018-01-01

Obesity increases the risk for various cardiovascular problems. Increase in body mass index is often an independent risk factor for the development of elevated blood pressure and clustering of various cardiovascular risk factors. To determine early markers of left ventricular affection in obese patients before the appearance of left ventricular hypertrophy. In this cross-sectional study, we evaluated 42 obese patients and 30 healthy controls. Their ages ranged from 6 to 19 years. Studied children were subjected to anthropometric, lipid profile, and serum Troponin I level measurements. Echocardiographic evaluation performed to assess the left ventricle included left ventricular dimension measurement using motion-mode echocardiography, based on which patients with left ventricular hypertrophy (10 patients) were eliminated, as well as conventional and tissue Doppler imaging. Tissue Doppler findings in the study groups showed that the ratio of transmitral early diastolic filling velocity to septal peak early diastolic myocardial velocity (E/e') was significantly higher in cases compared with controls [6.9±1.4 versus 9.0±1.6, p (Pearson's coefficient)=0.001, respectively]. The level of cardiac troponin I was significantly higher in cases compared with controls [0.14±0.39 ng/ml versus 0.01±0.01 ng/ml, p (Pearson's coefficient)=0.047, respectively] and there was a significant correlation between troponin I and transmitral early diastolic filling velocity to septal peak early diastolic myocardial velocity ratio (E/e') [R (correlation coefficient)=0.6]. Tissue Doppler Imaging and Troponin I evaluation proved useful tools to detect early affection of the left ventricle in obese patients even in the absence of left ventricular hypertrophy.

Aldosterone is associated with left ventricular hypertrophy in hemodialysis patients.

PubMed

Feniman De Stefano, Greicy Mara Mengue; Zanati-Basan, Silméia Garcia; De Stefano, Laercio Martins; Silva, Viviana Rugolo Oliveira E; Xavier, Patrícia Santi; Barretti, Pasqual; da Silva Franco, Roberto Jorge; Caramori, Jacqueline Costa Teixeira; Martin, Luis Cuadrado

2016-10-01

Patients with chronic kidney disease present a higher degree of left ventricular hypertrophy than expected for hypertension levels. In chronic kidney disease the plot between the quotient extracellular water/total body water and aldosterone is shifted up and to the right. There are few studies that verified the role of aldosterone in cardiac remodeling in this set of patients. The aim of this study was to evaluate the relationship between serum aldosterone and left ventricular mass index in patients with chronic kidney disease on hemodialysis. The patients were submitted to clinical and laboratory evaluation, bioelectrical impedance, echocardiography and ambulatory blood pressure monitoring. The 27 patients included were divided into two groups according to aldosterone level and compared with each other. The group of patients with higher aldosterone levels had higher left ventricular mass index. These groups were heterogeneous with regard to ambulatory systolic blood pressure, body mass index, and aldosterone levels and homogeneous with regard to the quotient extracellular water/total body water, renin-angiotensin-aldosterone system blockers, beta blocker use and other clinical characteristics. The association between aldosterone levels and left ventricular mass index was adjusted to confounding variables by a multiple linear regression analysis in which aldosterone was independently associated with left ventricular mass index. The data presented are consistent with a pathogenic role of aldosterone in left ventricular hypertrophy in patients with chronic kidney dialysis in dialysis patients. ClinicalTrials.gov identifier: NCT01128101. © The Author(s), 2016.

Isovolumic relaxation period as an index of left ventricular relaxation under different afterload conditions--comparison with the time constant of left ventricular pressure decay in the dog.

PubMed

Ochi, H; Ikuma, I; Toda, H; Shimada, T; Morioka, S; Moriyama, K

1989-12-01

In order to determine whether isovolumic relaxation period (IRP) reflects left ventricular relaxation under different afterload conditions, 17 anesthetized, open chest dogs were studied, and the left ventricular pressure decay time constant (T) was calculated. In 12 dogs, angiotensin II and nitroprusside were administered, with the heart rate constant at 90 beats/min. Multiple linear regression analysis showed that the aortic dicrotic notch pressure (AoDNP) and T were major determinants of IRP, while left ventricular end-diastolic pressure was a minor determinant. Multiple linear regression analysis, correlating T with IRP and AoDNP, did not further improve the correlation coefficient compared with that between T and IRP. We concluded that correction of the IRP by AoDNP is not necessary to predict T from additional multiple linear regression. The effects of ascending aortic constriction or angiotensin II on IRP were examined in five dogs, after pretreatment with propranolol. Aortic constriction caused a significant decrease in IRP and T, while angiotensin II produced a significant increase in IRP and T. IRP was affected by the change of afterload. However, the IRP and T values were always altered in the same direction. These results demonstrate that IRP is substituted for T and it reflects left ventricular relaxation even in different afterload conditions. We conclude that IRP is a simple parameter easily used to evaluate left ventricular relaxation in clinical situations.

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device.

PubMed

Gohean, Jeffrey R; George, Mitchell J; Pate, Thomas D; Kurusz, Mark; Longoria, Raul G; Smalling, Richard W

2013-01-01

The purpose of this investigation is to use a computational model to compare a synchronized valveless pulsatile left ventricular assist device with continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate the support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous pulsatile valveless dual-piston positive displacement pump. These results were compared with measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared with the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device.

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device

PubMed Central

Gohean, Jeffrey R.; George, Mitchell J.; Pate, Thomas D.; Kurusz, Mark; Longoria, Raul G.; Smalling, Richard W.

2012-01-01

The purpose of this investigation is to utilize a computational model to compare a synchronized valveless pulsatile left ventricular assist device to continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous, pulsatile, valveless, dual piston positive displacement pump. These results were compared to measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared to the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device. PMID:23438771

Left ventricular function abnormalities as a manifestation of silent myocardial ischemia.

PubMed

Lambert, C R; Conti, C R; Pepine, C J

1986-11-01

A large body of evidence exists indicating that left ventricular dysfunction is a common occurrence in patients with severe coronary artery disease and represents silent or asymptomatic myocardial ischemia. Such dysfunction probably occurs early in the time course of every ischemic episode in patients with coronary artery disease whether symptoms are eventually manifested or not. The pathophysiology of silent versus symptomatic left ventricular dysfunction due to ischemia appears to be identical. Silent ischemia-related left ventricular dysfunction can be documented during spontaneous or stress-induced perturbations in the myocardial oxygen supply/demand ratio. It also may be detected by nitroglycerin-induced improvement in ventricular function or by salutary changes in wall motion following revascularization. Silent left ventricular dysfunction is a very early occurrence during ischemia and precedes electrocardiographic abnormalities. In this light, its existence should always be kept in mind when dealing with patients with ischemic heart disease. It can be hypothesized that because silent ischemia appears to be identical to ischemia with symptoms in a pathophysiologic sense, prognosis and treatment in both cases should be the same.

Evaluation of effect of atorvastatin on left ventricular systolic function in rats with myocardial infarction via 2D-STI technique.

PubMed

Hua, Yan; Xie, Manying; Yin, Jiabao; Wang, Yu; Gan, Ling; Sang, Ming; Sun, Xiaodong; Li, Mingyang; Liu, Shanjun; Xu, Jinzhi

2018-05-01

This report aims to evaluate the effect of atorvastatin (Ator) on left ventricular systolic function in myocardial infarction (MI) rats. Forty healthy adult Sprague-Dawley rats were randomly divided into four groups: Ator group, MI group, sham-operation group and normal group. The left anterior descending coronary arteries were ligated to establish the MI model; after modeling, the Ator group was treated with Ator for 4 consecutive weeks. The echocardiographic detection was performed; the left ventricular myocardial systolic peak velocities, strain and strain rates were analyzed using the 2D-STI technique. After 4 weeks, myocardial tissues were taken from all rats and received the pathological examination. Left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) in Ator group and MI group were increased after operation, but left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were decreased; myocardial function were decreased significantly (p<0.05). After Ator treatment, myocardial function at the 3rd and 4th week after operation increased significantly (p<0.05). After Ator treatment, LVEDD and LVESD decreased while LVEF and LVFS increased in Ator group at the 3rd and 4th week after operation compared with MI group (p<0.05). At the 4th week after operation, LVEDD and LVESD in Ator group were decreased compared with those at the 1st and 2nd week after operation, but LVEF and LVFS were increased compared with those at the 1st, 2nd and 3rd week after operation (p<0.05). Pathological examination showed that necrosis and fibrosis of myocardial cells and inflammatory reaction were obvious in MI group. The inflammatory reaction of myocardial cells and myocardial fibrosis were lighter in Ator group. Ator can effectively improve the left ventricular systolic function in MI rats, which could be related to the reduction of response to inflammation and fibrosis.

Evaluation of Left and Right Atrial Function in Patients with Coronary Slow-Flow Phenomenon Using Two-Dimensional Speckle Tracking Echocardiography.

PubMed

Wang, Yonghuai; Zhang, Yan; Ma, Chunyan; Guan, Zhengyu; Liu, Shuang; Zhang, Weixin; Li, Yuling; Yang, Jun

2016-06-01

Coronary slow-flow phenomenon (CSFP) is an angiographic diagnosis characterized by delayed coronary opacification in the absence of obstructive coronary artery disease. Currently, several investigators are focusing on ventricular function assessment in patients with CSFP; however, there is a paucity of data on their atrial function. This study was performed to evaluate left atrial (LA) and right atrial (RA) function in patients with CSFP. Eighty-two patients with CSFP and 55 controls without CSFP were enrolled in the study. Diagnosis of CSFP was made by thrombolysis in myocardial infarction frame count (TFC). The LA and RA global longitudinal strain and strain rate during systole (Ss, SRs), during early diastole (Se, SRe), and during late diastole (Sa, SRa) were measured using two-dimensional speckle tracking echocardiography. In the CSFP group, LA Se and SRe decreased, while LA Sa and SRa increased, compared with the control group. RA Se and SRe were lower in patients with CSFP than in the controls. LA conduit function decreased in patients with CSFP, while contractile function increased. RA conduit function also decreased in patients with CSFP. © 2016, Wiley Periodicals, Inc.

In-vivo characterization of 2D residence time maps in the left ventricle

NASA Astrophysics Data System (ADS)

Rossini, Lorenzo; Martinez-Legazpi, Pablo; Bermejo, Javier; Benito, Yolanda; Alhama, Marta; Yotti, Raquel; Perez Del Villar, Candelas; Gonzalez-Mansilla, Ana; Barrio, Alicia; Fernandez-Aviles, Francisco; Shadden, Shawn; Del Alamo, Juan Carlos

2014-11-01

Thrombus formation is a multifactorial process involving biology and hemodynamics. Blood stagnation and wall shear stress are linked to thrombus formation. The quantification of residence time of blood in the left ventricle (LV) is relevant for patients affected by ventricular contractility dysfunction. We use a continuum formulation to compute 2D blood residence time (TR) maps in the LV using in-vivo 2D velocity fields in the apical long axis plane obtained from Doppler-echocardiography images of healthy and dilated hearts. The TR maps are generated integrating in time an advection-diffusion equation of a passive scalar with a time-source term. This equation represents the Eulerian translation of DTR / D t = 1 and is solved numerically with a finite volume method on a Cartesian grid using an immersed boundary for the LV wall. Changing the source term and the boundary conditions allows us to track blood transport (direct and retained flow) in the LV and the topology of early (E) and atrial (A) filling waves. This method has been validated against a Lagrangian Coherent Structures analysis, is computationally inexpensive and observer independent, making it a potential diagnostic tool in clinical settings.

Gi proteins regulate adenylyl cyclase activity independent of receptor activation.

PubMed

Melsom, Caroline Bull; Ørstavik, Øivind; Osnes, Jan-Bjørn; Skomedal, Tor; Levy, Finn Olav; Krobert, Kurt Allen

2014-01-01

Despite the view that only β2- as opposed to β1-adrenoceptors (βARs) couple to G(i), some data indicate that the β1AR-evoked inotropic response is also influenced by the inhibition of Gi. Therefore, we wanted to determine if Gi exerts tonic receptor-independent inhibition upon basal adenylyl cyclase (AC) activity in cardiomyocytes. We used the Gs-selective (R,R)- and the Gs- and G(i)-activating (R,S)-fenoterol to selectively activate β2ARs (β1AR blockade present) in combination with Gi inactivation with pertussis toxin (PTX). We also determined the effect of PTX upon basal and forskolin-mediated responses. Contractility was measured ex vivo in left ventricular strips and cAMP accumulation was measured in isolated ventricular cardiomyocytes from adult Wistar rats. PTX amplified both the (R,R)- and (R,S)-fenoterol-evoked maximal inotropic response and concentration-dependent increases in cAMP accumulation. The EC50 values of fenoterol matched published binding affinities. The PTX enhancement of the Gs-selective (R,R)-fenoterol-mediated responses suggests that Gi regulates AC activity independent of receptor coupling to Gi protein. Consistent with this hypothesis, forskolin-evoked cAMP accumulation was increased and inotropic responses to forskolin were potentiated by PTX treatment. In non-PTX-treated tissue, phosphodiesterase (PDE) 3 and 4 inhibition or removal of either constitutive muscarinic receptor activation of Gi with atropine or removal of constitutive adenosine receptor activation with CGS 15943 had no effect upon contractility. However, in PTX-treated tissue, PDE3 and 4 inhibition alone increased basal levels of cAMP and accordingly evoked a large inotropic response. Together, these data indicate that Gi exerts intrinsic receptor-independent inhibitory activity upon AC. We propose that PTX treatment shifts the balance of intrinsic G(i) and Gs activity upon AC towards Gs, enhancing the effect of all cAMP-mediated inotropic agents.

Gi Proteins Regulate Adenylyl Cyclase Activity Independent of Receptor Activation

PubMed Central

Melsom, Caroline Bull; Ørstavik, Øivind; Osnes, Jan-Bjørn; Skomedal, Tor; Levy, Finn Olav; Krobert, Kurt Allen

2014-01-01

Background and purpose Despite the view that only β2- as opposed to β1-adrenoceptors (βARs) couple to Gi, some data indicate that the β1AR-evoked inotropic response is also influenced by the inhibition of Gi. Therefore, we wanted to determine if Gi exerts tonic receptor-independent inhibition upon basal adenylyl cyclase (AC) activity in cardiomyocytes. Experimental approach We used the Gs-selective (R,R)- and the Gs- and Gi-activating (R,S)-fenoterol to selectively activate β2ARs (β1AR blockade present) in combination with Gi inactivation with pertussis toxin (PTX). We also determined the effect of PTX upon basal and forskolin-mediated responses. Contractility was measured ex vivo in left ventricular strips and cAMP accumulation was measured in isolated ventricular cardiomyocytes from adult Wistar rats. Key results PTX amplified both the (R,R)- and (R,S)-fenoterol-evoked maximal inotropic response and concentration-dependent increases in cAMP accumulation. The EC50 values of fenoterol matched published binding affinities. The PTX enhancement of the Gs-selective (R,R)-fenoterol-mediated responses suggests that Gi regulates AC activity independent of receptor coupling to Gi protein. Consistent with this hypothesis, forskolin-evoked cAMP accumulation was increased and inotropic responses to forskolin were potentiated by PTX treatment. In non-PTX-treated tissue, phosphodiesterase (PDE) 3 and 4 inhibition or removal of either constitutive muscarinic receptor activation of Gi with atropine or removal of constitutive adenosine receptor activation with CGS 15943 had no effect upon contractility. However, in PTX-treated tissue, PDE3 and 4 inhibition alone increased basal levels of cAMP and accordingly evoked a large inotropic response. Conclusions and implications Together, these data indicate that Gi exerts intrinsic receptor-independent inhibitory activity upon AC. We propose that PTX treatment shifts the balance of intrinsic Gi and Gs activity upon AC towards Gs, enhancing the effect of all cAMP-mediated inotropic agents. PMID:25203113

Cardiac structure and function in relation to cardiovascular risk factors in Chinese

PubMed Central

2012-01-01

Background Cardiac structure and function are well-studied in Western countries. However, epidemiological data is still scarce in China. Methods Our study was conducted in the framework of cardiovascular health examinations for the current and retired employees of a factory and their family members. According to the American Society of Echocardiography recommendations, we performed echocardiography to evaluate cardiac structure and function, including left atrial volume, left ventricular hypertrophy and diastolic dysfunction. Results The 843 participants (43.0 years) included 288 (34.2%) women, and 191 (22.7%) hypertensive patients, of whom 82 (42.9%) took antihypertensive drugs. The prevalence of left atrial enlargement, left ventricular hypertrophy and concentric remodeling was 2.4%, 5.0% and 12.7%, respectively. The prevalence of mild and moderate-to-severe left ventricular diastolic dysfunction was 14.2% and 3.3%, respectively. The prevalence of these cardiac abnormalities significantly (P ≤ 0.002) increased with age, except for the moderate-to-severe left ventricular diastolic dysfunction. After adjustment for age, gender, body height and body weight, left atrial enlargement was associated with plasma glucose (P = 0.009), and left ventricular hypertrophy and diastolic dysfunction were significantly associated with systolic and diastolic blood pressure (P ≤ 0.03), respectively. Conclusions The prevalence of cardiac structural and functional abnormalities increased with age in this Chinese population. Current drinking and plasma glucose had an impact on left atrial enlargement, whereas systolic and diastolic blood pressures were major correlates for left ventricular hypertrophy and diastolic dysfunction, respectively. PMID:23035836

ASSESSMENT OF DIASTOLIC DYSFUNCTION, ARTERIAL STIFFNESS, AND CAROTID INTIMA-MEDIA THICKNESS IN PATIENTS WITH ACROMEGALY.

PubMed

Cansu, Güven Barış; Yılmaz, Nusret; Yanıkoğlu, Atakan; Özdem, Sebahat; Yıldırım, Aytül Belgi; Süleymanlar, Gültekin; Altunbaş, Hasan Ali

2017-05-01

Early diagnosis and treatment of cardiovascular diseases, the most frequent cause of morbidity and mortality in acromegaly, may be an efficient approach to extending the lifespan of affected patients. Therefore, it is crucial to determine any cardiovascular diseases in the subclinical period. The study objectives were to determine markers of subclinical atherosclerosis and asses heart structure and function. This was a cross-sectional, single-center study of 53 patients with acromegaly and 22 age- and sex-matched healthy individuals. Carotid intima-media thickness (CIMT), pulse-wave velocity (PWV), and echocardiographic data were compared between these groups. CIMT and PWV were higher in the acromegaly group than in the healthy group (P = .008 and P = .002, respectively). Echocardiography showed that left ventricular diastolic dysfunction was present in 11.3% of patients. Left ventricular mass index and left atrial volume index were higher in the patients (P = .016 and P<.001, respectively). No differences in the CIMT, PWV, or echocardiographic measurements were identified between the patients with biochemically controlled and uncontrolled acromegaly and the control group. Our results showed that subclinical atherosclerosis (i.e., CIMT and PWV markers) and heart structure and function were worse in patients with acromegaly than in healthy individuals. Because there were no differences in these parameters between patients with controlled and uncontrolled acromegaly, our results suggest that the structural and functional changes do not reverse with biochemical control. AA = active acromegaly BSA = body surface area CA = biochemically controlled acromegaly CH = concentric hypertrophy CIMT = carotid intima-media thickness DBP = diastolic blood pressure DM = diabetes mellitus ECHO = echocardiography EDV = enddiastolic volume EF = ejection fraction ESV = endsystolic volume GH = growth hormone HC = healthy control HL = hyperlipidemia HT = hypertension IGF-1 = insulin-like growth factor 1 LA = left atrial LAV = left atrial volume LAVI = left atrial volume index LV = left ventricular LVDD = left ventricular diastolic dysfunction LVEF = left ventricular ejection fraction LVH = left ventricular hypertrophy LVMI = left ventricular mass index PWV = pulse-wave velocity RWT = relative wall thickness.

Amalaki rasayana, a traditional Indian drug enhances cardiac mitochondrial and contractile functions and improves cardiac function in rats with hypertrophy.

PubMed

Kumar, Vikas; Aneesh, Kumar A; Kshemada, K; Ajith, Kumar G S; Binil, Raj S S; Deora, Neha; Sanjay, G; Jaleel, A; Muraleedharan, T S; Anandan, E M; Mony, R S; Valiathan, M S; Santhosh, Kumar T R; Kartha, C C

2017-08-17

We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated. Histology, gene and protein expression analysis were done in heart tissues. Chemical composition of AR was analyzed by HPLC, HPTLC and LC-MS. AR intake improved (P < 0.05) cardiac function in aging rats and decreased LVH (P < 0.05) in AC rats as well as increased (P < 0.05) fatigue time in treadmill exercise in both groups. In heart tissues of AR administered rats of both the groups, SERCA2, CaM, Myh11, antioxidant, autophagy, oxidative phosphorylation and TCA cycle proteins were up regulated. ADRB1/2 and pCREB expression were increased; pAMPK, NF-kB were decreased. AR has thus a beneficial effect on myocardial energetics, muscle contractile function and exercise tolerance capacity.

Regression of left ventricular dilation after percutaneous closure of a large intralobar pulmonary sequestration.

PubMed

Alvarez, Alejandro; Borgia, Francesco; Guccione, Paolo

2010-02-01

We describe an infant of 8 months who presented with left ventricular dilation due to an extensive intralobar sequestration of the right lung. The pulmonary sequestration was associated with a patent arterial duct and a right aortic arch. Percutaneous closure of the anomalous aberrant artery feeding the sequestrated lung resulted in prompt regression of the left ventricular enlargement.

Left ventricular assist device and drug therapy for the reversal of heart failure.

PubMed

Birks, Emma J; Tansley, Patrick D; Hardy, James; George, Robert S; Bowles, Christopher T; Burke, Margaret; Banner, Nicholas R; Khaghani, Asghar; Yacoub, Magdi H

2006-11-02

In patients with severe heart failure, prolonged unloading of the myocardium with the use of a left ventricular assist device has been reported to lead to myocardial recovery in small numbers of patients for varying periods of time. Increasing the frequency and durability of myocardial recovery could reduce or postpone the need for subsequent heart transplantation. We enrolled 15 patients with severe heart failure due to nonischemic cardiomyopathy and with no histologic evidence of active myocarditis. All had markedly reduced cardiac output and were receiving inotropes. The patients underwent implantation of left ventricular assist devices and were treated with lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodeling. Once regression of left ventricular enlargement had been achieved, the beta2-adrenergic-receptor agonist clenbuterol was administered to prevent myocardial atrophy. Eleven of the 15 patients had sufficient myocardial recovery to undergo explantation of the left ventricular assist device a mean (+/-SD) of 320+/-186 days after implantation of the device. One patient died of intractable arrhythmias 24 hours after explantation; another died of carcinoma of the lung 27 months after explantation. The cumulative rate of freedom from recurrent heart failure among the surviving patients was 100% and 88.9% 1 and 4 years after explantation, respectively. The quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire score at 3 years was nearly normal. Fifty-nine months after explantation, the mean left ventricular ejection fraction was 64+/-12%, the mean left ventricular end-diastolic diameter was 59.4+/-12.1 mm, the mean left ventricular end-systolic diameter was 42.5+/-13.2 mm, and the mean maximal oxygen uptake with exercise was 26.3+/-6.0 ml per kilogram of body weight per minute. In this single-center study, we found that sustained reversal of severe heart failure secondary to nonischemic cardiomyopathy could be achieved in selected patients with the use of a left ventricular assist device and a specific pharmacologic regimen. Copyright 2006 Massachusetts Medical Society.

Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes.

PubMed

Matsutani, Daisuke; Sakamoto, Masaya; Kayama, Yosuke; Takeda, Norihiko; Horiuchi, Ryuzo; Utsunomiya, Kazunori

2018-05-22

Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure. The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated. We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM. This study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM. A total of 38 patients with T2DM were consecutively recruited for this study. Left ventricular diastolic function was assessed by echocardiography. The primary study outcome was a change in the septal E/e' as a parameter of left ventricular diastolic function. A total of 37 patients (25 males and 12 females) were included in the analysis. Mean age of participants was 64.2 ± 8.1 years (mean ± SD), mean duration of diabetes was 13.5 ± 8.1 years, and mean HbA1c was 7.9 ± 0.7%. Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease. Canagliflozin significantly improved left ventricular diastolic function (septal E/e' ratio 13.7 ± 3.5-12.1 ± 2.8, p = 0.001). Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e' ratio (p = 0.002). In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e' ratio. This study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM. The benefit was especially apparent in patients with substantially improved hemoglobin values. Trial registration UMIN Clinical Trials Registry UMIN000028141.

Left ventricular geometric patterns in end-stage kidney disease: Determinants and course over time.

PubMed

Nubé, Menso J; Hoekstra, Tiny; Doganer, Volkan; Bots, Michiel L; Blankestijn, Peter J; van den Dorpel, Marinus; Kamp, Otto; Ter Wee, Piet M; de Roij van Zuijdewijn, Camiel L M; Grooteman, Muriel P C

2018-02-20

While concentric left ventricular hypertrophy (cLVH) predominates in non-dialysis-dependent chronic kidney disease (CKD), eccentric left ventricular hypertrophy (eLVH) is most prevalent in dialysis-dependent CKD stage 5 (CKD5D). In these patients, the risk of sudden death is 5× higher than in individuals with cLVH. Currently, it is unknown which factors determine left ventricular (LV) geometry and how it changes over time in CKD5D. Data from participants of the CONvective TRAnsport Study who underwent serial transthoracic echocardiography were used. Based on left ventricular mass (LVM) and relative wall thickness (RWT), 4 types of left ventricular geometry were distinguished: normal, concentric remodeling, eLVH, and cLVH. Determinants of eLVH were assessed with logistic regression. Left ventricular geometry of patients who died and survived were compared. Long-term changes in RWT and LVM were evaluated with a linear mixed model. Three hundred twenty-two patients (63.1 ± 13.3 years) were included. At baseline, LVH was present in 71% (cLVH: 27%; eLVH: 44%). Prior cardiovascular disease (CVD) was positively associated with eLVH and ß-blocker use inversely. None of the putative volume parameters showed any relationship with eLVH. Although eLVH was most prevalent in non-survivors, the distribution of left ventricular geometry did not vary over time. The finding that previous CVD was positively associated with eLVH may result from the permanent high cardiac output and the strong tendency for aortic valve calcification in this group of long-term hemodialysis patients, who suffer generally also from chronic anemia and various other metabolic derangements. No association was found between eLVH and parameters of fluid balance. The distribution of left ventricular geometry did not alter over time. The assumption that LV geometry worsens over time in susceptible individuals, who then suffer from a high risk of dying, may explain these findings. © 2018 The Authors Hemodialysis International published by Wiley Periodicals, Inc. on behalf of International Society for Hemodialysis.

Early results of MitraClip system implantation by real-time three-dimensional speckle-tracking left ventricle analysis.

PubMed

Scandura, Salvatore; Dipasqua, Fabio; Gargiulo, Giuseppe; Capodanno, Davide; Caggegi, Anna; Grasso, Carmelo; Mangiafico, Sarah; Pistritto, Anna Maria; Immè, Sebastiano; Chiarandà, Marta; Ministeri, Margherita; Ronsivalle, Giuseppe; Cannata, Stefano; Arcidiacono, Antonio Andrea; Capranzano, Piera; Tamburino, Corrado

2016-11-01

To appraise the early effect of percutaneous mitral valve repair with the MitraClip system on myocardial function using real-time three-dimensional speckle-tracking echocardiography (3D-STE). Consecutive patients with moderate-to-severe or severe mitral regurgitation, undergoing mitral valve repair with the MitraClip system, were prospectively evaluated during the peri-procedural workout and follow-up. Left ventricular deformation was evaluated by a two-dimensional and 3D speckle-tracking analysis. 3D-STE acquisitions were elaborated obtaining real-time 3D global longitudinal strain evaluation, and by appraising both volumetric and hemodynamic parameters (i.e. left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, cardiac output, and stroke volume). In all, 30 patients were included. At 1-month follow-up, 3D-STE analysis revealed no changes in left ventricular end-diastolic volume (162.6 ± 73.7 ml at baseline vs. 159.8 ± 64.5 ml at 1-month follow-up; P = 0.63) and a downward trend in left ventricular end-systolic volume (104.7 ± 52.0 vs. 100.1 ± 50.4 ml, respectively; P = 0.06). Left ventricular ejection fraction did not significantly increase (38.1 ± 11.3% at baseline vs. 39.4 ± 11.0% at 1-month follow-up; P = 0.20). No significant changes were reported in cardiac output (4.3 ± 2.0 l/min at baseline vs. 4.0 ± 1.5 l/min at follow-up; P = 0.377) and in stroke volume (59.5 ± 25.5 ml at baseline vs. 59.9 ± 20.7 ml at follow-up; P = 0.867). On the contrary, left ventricular deformation capability significantly improved, with the real-time 3D global longitudinal strain value changing from -9.8 ± 4.1% at baseline to -11.0 ± 4.4% at follow-up (P = 0.018). Accurately assessing myocardial function by the use of 3D-STE, this study reported irrelevant early changes in left ventricular size, but a positive effect on left ventricular deformation capability following mitral valve repair with the MitraClip system. These preliminary results need to be confirmed in larger series and extended to long-term follow-up.

Right Ventricular Ejection Fraction Is Incremental to Left Ventricular Ejection Fraction for the Prediction of Future Arrhythmic Events in Patients With Systolic Dysfunction.

PubMed

Mikami, Yoko; Jolly, Umjeet; Heydari, Bobak; Peng, Mingkai; Almehmadi, Fahad; Zahrani, Mohammed; Bokhari, Mahmoud; Stirrat, John; Lydell, Carmen P; Howarth, Andrew G; Yee, Raymond; White, James A

2017-01-01

Left ventricular ejection fraction remains the primary risk stratification tool used in the selection of patients for implantable cardioverter defibrillator therapy. However, this solitary marker fails to identify a substantial portion of patients experiencing sudden cardiac arrest. In this study, we examined the incremental value of considering right ventricular ejection fraction for the prediction of future arrhythmic events in patients with systolic dysfunction using the gold standard of cardiovascular magnetic resonance. Three hundred fourteen consecutive patients with ischemic cardiomyopathy or nonischemic dilated cardiomyopathy undergoing cardiovascular magnetic resonance were followed for the primary outcome of sudden cardiac arrest or appropriate implantable cardioverter defibrillator therapy. Blinded quantification of left ventricular and right ventricular (RV) volumes was performed from standard cine imaging. Quantification of fibrosis from late gadolinium enhancement imaging was incrementally performed. RV dysfunction was defined as right ventricular ejection fraction ≤45%. Among all patients (164 ischemic cardiomyopathy, 150 nonischemic dilated cardiomyopathy), the mean left ventricular ejection fraction was 32±12% (range, 6-54%) with mean right ventricular ejection fraction of 48±15% (range, 7-78%). At a median of 773 days, 49 patients (15.6%) experienced the primary outcome (9 sudden cardiac arrest, 40 appropriate implantable cardioverter defibrillator therapies). RV dysfunction was independently predictive of the primary outcome (hazard ratio=2.98; P=0.002). Among those with a left ventricular ejection fraction >35% (N=121; mean left ventricular ejection fraction, 45±6%), RV dysfunction provided an adjusted hazard ratio of 4.2 (P=0.02). RV dysfunction is a strong, independent predictor of arrhythmic events. Among patients with mild to moderate LV dysfunction, a cohort greatly contributing to global sudden cardiac arrest burden, this marker provides robust discrimination of high- versus low-risk subjects. © 2017 American Heart Association, Inc.

Influence of microalbuminuria on left ventricular geometry and function in hypertensive patients with type 2 diabetes mellitus.

PubMed

Picca, Maurizio; Agozzino, Francesco; Pelosi, Giancarlo

2003-01-01

An increased urinary albumin excretion (UAE) is associated with an augmented risk of cardiovascular disease in diabetic patients and in non-diabetic subjects. Left ventricular hypertrophy has been demonstrated to be a powerful predictor of cardiovascular morbidity and mortality in arterial hypertension and when the ventricular geometry is concentric the relation is even stronger. This echocardiographic and Doppler study was designed to evaluate the influence of microalbuminuria on the left ventricular geometry and function in hypertensive patients with type 2 diabetes melitus. Forty-two patients (16 males, 26 females, mean age 59.6 +/- 6.7 years) with mild-to-moderate essential hypertension and type 2 diabetes mellitus were enrolled in the study. Twenty-one patients had an elevated UAE (group 1) and 21 a normal UAE (group 2). M-mode (under two-dimensional control) and Doppler echocardiography were performed after a 4-week washout period off antihypertensive therapy. The left ventricular mass index was found to be greater than the partition value of 51 g/m2.7 in both groups but was significantly higher (p < 0.001) in group 1. The midwall fractional shortening was significantly lower (p < 0.001) in group 1 in comparison with group 2. The E/A ratio was impaired in both groups but was more significantly reduced (p < 0.02) in group 1. There was a significantly higher prevalence of a left ventricular concentric hypertrophy pattern (19/21 patients, p < 0.001) in group 1. In hypertensive patients with type 2 diabetes mellitus, an elevated UAE is associated with an increased left ventricular mass index, a higher prevalence of a concentric left ventricular hypertrophy pattern, a depressed midwall systolic performance and a markedly impaired diastolic function...

Larger late sodium current density as well as greater sensitivities to ATX II and ranolazine in rabbit left atrial than left ventricular myocytes.

PubMed

Luo, Antao; Ma, Jihua; Song, Yejia; Qian, Chunping; Wu, Ying; Zhang, Peihua; Wang, Leilei; Fu, Chen; Cao, Zhenzhen; Shryock, John C

2014-02-01

An increase of cardiac late sodium current (INa.L) is arrhythmogenic in atrial and ventricular tissues, but the densities of INa.L and thus the potential relative contributions of this current to sodium ion (Na(+)) influx and arrhythmogenesis in atria and ventricles are unclear. In this study, whole-cell and cell-attached patch-clamp techniques were used to measure INa.L in rabbit left atrial and ventricular myocytes under identical conditions. The density of INa.L was 67% greater in left atrial (0.50 ± 0.09 pA/pF, n = 20) than in left ventricular cells (0.30 ± 0.07 pA/pF, n = 27, P < 0.01) when elicited by step pulses from -120 to -20 mV at a rate of 0.2 Hz. Similar results were obtained using step pulses from -90 to -20 mV. Anemone toxin II (ATX II) increased INa.L with an EC50 value of 14 ± 2 nM and a Hill slope of 1.4 ± 0.1 (n = 9) in atrial myocytes and with an EC50 of 21 ± 5 nM and a Hill slope of 1.2 ± 0.1 (n = 12) in ventricular myocytes. Na(+) channel open probability (but not mean open time) was greater in atrial than in ventricular cells in the absence and presence of ATX II. The INa.L inhibitor ranolazine (3, 6, and 9 μM) reduced INa.L more in atrial than ventricular myocytes in the presence of 40 nM ATX II. In summary, rabbit left atrial myocytes have a greater density of INa.L and higher sensitivities to ATX II and ranolazine than rabbit left ventricular myocytes.

Left ventricular rotation and torsion in patients with perimembranous ventricular septal defect.

PubMed

Zhuang, Yan; Yong, Yong-hong; Yao, Jing; Ji, Ling; Xu, Di

2014-03-01

Assessment of left ventricular (LV) rotation has become an important approach for quantifying LV function. In this study, we sought to analyze LV rotation and twist using speckle tracking imaging (STI) in adult patients with isolated ventricular septal defects. Using STI, the peak rotation and time to peak rotation of 6 segments in basal and apical short-axis were measured, respectively, in 32 patients with ventricular septal defect and 30 healthy subjects as controls. The global rotation of the 6 segments in basal and apical and LV twist versus time profile were drawn, the peak rotation and twist of LV were calculated. All the time to peak rotation/twist were expressed as a percentage of end-systole (end-systole = 100%). Left ventricular ejection fraction was measured by biplane Simpson method. In patients group, the peak rotation of posterior, inferior, and postsept wall in basal was higher(P ≤ 0.05) and LV twist was also higher (P ≤ 0.05) than healthy controls. There were no significant differences between 2 groups in the peak rotation of the other 9 segments and left ventricular ejection fraction. Different from the control group, the time to peak rotation of the 6 segments in basal were delayed and the global rotation of the base was delayed (P ≤ 0.05) in ventricular septal defect group. Left ventricular volume overload due to ventricular septal defect has significant effect on LV rotation and twist, and LV rotation and twist may be a new index predicting LV systolic function. © 2013, Wiley Periodicals, Inc.

Myocardial scar location as detected by cardiac magnetic resonance is associated with the outcome in heart failure patients undergoing surgical ventricular reconstruction.

PubMed

Castelvecchio, Serenella; Careri, Giulia; Ambrogi, Federico; Camporeale, Antonia; Menicanti, Lorenzo; Secchi, Francesco; Lombardi, Massimo

2018-01-01

Post-infarction myocardial scar causes adverse left ventricular remodelling and negatively affects the prognosis. We sought to investigate whether scar extent and location obtained by cardiac magnetic resonance may affect the reverse remodelling and survival of heart failure patients undergoing surgical ventricular reconstruction. From January 2011 to December 2015, 151 consecutive patients with previous myocardial infarction and left ventricular remodelling underwent surgical ventricular reconstruction at our Institution, of which 88 (58%) patients had a preoperative protocol-standardized late gadolinium enhancement (LGE)-cardiac magnetic resonance examination during the week before surgery. We excluded 40 patients with devices (26%), 15 patients with irregular heart rhythm (permanent atrial fibrillation, 10% not included in the device group) or mixed contraindications (severe claustrophobia or presence of material magnetic resonance not compatible). Among the 145 survivors, 11 patients received an implantable cardioverter defibrillator after surgery (mostly for persistent low ejection fraction) and were excluded as well, yielding a total of 59 patients (48 men, aged 65 ± 9 years) who repeated a protocol-standardized LGE-cardiac magnetic resonance examination even 6 months postoperatively and therefore represent the study population. Patients were grouped according to the presence of LGE in the antero-basal left ventricular segments (Group A) or the absence of LGE in the same segments (Group B). The postoperative left ventricular end-systolic volume index was considered the primary end-point. After surgery, left ventricular end-systolic volume index and end-diastolic volume index significantly decreased (P < 0.001, for both), while diastolic sphericity index and ejection fraction significantly increased (P = 0.015 and P < 0.001, respectively). The presence of LGE in the antero-basal left ventricular segments (10 patients, Group A) was the only independent predictor of outcome (P = 0.02) at multivariate analysis, being the postoperative left ventricular end-systolic volume index significantly higher compared to that of patients of Group B (49 patients) (78 ± 26 ml/m2 vs 55 ± 20 ml/m2, P = 0.003). Furthermore, patients with a postoperative left ventricular end-systolic volume index >60 ml/m2 showed a higher risk of cardiac events (hazard ratio = 3.67, P = 0.02). In patients undergoing surgical ventricular reconstruction, LGE scar location affects the left ventricular reverse remodelling, which in turn might limit the survival benefit. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

EDUCATIONAL SERIES IN CONGENITAL HEART DISEASE: Congenital left-sided heart obstruction

PubMed Central

Carr, Michelle; Curtis, Stephanie; Marek, Jan

2018-01-01

Congenital obstruction of the left ventricular outflow tract remains a significant problem and multilevel obstruction can often coexist. Obstruction can take several morphological forms and may involve the subvalvar, valvar or supravalvar portion of the aortic valve complex. Congenital valvar stenosis presenting in the neonatal period represents a spectrum of disorders ranging from the hypoplastic left heart syndrome to almost normal hearts. Treatment options vary dependent on the severity of the left ventricular outflow tract obstruction (LVOTO) and the variable degree of left ventricular hypoplasia as well as the associated lesions such as arch hypoplasia and coarctation. PMID:29681546

Right ventricular pressure response to exercise in adults with isolated ventricular septal defect closed in early childhood.

PubMed

Moller, Thomas; Lindberg, Harald; Lund, May Brit; Holmstrom, Henrik; Dohlen, Gaute; Thaulow, Erik

2018-06-01

We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30-45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score -0.4, 95% CI -2.8-0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.

Computational model based approach to analysis ventricular arrhythmias: Effects of dysfunction calcium channels

NASA Astrophysics Data System (ADS)

Gulothungan, G.; Malathi, R.

2018-04-01

Disturbed sodium (Na+) and calcium (Ca2+) handling is known to be a major predisposing factor for life-threatening cardiac arrhythmias. Cardiac contractility in ventricular tissue is prominent by Ca2+ channels like voltage dependent Ca2+ channels, sodium-calcium exchanger (Na+-Ca2+x) and sacroplasmicrecticulum (SR) Ca2+ pump and leakage channels. Experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. Our aim of this article is to study the impact on action potential (AP) generation and propagation in single ventricular myocyte and ventricular tissue under different dysfunction Ca2+ channels condition. In enhanced activity of Na+-Ca2+x, single myocyte produces AP duration (APD90) and APD50 is significantly smaller (266 ms and 235 ms). Its Na+-Ca2+x current at depolarization is increases 60% from its normal level and repolarization current goes more negative (nonfailing= -0.28 pA/pF and failing= -0.47 pA/pF). Similarly, same enhanced activity of Na+-Ca2+x in 10 mm region of ventricular sheet, raises the plateau potential abruptly, which ultimately affects the diastolic repolarization. Compare with normal ventricular sheet region of 10 mm, 10% of ventricular sheet resting state is reduces and ventricular sheet at time 250 ms is goes to resting state very early. In hypertrophy condition, single myocyte produces APD90 and APD50 is worthy of attention smaller (232 mS and 198 ms). Its sodium-potassium (Na+-K+) pump current is 75% reduces from its control conditions (0.13 pA/pF). Hypertrophy condition, 50% of ventricular sheet is reduces to minimum plateau potential state, that starts the repolarization process very early and reduces the APD. In a single failing SR Ca2+ channels myocyte, recovery of Ca2+ concentration level in SR reduces upto 15% from its control myocytes. At time 290 ms, 70% of ventricular sheet is in dysfunction resting potential state in the range -83 mV and ventricular sheet at time 295 ms is goes to 65% dysfunction resting state. Therefore we concluded that shorter APD, instability resting potential and affected calcium induced calcium release (CICR) due to dysfunction Ca2+ channels is potentially have a substantial effect on cardiac contractility and relaxation. Computational study on ventricular tissue AP and its underlying ionic channel currents could help to elucidate possible arrhythmogenic mechanism on a cellular level.

Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops.

PubMed

Dekker, A L A J; Phelps, B; Dijkman, B; van der Nagel, T; van der Veen, F H; Geskes, G G; Maessen, J G

2004-06-01

Patients in heart failure with left bundle branch block benefit from cardiac resynchronization therapy. Usually the left ventricular pacing lead is placed by coronary sinus catheterization; however, this procedure is not always successful, and patients may be referred for surgical epicardial lead placement. The objective of this study was to develop a method to guide epicardial lead placement in cardiac resynchronization therapy. Eleven patients in heart failure who were eligible for cardiac resynchronization therapy were referred for surgery because of failed coronary sinus left ventricular lead implantation. Minithoracotomy or thoracoscopy was performed, and a temporary epicardial electrode was used for biventricular pacing at various sites on the left ventricle. Pressure-volume loops with the conductance catheter were used to select the best site for each individual patient. Relative to the baseline situation, biventricular pacing with an optimal left ventricular lead position significantly increased stroke volume (+39%, P =.01), maximal left ventricular pressure derivative (+20%, P =.02), ejection fraction (+30%, P =.007), and stroke work (+66%, P =.006) and reduced end-systolic volume (-6%, P =.04). In contrast, biventricular pacing at a suboptimal site did not significantly change left ventricular function and even worsened it in some cases. To optimize cardiac resynchronization therapy with epicardial leads, mapping to determine the best pace site is a prerequisite. Pressure-volume loops offer real-time guidance for targeting epicardial lead placement during minimal invasive surgery.

Double-chambered left ventricle in a cat.

PubMed

Smith, Paul J; Tarazi, Marwan N; Ho, Siew Yen

2014-06-01

Double-chambered left ventricle is a rare congenital disorder in which the left ventricular cavity is subdivided into two cavities by an anomalous septum or muscle band. We describe a case of double-chambered left ventricle, most likely caused by the presence of excessive left ventricular bands, in an asymptomatic cat. Copyright © 2014 Elsevier B.V. All rights reserved.

Treatment of dilated cardiomyopathy with carvedilol in children.

PubMed

Erdoğan, Ilkay; Ozer, Sema; Karagöz, Tevfik; Celiker, Alpay; Ozkutlu, Süheyla; Alehan, Dursun

2009-01-01

We performed a study to examine the clinical use of carvedilol, its dosage and its effects on systolic functions in children. Twenty-one patients with dilated cardiomyopathy who were treated with carvedilol adjacent to standard heart failure therapy were enrolled in the study. Echocardiographic assessment was obtained before and during carvedilol therapy, and left ventricular fractional shortening and left ventricular ejection fraction were determined in order to estimate left ventricular function. At a follow-up of six months, left ventricular ejection fraction and fractional shortening significantly improved from 38 +/- 10% to 53 +/- 13% and from 19 +/- 6 % to 27 +/- 8%, respectively, following carvedilol treatment. The results of the present study indicate that carvedilol is well tolerated in children with dilated cardiomyopathy and there is a significant improvement in the clinical status and left ventricular ejection fraction in patients not responding to conventional therapy. Patient selection criteria, optimal timing of carvedilol therapy, its dosage and its long-term effects need to be investigated with multi-institutional trials and large numbers of patients.

Left ventricular to left atrial communication secondary to a paraaortic abscess: color flow Doppler documentation.

PubMed

Fisher, E A; Estioko, M R; Stern, E H; Goldman, M E

1987-07-01

Aortic root abscess occurs frequently in aortic prosthetic valve infective endocarditis. The present echocardiographic report documents a ruptured abscess that led to a direct communication between the left ventricular outflow tract and the left atrium confirmed by real-time (color flow) Doppler imaging.

[Measurement of left atrial and ventricular volumes in real-time 3D echocardiography. Validation by nuclear magnetic resonance

NASA Technical Reports Server (NTRS)

Bauer, F.; Shiota, T.; Qin, J. X.; White, R. D.; Thomas, J. D.

2001-01-01

The measurement of the left ventricular ejection fraction is important for the evaluation of cardiomyopathy and depends on the measurement of left ventricular volumes. There are no existing conventional echocardiographic means of measuring the true left atrial and ventricular volumes without mathematical approximations. The aim of this study was to test anew real time 3-dimensional echocardiographic system of calculating left atrial and ventricular volumes in 40 patients after in vitro validation. The volumes of the left atrium and ventricle acquired from real time 3-D echocardiography in the apical view, were calculated in 7 sections parallel to the surface of the probe and compared with atrial (10 patients) and ventricular (30 patients) volumes calculated by nuclear magnetic resonance with the simpson method and with volumes of water in balloons placed in a cistern. Linear regression analysis showed an excellent correlation between the real volume of water in the balloons and volumes given in real time 3-dimensional echocardiography (y = 0.94x + 5.5, r = 0.99, p < 0.001, D = -10 +/- 4.5 ml). A good correlation was observed between real time 3-dimensional echocardiography and nuclear magnetic resonance for the measurement of left atrial and ventricular volumes (y = 0.95x - 10, r = 0.91, p < 0.001, D = -14.8 +/- 19.5 ml and y = 0.87x + 10, r = 0.98, P < 0.001, D = -8.3 +/- 18.7 ml, respectively. The authors conclude that real time three-dimensional echocardiography allows accurate measurement of left heart volumes underlying the clinical potential of this new 3-D method.

Association between hippuric acid and left ventricular hypertrophy in maintenance hemodialysis patients.

PubMed

Yu, Teng-Hung; Tang, Wei-Hua; Lu, Yung-Chuan; Wang, Chao-Ping; Hung, Wei-Chin; Wu, Cheng-Ching; Tsai, I-Ting; Chung, Fu-Mei; Houng, Jer-Yiing; Lan, Wen-Chun; Lee, Yau-Jiunn

2018-05-22

Left ventricular hypertrophy (LVH) is one of the most common cardiac abnormalities in patients with end-stage renal disease. Hippuric acid (HA), a harmful uremic toxin, is known to be elevated in patients with uremia, and serum HA levels are associated with neurological symptoms, metabolic acidosis, and accelerated renal damage associated with chronic kidney disease. However, the pathophysiological role of HA in patients with uremia remains unclear. We investigated the association between serum HA levels and echocardiographic measurements in patients undergoing hemodialysis (HD) treatment. Eighty consecutive patients treated at a single HD center (44 males, 36 females; mean age 66 y, mean HD duration 6 y) were included in this study. Comprehensive echocardiography was performed after HD. Blood samples were obtained before HD. Pearson's correlation analysis revealed that serum HA levels were positively correlated with diastolic blood pressure, serum creatinine, left ventricular mass index, end diastolic interventricular septal thickness, left ventricular end-diastolic diameter, left ventricular end systolic diameter, end systolic left ventricular posterior wall thickness, and left atrium diameter, and negatively correlated with age. Furthermore, the HD patients with LVH had higher median serum HA levels than those without LVH (34.2 vs. 18.1 μg/ml, p = 0.003). Multiple logistic regression analysis revealed that HA was independently associated with LVH even after adjusting for known biomarkers. Moreover, the receiver operator characteristics curve of HA showed that a HA level of >26.9 μg/ml was associated with LVH. HA was significantly associated with LVH. HA could be a novel biomarker of left ventricular overload, which is closely associated with an increased risk of death in HD patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Cardiothoracic ratio for prediction of left ventricular dilation: a systematic review and pooled analysis.

PubMed

Loomba, Rohit S; Shah, Parinda H; Nijhawan, Karan; Aggarwal, Saurabh; Arora, Rohit

2015-03-01

Increased cardiothoracic ratio noted on chest radiographs often prompts concern and further evaluation with additional imaging. This study pools available data assessing the utility of cardiothoracic ratio in predicting left ventricular dilation. A systematic review of the literature was conducted to identify studies comparing cardiothoracic ratio by chest x-ray to left ventricular dilation by echocardiography. Electronic databases were used to identify studies which were then assessed for quality and bias, with those with adequate quality and minimal bias ultimately being included in the pooled analysis. The pooled data were used to determine the sensitivity, specificity, positive predictive value and negative predictive value of cardiomegaly in predicting left ventricular dilation. A total of six studies consisting of 466 patients were included in this analysis. Cardiothoracic ratio had 83.3% sensitivity, 45.4% specificity, 43.5% positive predictive value and 82.7% negative predictive value. When a secondary analysis was conducted with a pediatric study excluded, a total of five studies consisting of 371 patients were included. Cardiothoracic ratio had 86.2% sensitivity, 25.2% specificity, 42.5% positive predictive value and 74.0% negative predictive value. Cardiothoracic ratio as determined by chest radiograph is sensitive but not specific for identifying left ventricular dilation. Cardiothoracic ratio also has a strong negative predictive value for identifying left ventricular dilation.

Effect of HeartMate left ventricular assist device on cardiac autonomic nervous activity.

PubMed

Kim, S Y; Montoya, A; Zbilut, J P; Mawulawde, K; Sullivan, H J; Lonchyna, V A; Terrell, M R; Pifarré, R

1996-02-01

Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology. This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation. The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance. The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.

Doppler echocardiographic analysis of left ventricular filling in treated hypertensive patients.

PubMed

Phillips, R A; Coplan, N L; Krakoff, L R; Yeager, K; Ross, R S; Gorlin, R; Goldman, M E

1987-02-01

Early detection and prevention of cardiac dysfunction is an important goal in the management of hypertensive patients. In this study, Doppler echocardiography was used to evaluate the pattern of left ventricular diastolic filling in 38 subjects: 18 treated hypertensive patients (blood pressure 141 +/- 17/83 +/- 10 mm Hg, mean +/- SD) without other coronary risk factors and 20 risk-free normotensive subjects of similar age (47 +/- 10 and 49 +/- 13 years, respectively). Peak velocity of late left ventricular filling due to the atrial contraction was greater in hypertensive compared with normotensive subjects (69 +/- 14 versus 52 +/- 13 cm/s; p less than 0.001). Peak velocity of late filling was significantly greater in hypertensive versus normotensive subjects in those aged 50 years or younger and those older than age 50 (65 +/- 12 versus 50 +/- 11; p less than 0.01 and 75 +/- 15 versus 56 +/- 15 cm/s; p less than 0.05, respectively). In hypertensive subjects, peak velocity of late filling did not correlate with routine indexes of hypertensive heart disease (including posterior wall thickness and left ventricular mass), systolic and diastolic blood pressure or duration of hypertension. These results indicate that increased velocity of late left ventricular filling may be independent of left ventricular hypertrophy and persist despite effective blood pressure control.

The effects of hypoxemia on myocardial blood flow during exercise.

PubMed

Paridon, S M; Bricker, J T; Dreyer, W J; Reardon, M; Smith, E O; Porter, C B; Michael, L; Fisher, D J

1989-03-01

We evaluated the adequacy of regional and transmural blood flow during exercise and rapid pacing after 1 wk of hypoxemia. Seven mature mongrel dogs were made hypoxemic (mean O2 saturation = 72.4%) by anastomosis of left pulmonary artery to left atrial appendage. Catheters were placed in the left atrium, right atrium, pulmonary artery, and aorta. Atrial and ventricular pacing wires were placed. An aortic flow probe was placed to measure cardiac output. Ten nonshunted dogs, similarly instrumented, served as controls. Recovery time was approximately 1 wk. Cardiac output, mean aortic pressure, and oxygen saturation were measured at rest, with ventricular pacing, atrial pacing, and with treadmill exercise. Ventricular and atrial pace and exercise were at a heart rate of 200. Right ventricular free wall, left ventricular free wall, and septal blood flow were measured with radionuclide-labeled microspheres. Cardiac output, left atrial blood pressure, and aortic blood pressure were similar between the two groups of dogs in all testing states. Myocardial blood flow was significantly higher in the right and left ventricular free wall in the hypoxemic animals during resting and exercise testing states. Myocardial oxygen delivery was similar between the two groups of animals. Pacing resulted in an increase in myocardial blood flow in the control animals but not the hypoxemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Asynchronous (segmental early) relaxation impairs left ventricular filling in patients with coronary artery disease and normal systolic function.

PubMed

Vanoverschelde, J L; Wijns, W; Michel, X; Cosyns, J; Detry, J M

1991-11-01

Asynchronous segmental early relaxation, defined as a localized early segmental outward motion of the left ventricular endocardium during isovolumetric relaxation, has been associated with an altered left ventricular relaxation rate. To determine whether asynchronous segmental early relaxation also results in impaired left ventricular filling, early diastolic ventricular wall motion and Doppler-derived left ventricular filling indexes were examined in 25 patients with documented coronary artery disease and normal systolic function. Patients were further classified into two groups according to the presence (n = 15, group 1) or absence (n = 10, group 2) of asynchronous early relaxation at left ventriculography. A third group of 10 age-matched normal subjects served as a control group. No differences were observed between the two patient groups with coronary artery disease with respect to age, gender distribution, heart rate, left ventricular systolic and diastolic pressures or extent and severity of coronary artery disease. No differences in transmitral filling dynamics were observed between group 2 patients and age-matched control subjects. Conversely, group 1 patients had significantly lower peak early filling velocities (44 +/- 11 vs. 58 +/- 11 cm/s, p less than 0.01), larger atrial filling fraction (45 +/- 4% vs. 38 +/- 4%, p less than 0.001), lower ratio of early to late transmitral filling velocities (0.6 +/- 0.08 vs. 0.99 +/- 0.18, p less than 0.001) and a longer isovolumetric relaxation period (114 +/- 12 vs. 90 +/- 6 ms, p less than 0.001) compared with group 2 patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Isovolumic relaxation time varies predictably with its time constant and aortic and left atrial pressures: implications for the noninvasive evaluation of ventricular relaxation.

PubMed

Thomas, J D; Flachskampf, F A; Chen, C; Guererro, J L; Picard, M H; Levine, R A; Weyman, A E

1992-11-01

The isovolumic relaxation time (IVRT) is an important noninvasive index of left ventricular diastolic function. Despite its widespread use, however, the IVRT has not been related analytically to invasive parameters of ventricular function. Establishing such a relationship would make the IVRT more useful by itself and perhaps allow it to be combined more precisely with other noninvasive parameters of ventricular filling. The purpose of this study was to validate such a quantitative relationship. Assuming isovolumic relaxation to be a monoexponential decay of ventricular pressure (pv) to a zero-pressure asymptote, it was postulated that the time interval from aortic valve closure (when pv = p(o)) until mitral valve opening (when pv = left atrial pressure, pA) would be given analytically by IVRT = tau[log(p(o))-log(pA)], where tau is the time constant of isovolumic relaxation and log is to the base e. To test this hypothesis we analyzed data from six canine experiments in which ventricular preload and afterload were controlled nonpharmacologically. In addition, tau was adjusted with the use of beta-adrenergic blockade and calcium infusion, as well as with hypothermia. In each experiment data were collected before and after the surgical formation of mitral stenosis, performed to permit the study of a wide range of left atrial pressures. High-fidelity left atrial, left ventricular, and aortic root pressures were digitized, the IVRT was measured from the aortic dicrotic notch until the left atrioventricular pressure crossover point, and tau was calculated by nonlinear least-squares regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*.

PubMed

Landesberg, Giora; Jaffe, Allan S; Gilon, Dan; Levin, Phillip D; Goodman, Sergey; Abu-Baih, Abed; Beeri, Ronen; Weissman, Charles; Sprung, Charles L; Landesberg, Amir

2014-04-01

Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis. Prospective, analytic cohort study. Tertiary academic institute. A cohort of ICU patients with severe sepsis or septic shock. Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock. Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e'-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and -2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s'-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e'-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e'-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively). Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

Evaluation of right heart function in a rat model using modified echocardiographic views.

PubMed

Bernardo, Ivan; Wong, James; Wlodek, Mary E; Vlahos, Ross; Soeding, Paul

2017-01-01

Echocardiography plays a major role in assessing cardiac function in animal models. We investigated use of a modified parasternal mid right-ventricular (MRV) and right ventricle (RV) outflow (RVOT) view, in assessing RV size and function, and the suitability of advanced 2D-strain analysis. 15 WKY rats were examined using transthoracic echocardiography. The left heart was assessed using standard short and long axis views. For the right ventricle a MRV and RVOT view were used to measure RV chamber and free wall area. 2D-strain analysis was applied to both ventricles using off-line analysis. RV chamber volume was determined by injection of 2% agarose gel, and RV free wall dissected and weighed. Echocardiography measurement was correlated with necropsy findings. The RV mid-ventricular dimension (R1) was 0.42±0.07cm and the right ventricular outflow tract dimension (R2) was 0.34±0.06cm, chamber end-diastolic area measurements were 0.38±0.09cm2 and 0.29±0.08cm2 for MRV and RVOT views respectively. RVOT and MRV chamber area correlated with gel mass. Doppler RV stroke volume was 0.32±0.08ml, cardiac output (CO) 110±27 ml.min-1 and RV free wall contractility assessed using 2D-strain analysis was demonstrated. We have shown that modified MRV and RVOT views can provide detailed assessment of the RV in rodents, with 2D-strain analysis of the RV free wall potentially feasible.

[Left ventricular hypertrophy in black African subjects with artery hypertension: Results of a cross-sectional survey conducted in semi-rural area in Senegal].

PubMed

Mbaye, A; Dodo, B; Ngaïde, A A; Sy, N F; Babaka, K; Mingou, J S; Faye, M; Niang, K; Sarr, S A; Dioum, M; Bodian, M; Ndiaye, M B; Kane, A D; Ndour-Mbaye, M; Diao, M; Diack, B; Kane, M; Diagne-Sow, D; Thiaw, I; Kane, A

2017-09-01

To assess the prevalence of left ventricular hypertrophy according to electrocardiographic and echocardiographic criteria among hypertensive patients living in semi-rural Senegalese area. According to the World Health Organization STEPSwise approach, we conducted, in November 2012, a cross-sectional and exhaustive study in the population aged at least 35 years old and living for at least six months in the semi-rural area of Guéoul. We researched electrocardiographic and echocardiographic left ventricular hypertrophy in hypertensive subjects. Data were analyzed with SPSS 18.0 software version. The significance level was agreed for a value of P<0.05. We examined 1411 subjects aged on average of 48.5±12.7 years. In total, 654 subjects were hypertensive and screening of left ventricular hypertrophy (LVH) was effective in 515 of them. According to Sokolow-Lyon index, 86 subjects (16.7%) presented electrocardiographic LVH, more frequently in men (P=0.002). According to Cornell index and Cornell product, LVH was founded respectively in 66 (12.8%) and 52 subjects (10.1%), more frequently in female (P=0.0001; P=0.004). It was more common in grade 3 of hypertension however criteria. In echocardiography, prevalence of LVH was 2.2% (13 cases) according to the left ventricular mass, 9.3% (48 cases) according to the left ventricular mass indexed to body surface area and 8.2% (42 cases) according to the left ventricular mass indexed to height 2.7 . LVH was significantly correlated with the electrocardiographic LVH according to Sokolow-Lyon index (P<0.0001) and the grade 3 of hypertension (P=0.003). Although rare in hypertensive Senegalese living in semi-rural area, left ventricular hypertrophy is correlated with severity of grade of hypertension. Screening by electrocardiogram will allow better follow-up of these hypertensive subjects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy.

PubMed

de Oliveira, Luciano Fonseca Lemos; Romano, Minna Moreira Dias; de Carvalho, Eduardo Elias Vieira; Cabeza, Jorge Mejia; Salgado, Hélio Cesar; Fazan Júnior, Rubens; Costa, Renata Sesti; da Silva, João Santana; Higuchi, Maria de Lourdes; Maciel, Benedito Carlos; Cunha-Neto, Edécio; Marin-Neto, José Antônio; Simões, Marcus Vinícius

2016-01-21

Chronic Chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities (WMA), mainly in the early stages of disease. This study aimed at investigating the detection of WMA and its correlation with the underlying histopathological changes in a chronic Chagas cardiomyopathy model in hamsters. Female Syrian hamsters (n=34) infected with 3.5×10(4) or 10(5) blood trypomastigote Trypanosoma cruzi (Y strain) forms and an uninfected control group (n=7) were investigated. After 6 or 10 months after the infection, the animals were submitted to in vivo evaluation of global and segmental left ventricular systolic function by echocardiography, followed by euthanasia and histological analysis for quantitative assessment of fibrosis and inflammation with tissue sampling in locations coinciding with the left ventricular wall segmentation employed at the in vivo echocardiographic evaluation. Ten of the 34 infected animals (29%) showed reduced left ventricular ejection fraction (<73%). Left ventricular ejection fraction was more negatively correlated with the intensity of inflammation (r=-0.63; P<0.0001) than with the extent of fibrosis (r=-0.36; P=0.036). Among the 24 animals with preserved left ventricular ejection fraction (82.9±5.5%), 8 (33%) showed segmental WMA predominating in the apical, inferior, and posterolateral segments. The segments exhibiting WMA, in comparison to those with normal wall motion, showed a greater extent of fibrosis (9.3±5.7% and 7±6.3%, P<0.0001) and an even greater intensity of inflammation (218.0±111.6 and 124.5±84.8 nuclei/mm², P<0.0001). Isolated WMA with preserved global systolic left ventricular function is frequently found in Syrian hamsters with experimental chronic Chagas cardiomyopathy whose underlying histopathological features are mainly inflammatory. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Ventricular-Arterial Coupling and Exercise-Induced Pulmonary Hypertension During Low-Level Exercise in Heart Failure With Preserved or Reduced Ejection Fraction.

PubMed

Obokata, Masaru; Nagata, Yasufumi; Kado, Yuichiro; Kurabayashi, Masahiko; Otsuji, Yutaka; Takeuchi, Masaaki

2017-03-01

Exercise-induced pulmonary hypertension (EIPH) may develop even at low workloads in heart failure (HF) patients. Ventricular-arterial stiffening plays an important role in the pathophysiology of HF with preserved ejection fraction (HFpEF). This study aimed to compare the response of ventricular-arterial coupling and PH during low-level exercise between HFpEF and HF with reduced EF (HFrEF). Echocardiography was performed at rest and during 10 W of bicycle exercise in HFpEF (n = 37) and HFrEF (n = 43). Load-independent contractility (end-systolic elastance [Ees], preload recruitable stroke work [PRSW], and peak power index [PWRI]), arterial afterload (arterial elastance [Ea]), and ventricular-arterial interaction (Ea/Ees) were measured with the use of a noninvasive single-beat technique. EIPH was defined as an estimated pulmonary arterial systolic pressure (PASP) of ≥50 mm Hg at 10 W of exercise. PASP was significantly increased during 10 W of exercise in both HF types, and ~50% of HFpEF patients developed EIPH. Arterial afterload was increased significantly during exercise in both groups. HFrEF and HFpEF patients showed a significant increase in LV contractility assessed by Ees, PRSW, and PWRI during exercise. Although Ea/Ees ratio decreased significantly in HFrEF, reduction in Ea/Ees was attenuated because of blunted Ees increases in patients with HFpEF compared with HFrEF. Even at low-level exercise, ~50% of HFpEF patients developed EIPH. Reduction in Ea/Ees was attenuated owing to less Ees increase in HFpEF compared with HFrEF. Further studies are needed to elucidate the association between ventricular-arterial coupling and EIPH in HFpEF. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel approaches to determine contractile function of the isolated adult zebrafish ventricular cardiac myocyte.

PubMed

Dvornikov, Alexey V; Dewan, Sukriti; Alekhina, Olga V; Pickett, F Bryan; de Tombe, Pieter P

2014-05-01

The zebrafish (Danio rerio) has been used extensively in cardiovascular biology, but mainly in the study of heart development. The relative ease of its genetic manipulation may indicate the suitability of this species as a cost-effective model system for the study of cardiac contractile biology. However, whether the zebrafish heart is an appropriate model system for investigations pertaining to mammalian cardiac contractile structure-function relationships remains to be resolved. Myocytes were isolated from adult zebrafish hearts by enzymatic digestion, attached to carbon rods, and twitch force and intracellular Ca(2+) were measured. We observed the modulation of twitch force, but not of intracellular Ca(2+), by both extracellular [Ca(2+)] and sarcomere length. In permeabilized cells/myofibrils, we found robust myofilament length-dependent activation. Moreover, modulation of myofilament activation-relaxation and force redevelopment kinetics by varied Ca(2+) activation levels resembled that found previously in mammalian myofilaments. We conclude that the zebrafish is a valid model system for the study of cardiac contractile structure-function relationships.

Reference values of left heart echocardiographic dimensions and mass in male peri-pubertal athletes.

PubMed

Cavarretta, Elena; Maffessanti, Francesco; Sperandii, Fabio; Guerra, Emanuele; Quaranta, Federico; Nigro, Antonia; Minati, Monia; Rebecchi, Marco; Fossati, Chiara; Calò, Leonardo; Pigozzi, Fabio

2018-01-01

Background Several articles have proposed reference values in healthy paediatric subjects, but none of them has evaluated a large population of healthy trained adolescents. Design The study purpose was to establish normal echocardiographic measurements of left heart (aortic root, left atrium and left ventricular dimensions and mass) in relation to age, weight, height, body mass index, body surface area and training hours in this specific population. Methods We retrospectively evaluated 2151 consecutive, healthy, peri-pubertal athletes (100% male, mean age 12.4 ± 1.4 years, range 8-18) referred to a single centre for pre-participation screening. All participants were young soccer athletes who trained for a mean of 7.2 ± 1.1 h per week. Results Left ventricular internal diameters, wall thickness, left ventricular mass, aortic root and left atrium diameters were significantly correlated to age, body surface area, height and weight ( p < 0.01). Age, height, weight and body surface area were found associated with chamber size, while body mass index and training hours were not. Inclusion of both age and body size parameters in the statistical models resulted in improved overall explained variance for diameters and left ventricular mass. Conclusion Equations, mean values and percentile charts for the different age groups may be useful as reference data in efficiently assessing left ventricular parameters in young athletes.

[A Comparison Study on Early Damage Detection of Left Ventricular Function Based on Doppler Imaging Method for Children with Tumor].

PubMed

Liu, Ying; Zhang, Haowei; Zhang, Hang

2015-12-01

The early damage detection and evaluation are of great significance in treatment and prognosis to the left ventricular function for children with tumor. In this paper, it is reported that the early damage of the left ventricular function was observed by pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI) in our laboratory. Eighty children half a year to fourteen years old were included in this study. The cardiac function indices in chemotherapy group and control group were measured and compared. The results showed that there was significant difference in mitral and tricuspid annulus flow spectrum between the two groups. Compared with PWD,TDI is more prompt, objective and accurate in detecting early damage of left ventricular function in children with tumor. And TDI is a good method for early identification of ventricular function damage in children with tumor.

Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study.

PubMed

Danias, Peter G; Tritos, Nicholas A; Stuber, Matthias; Kissinger, Kraig V; Salton, Carol J; Manning, Warren J

2003-07-01

Obesity is a major health problem in the Western world. Among obese subjects cardiac pathology is common, but conventional noninvasive imaging modalities are often suboptimal for detailed evaluation of cardiac structure and function. We investigated whether cardiovascular magnetic resonance imaging (CMR) can better characterize possible cardiac abnormalities associated with obesity, in the absence of other confounding comorbidities. In this prospective cross-sectional study, CMR was used to quantify left and right ventricular volumes, ejection fraction, mass, cardiac output, and apical left ventricular rotation in 25 clinically healthy obese men and 25 age-matched lean controls. Obese subjects had higher left ventricular mass (203 +/- 38 g vs. 163 +/- 22 g, p < 0.001), end-diastolic volume (176 +/- 29 mL vs. 156 +/- 25 mL, p < 0.05), and cardiac output (8.2 +/- 1.2 L/min vs. 6.4 +/- 1.3 L/min, p < 0.001). The obese also had increased right ventricular mass (105 +/- 25 g vs. 87 +/- 18 g, p < 0.005) and end-diastolic volume (179 +/- 36 mL vs. 155 +/- 28 mL, p < 0.05). When indexed for height, differences in left and right ventricular mass, and left ventricular end-diastolic volume remained significant. Apical left ventricular rotation and rotational velocity patterns were also different between obese and lean subjects. Obesity is independently associated with remodeling of the heart. Cardiovascular magnetic resonance imaging identifies subtle cardiac abnormalities and may be the preferred imaging technique to evaluate cardiac structure and function in the obese.

Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling

PubMed Central

Yamaguchi, Osamu; Higuchi, Yoshiharu; Hirotani, Shinichi; Kashiwase, Kazunori; Nakayama, Hiroyuki; Hikoso, Shungo; Takeda, Toshihiro; Watanabe, Tetsuya; Asahi, Michio; Taniike, Masayuki; Matsumura, Yasushi; Tsujimoto, Ikuko; Hongo, Kenichi; Kusakari, Yoichiro; Kurihara, Satoshi; Nishida, Kazuhiko; Ichijo, Hidenori; Hori, Masatsugu; Otsu, Kinya

2003-01-01

Left ventricular remodeling that occurs after myocardial infarction (MI) and pressure overload is generally accepted as a determinant of the clinical course of heart failure. The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1 is involved in development of left ventricular remodeling. ASK-/- hearts showed no morphological or histological defects. Echocardiography and cardiac catheterization revealed normal global structure and function. Left ventricular structural and functional remodeling were determined 4 weeks after coronary artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had significantly smaller increases in left ventricular end-diastolic and end-systolic ventricular dimensions and smaller decreases in fractional shortening in both experimental models compared with WT mice. The number of terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes after MI or TAC was decreased in ASK-/- compared with that in WT mice. Overexpression of a constitutively active mutant of ASK1 induced apoptosis in isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important role in regulating left ventricular remodeling by promoting apoptosis. PMID:14665690

[The effect of atrial pacing on left ventricular diastolic function and BNP levels in patients with DDD pacemaker].

PubMed

Apali, Zeynep; Bayata, Serdar; Yeşil, Murat; Arikan, Erdinç; Postaci, Nursen

2010-08-01

We aimed to investigate the effect of atrial pacing on left ventricular diastolic function and brain natriuretic peptide (BNP) levels in patients with DDD pacemaker. Thirty patients with complete atrio-ventricular (AV) block and DDD pacemaker were included. All patients had normal left ventricular systolic function. Echocardiographic diastolic function parameters (transmitral and tissue Doppler velocities during early (E and E') and late (A and A') filling) and NT-pro-BNP levels were evaluated prospectively during atrial sensing and pacing periods. Echocardiographic data were compared with paired sample t test and NT-pro-BNP levels were compared with Wilcoxon test. Echocardiographic E/A, E'/A', E/E' ratios were calculated as 0.72+/-0.34, 0.61+/-0.21 and 8.76+/-2.58 during atrial sensing period. Same parameters were found as 0.71+/-0.23, 0.64+/-0.16 and 8.93+/-3.16 respectively during atrial pacing period. Echocardiographic left ventricular diastolic function parameters were not significantly different during atrial pacing and atrial sensing periods. Median plasma NT-pro-BNP levels were measured as 142 pg/ml (min-max 47-563 pg/ml) and 147 pg/ml (min-max 33-1035 pg/ml) during atrial sensing and pacing periods respectively. These levels were not significantly different (p=0.86). The result of this study has shown that, atrial pacing has not any additional detrimental effect on left ventricular diastolic function parameters in paced patients with normal left ventricular systolic function.

Chasing the reflected wave back into the heart: a new hypothesis while the jury is still out

PubMed Central

Codreanu, Ion; Robson, Matthew D; Rider, Oliver J; Pegg, Tammy J; Jung, Bernd A; Dasanu, Constantin A; Clarke, Kieran; Holloway, Cameron J

2011-01-01

Background: Arterial stiffness directly influences cardiac function and is independently associated with cardiovascular risk. However, the influence of the aortic reflected pulse pressure wave on left ventricular function has not been well characterized. The aim of this study was to obtain detailed information on regional ventricular wall motion patterns corresponding to the propagation of the reflected aortic wave on ventricular segments. Methods: Left ventricular wall motion was investigated in a group of healthy volunteers (n = 14, age 23 ± 3 years), using cardiac magnetic resonance navigator-gated tissue phase mapping. The left ventricle was divided into 16 segments and regional wall motion was studied in high temporal detail. Results: Corresponding to the expected timing of the reflected aortic wave reaching the left ventricle, a characteristic “notch” of regional myocardial motion was seen in all radial, circumferential, and longitudinal velocity graphs. This notch was particularly prominent in septal segments adjacent to the left ventricular outflow tract on radial velocity graphs and in anterior and posterior left ventricular segments on circumferential velocity graphs. Similarly, longitudinal velocity graphs demonstrated a brief deceleration in the upward recoil motion of the entire ventricle at the beginning of diastole. Conclusion: These results provide new insights into the possible influence of the reflected aortic waves on ventricular segments. Although the association with the reflected wave appears to us to be unambiguous, it represents a novel research concept, and further studies enabling the actual recording of the pulse wave are required. PMID:21731888

Amiodarone. Haemodynamic profile during intravenous administration and effect on pacing-induced ischaemia in man.

PubMed

Remme, W J; van Hoogenhuyze, D C; Kruyssen, D A; Krauss, X H; Storm, C J

1985-03-01

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti-ischaemic properties are mainly based on a reduction of myocardial oxygen demand, rather than on an improvement in coronary flow. It is concluded then, that amiodarone has significant haemodynamic effects as manifested by an early reduction in vascular resistance and a late negative inotropic effect. Although vasodilatation of short duration caused by its solvent, polysorbate 80, also occurs, the overall cardiovascular changes are caused by the direct, intrinsic haemodynamic effects of amiodarone alone. The important anti-ischaemic properties of amiodarone appear to result primarily from these cardiovascular actions and the inherent reduction in myocardial oxygen demand.

Ventricular dilation and electrical dyssynchrony synergistically increase regional mechanical nonuniformity but not mechanical dyssynchrony: a computational model.

PubMed

Kerckhoffs, Roy C P; Omens, Jeffrey H; McCulloch, Andrew D; Mulligan, Lawrence J

2010-07-01

Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation. All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97+/-0.004, 0.010+/-0.002, and 78+/-1 milliseconds, respectively. With dilation alone, CURE decreased 2.0+/-0.07%, ISF increased 58+/-47%, and WTpeak increased 31+/-3%. With dyssynchronous activation alone, CURE decreased 15+/-0.6%, ISF increased 14-fold (+/-3), and WTpeak increased 121+/-4%. With the combination of dilation and dyssynchronous activation, CURE decreased 23+/-0.8%, ISF increased 20-fold (+/-5), and WTpeak increased 147+/-5%. Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy.

Milrinone Relaxes Pulmonary Veins in Guinea Pigs and Humans

PubMed Central

Rieg, Annette D.; Suleiman, Said; Perez-Bouza, Alberto; Braunschweig, Till; Spillner, Jan W.; Schröder, Thomas; Verjans, Eva; Schälte, Gereon; Rossaint, Rolf; Uhlig, Stefan; Martin, Christian

2014-01-01

Introduction The phosphodiesterase-III inhibitor milrinone improves ventricular contractility, relaxes pulmonary arteries and reduces right ventricular afterload. Thus, it is used to treat heart failure and pulmonary hypertension (PH). However, its action on pulmonary veins (PVs) is not defined, although particularly PH due to left heart disease primarily affects the pulmonary venous bed. We examined milrinone-induced relaxation in PVs from guinea pigs (GPs) and humans. Material and Methods Precision-cut lung slices (PCLS) were prepared from GPs or from patients undergoing lobectomy. Milrinone-induced relaxation was studied by videomicroscopy in naïve PVs and in PVs pre-constricted with the ETA-receptor agonist BP0104. Baseline luminal area was defined as 100%. Intracellular cAMP was measured by ELISA and milrinone-induced changes of segmental vascular resistances were studied in the GP isolated perfused lung (IPL). Results In the IPL (GP), milrinone (10 µM) lowered the postcapillary resistance of pre-constricted vessels. In PCLS (GP), milrinone relaxed naïve and pre-constricted PVs (120%) and this relaxation was attenuated by inhibition of protein kinase G (KT 5823), adenyl cyclase (SQ 22536) and protein kinase A (KT 5720), but not by inhibition of NO-synthesis (L-NAME). In addition, milrinone-induced relaxation was dependent on the activation of KATP-, BKCa 2+- and Kv-channels. Human PVs also relaxed to milrinone (121%), however only if pre-constricted. Discussion Milrinone relaxes PVs from GPs and humans. In GPs, milrinone-induced relaxation is based on KATP-, BKCa 2+- and Kv-channel-activation and on cAMP/PKA/PKG. The relaxant properties of milrinone on PVs lead to reduced postcapillary resistance and hydrostatic pressures. Hence they alleviate pulmonary edema and suggest beneficial effects of milrinone in PH due to left heart disease. PMID:24498166

Milrinone relaxes pulmonary veins in guinea pigs and humans.

PubMed

Rieg, Annette D; Suleiman, Said; Perez-Bouza, Alberto; Braunschweig, Till; Spillner, Jan W; Schröder, Thomas; Verjans, Eva; Schälte, Gereon; Rossaint, Rolf; Uhlig, Stefan; Martin, Christian

2014-01-01

The phosphodiesterase-III inhibitor milrinone improves ventricular contractility, relaxes pulmonary arteries and reduces right ventricular afterload. Thus, it is used to treat heart failure and pulmonary hypertension (PH). However, its action on pulmonary veins (PVs) is not defined, although particularly PH due to left heart disease primarily affects the pulmonary venous bed. We examined milrinone-induced relaxation in PVs from guinea pigs (GPs) and humans. Precision-cut lung slices (PCLS) were prepared from GPs or from patients undergoing lobectomy. Milrinone-induced relaxation was studied by videomicroscopy in naïve PVs and in PVs pre-constricted with the ETA-receptor agonist BP0104. Baseline luminal area was defined as 100%. Intracellular cAMP was measured by ELISA and milrinone-induced changes of segmental vascular resistances were studied in the GP isolated perfused lung (IPL). In the IPL (GP), milrinone (10 µM) lowered the postcapillary resistance of pre-constricted vessels. In PCLS (GP), milrinone relaxed naïve and pre-constricted PVs (120%) and this relaxation was attenuated by inhibition of protein kinase G (KT 5823), adenyl cyclase (SQ 22536) and protein kinase A (KT 5720), but not by inhibition of NO-synthesis (L-NAME). In addition, milrinone-induced relaxation was dependent on the activation of K ATP-, BK Ca (2+)- and Kv-channels. Human PVs also relaxed to milrinone (121%), however only if pre-constricted. Milrinone relaxes PVs from GPs and humans. In GPs, milrinone-induced relaxation is based on K ATP-, BK Ca (2+)- and Kv-channel-activation and on cAMP/PKA/PKG. The relaxant properties of milrinone on PVs lead to reduced postcapillary resistance and hydrostatic pressures. Hence they alleviate pulmonary edema and suggest beneficial effects of milrinone in PH due to left heart disease.

Analysis of left ventricular function of the mouse heart during experimentally induced hyperthyroidism and recovery.

PubMed

Hübner, Neele Saskia; Merkle, Annette; Jung, Bernd; von Elverfeldt, Dominik; Harsan, Laura-Adela

2015-01-01

Many of the clinical manifestations of hyperthyroidism are due to the ability of thyroid hormones to alter myocardial contractility and cardiovascular hemodynamics, leading to cardiovascular impairment. In contrast, recent studies highlight also the potential beneficial effects of thyroid hormone administration for clinical or preclinical treatment of different diseases such as atherosclerosis, obesity and diabetes or as a new therapeutic approach in demyelinating disorders. In these contexts and in the view of developing thyroid hormone-based therapeutic strategies, it is, however, important to analyze undesirable secondary effects on the heart. Animal models of experimentally induced hyperthyroidism therefore represent important tools for investigating and monitoring changes of cardiac function. In our present study we use high-field cardiac MRI to monitor and follow-up longitudinally the effects of prolonged thyroid hormone (triiodothyronine) administration focusing on murine left ventricular function. Using a 9.4 T small horizontal bore animal scanner, cinematographic MRI was used to analyze changes in ejection fraction, wall thickening, systolic index and fractional shortening. Cardiac MRI investigations were performed after sustained cycles of triiodothyronine administration and treatment arrest in adolescent (8 week old) and adult (24 week old) female C57Bl/6 N mice. Triiodothyronine supplementation of 3 weeks led to an impairment of cardiac performance with a decline in ejection fraction, wall thickening, systolic index and fractional shortening in both age groups but with a higher extent in the group of adolescent mice. However, after a hormonal treatment cessation of 3 weeks, only young mice are able to partly restore cardiac performance in contrast to adult mice lacking this recovery potential and therefore indicating a presence of chronically developed heart pathology. Copyright © 2014 John Wiley & Sons, Ltd.

Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy.

PubMed

Nikolaidis, Lazaros A; Elahi, Dariush; Hentosz, Teresa; Doverspike, Aaron; Huerbin, Rhonda; Zourelias, Lee; Stolarski, Carol; Shen, You-tang; Shannon, Richard P

2004-08-24

The failing heart demonstrates a preference for glucose as its metabolic substrate. Whether enhancing myocardial glucose uptake favorably influences left ventricular (LV) contractile performance in heart failure remains uncertain. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with potent insulinotropic effects the action of which is attenuated when glucose levels fall below 4 mmol. We examined the impact of recombinant GLP-1 (rGLP-1) on LV and systemic hemodynamics and myocardial substrate uptake in conscious dogs with advanced dilated cardiomyopathy (DCM) as a mechanism for overcoming myocardial insulin resistance and enhancing myocardial glucose uptake. Thirty-five dogs were instrumented and studied in the fully conscious state. Advanced DCM was induced by 28 days of rapid pacing. Sixteen dogs with advanced DCM received a 48-hour infusion of rGLP-1 (1.5 pmol x kg(-1) x min(-1)). Eight dogs with DCM served as controls and received 48 hours of a saline infusion (3 mL/d). Infusion of rGLP-1 was associated with significant (P<0.02) increases in LV dP/dt (98%), stroke volume (102%), and cardiac output (57%) and significant decreases in LV end-diastolic pressure, heart rate, and systemic vascular resistance. rGLP-1 increased myocardial insulin sensitivity and myocardial glucose uptake. There were no significant changes in the saline control group. rGLP-1 dramatically improved LV and systemic hemodynamics in conscious dogs with advanced DCM induced by rapid pacing. rGLP-1 has insulinomimetic and glucagonostatic properties, with resultant increases in myocardial glucose uptake. rGLP-1 may be a useful metabolic adjuvant in decompensated heart failure.

Heart dysfunction induced by choline-deficiency in adult rats: the protective role of L-carnitine.

PubMed

Strilakou, Athina A; Lazaris, Andreas C; Perelas, Apostolos I; Mourouzis, Iordanis S; Douzis, Ioannis Ch; Karkalousos, Petros L; Stylianaki, Aikaterini Th; Pantos, Costas I; Liapi, Charis A

2013-06-05

Choline is a B vitamin co-factor and its deficiency seems to impair heart function. Carnitine, a chemical analog of choline, has been used as adjunct in the management of cardiac diseases. The study investigates the effects of choline deficiency on myocardial performance in adult rats and the possible modifications after carnitine administration. Wistar Albino rats (n=24), about 3 months old, were randomized into four groups fed with: (a) standard diet (control-CA), (b) choline deficient diet (CDD), (c) standard diet and carnitine in drinking water 0.15% w/v (CARN) and (d) choline deficient diet and carnitine (CDD+CARN). After four weeks of treatment, we assessed cardiac function under isometric conditions using the Langendorff preparations [Left Ventricular Developed Pressure (LVDP-mmHg), positive and negative first derivative of LVDP were evaluated], measured serum homocysteine and brain natriuretic peptide (BNP) levels and performed histopathology analyses. In the CDD group a compromised myocardium contractility compared to control (P=0.01), as assessed by LVDP, was noted along with a significantly impaired diastolic left ventricular function, as assessed by (-) dp/dt (P=0.02) that were prevented by carnitine. Systolic force, assessed by (+) dp/dt, showed no statistical difference between groups. A significant increase in serum BNP concentration was found in the CDD group (P<0.004) which was attenuated by carnitine (P<0.05), whereas homocysteine presented contradictory results (higher in the CDD+CARN group). Heart histopathology revealed a lymphocytic infiltration of myocardium and valves in the CDD group that was reduced by carnitine. In conclusion, choline deficiency in adult rats impairs heart performance; carnitine acts against these changes. Copyright © 2013 Elsevier B.V. All rights reserved.

Algisyl-LVR™ with coronary artery bypass grafting reduces left ventricular wall stress and improves function in the failing human heart☆,☆☆

PubMed Central

Lee, Lik Chuan; Wall, Samuel T.; Klepach, Doron; Ge, Liang; Zhang, Zhihong; Lee, Randall J.; Hinson, Andy; Gorman, Joseph H.; Gorman, Robert C.; Guccione, Julius M.

2013-01-01

Background Left ventricular (LV) wall stress reduction is a cornerstone in treating heart failure. Large animal models and computer simulations indicate that adding non-contractile material to the damaged LV wall can potentially reduce myofiber stress. We sought to quantify the effects of a novel implantable hydrogel (Algisyl-LVR™) treatment in combination with coronary artery bypass grafting (i.e. Algisyl-LVR™+CABG) on both LV function and wall stress in heart failure patients. Methods and results Magnetic resonance images obtained before treatment (n=3), and at 3 months (n=3) and 6 months (n=2) afterwards were used to reconstruct the LV geometry. Cardiac function was quantified using end-diastolic volume (EDV), end-systolic volume (ESV), regional wall thickness, sphericity index and regional myofiber stress computed using validated mathematical modeling. The LV became more ellipsoidal after treatment, and both EDV and ESV decreased substantially 3 months after treatment in all patients; EDV decreased from 264±91 ml to 146±86 ml and ESV decreased from 184±85 ml to 86±76 ml. Ejection fraction increased from 32±8% to 47±18% during that period. Volumetric-averaged wall thickness increased in all patients, from 1.06±0.21 cm (baseline) to 1.3±0.26 cm (3 months). These changes were accompanied by about a 35% decrease in myofiber stress at end-of-diastole and at end-of-systole. Post-treatment myofiber stress became more uniform in the LV. Conclusions These results support the novel concept that Algisyl-LVR™+CABG treatment leads to decreased myofiber stress, restored LV geometry and improved function. PMID:23394895

Phytochemical screening and evaluation of cardioprotective activity of ethanolic extract of Ocimum basilicum L. (basil) against isoproterenol induced myocardial infarction in rats

PubMed Central

2012-01-01

Background and the purpose of the study The objectives of the present study were phytochemical screening and study of the effects of ethanolic extract of aerial parts of Ocimum basilicum (basil) on cardiac functions and histopathological changes in isoproterenol-induced myocardial infarction (MI). Methods The leaves of the plant were extracted with ethanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. High-performance TLC analysis and subsequent CAMAG's TLC scanning were performed to quantify rosmarinic acid content. Wistar rats were assigned to 6 groups of normal control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg of the extract two times per day concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used to induce MI. Results Phytochemical screening indicated the presence of phenolic compounds (5.36%) and flavonoids (1.86%). Rosmarinic acid was the principal phenolic compound with a 15.74% existence. The ST-segment elevation induced by isoproterenol was significantly suppressed by all doses of the extract. A severe myocardial necrosis and fibrosis with a sharp reduction in left ventricular contractility and a marked increase in left ventricular end-diastolic pressure were seen in the isoproterenol group, all of which were significantly improved by the extract treatment. In addition to in-vitro antioxidant activity, the extract significantly suppressed the elevation of malondialdehyde levels both in the serum and the myocardium. Conclusion The results of the study demonstrate that Ocimum basilicum strongly protected the myocardium against isoproterenol-induced infarction and suggest that the cardioprotective effects could be related to antioxidative activities. PMID:23351503

Prognostic value of coronary collaterals in patients with acute coronary syndromes.

PubMed

Kurtul, Alparslan; Ozturk, Selcuk

2017-08-01

The presence of good coronary collateral circulation (CCC) can protect and preserve myocardium from ischemia, increase myocardial contractility, and reduce adverse clinical events. However, its impact on mortality is still a topic of debate, particularly in acute coronary syndrome (ACS). The aim of this study was to investigate the association of CCC with cardiac risk factors and in-hospital mortality in patients hospitalized with a diagnosis of ACS. The study population included 2286 patients with ACS who underwent coronary angiography and were found to have at least 90% significant lesion in at least one major coronary artery. The CCC was graded according to the Rentrop classification. The patients were classified into a poor CCC group (Rentrop grades 0-1, n=1859) or a good CCC group (Rentrop grades 2-3, n=427). Patients with good CCC had more high-risk patient characteristics such as older age, higher rate of Killip class of at least 2 at admission, lower left ventricular ejection fraction, and impaired renal functions compared with the patients with poor CCC. In multivariate analysis, the presence of good CCC [odds ratio (OR): 2.000; 95% confidence interval: 1.116-3.585; P=0.020], left ventricular ejection fraction less than 40% (OR: 2.381; P=0.003), Killip class of at least 2 at admission (OR: 3.609; P<0.001), age of at least 65 years (OR: 2.975; P=0.003), and hemoglobin (OR: 0.797; P=0.003) were independent predictors of in-hospital mortality. In contrast to previous studies, our study did not confirm a beneficial role of good CCC in patients with ACS; the presence of good CCC was even independently associated with increased in-hospital mortality in the multivariate analysis.

Operative contractility: a functional concept of the inotropic state.

PubMed

Curiel, Roberto; Perez-Gonzalez, Juan; Torres, Edwar; Landaeta, Ruben; Cerrolaza, Miguel

2005-10-01

1. Initial unsuccessful attempts to evaluate ventricular function in terms of the 'heart as a pump' led to focusing on the 'heart as a muscle' and to the concept of myocardial contractility. However, no clinically ideal index exists to assess the contractile state. The aim of the present study was to develop a mathematical model to assess cardiac contractility. 2. A tri-axial system was conceived for preload (PL), afterload (AL) and contractility, where stroke volume (SV) was represented as the volume of the tetrahedron. Based on this model, 'operative' contractility ('OperCon') was calculated from the readily measured values of PL, AL and SV. The model was tested retrospectively under a variety of different experimental and clinical conditions, in 71 studies in humans and 29 studies in dogs. A prospective echocardiographic study was performed in 143 consecutive subjects to evaluate the ability of the model to assess contractility when SV and PL were measured volumetrically (mL) or dimensionally (cm). 3. With inotropic interventions, OperCon changes were comparable to those of ejection fraction (EF), velocity of shortening (Vcf) and dP/dt-max. Only with positive inotropic interventions did elastance (Ees) show significantly larger changes. With load manipulations, OperCon showed significantly smaller changes than EF and Ees and comparable changes to Vcf and dP/dt-max. Values of OperCon were similar when AL was represented by systolic blood pressure or wall stress and when volumetric or dimensional values were used. 4. Operative contractility is a reliable, simple and versatile method to assess cardiac contractility.

Dynamical relations for left ventricular ejection - Flow rate, momentum, force and impulse

NASA Technical Reports Server (NTRS)

Back, L. H.; Selzer, R. H.; Gordon, D. G.; Ledbetter, D. C.; Crawford, D. W.

1984-01-01

An investigation was carried out to quantitatively evaluate left ventricular volume flow rate, momentum, force and impulse derived from application of conservation principles for mass and momentum of blood within the ventricle during the ejection phase. An automated digital image processing system was developed and applied to left ventricular angiograms which are computer processed and analyzed frame by frame to determine the dynamical relations by numerical methods. The initial experience with force and impulse has indicated that neither quantity seemed to be a sensitive indicator of coronary artery disease as evaluated by qualitative angiography for the particular patient group studied. Utilization of the dynamical relations in evaluating human left ventricular performance requires improved means of measurement and interpretation of clinical studies.

[Acute left ventricular systolic dysfunction after pericardial effusion drainage].

PubMed

Brauner, F B; Nunes, C E; Fabra, R; Riesgo, A; Thomé, L G

1997-12-01

A patient with a thymoma and initially normal ventricular systolic function developed cardiac tamponade, which was relieved by pericardiocentesis. After four days, the tumor was removed and, one week after the relief of tamponade, she developed severe left ventricular systolic dysfunction, that recovered in three days with venous therapy.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance

PubMed Central

van Geuns, Robert‐Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J.G.M.

2017-01-01

Abstract Aims Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast‐enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. Methods and results We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast‐enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non‐invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Conclusions Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. PMID:29154434

Accurate means of detecting and characterizing abnormal patterns of ventricular activation by phase image analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Botvinick, E.H.; Frais, M.A.; Shosa, D.W.

1982-08-01

The ability of scintigraphic phase image analysis to characterize patterns of abnormal ventricular activation was investigated. The pattern of phase distribution and sequential phase changes over both right and left ventricular regions of interest were evaluated in 16 patients with normal electrical activation and wall motion and compared with those in 8 patients with an artificial pacemaker and 4 patients with sinus rhythm with the Wolff-Parkinson-White syndrome and delta waves. Normally, the site of earliest phase angle was seen at the base of the interventricular septum, with sequential change affecting the body of the septum and the cardiac apex andmore » then spreading laterally to involve the body of both ventricles. The site of earliest phase angle was located at the apex of the right ventricle in seven patients with a right ventricular endocardial pacemaker and on the lateral left ventricular wall in one patient with a left ventricular epicardial pacemaker. In each case the site corresponded exactly to the position of the pacing electrode as seen on posteroanterior and left lateral chest X-ray films, and sequential phase changes spread from the initial focus to affect both ventricles. In each of the patients with the Wolff-Parkinson-White syndrome, the site of earliest ventricular phase angle was located, and it corresponded exactly to the site of the bypass tract as determined by endocardial mapping. In this way, four bypass pathways, two posterior left paraseptal, one left lateral and one right lateral, were correctly localized scintigraphically. On the basis of the sequence of mechanical contraction, phase image analysis provides an accurate noninvasive method of detecting abnormal foci of ventricular activation.« less

The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output.

PubMed

Smerup, Morten; Damkjær, Mads; Brøndum, Emil; Baandrup, Ulrik T; Kristiansen, Steen Buus; Nygaard, Hans; Funder, Jonas; Aalkjær, Christian; Sauer, Cathrine; Buchanan, Rasmus; Bertelsen, Mads Frost; Østergaard, Kristine; Grøndahl, Carsten; Candy, Geoffrey; Hasenkam, J Michael; Secher, Niels H; Bie, Peter; Wang, Tobias

2016-02-01

Giraffes--the tallest extant animals on Earth--are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. Arterial pressure may exceed 300 mmHg and has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass. It thus remains unexplained how the normal-sized giraffe heart generates such massive arterial pressures. We hypothesized that giraffe hearts have a small intraventricular cavity and a relatively thick ventricular wall, allowing for generation of high arterial pressures at normal left ventricular wall tension. In nine anaesthetized giraffes (495±38 kg), we determined in vivo ventricular dimensions using echocardiography along with intraventricular and aortic pressures to calculate left ventricular wall stress. Cardiac output was also determined by inert gas rebreathing to provide an additional and independent estimate of stroke volume. Echocardiography and inert gas-rebreathing yielded similar cardiac outputs of 16.1±2.5 and 16.4±1.4 l min(-1), respectively. End-diastolic and end-systolic volumes were 521±61 ml and 228±42 ml, respectively, yielding an ejection fraction of 56±4% and a stroke volume of 0.59 ml kg(-1). Left ventricular circumferential wall stress was 7.83±1.76 kPa. We conclude that, relative to body mass, a small left ventricular cavity and a low stroke volume characterizes the giraffe heart. The adaptations result in typical mammalian left ventricular wall tensions, but produce a lowered cardiac output. © 2016. Published by The Company of Biologists Ltd.

[Experts consensus on the management of the right heart function in critically ill patients].

PubMed

Wang, X T; Liu, D W; Zhang, H M; Long, Y; Guan, X D; Qiu, H B; Yu, K J; Yan, J; Zhao, H; Tang, Y Q; Ding, X; Ma, X C; Du, W; Kang, Y; Tang, B; Ai, Y H; He, H W; Chen, D C; Chen, H; Chai, W Z; Zhou, X; Cui, N; Wang, H; Rui, X; Hu, Z J; Li, J G; Xu, Y; Yang, Y; Ouyan, B; Lin, H Y; Li, Y M; Wan, X Y; Yang, R L; Qin, Y Z; Chao, Y G; Xie, Z Y; Sun, R H; He, Z Y; Wang, D F; Huang, Q Q; Jiang, D P; Cao, X Y; Yu, R G; Wang, X; Chen, X K; Wu, J F; Zhang, L N; Yin, M G; Liu, L X; Li, S W; Chen, Z J; Luo, Z

2017-12-01

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.