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Sample records for adverse ventricular remodeling

  1. Pathological Role of Serum- and Glucocorticoid-Regulated Kinase 1 in Adverse Ventricular Remodeling

    PubMed Central

    Das, Saumya; Aiba, Takeshi; Rosenberg, Michael; Hessler, Katherine; Xiao, Chunyang; Quintero, Pablo A.; Ottaviano, Filomena G.; Knight, Ashley C.; Graham, Evan L.; Boström, Pontus; Morissette, Michael R.; del Monte, Federica; Begley, Michael J.; Cantley, Lewis C.; Ellinor, Patrick T.; Tomaselli, Gordon F.; Rosenzweig, Anthony

    2012-01-01

    Background Heart failure is a growing cause of morbidity and mortality. Cardiac PI3-kinase signaling promotes cardiomyocyte survival and function but is paradoxically activated in heart failure, suggesting chronic activation of this pathway may become maladaptive. Here we investigated the downstream PI3-kinase effector, SGK1 (serum- and glucocorticoid-regulated kinase-1), in heart failure and its complications. Methods and Results We found that cardiac SGK1 is activated in human and murine heart failure. We investigated the role of SGK1 in the heart using cardiac-specific expression of constitutively-active or dominant-negative SGK1. Cardiac-specific activation of SGK1 in mice increased mortality, cardiac dysfunction, and ventricular arrhythmias. The pro-arrhythmic effects of SGK1 were linked to biochemical and functional changes in the cardiac sodium channel and could be reversed by treatment with ranolazine, a blocker of the late sodium current. Conversely, cardiac-specific inhibition of SGK1 protected mice after hemodynamic stress from fibrosis, heart failure, and sodium channel alterations. Conclusions SGK1 appears both necessary and sufficient for key features of adverse ventricular remodeling and may provide a novel therapeutic target in cardiac disease. PMID:23019294

  2. Berberine attenuates adverse left ventricular remodeling and cardiac dysfunction after acute myocardial infarction in rats: role of autophagy.

    PubMed

    Zhang, Yao-Jun; Yang, Shao-Hua; Li, Ming-Hui; Iqbal, Javaid; Bourantas, Christos V; Mi, Qiong-Yu; Yu, Yi-Hui; Li, Jing-Jing; Zhao, Shu-Li; Tian, Nai-Liang; Chen, Shao-Liang

    2014-12-01

    The present study aimed to test the hypothesis that berberine, a plant-derived anti-oxidant, attenuates adverse left ventricular remodelling and improves cardiac function in a rat model of myocardial infarction (MI). Furthermore, the potential mechanisms that mediated the cardioprotective actions of berberine, in particular the effect on autophagy, were also investigated. Acute MI was induced by ligating the left anterior descending coronary artery of Sprague-Dawley rats. Cardiac function was assessed by transthoracic echocardiography. The protein activity/levels of autophagy related to signalling pathways (e.g. LC-3B, Beclin-1) were measured in myocardial tissue by immunohistochemical staining and western blot. Four weeks after MI, berberine significantly prevented cardiac dysfunction and adverse cardiac remodelling. MI rats treated with low dose berberine (10 mg/kg per day) showed higher left ventricular ejection fraction and fractional shortening than those treated with high-dose berberine (50 mg/kg per day). Both doses reduced interstitial fibrosis and post-MI adverse cardiac remodelling. The cardioprotective action of berberine was associated with increased LC-3B II and Beclin-1 expressions. Furthermore, cardioprotection with berberine was potentially related to p38 MAPK inhibition and phospho-Akt activation. The present in vivo study showed that berberine is effective in promoting autophagy, and subsequently attenuating left ventricular remodelling and cardiac dysfunction after MI. The potential underlying mechanism is augmentation of autophagy through inhibition of p38 MAPK and activation of phospho-Akt signalling pathways.

  3. Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

    2016-01-01

    Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

  4. Biomass fuel smoke exposure was associated with adverse cardiac remodeling and left ventricular dysfunction in Peru.

    PubMed

    Burroughs Peña, M S; Velazquez, E J; Rivera, J D; Alenezi, F; Wong, C; Grigsby, M; Davila-Roman, V G; Gilman, R H; Miranda, J J; Checkley, W

    2016-12-19

    While household air pollution from biomass fuel combustion has been linked to cardiovascular disease, the effects on cardiac structure and function have not been well described. We sought to determine the association between biomass fuel smoke exposure and cardiac structure and function by transthoracic echocardiography. We identified a random sample of urban and rural residents living in the high-altitude region of Puno, Peru. Daily biomass fuel use was self-reported. Participants underwent transthoracic echocardiography. Multivariable linear regression was used to examine the relationship of biomass fuel use with echocardiographic measures of cardiac structure and function, adjusting for age, sex, height, body mass index, diabetes, physical activity, and tobacco use. One hundred and eighty-seven participants (80 biomass fuel users and 107 non-users) were included in this analysis (mean age 59 years, 58% women). After adjustment, daily exposure to biomass fuel smoke was associated with increased left ventricular internal diastolic diameter (P=.004), left atrial diameter (P=.03), left atrial area (four-chamber) (P=.004) and (two-chamber) (P=.03), septal E' (P=.006), and lateral E' (P=.04). Exposure to biomass fuel smoke was also associated with worse global longitudinal strain in the two-chamber view (P=.01). Daily biomass fuel use was associated with increased left ventricular size and decreased left ventricular systolic function by global longitudinal strain.

  5. Residual Myocardial Iron Following Intramyocardial Hemorrhage During the Convalescent Phase of Reperfused ST-Segment–Elevation Myocardial Infarction and Adverse Left Ventricular Remodeling

    PubMed Central

    Bulluck, Heerajnarain; Rosmini, Stefania; Abdel-Gadir, Amna; White, Steven K.; Bhuva, Anish N.; Treibel, Thomas A.; Fontana, Marianna; Ramlall, Manish; Hamarneh, Ashraf; Sirker, Alex; Herrey, Anna S.; Manisty, Charlotte; Yellon, Derek M.; Kellman, Peter; Moon, James C.

    2016-01-01

    Background— The presence of intramyocardial hemorrhage (IMH) in ST-segment–elevation myocardial infarction patients reperfused by primary percutaneous coronary intervention has been associated with residual myocardial iron at follow-up, and its impact on adverse left ventricular (LV) remodeling is incompletely understood and is investigated here. Methods and Results— Forty-eight ST-segment–elevation myocardial infarction patients underwent cardiovascular magnetic resonance at 4±2 days post primary percutaneous coronary intervention, of whom 40 had a follow-up scan at 5±2 months. Native T1, T2, and T2* maps were acquired. Eight out of 40 (20%) patients developed adverse LV remodeling. A subset of 28 patients had matching T2* maps, of which 15/28 patients (54%) had IMH. Eighteen of 28 (64%) patients had microvascular obstruction on the acute scan, of whom 15/18 (83%) patients had microvascular obstruction with IMH. On the follow-up scan, 13/15 patients (87%) had evidence of residual iron within the infarct zone. Patients with residual iron had higher T2 in the infarct zone surrounding the residual iron when compared with those without. In patients with adverse LV remodeling, T2 in the infarct zone surrounding the residual iron was also higher than in those without (60 [54–64] ms versus 53 [51–56] ms; P=0.025). Acute myocardial infarct size, extent of microvascular obstruction, and IMH correlated with the change in LV end-diastolic volume (Pearson’s rho of 0.64, 0.59, and 0.66, respectively; P=0.18 and 0.62, respectively, for correlation coefficient comparison) and performed equally well on receiver operating characteristic curve for predicting adverse LV remodeling (area under the curve: 0.99, 0.94, and 0.95, respectively; P=0.19 for receiver operating characteristic curve comparison). Conclusions— The majority of ST-segment–elevation myocardial infarction patients with IMH had residual myocardial iron at follow-up. This was associated with

  6. [Ventricular "remodeling" after myocardial infarction].

    PubMed

    Cohen-Solal, A; Himbert, D; Guéret, P; Gourgon, R

    1991-06-01

    Cardiac failure is the principal medium-term complication of myocardial infarction. Changes in left ventricular geometry are observed after infarction, called ventricular remodeling, which, though compensatory initially, cause ventricular failure in the long-term. Experimental and clinical studies suggest that early treatment by coronary recanalisation, trinitrin and angiotensin converting enzyme inhibitors may prevent or limit the expansion and left ventricular dilatation after infarction, so improving ventricular function, and, at least in the animal, reduce mortality. Large scale trials with converting enzyme inhibitors are currently under way to determine the effects of this new therapeutic option. It would seem possible at present, independently of any reduction in the size of the infarction, to reduce or delay left ventricular dysfunction by interfering with the natural process of dilatation and ventricular modeling after infarction.

  7. Ventricular remodeling in global ischemia.

    PubMed

    Anversa, P; Zhang, X; Li, P; Olivetti, G; Cheng, W; Reiss, K; Sonnenblick, E H; Kajstura, J

    1995-06-01

    To determine the effects of chronic constriction of the left coronary artery on the function and structure of the heart, coronary artery narrowing was surgically induced in rats and ventricular pump performance, extent and distribution of myocardial damage, and the hypertrophic and hyperplastic response of myocytes were examined. Alterations in cardiac hemodynamics were found in all rats, but the characteristics of the physiological properties of the heart allowed a separation of the animals into two groups which exhibited left ventricular dysfunction and failure, respectively. Left ventricular hypertrophy occurred in both groups and was characterized by ventricular dilatation and wall thinning which were more severe in the failing animals. Multiple foci of myocardial damage across the wall were seen in all animals but tissue injury was more prominent in the endomyocardium and in failing rats. The anatomical and hemodynamic changes resulted in a significant increase in diastolic wall stress which paralleled the depression in ventricular performance. Myocyte cell loss and myocyte cellular hypertrophy were more severe with ventricular failure than with dysfunction. Finally, diastolic overload appeared to be coupled with activation of the DNA synthetic machinery of myocytes and nuclear mitotic division. In conclusion, a fixed lesion of the left coronary artery leads to abnormalities in cardiac dynamics with marked increases in diastolic wall stress and extensive ventricular remodeling in spite of compensatory myocyte cellular hypertrophy and hyperplasia in the remaining viable tissue.

  8. Rapid Surface Cooling by ThermoSuit System Dramatically Reduces Scar Size, Prevents Post-Infarction Adverse Left Ventricular Remodeling, and Improves Cardiac Function in Rats

    PubMed Central

    Dai, Wangde; Herring, Michael J; Hale, Sharon L; Kloner, Robert A

    2015-01-01

    Background The long-term effects of transient hypothermia by the non-invasive ThermoSuit apparatus on myocardial infarct (MI) scar size, left ventricular (LV) remodeling, and LV function were assessed in rat MI model. Methods and Results Rats were randomized to normothermic or hypothermic groups (n=14 in each group) and subjected to 30 minutes coronary artery occlusion and 6 weeks of reperfusion. For hypothermia therapy, rats were placed into the ThermoSuit apparatus at 2 minutes after the onset of coronary artery occlusion, were taken out of the apparatus when the core body temperature reached 32°C (in ≈8 minutes), and were then allowed to rewarm. After 6 weeks of recovery, rats treated with hypothermia demonstrated markedly reduced scar size (expressed as % of left ventricular area: hypothermia, 6.5±1.1%; normothermia, 19.4±1.7%; P=1.3×10−6); and thicker anterior LV wall (hypothermia, 1.57±0.09 mm; normothermia, 1.07±0.05 mm; P=3.4×10−5); decreased postmortem left ventricular volume (hypothermia, 0.45±0.04 mL; normothermia, 0.6±0.03 mL; P=0.028); and better LV fractional shortening by echocardiography (hypothermia, 37.2±2.8%; normothermia, 18.9±2.3%; P=0.0002) and LV ejection fraction by LV contrast ventriculography (hypothermia, 66.8±2.3%; normothermia, 56.0±2.0%; P=0.0014). Conclusions Rapid, transient non-invasive surface cooling with the ThermoSuit apparatus in the acute phase of MI decreased scar size by 66.5%, attenuated adverse post-infarct left ventricular dilation and remodeling, and improved cardiac function in the chronic phase of experimental MI. PMID:26116692

  9. Sustained myocardial production of stromal cell-derived factor-1α was associated with left ventricular adverse remodeling in patients with myocardial infarction.

    PubMed

    Uematsu, Manabu; Yoshizaki, Toru; Shimizu, Takuya; Obata, Jun-ei; Nakamura, Takamitsu; Fujioka, Daisuke; Watanabe, Kazuhiro; Watanabe, Yosuke; Kugiyama, Kiyotaka

    2015-11-15

    The role of stromal cell-derived factor-1α (SDF-1α) expressed in infarcted myocardium is unknown in humans. We examined whether SDF-1α produced in an infarcted myocardial lesion may play a role in left ventricle (LV) remodeling and dysfunction in patients with acute myocardial infarction (AMI). We measured SDF-1α levels in plasma obtained from aortic root (AO) and anterior interventricular vein (AIV) in the early phase (2 wk after MI) and the chronic phase (6 mo after MI) in 80 patients with anterior MI. An increment in SDF-1α level from AO to AIV, reflecting SDF-1α release from infarcted myocardium, was more frequent in patients with MI in the early phase of MI [n = 52 (65%), P = 0.03] but not in the chronic phase of MI [n = 46 (58%), P = 0.11] compared with that in control patients [n = 6/17 (35%)]. On linear regression analysis, the transmyocardial gradient in SDF-1α level in the chronic phase of MI was correlated with percentage changes in LV end-diastolic volume index (r = 0.39, P < 0.001), LV end-systolic volume index (r = 0.38, P < 0.001), and LV ejection fraction (r = -0.26, P = 0.01) 6 mo after AMI. By contrast, the transmyocardial gradient of SDF-1α in the early phase of MI had no significant correlations. In conclusion, the production of SDF-1α in infarcted myocardium in the chronic phase of MI was associated with LV adverse remodeling and progressive dysfunction in AMI survivors.

  10. Ventricular remodeling in heart failure: the role of myocardial collagen.

    PubMed

    Janicki, J S; Brower, G L; Henegar, J R; Wang, L

    1995-01-01

    Collagen which is present in the myocardium in relatively small amounts is the most abundant structural protein of the connective tissue network. Its structural organization consists of a complex weave of collagen fibers that surrounds and interconnects myocytes, groups of myocytes, muscle fibers and muscle bundles. The conformation of interstitial fibrillar collagen makes it highly resistant to degradation by all proteinases other than specific collagenases. In hearts with myocardial damage secondary to myocardial infarction, chronic ischemia, inflammation, or cardiomyopathy, a complex sequence of compensatory events occur that eventually result in an adverse left ventricular remodeling. This continual state of remodeling is characterized by persistent collagenase activity, fibrillar collagen degradation, and progressive myocyte loss. The net effect is a shift in the balance between collagen synthesis and degradation which leads to an inadequate fibrillar collagen matrix, progressive ventricular dilatation and sphericalization with wall thinning and eventual congestive heart failure.

  11. Ventricular remodeling: from bedside to molecule.

    PubMed

    Jaffe, R; Flugelman, M Y; Halon, D A; Lewis, B S

    1997-01-01

    The multiple mechanisms that bring about the decompensation of the hypertrophic remodeled myocardium are synergistic and not fully understood. Our current hypothesis is that the increased stress on the ventricle is initially offset by compensatory myocardial hypertrophy. In many instances, however, progressive ventricular dilatation and heart failure occur as a result of maladaptive hypertrophy (abnormal myosin-actin production), programmed cell death (apoptosis) and/or changes in the interstitial vasculature and collagen composition. The molecular and genetic background to these processes includes changes in myocardial gene expression, activation of the local tissue renin-angiotensin and other neurohormonal systems, increased matrix metalloproteinase activity (including collagenase), and expression of certain components of the immune system, such as TNF-alpha. Future research will hopefully provide better methods for limiting the remodeling-ventricular dilatation process by novel pharmacotherapies, gene therapy and, possibly, surgical therapy, and determine the impact of such interventions on survival.

  12. The pathophysiologic process of ventricular remodeling: from infarct to failure.

    PubMed

    Paul, S

    1995-05-01

    In the past, hypertensive heart disease was the principal cause of congestive heart failure, but currently ischemic heart disease is the major etiologic factor. In the last 20 years, the role of myocardial infarction (MI) and the subsequent alteration in ventricular architecture of the infarcted and noninfarcted myocardium have become increasingly associated with a phenomenon known as ventricular remodelling. This process consists of left ventricular wall thinning in the infarction area, ventricular chamber dilatation, and compensatory hypertrophy of the noninfarcted portion of the myocardium. This article describes the pathophysiologic transformation that begins with MI and ventricular remodeling and ends in congestive heart failure.

  13. Postinfarct Left Ventricular Remodelling: A Prevailing Cause of Heart Failure

    PubMed Central

    Galli, Alessio; Lombardi, Federico

    2016-01-01

    Heart failure is a chronic disease with high morbidity and mortality, which represents a growing challenge in medicine. A major risk factor for heart failure with reduced ejection fraction is a history of myocardial infarction. The expansion of a large infarct scar and subsequent regional ventricular dilatation can cause postinfarct remodelling, leading to significant enlargement of the left ventricular chamber. It has a negative prognostic value, because it precedes the clinical manifestations of heart failure. The characteristics of the infarcted myocardium predicting postinfarct remodelling can be studied with cardiac magnetic resonance and experimental imaging modalities such as diffusion tensor imaging can identify the changes in the architecture of myocardial fibers. This review discusses all the aspects related to postinfarct left ventricular remodelling: definition, pathogenesis, diagnosis, consequences, and available therapies, together with experimental interventions that show promising results against postinfarct remodelling and heart failure. PMID:26989555

  14. Passive ventricular remodeling in cardiac disease: focus on heterogeneity

    PubMed Central

    Kessler, Elise L.; Boulaksil, Mohamed; van Rijen, Harold V. M.; Vos, Marc A.; van Veen, Toon A. B.

    2014-01-01

    Passive ventricular remodeling is defined by the process of molecular ventricular adaptation to different forms of cardiac pathophysiology. It includes changes in tissue architecture, such as hypertrophy, fiber disarray, alterations in cell size and fibrosis. Besides that, it also includes molecular remodeling of gap junctions, especially those composed by Connexin43 proteins (Cx43) in the ventricles that affect cell-to-cell propagation of the electrical impulse, and changes in the sodium channels that modify excitability. All those alterations appear mainly in a heterogeneous manner, creating irregular and inhomogeneous electrical and mechanical coupling throughout the heart. This can predispose to reentry arrhythmias and adds to a further deterioration into heart failure. In this review, passive ventricular remodeling is described in Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy (ICM), and Arrhythmogenic Cardiomyopathy (ACM), with a main focus on the heterogeneity of those alterations mentioned above. PMID:25566084

  15. Role of thyroid hormones in ventricular remodeling.

    PubMed

    Rajagopalan, Viswanathan; Gerdes, A Martin

    2015-04-01

    Cardiac remodeling includes alterations in molecular, cellular, and interstitial systems contributing to changes in size, shape, and function of the heart. This may be the result of injury, alterations in hemodynamic load, neurohormonal effects, electrical abnormalities, metabolic changes, etc. Thyroid hormones (THs) serve as master regulators for diverse remodeling processes of the cardiovascular system-from the prenatal period to death. THs promote a beneficial cardiomyocyte shape and improve contractility, relaxation, and survival via reversal of molecular remodeling. THs reduce fibrosis by decreasing interstitial collagen and reduce the incidence and duration of arrhythmias via remodeling ion channel expression and function. THs restore metabolic function and also improve blood flow both by direct effects on the vessel architecture and decreasing atherosclerosis. Optimal levels of THs both in the circulation and in cardiac tissues are critical for normal homeostasis. This review highlights TH-based remodeling and clinically translatable strategies for diverse cardiovascular disorders.

  16. Relationship between Left Ventricular Structural and Metabolic Remodelling in Type 2 Diabetes Mellitus

    PubMed Central

    Levelt, Eylem; Mahmod, Masliza; Piechnik, Stefan K.; Ariga, Rina; Francis, Jane M.; Rodgers, Christopher T.; Clarke, William T.; Sabharwal, Nikant; Schneider, Jurgen E.; Karamitsos, Theodoros D.; Clarke, Kieran; Rider, Oliver J.; Neubauer, Stefan

    2016-01-01

    Concentric left ventricular (LV) remodelling is associated with adverse cardiovascular events and is frequently observed in patients with type 2 diabetes mellitus (T2DM). Despite this, the cause of concentric remodelling in diabetes, per se, is unclear, but may be related to cardiac steatosis and impaired myocardial energetics. Thus, we investigated the relationship amongst myocardial metabolic changes and LV remodelling in T2DM. Forty-six non-hypertensive T2DM patients and twenty matched controls underwent cardiovascular magnetic resonance to assess LV remodelling (LV mass to LV end diastolic volume ratio-LVMVR), function, pre- and post-contrast tissue characterisation using T1 mapping, 1H-, 31P-magnetic resonance spectroscopy for myocardial triglyceride content (MTG) and phosphocreatine to ATP ratio (PCr/ATP) respectively. When compared to body mass index and blood pressure matched controls, diabetes was associated with: concentric LV remodelling, higher MTG, impaired myocardial energetics and impaired systolic strain indicating a subtle contractile dysfunction. Importantly, cardiac steatosis independently predicted concentric remodelling and systolic strain. Extracellular volume fraction was unchanged, indicating absence of fibrosis. In conclusion, cardiac steatosis may contribute to LV concentric remodelling and contractile dysfunction in diabetes. As cardiac steatosis is modifiable, strategies aimed at reducing myocardial triglyceride may be beneficial in reversing concentric remodelling and improving contractile function in the diabetic heart. PMID:26438611

  17. Relationship Between Left Ventricular Structural and Metabolic Remodeling in Type 2 Diabetes.

    PubMed

    Levelt, Eylem; Mahmod, Masliza; Piechnik, Stefan K; Ariga, Rina; Francis, Jane M; Rodgers, Christopher T; Clarke, William T; Sabharwal, Nikant; Schneider, Jurgen E; Karamitsos, Theodoros D; Clarke, Kieran; Rider, Oliver J; Neubauer, Stefan

    2016-01-01

    Concentric left ventricular (LV) remodeling is associated with adverse cardiovascular events and is frequently observed in patients with type 2 diabetes mellitus (T2DM). Despite this, the cause of concentric remodeling in diabetes per se is unclear, but it may be related to cardiac steatosis and impaired myocardial energetics. Thus, we investigated the relationship between myocardial metabolic changes and LV remodeling in T2DM. Forty-six nonhypertensive patients with T2DM and 20 matched control subjects underwent cardiovascular magnetic resonance to assess LV remodeling (LV mass-to-LV end diastolic volume ratio), function, tissue characterization before and after contrast using T1 mapping, and (1)H and (31)P magnetic resonance spectroscopy for myocardial triglyceride content (MTG) and phosphocreatine-to-ATP ratio, respectively. When compared with BMI- and blood pressure-matched control subjects, subjects with diabetes were associated with concentric LV remodeling, higher MTG, impaired myocardial energetics, and impaired systolic strain indicating a subtle contractile dysfunction. Importantly, cardiac steatosis independently predicted concentric remodeling and systolic strain. Extracellular volume fraction was unchanged, indicating the absence of fibrosis. In conclusion, cardiac steatosis may contribute to concentric remodeling and contractile dysfunction of the LV in diabetes. Because cardiac steatosis is modifiable, strategies aimed at reducing MTG may be beneficial in reversing concentric remodeling and improving contractile function in the hearts of patients with diabetes.

  18. Right ventricular remodeling in pulmonary hypertension.

    PubMed

    Franco, Veronica

    2012-07-01

    The right ventricle (RV) is in charge of pumping blood to the lungs for oxygenation. Pulmonary arterial hypertension (PAH) is characterized by high pulmonary vascular resistance and vascular remodeling, which results in a striking increase in RV afterload and subsequent failure. There is still unexploited potential for therapies that directly target the RV with the aim of supporting and protecting the right side of the heart, striving to prolong survival in patients with PAH.

  19. [Physiopathology of left ventricular remodeling after myocardial infarction].

    PubMed

    Bassand, J P; Anguenot, T

    1991-12-01

    The geometry of both the infarcted and non-infarcted zone of the left ventricle changes after myocardial infarction. Two mechanisms are involved: expansion of the infarcted zone and secondary dilatation of the non-infarcted zone. The necrosed area undergoes an inflammatory reaction followed by fibrosis which end up as a sca within a period of a few days to a few weeks. During this period if fibrous scarring the infarcted, thinned myocardium undergoes progressive expansion which starts in the first hours of the myocardial infarction. The loss of left ventricular systolic function related to the infarct and volumic overload created by expansion of the infarct influence the secondary development of dilatation of the non-infarcted zones. This dilatation results in restoration of left ventricular stroke volume but at the price of increased wall stress, which itself induces compensatory wall hypertrophy. These phenomena are more pronounced when the initial infarction is extensive and if they are sustained, they result in definitive myocardial failure. Several factors influence remodeling: the size of the infarct, arterial patency, wall stress and the quality of the scarring process itself. Therapeutic interventions of each of these factors can influence the remodeling. Limitation of infarct size by thrombolytic therapy, arterial revascularisation, even when performed late, seem capable of limiting expansion of the necrosed zone. Pharmacodynamic intervention of left ventricular afterload also affects ventricular remodeling. Nitrate derivatives, vasodilator therapy in general and converting enzyme inhibitors have been shown to be effective.

  20. [Early left ventricular remodelling following acute coronary accident].

    PubMed

    Gaertner, Roger; Logeart, Damien; Michel, Jean-Baptiste; Mercadier, Jean-Jacques

    2004-01-01

    Ventricular remodelling following acute coronary syndromes is both complex and multiform. It is due to the response of the myocardium to the different agressions associated with these syndromes, in particular the ischemia and necrosis downstream of the occluded artery. We must not however neglect the role of the remodelling of the lesions resulting from spontaneous reperfusion or provoked by the cells and tissues associated with coronary microcirculation embolisms and the no-reflow phenomenon. Acute post-infarct remodelling is dominated by early ventricular dilatation which largely affects late prognosis, necrosis elimination and its replacement by a fibrotic scar in parallel with a compensatory hypertrophy of the non-infarcted myocardium. The diverse cellular and molecular components of this remodelling are increasingly well-known, allowing us to better explain the beneficial effects of the currently available medications and providing us with new potential therapeutic targets. A grading of this knowledge associated with the identification of new risk factors and early therapeutic interventions should help us to further limit the deleterious aspects of this remodelling in the goal of preventing, or at least delaying, the devolution towards heart failure.

  1. Prediction of Left Ventricular Remodeling after a Myocardial Infarction: Role of Myocardial Deformation: A Systematic Review and Meta-Analysis

    PubMed Central

    Huttin, Olivier; Coiro, Stefano; Selton-Suty, Christine; Juillière, Yves; Donal, Erwan; Magne, Julien; Sadoul, Nicolas; Zannad, Faiez; Rossignol, Patrick; Girerd, Nicolas

    2016-01-01

    Aims Left ventricular (LV) adverse or reverse remodeling after ST-segment elevation myocardial infarction (MI) is the best outcome to assess the benefit of revascularization. Speckle tracking echocardiography (STE) may accurately identify early deformation impairment, while also being predictive of LV remodeling during follow-up. This systematic analysis aimed to provide a comprehensive review of current findings on STE as a predictor of LV remodeling after MI. Methods PubMed databases were searched through December 2014 to identify studies in adults targeting the association between LV remodeling and STE. Meta-regression was performed for longitudinal analysis. Results A total of 23 prospective studies (3066 patients) were found eligible. Eleven studies reported an association between STE and adverse remodeling and twelve studies with reverse remodeling. Using peak systolic longitudinal strain, the most accurate cut-off to predict adverse remodeling and reverse remodeling ranged from -12.8% to -10.2% and from -13.7% to -9.5%, respectively. In smaller studies, assessment of circumferential strain and torsion showed additive value in predicting remodeling. Meta-regression analysis revealed that longitudinal STE was associated with adverse remodeling (pooled univariable OR = 1.27, 1.17–1.38, p<0.001; pooled multivariable OR = 1.38, 1.13–1.70, p = 0.002) while pooled ORs of longitudinal STE only tended to predict reverse remodeling (pooled OR = 0.75, 0.54–1.06, p = 0.09). Conclusions This systematic review suggests that STE is associated with changes in LV volume or function regardless of underlying mechanisms and deformation direction. Meta-regression demonstrates a strong association between peak longitudinal systolic strain and adverse remodeling. Added STE predictive value over other clinical, biological and imaging variables remains to be proven. PMID:28036335

  2. The Effect of Rosuvastatin on Inflammation, Matrix Turnover and Left Ventricular Remodeling in Dilated Cardiomyopathy: A Randomized, Controlled Trial

    PubMed Central

    Gjertsen, Erik; Ueland, Thor; Yndestad, Arne; Godang, Kristin; Stueflotten, Wenche; Andreassen, Johanna; Svendsmark, Rolf; Smith, Hans-Jørgen; Aakhus, Svend; Aukrust, Pål; Gullestad, Lars

    2014-01-01

    Background Dilated cardiomyopathy is characterized by left ventricular dilatation and dysfunction. Inflammation and adverse remodeling of the extracellular matrix may be involved in the pathogenesis. Statins reduce levels of low density lipoprotein cholesterol, but may also attenuate inflammation and affect matrix remodeling. We hypothesized that treatment with rosuvastatin would reduce or even reverse left ventricular remodeling in dilated cardiomyopathy. Materials and Methods In this multicenter, randomized, double blind, placebo-controlled study, 71 patients were randomized to 10 mg of rosuvastatin or matching placebo. Physical examination, blood sampling, echocardiography and cardiac magnetic resonance imaging were performed at baseline and at six months’ follow-up. The pre-specified primary end point was the change in left ventricular ejection fraction from baseline to six months. Results Over all, left ventricular ejection fraction improved 5 percentage points over the duration of the study, but there was no difference in the change in left ventricular ejection fraction between patients allocated to rosuvastatin and those allocated to placebo. Whereas serum low density lipoprotein cholesterol concentration fell significantly in the treatment arm, rosuvastatin did not affect plasma or serum levels of a wide range of inflammatory variables, including C-reactive protein. The effect on markers of extracellular matrix remodeling was modest. Conclusion Treatment with rosuvastatin does not improve left ventricular ejection fraction in patients with dilated cardiomyopathy. Trial Registration ClinicalTrials.gov NCT00505154 PMID:24586994

  3. Estrogen inhibits mast cell chymase release to prevent pressure overload-induced adverse cardiac remodeling.

    PubMed

    Li, Jianping; Jubair, Shaiban; Janicki, Joseph S

    2015-02-01

    Estrogen regulation of myocardial chymase and chymase effects on cardiac remodeling are unknown. To test the hypothesis that estrogen prevents pressure overload-induced adverse cardiac remodeling by inhibiting mast cell (MC) chymase release, transverse aortic constriction or sham surgery was performed in 7-week-old intact and ovariectomized (OVX) rats. Three days before creating the constriction, additional groups of OVX rats began receiving 17β-estradiol, a chymase inhibitor, or a MC stabilizer. Left ventricular function, cardiomyocyte size, collagen volume fraction, MC density and degranulation, and myocardial and plasma chymase levels were assessed 18 days postsurgery. Aortic constriction resulted in ventricular hypertrophy in intact and OVX groups, whereas collagen volume fraction was increased only in OVX rats. Chymase protein content was increased by aortic constriction in the intact and OVX groups, with the magnitude of the increase being greater in OVX rats. MC density and degranulation, plasma chymase levels, and myocardial active transforming growth factor-β1 levels were increased by aortic constriction only in OVX rats. Estrogen replacement markedly attenuated the constriction-increased myocardial chymase, MC density and degranulation, plasma chymase, and myocardial active transforming growth factor-β1, as well as prevented ventricular hypertrophy and increased collagen volume fraction. Chymostatin attenuated the aortic constriction-induced ventricular hypertrophy and collagen volume fraction in the OVX rats similar to that achieved by estrogen replacement. Nedocromil yielded similar effects, except for the reduction of chymase content. We conclude that the estrogen-inhibited release of MC chymase is responsible for the cardioprotection against transverse aortic constriction-induced adverse cardiac remodeling.

  4. Echocardiographic Predictors for Left Ventricular Remodeling after Acute ST Elevation Myocardial Infarction with Low Risk Group: Speckle Tracking Analysis

    PubMed Central

    Na, Hyun-Min; Lee, Joo Myung; Cha, Myung-Jin; Yoon, Yeonyee E.; Lee, Seung-Pyo; Kim, Hyung-Kwan; Kim, Yong-Jin; Sohn, Dae-Won

    2016-01-01

    Background We sought to assess echocardiographic predictors of left ventricular (LV) adverse remodeling after successfully reperfused acute ST elevation myocardial infarction (STEMI). LV remodeling is commonly found in STEMI patients and it may suggest adverse outcome in acute myocardial infarction. We sought to identify whether 2D strain and torsion be independent parameters for prediction of LV adverse remodeling. Methods We investigated 208 patients with low-risk STEMI patients who had follow up echocardiography at 6 or more months. After clinical assessments, all patients received revascularization according to current guideline. LV remodeling was defined as > 20% increase in end-diastolic volume (EDV) at follow up. Results During the follow-up (11.9 ± 5.3 months), 53 patients (25.5%) showed LV remodeling. In univariate analysis, EDV, end-systolic volume, deceleration time (DT), CK-MB, and global longitudinal strain (GLS) were associated with LV remodeling. In multivariate analysis, EDV [hazard ratio (HR): 0.922, 95% confidence interval (CI): 0.897–0.948, p< 0.001], GLS (HR: 0.842, 95% CI: 0.728–0.974, p = 0.020), DT (HR: 0.989, 95% CI: 0.980–0.998, p = 0.023) and CK-MB (HR: 1.003, 95% CI: 1.000–1.005, p = 0.033) independently predicted LV remodeling. However, global circumferential strain, net twist, and twist or untwist rate were not associated with remodeling. Conclusion Of various parameters of speckle strain, only GLS predicted adverse remodeling in STEMI patients. PMID:27358705

  5. Left ventricular structure and remodeling in patients with COPD

    PubMed Central

    Pelà, Giovanna; Li Calzi, Mauro; Pinelli, Silvana; Andreoli, Roberta; Sverzellati, Nicola; Bertorelli, Giuseppina; Goldoni, Matteo; Chetta, Alfredo

    2016-01-01

    Background Data on cardiac alterations such as left ventricular (LV) hypertrophy, diastolic dysfunction, and lower stroke volume in patients with COPD are discordant. In this study, we investigated whether early structural and functional cardiac changes occur in patients with COPD devoid of manifest cardiovascular disease, and we assessed their associations with clinical and functional features. Methods Forty-nine patients with COPD belonging to all Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes were enrolled and compared with 36 controls. All subjects underwent clinical history assessment, lung function testing, blood pressure measurement, electrocardiography, and conventional and Doppler tissue echocardiography. Patients were also subjected to computed tomography to quantify emphysema score. Results Patients with COPD had lower LV cavity associated with a marked increase in relative wall thickness (RWT), suggesting concentric remodeling without significant changes in LV mass. RWT was significantly associated with ratio of the forced expiratory volume in 1 second to the forced vital capacity and emphysema score and was the only cardiac parameter that – after multivariate analysis – significantly correlated with COPD conditions in all individuals. Receiver operating characteristic curve analysis showed that RWT (with a cutoff point of 0.42) predicted the severity of COPD with 83% specificity and 56% sensitivity (area under the curve =0.69, 95% confidence interval =0.59–0.81). Patients with COPD showed right ventricular to be functional but no structural changes. Conclusion Patients with COPD without evident cardiovascular disease exhibit significant changes in LV geometry, resulting in concentric remodeling. In all individuals, RWT was significantly and independently related to COPD. However, its prognostic role should be determined in future studies. PMID:27257378

  6. Cardiac mast cell regulation of matrix metalloproteinase-related ventricular remodeling in chronic pressure or volume overload.

    PubMed

    Janicki, Joseph S; Brower, Gregory L; Gardner, Jason D; Forman, Mary F; Stewart, James A; Murray, David B; Chancey, Amanda L

    2006-02-15

    The chronic elevation in ventricular wall stress secondary to ventricular volume or pressure overload leads to structural remodeling of the muscular, vascular and extracellular matrix components of the myocardium. While initially a compensatory response, the progressive hypertrophy and ventricular dilatation induced by this condition ultimately have a detrimental effect on ventricular function, resulting in heart failure. Fibrillar collagen provides the skeletal framework which interconnects the cardiomyocytes, thereby maintaining ventricular shape and size and contributing to tissue stiffness. Accordingly, these myocardial collagen fibers must be disrupted for ventricular dilatation, sphericalization and wall thinning to occur. The presence of an abundant, latent matrix metalloproteinase (MMP) population which coexists with myocardial fibrillar collagen has been documented. Thus, the potential for collagen degradation to exceed synthesis exists should there be significant activation of this latent MMP system. Mast cells are known to store and release a variety of biologically active mediators including TNF-alpha and proteases such as tryptase and chymase, which can induce MMP activation. Increased cardiac mast cell density has been implicated in the pathophysiology of human end-stage cardiomyopathy and experimental myocardial infarction, hypertension and chronic volume overload secondary to mitral regurgitation and aorto-caval fistula. The potential role of cardiac mast cells in activating MMPs, which then results in fibrillar collagen degradation and adverse myocardial remodeling secondary to chronic volume and pressure overload will be the subject of this review.

  7. Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload

    PubMed Central

    Nielsen, Eva Amalie; Sun, Mei; Honjo, Osami; Hjortdal, Vibeke E.; Redington, Andrew N.; Friedberg, Mark K.

    2016-01-01

    Background Pulmonary arterial hypertension is usually fatal due to right ventricular failure and is frequently associated with co-existing left ventricular dysfunction. Endothelin-1 is a powerful pro-fibrotic mediator and vasoconstrictor that is elevated in pulmonary arterial hypertension. Endothelin receptor blockers are commonly used as pulmonary vasodilators, however their effect on biventricular injury, remodeling and function, despite elevated isolated right ventricular afterload is unknown. Methods Elevated right ventricular afterload was induced by progressive pulmonary artery banding. Seven rabbits underwent pulmonary artery banding without macitentan; 13 received pulmonary artery banding + macitentan; and 5 did not undergo inflation of the pulmonary artery band (sham-operated controls). Results: Right and left ventricular collagen content was increased with pulmonary artery banding compared to sham-operated controls and ameliorated by macitentan. Right ventricular fibrosis signaling (connective tissue growth factor and endothelin-1 protein levels); extra-cellular matrix remodeling (matrix-metalloproteinases 2 and 9), apoptosis and apoptosis-related peptides (caspases 3 and 8) were increased with pulmonary artery banding compared with sham-operated controls and decreased with macitentan. Conclusion Isolated right ventricular afterload causes biventricular fibrosis, right ventricular apoptosis and extra cellular matrix remodeling, mediated by up-regulation of endothelin-1 and connective tissue growth factor signaling. These pathological changes are ameliorated by dual endothelin receptor blockade despite persistent elevated right ventricular afterload. PMID:26765263

  8. Left ventricular remodeling after experimental myocardial cryoinjury in rats.

    PubMed

    Ciulla, Michele M; Paliotti, Roberta; Ferrero, Stefano; Braidotti, Paola; Esposito, Arturo; Gianelli, Umberto; Busca, Giuseppe; Cioffi, Ugo; Bulfamante, Gaetano; Magrini, Fabio

    2004-01-01

    The standard coronary ligation, the most studied model of experimental myocardial infarction in rats, is limited by high mortality and produces unpredictable areas of necrosis. To standardize the location and size of the infarct and to elucidate the mechanisms of myocardial remodeling and its progression to heart failure, we studied the functional, structural, and ultrastructural changes of myocardial infarction produced by experimental myocardial cryoinjury. The cryoinjury was successful in 24 (80%) of 30 male adult CD rats. A subepicardial infarct was documented on echocardiograms, with an average size of about 21%. Macroscopic examination reflected closely the stamp of the instrument used, without transition zones to viable myocardium. Histological examination, during the acute setting, revealed an extensive area of coagulation necrosis and hemorrhage in the subepicardium. An inflammatory infiltrate was evident since the 7th hour, whereas the reparative phase started within the first week, with proliferation of fibroblasts, endothelial cells, and myocytes. From the 7th day, deposition of collagen fibers was reported with a reparative scar completed at the 30th day. Ultrastructural study revealed vascular capillary damage and irreversible alterations of the myocytes in the acute setting and confirmed the histological findings of the later phases. The damage was associated with a progressive left ventricular (LV) remodeling, including thinning of the infarcted area, hypertrophy of the noninfarcted myocardium, and significant LV dilation. This process started from the 60th day and progressed over the subsequent 120 days period; at 180 days, a significant increase in LV filling pressure, indicative of heart failure, was found. In conclusion, myocardial cryodamage, although different in respect to ischemic damage, causes a standardized injury reproducing the cellular patterns of coagulation necrosis, early microvascular reperfusion, hemorrhage, inflammation

  9. Rutaecarpine attenuates hypoxia-induced right ventricular remodeling in rats.

    PubMed

    Li, Wen-Qun; Li, Xiao-Hui; Du, Jie; Zhang, Wang; Li, Dai; Xiong, Xiao-Ming; Li, Yuan-Jian

    2016-07-01

    Rutaecarpine has been shown to exhibit wide pharmacological effects in the cardiovascular system via stimulation of calcitonin gene-related peptide (CGRP) release. In the present study, the effect of rutaecarpine on hypoxia-induced right ventricular (RV) remodeling and the underlying mechanisms were evaluated. RV remodeling was induced by hypoxia (10 % O2, 3 weeks) in rats. Rats were treated with rutaecarpine (20 or 40 mg/kg) by intragastric administration. Proliferation of cardiac fibroblasts was induced by TGF-β1 (5 ng/mL) and determined by MTS and EdU incorporation method. Cardiac fibroblasts were treated with exogenous CGRP (10 or 100 nM). The concentrations of CGRP and TGF-β1 in plasma were measured by ELISA. The expression of eIF3a, p27, α-SMA, collagen-I/III, ANP, and BNP were measured by real-time PCR or western blot. Hypoxia induced an increase of right ventricle systolic pressure (RVSP), ration of RV/LV+S, and RV/tibial length in rats, while cardiac hypertrophy, apoptosis, and fibrosis were detected. The expression of ANP, BNP, α-SMA, collagen-I, collagen-III, eIF3a, and TGF-β1 was up-regulated, and the expression of p27 was down-regulated in the right ventricle of hypoxia-treated rats. The plasma concentration of CGRP was decreased and TGF-β1 was increased in hypoxia-treated rats. All of these effects induced by hypoxia were attenuated by rutaecarpine in a dose-dependent manner. In cultured cardiac fibroblasts, TGF-β1 significantly promoted the proliferation and up-regulated the expression of α-SMA and collagen-I/III, while the expression of eIF3a was up-regulated and the expression of p27 was down-regulated. The effects of TGF-β1 were attenuated by CGRP. CGRP8-37, a selective CGRP receptor antagonist, abolished the effects of CGRP. Rutaecarpine attenuates hypoxia-induced RV remodeling via stimulation of CGRP release, and the effects of rutaecarpine involve the eIF3a/p27 pathway.

  10. Stretch-activated pathways and left ventricular remodeling.

    PubMed

    Force, Thomas; Michael, Ashour; Kilter, Heiko; Haq, Syed

    2002-12-01

    Stretch of cardiomyocytes in vivo occurs in response to a number of stimuli, including pressure or volume overload, but it is most clearly seen following relatively large, acute myocardial infarctions. It is in this setting that stretch is most clearly related to the pathogenesis of heart failure. Stretch of the remote, noninfacted myocardium leads to the activation of a large number of cellular signal transduction pathways, which sets into motion a series of what are designed to be compensatory responses to the increased wall stress on the surviving myocardium. Herein, we will discuss the cellular pathways activated by cell stretch, which appear to trigger the initial steps in the pathogenesis of ventricular dilatation following myocardial infarction. We will discuss what is known of the "stretch sensors," which convert the mechanical stimulus into molecular signals. I will then introduce the specific cellular signaling pathways activated by stretch and discuss the evidence for their involvement in remodeling. Since many of these pathways will be covered in more detail in specific sections to follow, this will serve as an introduction to stretch-activated signaling. Finally, we will briefly examine later phases of the response, including advanced heart failure. The goal is to identify molecular modulators that might serve as targets for pharmacologic or molecular intervention.

  11. Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

    PubMed Central

    Thoonen, Robrecht; Ernande, Laura; Cheng, Juan; Nagasaka, Yasuko; Yao, Vincent; Miranda-Bezerra, Alexandre; Chen, Chan; Chao, Wei; Panagia, Marcello; Sosnovik, David E.; Puppala, Dheeraj; Armoundas, Antonis A.; Hindle, Allyson; Bloch, Kenneth D.; Buys, Emmanuel S.; Scherrer-Crosbie, Marielle

    2015-01-01

    Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1−/−) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1−/− mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1−/− mice. UCP1−/− mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1−/− mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1−/− BAT transplanted to either UCP1−/− or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1−/− mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1−/− mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy. PMID:25968336

  12. CT-1-CP-induced ventricular electrical remodeling in mice.

    PubMed

    Chen, Shu-fen; Wei, Tao-zhi; Rao, Li-ya; Xu, Ming-guang; Dong, Zhan-ling

    2015-02-01

    The chronic effects of carboxyl-terminal polypeptide of Cardiotrophin-1 (CT-1-CP) on ventricular electrical remodeling were investigated. CT-1-CP, which contains 16 amino acids in sequence of the C-terminal of Cardiotrophin-1, was selected and synthesized, and then administered to Kunming mice (aged 5 weeks) by intraperitoneal injection (500 ng·g⁻¹·day⁻¹) (4 groups, n=10 and female: male=1:1 in each group) for 1, 2, 3 and 4 weeks, respectively. The control group (n=10, female: male=1:1) was injected by physiological saline for 4 weeks. The epicardial monophasic action potential (MAP) was recorded by using a contact-type MAP electrode placed vertically on the left ventricular (LV) epicardium surface, and the electrocardiogram (ECG) signal in lead II was monitored synchronously. ECG intervals (RR, PR, QRS and QT) and the amplitude of MAP (Am), the maximum upstroke velocity (Vmax), as well as action potential durations (APDs) at different repolarization levels (APD30, APD50, APD70, and APD90) of MAP were determined and analyzed in detail. There were no significant differences in RR and P intervals between CT-1-CP-treated groups and control group, but the PR segment and the QRS complex were greater in the former than in the latter (F=2.681 and 5.462 respectively, P<0.05). Though QT interval and the corrected QT interval (QTc) were shorter in CT-1-CP-treated groups than in control group, the QT dispersion (QTd) of them was greater in the latter than in the former (F=3.090, P<0.05) and increased with the time. The ECG monitoring synchronously with the MAP showed that the compression of MAP electrode on the left ventricular epicardium induced performance similar to myocardium ischemia. As compared with those before chest-opening, the PR segment and QT intervals remained basically unchanged in control group, but prolonged significantly in all CT-1-CP-treated groups and the prolongation of QT intervals increased gradually along with the time of exposure to CT-1-CP

  13. Radiotherapy-induced right ventricular remodelling: The missing piece of the puzzle.

    PubMed

    Tadic, Marijana; Cuspidi, Cesare; Hering, Dagmara; Venneri, Lucia; Grozdic-Milojevic, Isidora

    2017-02-01

    The number of studies demonstrating that right ventricular structure, function and mechanics are valuable predictors of cardiovascular and total morbidity and mortality in patients with a wide range of cardiovascular conditions is constantly increasing. Most studies that evaluated the influence of radiotherapy on the heart focused on left ventricular remodelling, which is why current guidelines only recommend detailed assessment of the left ventricle. Data regarding right ventricular changes in cancer patients treated with radiotherapy are scarce. Given that radiotherapy more often induces late cardiac impairment - unlike chemotherapy-induced cardiotoxicity, which is usually acute - it is quite reasonable to follow these patients echocardiographically for a long time (even for 20years after initiation of radiotherapy). Investigations that have followed cancer survivors for at least 10years after radiotherapy agree that right ventricular structure, systolic/diastolic function and mechanics are significantly impaired. The mechanisms of radiation-induced right ventricular remodelling are still unclear, but it is thought that fibrosis is the dominant factor in myocardial remodelling and vascular changes. Many factors may contribute to right ventricular impairment during and after radiotherapy: cumulative radiation dose; dose per treatment; delivery technique; radiation target (chest and mediastinum); and co-morbidities. In this review, we aim to provide a comprehensive overview of the potential mechanisms of radiation-induced right ventricular remodelling, and to summarize clinical studies involving radiotherapy-treated cancer patients.

  14. Factors affecting left ventricular remodeling after valve replacement for aortic stenosis. An overview

    PubMed Central

    Villa, Emmanuel; Troise, Giovanni; Cirillo, Marco; Brunelli, Federico; Tomba, Margherita Dalla; Mhagna, Zen; Tasca, Giordano; Quaini, Eugenio

    2006-01-01

    Although a small percentage of patients with critical aortic stenosis do not develop left ventricle hypertrophy, increased ventricular mass is widely observed in conditions of increased afterload. There is growing epidemiological evidence that hypertrophy is associated with excess cardiac mortality and morbidity not only in patients with arterial hypertension, but also in those undergoing aortic valve replacement. Valve replacement surgery relieves the aortic obstruction and prolongs the life of many patients, but favorable or adverse left ventricular remodeling is affected by a large number of factors whose specific roles are still a subject of debate. Age, gender, hemodynamic factors, prosthetic valve types, myocyte alterations, interstitial structures, blood pressure control and ethnicity can all influence the process of left ventricle mass regression, and myocardial metabolism and coronary artery circulation are also involved in the changes occurring after aortic valve replacement. The aim of this overview is to analyze these factors in the light of our experience, elucidate the important question of prosthesis-patient mismatch by considering the method of effective orifice area, and discuss surgical timings and techniques that can improve the management of patients with aortic valve stenosis and maximize the probability of mass regression. PMID:16803632

  15. Right ventricular relative wall thickness as a predictor of outcomes and of right ventricular reverse remodeling for patients with pulmonary hypertension.

    PubMed

    Sano, Hiroyuki; Tanaka, Hidekazu; Motoji, Yoshiki; Fukuda, Yuko; Mochizuki, Yasuhide; Hatani, Yutaka; Matsuzoe, Hiroki; Hatazawa, Keiko; Shimoura, Hiroyuki; Ooka, Junichi; Ryo-Koriyama, Keiko; Nakayama, Kazuhiko; Matsumoto, Kensuke; Emoto, Noriaki; Hirata, Ken-Ichi

    2017-03-01

    Mid-term right ventricular (RV) reverse remodeling after treatment in patients with pulmonary hypertension (PH) is associated with long-term outcome as well as baseline RV remodeling. However, baseline factors influencing mid-term RV reverse remodeling after treatment and its prognostic capability remain unclear. We studied 54 PH patients. Mid-term RV remodeling was assessed in terms of the RV area, which was traced planimetrically at the end-systole (RVESA). RV reverse remodeling was defined as a relative decrease in the RVESA of at least 15% at 10.2 ± 9.4 months after treatment. Long-term follow-up was 5 years. Adverse events occurred in ten patients (19%) and mid-term RV reverse remodeling after treatment was observed in 37 (69%). Patients with mid-term RV reverse remodeling had more favorable long-term outcomes than those without (log-rank: p = 0.01). Multivariate logistic regression analysis showed that RV relative wall thickness (RV-RWT), as calculated as RV free-wall thickness/RV basal linear dimension at end-diastole, was an independent predictor of mid-term RV reverse remodeling (OR 1.334; 95% CI, 1.039-1.713; p = 0.03). Moreover, patients with RV-RWT ≥0.21 showed better long-term outcomes than did those without (log-rank p = 0.03), while those with RV-RWT ≥0.21 and mid-term RV reverse remodeling had the best long-term outcomes. Patients with RV-RWT <0.21 and without mid-term RV reverse remodeling, on the other hand, had worse long-term outcomes than other sub-groups. In conclusions, RV-RWT could predict mid-term RV reverse remodeling after treatment in PH patients, and was associated with long-term outcomes. Our finding may have clinical implications for better management of PH patients.

  16. Inhalation of hydrogen gas attenuates left ventricular remodeling induced by intermittent hypoxia in mice.

    PubMed

    Hayashi, Tetsuya; Yoshioka, Toshitaka; Hasegawa, Kenichi; Miyamura, Masatoshi; Mori, Tatsuhiko; Ukimura, Akira; Matsumura, Yasuo; Ishizaka, Nobukazu

    2011-09-01

    Sleep apnea syndrome increases the risk of cardiovascular morbidity and mortality. We previously reported that intermittent hypoxia increases superoxide production in a manner dependent on nicotinamide adenine dinucleotide phosphate and accelerates adverse left ventricular (LV) remodeling. Recent studies have suggested that hydrogen (H(2)) may have an antioxidant effect by reducing hydroxyl radicals. In this study, we investigated the effects of H(2) gas inhalation on lipid metabolism and LV remodeling induced by intermittent hypoxia in mice. Male C57BL/6J mice (n = 62) were exposed to intermittent hypoxia (repetitive cycle of 1-min periods of 5 and 21% oxygen for 8 h during daytime) for 7 days. H(2) gas (1.3 vol/100 vol) was given either at the time of reoxygenation, during hypoxic conditions, or throughout the experimental period. Mice kept under normoxic conditions served as controls (n = 13). Intermittent hypoxia significantly increased plasma levels of low- and very low-density cholesterol and the amount of 4-hydroxy-2-nonenal-modified protein adducts in the LV myocardium. It also upregulated mRNA expression of tissue necrosis factor-α, interleukin-6, and brain natriuretic peptide, increased production of superoxide, and induced cardiomyocyte hypertrophy, nuclear deformity, mitochondrial degeneration, and interstitial fibrosis. H(2) gas inhalation significantly suppressed these changes induced by intermittent hypoxia. In particular, H(2) gas inhaled at the timing of reoxygenation or throughout the experiment was effective in preventing dyslipidemia and suppressing superoxide production in the LV myocardium. These results suggest that inhalation of H(2) gas was effective for reducing oxidative stress and preventing LV remodeling induced by intermittent hypoxia relevant to sleep apnea.

  17. Cytokines profile in hypertensive patients with left ventricular remodeling and dysfunction.

    PubMed

    Kuznetsova, Tatiana; Haddad, Francois; Knez, Judita; Rosenberg-Hasson, Yael; Sung, Janine; Cauwenberghs, Nicholas; Thijs, Lutgarde; Karakikes, Ioannis; Maecker, Holden; Mahaffey, Kenneth W; Wu, Joseph C; Staessen, Jan A

    2015-12-01

    There is strong evidence that inflammatory mediators play a key role in the progression to heart failure in patients with systemic hypertension (HTN). The present study aimed to identify a set of cytokines that are associated with early left ventricular (LV) remodeling and dysfunction as captured by echocardiography in patients with HTN in a cross-sectional case-control study nested within the FLEMish study on ENvironment, Genes and Health Outcome. We identified three groups of participants from the cohort: normotensive subjects (normotension; n = 30), HTN with normal LV structure and function (HTN [LV-]; n = 30), and HTN with evidence of adverse LV remodeling (HTN [LV+]; n = 50). We measured cytokines using a 63-plex Luminex platform. Using partial least squares-discriminant analysis, we constructed three latent variables from the measured cytokines that explained 35%-45% of the variance between groups. We identified five common cytokines (interleukin 18, monokine induced by gamma interferon, hepatocyte growth factor, epithelial neutrophil-activating peptide 78, and vascular endothelial growth factor D) with a stable signal which had a major impact on the construction of the latent variables. Among these cytokines, after adjustment for confounders, interleukin 18 remained significantly different between HTN participants with and without LV involvement (P = .02). Moreover, granulocyte-macrophage colony-stimulating factor and leptin showed a consistent upward trend in all HTN patients compared with normotensive subjects. In conclusion, in HTN patients with LV remodeling or/and dysfunction, we identified a set of cytokines strongly associated with LV maladaptation. We also found a distinct profile of inflammatory biomarkers that characterize HTN.

  18. Mast Cell Inhibition Attenuates Myocardial Damage, Adverse Remodeling and Dysfunction during Fulminant Myocarditis in Rat

    PubMed Central

    Mina, Yair; Rinkevich-Shop, Shunit; Konen, Eli; Goitein, Orly; Kushnir, Tammar; Epstein, Frederick H.; Feinberg, Micha S.; Leor, Jonathan; Landa-Rouben, Natalie

    2013-01-01

    Background Myocarditis is a life-threatening heart disease characterized by myocardial inflammation, necrosis and chronic fibrosis. While mast cell inhibition has been suggested to prevents fibrosis in rat myocarditis, little is known about its effectiveness in attenuating cardiac remodeling and dysfunction in myocarditis. Thus, we sought to test the hypothesis that mast cell inhibition will attenuate the inflammatory reaction and associated left ventricular (LV) remodeling and dysfunction after fulminant autoimmune myocarditis. Methods and Results To induce experimental autoimmune myocarditis, we immunized 30 rats with porcine cardiac myosin twice at a 7-day interval. On day 8 animals were randomized into treatment either with an intraperitoneal (IP) injection of 25mg/kg of cromolyn sodium (n=13), or an equivalent volume (~0.5ml IP) of normal saline (n=11). All animals were scanned by serial echocardiography studies before treatment (baseline echocardiogram) and after 20 days of cromolyn sodium (28 days after immunization). Furthermore, serial cardiac magnetic resonance was performed in a subgroup of 12 animals. After 20 days of treatment (28 days from first immunization), hearts were harvested for histopathological analysis. By echocardiography, cromolyn sodium prevented LV dilatation and attenuated LV dysfunction, compared with controls. Postmortem analysis of hearts showed that cromolyn sodium reduced myocardial fibrosis, as well as the number and size of cardiac mast cells in the inflamed myocardium, compared with controls. Conclusions Our study suggests that mast cell inhibition with cromolyn sodium attenuates adverse LV remodeling and dysfunction in myocarditis. This mechanism-based therapy is clinically relevant and could improve the outcome of patients at risk for inflammatory cardiomyopathy and heart failure. PMID:23172937

  19. Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction.

    PubMed

    Park, Jae-Hyeong; Yoon, Jung Yeon; Ko, Seon Mi; Jin, Seon Ah; Kim, Jun Hyung; Cho, Chung-Hyun; Kim, Jin-Man; Lee, Jae-Hwan; Choi, Si Wan; Seong, In-Whan; Jeong, Jin Ok

    2011-08-31

    Cardiac lymphatic system in the remodeling after acute myocardial infarction (AMI) has been overlooked. We wanted to investigate the role of bone marrow-derived endothelial progenitor cells (EPCs) and their contribution to lymphatic distribution in myocardial remodeling after AMI. Mouse (C57bl/6J) MI models were created by ligation of the left anterior descending coronary artery and were treated with phosphate buffered saline (PBS) or EPCs. Real-time RT-PCR with 2- to 4-week myocardial tissue samples revealed that lymphangiogenetic factors such as vascular endothelial growth factor (VEGF)-C (8.5 fold, P < 0.05), VEGF-D (6.1 fold, P < 0.05), Lyve-1 (15 fold, P < 0.05), and Prox-1 (11 fold, P < 0.05) were expressed at significantly higher levels in the PBS group than the EPC group. The PBS group also showed a significantly higher density of lymphatic vessels in the peri-infarction area. Echocardiography showed that from 2 weeks after the treatment, left ventricle (LV) dimensions at both systole and diastole were significantly smaller in the EPC group than in the PBS group (P < 0.01) and LV fractional shortening was higher in the EPC group accordingly (P < 0.01). Lymphangiogenic markers increased in a mouse MI model. EPC transplantation decreased lymphangiogenesis and adverse ventricular remodeling after AMI. These novel findings suggest that new lymphatic vessels may be formed in severely damaged myocardium, and may be involved in adverse myocardial remodeling after AMI.

  20. Adverse ventricular-ventricular interactions in right ventricular pressure load: Insights from pediatric pulmonary hypertension versus pulmonary stenosis.

    PubMed

    Driessen, Mieke M P; Hui, Wei; Bijnens, Bart H; Dragulescu, Andreea; Mertens, Luc; Meijboom, Folkert J; Friedberg, Mark K

    2016-06-01

    Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular

  1. Adverse event prediction in patients with left ventricular assist devices.

    PubMed

    Tsipouras, Markos G; Karvounis, Evaggelos C; Tzallas, Alexandros T; Katertsidis, Nikolaos S; Goletsis, Yorgos; Frigerio, Maria; Verde, Alessandro; Trivella, Maria G; Fotiadis, Dimitrios I

    2013-01-01

    This work presents the Treatment Tool, which is a component of the Specialist's Decision Support Framework (SDSS) of the SensorART platform. The SensorART platform focuses on the management of heart failure (HF) patients, which are treated with implantable, left ventricular assist devices (LVADs). SDSS supports the specialists on various decisions regarding patients with LVADs including decisions on the best treatment strategy, suggestion of the most appropriate candidates for LVAD weaning, configuration of the pump speed settings, while also provides data analysis tools for new knowledge extraction. The Treatment Tool is a web-based component and its functionality includes the calculation of several acknowledged risk scores along with the adverse events appearance prediction for treatment assessment.

  2. Imidapril inhibits right ventricular remodeling induced by low ambient temperature in broiler chickens.

    PubMed

    Hao, Xue-Qin; Zhang, Shou-Yan; Cheng, Xiang-Chao; Li, Meng; Sun, Tong-Wen; Zhang, Ji-Liang; Guo, Wen; Li, Li

    2013-06-01

    This study explored the effect of imidapril on the right ventricular remodeling induced by low ambient temperature in broiler chickens. Twenty-four broiler chickens were randomly divided into 3 groups (n = 8), including the control group, low temperature group, and imidapril group. Chickens in the control group were raised at normal temperature, whereas chickens in the low temperature group and imidapril group were exposed to low ambient temperature (12 to 18°C) from 14 d of age until 45 d of age. At the same time, chickens in the imidapril group were gavaged with imidapril at 3 mg/kg once daily for 30 d. The thickness of the right ventricular wall was observed with echocardiography. The BW and wet lung weight as well as weight of right and left ventricles and ventricular septum were measured. Both wet lung weight index and right ventricular hypertrophy index were calculated. Pulmonary arterial systolic pressure was assessed according to echocardiography. The expression of ACE and ACE2 mRNA in the right ventricular myocardial tissue was quantified by real-time PCR. Proliferating cell nuclear antigen-positive cells were detected by immunohistostaining. The concentration of angiotensin (Ang) II and Ang (1-7) in the right ventricular myocardial tissue was measured with ELISA. The results showed that right ventricular hypertrophy index, wet lung weight index, pulmonary arterial systolic pressure, expression of ACE mRNA in the right ventricular tissue, Ang II concentration, and the thickness of the right ventricular wall in the low temperature group increased significantly compared with those in the control group and imidapril group. The ACE2 mRNA expression increased 36%, whereas Ang (1-7) concentration decreased significantly in the low temperature group compared with that in the control group and imidapril group. In conclusion, imidapril inhibits right ventricular remodeling induced by low ambient temperature in broiler chickens.

  3. Contribution of ventricular remodeling to pathogenesis of heart failure in rats.

    PubMed

    Brower, G L; Janicki, J S

    2001-02-01

    We previously reported an approximately 50% incidence of rats with symptoms of congestive heart failure (CHF) at 8 wk postinfrarenal aorto-caval fistula. However, it was not clear whether compensatory ventricular remodeling could continue beyond 8 wk or whether the remaining animals would have developed CHF or died. Therefore, the intent of this study was to complete the characterization of this model of sustained volume overload by determining the morbidity and mortality and the temporal response of left ventricular (LV) remodeling and function beyond 8 wk. The findings demonstrate an upper limit to LV hypertrophy and substantial increases in LV volume and compliance, matrix metalloproteinase activity, and collagen volume fraction associated with the development of CHF. There was an 80% incidence of morbidity and mortality following 21 wk of chronic volume overload. These findings indicate that the development of CHF is triggered by marked ventricular dilatation and increased compliance occurring once the myocardial hypertrophic response is exhausted.

  4. Integrated mechanisms of CaMKII-dependent ventricular remodeling

    PubMed Central

    Kreusser, Michael M.; Backs, Johannes

    2014-01-01

    CaMKII has been shown to be activated during different cardiac pathological processes, and CaMKII-dependent mechanisms contribute to pathological cardiac remodeling, cardiac arrhythmias, and contractile dysfunction during heart failure. Activation of CaMKII during cardiac stress results in a broad number of biological effects such as, on the one hand, acute effects due to phosphorylation of distinct cellular proteins as ion channels and calcium handling proteins and, on the other hand, integrative mechanisms by changing gene expression. This review focuses on transcriptional and epigenetic effects of CaMKII activation during chronic cardiac remodeling. Multiple mechanisms have been described how CaMKII mediates changes in cardiac gene expression. CaMKII has been shown to directly phosphorylate components of the cardiac gene regulation machinery. CaMKII phosphorylates several transcription factors such as CREB that induces the activation of specific gene programs. CaMKII activates transcriptional regulators also indirectly by phosphorylating histone deacetylases, especially HDAC4, which in turn inhibits transcription factors that drive cardiac hypertrophy, fibrosis, and dysfunction. Recent studies demonstrate that CaMKII also phosphorylate directly histones, which may contribute to changes in gene expression. These findings of CaMKII-dependent gene regulation during cardiac remodeling processes suggest novel strategies for CaMKII-dependent “transcriptional or epigenetic therapies” to control cardiac gene expression and function. Manipulation of CaMKII-dependent signaling pathways in the settings of pathological cardiac growth, remodeling, and heart failure represents an auspicious therapeutic approach. PMID:24659967

  5. Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

    PubMed Central

    Zhang, Jie; Fan, Guangpu; Zhao, Hui; Wang, Zhiwei; Li, Fei; Zhang, Peide; Zhang, Jing; Wang, Xu; Wang, Wei

    2017-01-01

    Cardiac fibrosis in post-myocardial infarction (MI), seen in both infarcted and non-infarcted myocardium, is beneficial to the recovery of heart function. But progressively pathological fibrosis impairs ventricular function and leads to poor prognosis. FAK has recently received attention as a potential mediator of fibrosis, our previous study reported that pharmacological inhibition of FAK can attenuate cardiac fibrosis in post MI models. However, the long-term effects on cardiac function and adverse cardiac remodelling were not clearly investigated. In this study, we tried to determine the preliminary mechanisms in regulating CF transformation to myofibroblasts and ECM synthesis relevant to the development of adverse cardiac remolding in vivo and in vitro. Our study provides even more evidence that FAK is directly related to the activation of CF in hypoxia condition in a dose-dependent and time-dependent manner. Pharmacological inhibition of FAK significantly reduces myofibroblast differentiation; our in vivo data demonstrated that a FAK inhibitor significantly decreases fibrotic score, and preserves partial left ventricular function. Both PI3K/AKT signalling and ERK1/2 are necessary for hypoxia-induced CF differentiation and ECM synthesis; this process also involves lysyl oxidase (LOX). These findings suggest that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. PMID:28225063

  6. Successful Ventricular Remodeling with Coronary Artery Bypass Grafting and Mitral Valve Repair in a Patient with Severe Heart Failure

    PubMed Central

    Letsou, George V.; Frazier, O. H.

    2006-01-01

    Left ventricular remodeling is becoming a frequent treatment for severe heart failure, but its use in combination with other surgical techniques is controversial. We report a case in which left ventricular remodeling was combined with coronary artery bypass grafting and mitral valve repair to treat a patient with severely depressed ejection fraction, mitral insufficiency, coronary artery disease, and a recent history of myocardial infarction. Cardiac function improved after the combined treatment. This case suggests that left ventricular remodeling can be used safely and effectively in conjunction with other surgical techniques. PMID:16878634

  7. Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling

    PubMed Central

    Oka, Toru; Xu, Jian; Kaiser, Robert A.; Melendez, Jaime; Hambleton, Michael; Sargent, Michelle A.; Lorts, Angela; Brunskill, Eric W.; Dorn, Gerald W.; Conway, Simon J.; Aronow, Bruce J.; Robbins, Jeffrey; Molkentin, Jeffery D.

    2009-01-01

    The cardiac extracellular matrix is a dynamic structural support network that is both influenced by, and a regulator of, pathological remodeling and hypertrophic growth. In response to pathologic insults the adult heart re-expresses the secreted extracellular matrix protein periostin (Pn). Here we show that Pn is critically involved in regulating the cardiac hypertrophic response, interstitial fibrosis, and ventricular remodeling following long-term pressure overload stimulation and myocardial infarction. Mice lacking the gene encoding Pn (Postn) were more prone to ventricular rupture in the first 10 days after a myocardial infarction, but surviving mice showed less fibrosis and better ventricular performance. Pn−/− mice also showed less fibrosis and hypertrophy following long-term pressure overload, suggesting an intimate relationship between Pn and the regulation of cardiac remodeling. In contrast, inducible overexpression of Pn in the heart protected mice from rupture following myocardial infarction and induced spontaneous hypertrophy with aging. With respect to a mechanism underlying these alterations, Pn−/− hearts showed an altered molecular program in fibroblast function. Indeed, fibroblasts isolated from Pn−/− hearts were less effective in adherence to cardiac myocytes and were characterized by a dramatic alteration in global gene expression (7% of all genes). These are the first genetic data detailing the function of Pn in the adult heart as a regulator of cardiac remodeling and hypertrophy. PMID:17569887

  8. The dynamic interaction between matrix metalloproteinase activity and adverse myocardial remodeling.

    PubMed

    Janicki, Joseph S; Brower, Gregory L; Gardner, Jason D; Chancey, Amanda L; Stewart, James A

    2004-01-01

    The process of cardiac remodeling in response to cardiac injury and/or persistent elevations in wall stress generally relates to the progressive changes that occur in ventricular chamber dimensions and the various components of the myocardium, in particular the cardiomyocytes and the extracellular matrix. Volume overload, pressure overload or myocardial injury produces a sustained abnormal elevation in myocardial wall stress which initiates cardiac remodeling that frequently results in ventricular decompensation and heart failure. Regardless of the inciting cause, there appear to be three distinct phases to this process. In the initial phase, fibrillar collagen is partially degraded secondary to increased matrix metalloproteinase (MMP) activity. Following this, there is a chronic compensatory phase during which MMP activity and collagen concentration return to normal while cardiomyocyte size continues to progressively increase. The final phase is attained once the compensatory hypertrophic mechanisms are exhausted and is characterized by elevated MMP activity, marked ventricular dilatation and prominent fibrosis. Details of this progressive, dynamic remodeling process and its effect on ventricular function during chronic volume overload, chronic pressure overload and following myocardial infarction will be the focus of this article.

  9. Role of Circulating Angiotensin Converting Enzyme 2 in Left Ventricular Remodeling following Myocardial Infarction: A Prospective Controlled Study

    PubMed Central

    Ortiz-Pérez, José T.; Riera, Marta; Bosch, Xavier; De Caralt, Teresa M.; Perea, Rosario J.; Pascual, Julio; Soler, María José

    2013-01-01

    Angiotensin-converting enzyme 2 (ACE2) cleaves Angiotensin-II to Angiotensin-(1–7), a cardioprotective peptide. Serum soluble ACE2 (sACE2) activity is raised in chronic heart failure, suggesting a compensatory role in left ventricular dysfunction. Our aim was to study the relationship between sACE2 activity, infarct size, left ventricular systolic function and remodeling following ST-elevation myocardial infarction (STEMI). A contrast-enhanced cardiac magnetic resonance study was performed acutely in 95 patients with first STEMI and repeated at 6 months to measure LV end-diastolic volume index, ejection fraction and infarct size. Baseline sACE2 activities, measured by fluorescent enzymatic assay 24 to 48 hours and at 7 days from admission, were compared to that obtained in 22 matched controls. Patients showed higher sACE2 at baseline than controls (104.4 [87.4–134.8] vs 74.9 [62.8–87.5] RFU/µl/hr, p<0.001). At seven days, sACE2 activity significantly increased from baseline (115.5 [92.9–168.6] RFU/µl/hr, p<0.01). An inverse correlation between sACE2 activity with acute and follow-up ejection fraction was observed (r = −0.519, p<0.001; r = −0.453, p = 0.001, respectively). Additionally, sACE2 directly correlated with infarct size (r = 0.373, p<0.001). Both, infarct size (β = −0.470 [95%CI:−0.691:−0.248], p<0.001) and sACE2 at 7 days (β = −0.025 [95%CI:−0.048:−0.002], p = 0.030) were independent predictors of follow-up ejection fraction. Patients with sACE2 in the upper tertile had a 4.4 fold increase in the incidence of adverse left ventricular remodeling (95% confidence interval: 1.3 to 15.2, p = 0.027). In conclusion, serum sACE2 activity rises in relation to infarct size, left ventricular systolic dysfunction and is associated with the occurrence of left ventricular remodeling. PMID:23630610

  10. Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction

    PubMed Central

    Fitzpatrick, J. Raymond; Frederick, John R.; McCormick, Ryan C.; Harris, David A.; Kim, Ah-Young; Muenzer, Jeffrey R.; Gambogi, Alex J.; Liu, Jing Ping; Paulson, E. Carter; Woo, Y. Joseph

    2011-01-01

    Objective Microvascular malperfusion after myocardial infarction leads to infarct expansion, adverse remodeling, and functional impairment. Native reparative mechanisms exist but are inadequate to vascularize ischemic myocardium. We hypothesized that a 3-dimensional human fibroblast culture (3DFC) functions as a sustained source of angiogenic cytokines, thereby augmenting native angiogenesis and limiting adverse effects of myocardial ischemia. Methods Lewis rats underwent ligation of the left anterior descending coronary artery to induce heart failure; experimental animals received a 3DFC scaffold to the ischemic region. Border-zone tissue was analyzed for the presence of human fibroblast surface protein, vascular endothelial growth factor, and hepatocyte growth factor. Cardiac function was assessed with echocardiography and pressure–volume conductance. Hearts underwent immunohistochemical analysis of angiogenesis by co-localization of platelet endothelial cell adhesion molecule and alpha smooth muscle actin and by digital analysis of ventricular geometry. Microvascular angiography was performed with fluorescein-labeled lectin to assess perfusion. Results Immunoblotting confirmed the presence of human fibroblast surface protein in rats receiving 3DFC, indicating survival of transplanted cells. Increased expression of vascular endothelial growth factor and hepatocyte growth factor in experimental rats confirmed elution by the 3DFC. Microvasculature expressing platelet endothelial cell adhesion molecule/alpha smooth muscle actin was increased in infarct and border-zone regions of rats receiving 3DFC. Microvascular perfusion was also improved in infarct and border-zone regions in these rats. Rats receiving 3DFC had increased wall thickness, smaller infarct area, and smaller infarct fraction. Echocardiography and pressure–volume measurements showed that cardiac function was preserved in these rats. Conclusions Application of a bioengineered 3DFC augments native

  11. Effects of Tribuli saponins on ventricular remodeling after myocardial infarction in hyperlipidemic rats.

    PubMed

    Guo, Yan; Shi, Da-Zhuo; Yin, Hui-Jun; Chen, Ke-Ji

    2007-01-01

    This experiment was designed to determine whether Tribuli saponins (TS) relieve left ventricular remodeling (VR) after myocardial infarction (MI) in a murine hyperlipemia (HL) model. MI and HL models were induced and high and low doses of TS and simvastatin were administrated to the rats. Four weeks later, echocardiographic observation was performed and the left and right ventricular weight index (LVWI, RVWI) was calculated. Echocardiographic results showed that both high dose of TS and simvastatin had a beneficial effect on increasing fractional shortening (FS) and ejection fraction (EF), reducing left ventricular end diastolic volume (LVEDV), systolic volume (LVESV), left ventricular dimension end diastole (LVDd) and systole (LVDs), and decreasing LVWI, as compared to those in the HL-MI model group (p < 0.05, 0.01). Both medicines had little impact on thickness of the anterior and posterior wall. No significant difference was observed between each treatment group (p > 0.05). In conclusion, TS not only lowered serum lipidemia, but also relieved left ventricular remodeling, and improved cardiac function in the early stage after MI.

  12. Activin A Predicts Left Ventricular Remodeling and Mortality in Patients with ST-Elevation Myocardial Infarction

    PubMed Central

    Lin, Jeng-Feng; Hsu, Shun-Yi; Teng, Ming-Sheng; Wu, Semon; Hsieh, Chien-An; Jang, Shih-Jung; Liu, Chih-Jen; Huang, Hsuan-Li; Ko, Yu-Lin

    2016-01-01

    Background Activin A levels increase in a variety of heart diseases including ST-elevation myocardial infarction (STEMI). The aim of this study is to investigate whether the level of activin A can be beneficial in predicting left ventricular remodeling, heart failure, and death in patients with ST-elevation myocardial infarction (STEMI). Methods We enrolled 278 patients with STEMI who had their activin A levels measured on day 2 of hospitalization. Echocardiographic studies were performed at baseline and were repeated 6 months later. Thereafter, the clinical events of these patients were followed for a maximum of 3 years, including all-cause death and readmission for heart failure. Results During hospitalization, higher activin A level was associated with higher triglyceride level, lower left ventricular ejection fraction (LVEF), and lower left ventricular end diastolic ventricular volume index (LVEDVI) in multivariable linear regression model. During follow-up, patients with activin A levels > 129 pg/ml had significantly lower LVEF, and higher LVEDVI at 6 months. Kaplan-Meier survival curves showed that activin A level > 129 pg/ml was a predictor of all-cause death (p = 0.022), but not a predictor of heart failure (p = 0.767). Conclusions Activin A level > 129 pg/ml predicts worse left ventricular remodeling and all-cause death in STEMI. PMID:27471355

  13. Left Ventricular Remodeling and Myocardial Recovery on Mechanical Circulatory Support

    PubMed Central

    Simon, Marc A; Primack, Brian A.; Teuteberg, Jeffrey; Kormos, Robert L; Bermudez, Christian; Toyoda, Yoshiya; Shah, Hemal; Gorcsan, John; McNamara, Dennis M

    2009-01-01

    Background Myocardial recovery after VAD is rare but appears more common in non-ischemic cardiomyopathies (NICM). We sought to evaluate left ventricular (LV) end diastolic diameter (LVEDD) for predicting recovery after ventricular assist device (VAD). Methods and Results NICM patients receiving long-term mechanical support 1996–2008 were reviewed. Subjects were divided into 3 groups: mild, moderate and severe dilation (Group A: LVEDD <6.0 cm [n=22]; Group B: 6.0–7.0 cm [n=32]; Group C: >7.0 cm [n=48], respectively). Overall, recovery (successful explant without transplantation) occurred in 14 of 102 subjects (14%). Of these, 2 died and 2 required transplantation within one year. Recovery was more common in patients without LV dilation (Groups A/B/C = 32%/22%/0 %, P<0.001), as was sustained recovery (alive and transplant free one year after explant; A/B/C =27%/10%/0%, P=0.001). Of the recovery patients in Group A, 6/7 (86%) had sustained recovery versus 3/6 (50%) in Group B. Conclusions Recovery occurred in 32% of NICM patients without significant LV dilation at time of VAD, the majority of whom experienced significant sustained recovery. Recovery was not evident in those with severe LV dilation. Routine echocardiography at the time of implant may assist in targeting patients for recovery after VAD. PMID:20142020

  14. Maternal Nutrient Restriction Predisposes Ventricular Remodeling in Adult Sheep Offspring

    PubMed Central

    Ge, Wei; Hu, Nan; George, Lindsey A.; Ford, Stephen P.; Nathanielsz, Peter W.; Wang, Xiaoming; Ren, Jun

    2012-01-01

    Maternal nutrient restriction during pregnancy is associated with the development of a “thrifty phenotype” in offspring, conferring increased prevalence of metabolic diseases in adulthood. To explore the possible mechanisms behind heart diseases in adulthood following maternal nutrient restriction, dams were fed a nutrient restricted (NR: 50%) or control (100%) diet from 28 to 78 d of gestation. Both groups were then fed 100% of requirements to lambing. At 6 yrs of age, female offspring of NR and control ewes of similar weight and body condition were subject to ad libitum feeding of a highly palatable diet for 12 wks. Cardiac geometry, post-insulin receptor signaling, autophagy and pro-inflammatory cytokines were evaluated in hearts from adult offspring. Our results indicated that maternal nutrient restriction overtly increased body weight gain and triggered cardiac remodeling in offspring following the 12-week ad libitum feeding. Phosphorylation of IRS1 was increased in left but not right ventricles from NR offspring. Levels of STAT3 were upregulated in left ventricles whereas expression of TNFα and TLR4 was enhanced in right ventricles in adult offspring of maternal nutrition restricted ewes. No significant differences were found in pan IRS-1, pan AMPK, pan Akt, pAMPK, pAkt, GLUT4, phosphorylated mTOR, Beclin-1 and LC3 II proteins in left and right ventricle between the control and NR offspring. These data revealed that maternal nutrient restriction during early to mid gestation may predispose adult offspring to cardiac remodeling possibly associated with phosphorylation of IRS1 as well as proinflammatory cytokines but not autophagy. PMID:23333094

  15. Angiotensin converting enzyme 2 gene expression increased compensatory for left ventricular remodeling in patients with end-stage heart failure.

    PubMed

    Ohtsuki, Masatsugu; Morimoto, Shin-ichiro; Izawa, Hideo; Ismail, Tevfik F; Ishibashi-Ueda, Hatsue; Kato, Yasuchika; Horii, Taiko; Isomura, Tadashi; Suma, Hisayoshi; Nomura, Masanori; Hishida, Hitoshi; Kurahashi, Hiroki; Ozaki, Yukio

    2010-11-19

    It has been reported that angiotensin converting enzyme (ACE) 2, a homologue of ACE, has direct effects on cardiac function. However, the role of ACE2 in the development of human heart failure is not fully understood. We evaluated the expression of the ACE2 gene by means of real-time RT-PCR in myocardium from 14 patients with end-stage heart failure. The amount of ACE2 mRNA positively correlated with left ventricular (LV) end-diastolic diameter (r(2)=0.56, p<0.01) but did not significantly correlate with LV ejection fraction or plasma brain natriuretic peptide levels. In conclusion, our data show that the up-regulation of the ACE2 gene in the LV myocardium of patients with severe heart failure was associated with the degree of LV dilatation and may thereby constitute an important adaptive mechanism to retard the progression of adverse LV remodeling.

  16. Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

    PubMed Central

    Reichert, Karla; Pereira do Carmo, Helison Rafael; Galluce Torina, Anali; Diógenes de Carvalho, Daniela; Carvalho Sposito, Andrei; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira-Filho, Lindemberg; Martins de Oliveira, Pedro Paulo

    2016-01-01

    Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events. PMID:27880844

  17. Cardioprotective effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats.

    PubMed

    Gao, Yan; Gao, Jianping; Chen, Changxun; Wang, Huilin; Guo, Juan; Wu, Rong

    2015-05-01

    The purpose of this study was to explore the effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats and to elucidate the underlying mechanisms. A rat model of ventricular remodeling after myocardial infarction was established by left coronary artery ligation. Rats with coronary artery ligation were randomly divided into five groups: control, plus 40 mg/kg captopril, plus 25 mg/kg polydatin, plus 50 mg/kg polydatin, and plus 100 mg/kg polydatin. The sham-operated group was used as a negative control. Rats were administered intragastrically with the corresponding drugs or drinking water for seven weeks. At the end of the treatment, the left ventricular weight index and heart weight index were assessed. The cross-sectional size of cardiomyocytes was measured by staining myocardium tissue with hematoxylin and eosin. Collagen content was counted by Sirius red in aqueous saturated picric acid. The concentrations of angiotensin I, angiotensin II, aldosterone, and endothelin 1 in myocardium or serum were determined by radioimmunoassay. Hydroxyproline and nitric oxide concentrations and glutathione peroxidase and catalase activities in serum were measured by ultraviolet spectrophotometry. Our results showed that seven weeks of polydatin treatment resulted in a significantly reduced left ventricular weight index, heart weight index, serum concentrations of hydroxyproline and aldosterone, an increased concentration of nitric oxide as well as enhanced activities of glutathione peroxidase and catalase. Myocardial angiotensin I, angiotensin II, and endothelin 1 levels were also reduced. The cardiomyocyte cross-sectional area and collagen deposition diminished. This study suggests that polydatin may attenuate ventricular remodeling after myocardial infarction in coronary artery ligation rats through restricting the excessive activation of the renin-angiotensin-aldosterone system and inhibiting peroxidation.

  18. Wnt5a attenuates hypoxia-induced pulmonary arteriolar remodeling and right ventricular hypertrophy in mice

    PubMed Central

    Jin, Yuling; Wang, Wang; Chai, Sanbao; Liu, Jie

    2015-01-01

    Hypoxic pulmonary hypertension (HPH), which is characterized by pulmonary arteriolar remodeling and right ventricular hypertrophy, is still a life-threatening disease with the current treatment strategies. The underlying molecular mechanisms of HPH remain unclear. Our previously published study showed that Wnt5a, one of the ligands in the Wnt family, was critically involved in the inhibition of hypoxia-induced pulmonary arterial smooth muscle cell proliferation by downregulation of β-catenin/cyclin D1 in vitro. In this study, we investigated the possible functions and mechanisms of Wnt5a in HPH in vivo. Recombinant mouse Wnt5a (rmWnt5a) or phosphate buffered saline (PBS) was administered to male C57/BL6 mice weekly from the first day to the end of the two or four weeks after exposed to hypoxia (10% O2). Hypoxia-induced pulmonary hypertension was associated with a marked increase in β-catenin/cyclin D1 expression in lungs. Right ventricular systolic pressure and right ventricular hypertrophy index were reduced in animals treated with rmWnt5a compared with PBS. Histology showed less pulmonary vascular remodeling and right ventricular hypertrophy in the group treated with rmWnt5a than with PBS. Treatment with rmWnt5a resulted in a concomitant reduction in β-catenin/cyclin D1 levels in lungs. These data demonstrate that Wnt5a exerts its beneficial effects on HPH by regulating pulmonary vascular remodeling and right ventricular hypertrophy in a manner that is associated with reduction in β-catenin/cyclin D1 signaling. A therapy targeting the β-catenin/cyclin D1 signaling pathway might be a potential strategy for HPH treatment. PMID:25956683

  19. Acute aortocaval fistula: role of low perfusion pressure and subendocardial remodeling on left ventricular function

    PubMed Central

    Mazzo, Flávia R R; de Carvalho Frimm, Clovis; Moretti, Ana Iochabel S; Guido, Maria C; Koike, Marcia K

    2013-01-01

    The experimental model of aortocaval fistula is a useful model of cardiac hypertrophy in response to volume overload. In the present study it has been used to investigate the pathologic subendocardial remodeling associated with the development of heart failure during the early phases (day 1, 3, and 7) following volume overload. Compared with sham treated rats, aortocaval fistula rats showed lower systemic blood pressure and higher left ventricular end-diastolic pressure This resulted in lower coronary driving pressure and left ventricular systolic and diastolic dysfunction. Signs of myocyte necrosis, leukocyte cell infiltration, fibroplasia and collagen deposition appeared sequentially in the subendocardium where remodeling was more prominent than in the non-subendocardium. Accordingly, increased levels of TNF-alpha, IL-1 beta, and IL-6, and enhanced MMP-2 activity were all found in the subendocardium of rats with coronary driving pressure ≤60 mmHg. The coronary driving pressure was inversely correlated with MMP-2 activity in subendocardium in all time-points studied, and blood flow in this region showed positive correlation with systolic and diastolic function at day 7. Thus the predominant subendocardial remodeling that occurs in response to low myocardial perfusion pressure during the acute phases of aortocaval fistula contributes to early left ventricular dysfunction. PMID:23593971

  20. Catestatin-A Novel Predictor of Left Ventricular Remodeling After Acute Myocardial Infarction

    PubMed Central

    Zhu, Dan; Xie, Hong; Wang, Xinyu; Liang, Ying; Yu, Haiyi; Gao, Wei

    2017-01-01

    Catestatin was discovered as a potent inhibitor of catecholamine secretion and plays important roles in the cardiovascular system. Our previous study demonstrates a close relationship between catestatin levels and prognosis of ST-elevation myocardial infarction (STEMI). Using the same population, the goal of this study is to investigate the ability of catestatin to predict left ventricular (LV) remodeling in STEMI patients. 72 patients and 30 controls were included. Catestatin was sampled after admission to the emergency room (ER), at day3 (D3), and day7 (D7) after STEMI. Echocardiography was performed at D3 and after 65 months for evaluation of LVEDD, EF, IVS, LVPW, E, A, E’, E/A, and E/E’. The changes of these parameters from D3 to 65 months were used to reflect the changes of ventricular structure and function. We found that plasma catestatin levels at D3 were highly correlated with the changes of LVEDD, EF, E, A, E’, E/A, as well as E/E’. Patients with higher catestatin levels developed worse ventricular function during the follow-up period. Single-point catestatin was effective to predict LVEDD change. And concurrently increasing catestatin and NT-proBNP levels predicted the highest risk of LV remodeling. This study suggests an important prognostic information of catestatin on LV remodeling.

  1. Transcriptional network analysis for the regulation of left ventricular hypertrophy and microvascular remodeling.

    PubMed

    Moreno-Moral, Aida; Mancini, Massimiliano; D'Amati, Giulia; Camici, Paolo; Petretto, Enrico

    2013-12-01

    Hypertension and cardiomyopathies share maladaptive changes of cardiac morphology, eventually leading to heart failure. These include left ventricular hypertrophy (LVH), myocardial fibrosis, and structural remodeling of coronary microcirculation, which is the morphologic hallmark of coronary microvascular dysfunction. To pinpoint the complex molecular mechanisms and pathways underlying LVH-associated cardiac remodeling independent of blood pressure effects, we employed gene network approaches to the rat heart. We used the Spontaneously Hypertensive Rat model showing many features of human hypertensive cardiomyopathy, for which we collected histological and histomorphometric data of the heart and coronary vasculature, and genome-wide cardiac gene expression. Here, we provide a large catalogue of gene co-expression networks in the heart that are significantly associated with quantitative variation in LVH, microvascular remodeling, and fibrosis-related traits. Many of these networks were significantly conserved to human idiopathic and/or ischemic cardiomyopathy patients, suggesting a potential role for these co-expressed genes in human heart disease.

  2. [Effect of berberine on left ventricular remodeling in renovascular hypertensive rats].

    PubMed

    Zhao, Hai-Ping; Hong, Ying; Xie, Jun-Da; Xie, Xin-Ran; Wang, Jing; Fan, Jiang-Bo

    2007-03-01

    The purpose of this study is to evaluate the effects and the underline mechanisms of berberine on the cardiac function and left ventricular remodeling in rats with renovascular hypertension. The renovascular hypertensive model was established by the two-kidney, two-clip (2K2C) method in Sprague-Dawley (SD) rats. Two weeks after surgery, all the operated SD rats were randomly assigned into four groups: (1) renovascular hypertensive model group; (2) berberine 5 mg x kg(-1) group; (3) berberine 10 mg x kg(-1) group; (4) captopril 45 mg x kg(-1) group; and the sham operated rats were used as control. Four weeks after the drugs were administered, the cardiac function was assessed. The ratios of heart weight to body weight (HW/BW), left ventricular weight to body weight (LVW/BW) and right ventricular weight to body weight (RVW/BW) were compared between groups. Coronal sections of the left ventricular tissue (LV) were prepared for paraffin sections, picrosirius red and HE staining was performed. The left ventricular wall thickness (LVWT), interventricular septal thickness (IVST), the parameters of myocardial fibrosis indicated by interstitial collagen volume fraction (ICVF) and perivascular collagen area (PVCA) were assessed. Nitric oxide (NO), adenosine cyclophosphate (cAMP) and guanosine cyclophosphate (cGMP) concentrations of left ventricular tissue were measured. Berberine 5 mg x kg(-1) and 10 mg x kg(-1) increased the left ventricular +/- dp/dt(max) and HR. Berberine 10 mg x kg(-1) decreased HW/BW and LVW/BW. The image analysis showed that both 5 and 10 mg x kg(-1) of berberine decreased LVWT, ICVF and PVCA, while increased the NO and cAMP contents in left ventricular tissue. Berberine could improve cardiac contractility of 2K2C model rats, and inhibit left ventricular remodeling especially myocardial fibrosis in renovascular hypertension rats. And such effects may partially associate with the increased NO and cAMP content in left ventricular tissue.

  3. Surgical Ventricular Restoration: An Operation To Reverse Remodeling - The Basic Science (Part I)

    PubMed Central

    Shanmugam, Ganesh; Ali, Imtiaz S

    2009-01-01

    Congestive heart failure as a consequence of ischemic heart disease is an increasing medical problem. Notwithstanding the huge advances in the medical and conventional surgical management of heart failure, eventual outcomes remain suboptimal. This 2 part article outlines the magnitude of the problem, the limitations of conventional therapies as they exist, and the use of newer procedures that directly address the restoration of ventricular pump function. The first part of the article deals with the pathology of different facets of the remodeling process, and the unique anatomy, geometry and flow dynamics as they pertain to ventricular function in the normal as well as the failing heart. It then details the limitations of conventional therapy, thereby laying the basis for the need and evolution of newer surgical procedures and ends with the selection of patients for ventricular restoration procedures and the pitfalls in the choice of patients for such newer techniques. PMID:21037851

  4. The effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline-induced right ventricular failure

    PubMed Central

    Bae, Hyun Kyung; Lee, Hyeryon; Kim, Kwan Chang

    2016-01-01

    Purpose Pulmonary arterial hypertension (PAH) leads to right ventricular failure (RVF) as well as an increase in pulmonary vascular resistance. Our purpose was to study the effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline (MCT)-induced RVF. Methods The rats were distributed randomly into 3 groups. The control (C) group, the monocrotaline (M) group (MCT 60 mg/kg) and the sildenafil (S) group (MCT 60 mg/kg+ sildenafil 30 mg/kg/day for 28 days). Masson Trichrome staining was used for heart tissues. Western blot analysis and immunohistochemical staining were performed. Results The mean right ventricular pressure (RVP) was significantly lower in the S group at weeks 1, 2, and 4. The number of intra-acinar arteries and the medial wall thickness of the pulmonary arterioles significantly lessened in the S group at week 4. The collagen content also decreased in heart tissues in the S group at week 4. Protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X, caspase-3, Bcl-2, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, endothelial nitric oxide synthase (eNOS), endothelin (ET)-1 and ET receptor A (ERA) in lung tissues greatly decreased in the S group at week 4 according to immunohistochemical staining. According to Western blotting, protein expression levels of troponin I, brain natriuretic peptide, caspase-3, Bcl-2, tumor necrosis factor-α, IL-6, MMP-2, eNOS, ET-1, and ERA in heart tissues greatly diminished in the S group at week 4. Conclusion Sildenafil alleviated right ventricular hypertrophy and mean RVP. These data suggest that sildenafil improves right ventricular function. PMID:27462355

  5. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms

    PubMed Central

    Liu, Yonggang; Goodson, Jamie M.; Zhang, Bo; Chin, Michael T.

    2015-01-01

    Exposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation. PMID:26042051

  6. Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium

    PubMed Central

    Weber, Karl T.; Weglicki, William B.; Simpson, Robert U.

    2009-01-01

    Hypertension and heart failure are worldwide health problems of ever-increasing proportions. A failure of the heart, during either systolic and/or diastolic phases of the cardiac cycle, has its origins rooted in an adverse structural, biochemical, and molecular remodelling of myocardium that involves its cellular constituents, extracellular matrix, and intramural coronary vasculature. Herein we focus on the pathogenic role of a dyshomeostasis of several macro- (i.e. Ca2+ and Mg2+) and micronutrients (i.e. Zn2+, Se2+, and vitamin D) in contributing to adverse remodelling of the myocardium and its failure as a pulsatile muscular pump. An improved understanding of how these macro- and micronutrients account for the causes and consequences of adverse myocardial remodelling carries with it the potential of identifying new biomarkers predictive of risk, onset and progression, and response to intervention(s), which could be monitored non-invasively and serially over time. Moreover, such incremental knowledge will serve as the underpinning to the development of novel strategies aimed at preventing and/or regressing the ongoing adverse remodelling of myocardium. The time is at hand to recognize the importance of macro- and micronutrient dyshomeostasis in the evaluation and management of hypertension and heart failure. PMID:18835843

  7. Classification and Prognostic Evaluation of Left Ventricular Remodeling in Patients With Asymptomatic Heart Failure.

    PubMed

    Pugliese, Nicola Riccardo; Fabiani, Iacopo; La Carrubba, Salvatore; Conte, Lorenzo; Antonini-Canterin, Francesco; Colonna, Paolo; Caso, Pio; Benedetto, Frank; Santini, Veronica; Carerj, Scipione; Romano, Maria Francesca; Citro, Rodolfo; Di Bello, Vitantonio

    2017-01-01

    Patients with asymptomatic heart failure (HF; stage A and B) are characterized by maladaptive left ventricular (LV) remodeling. Classic 4-group classification of remodeling considers only LV mass index and relative wall thickness as variables. Complex remodeling classification (CRC) includes also LV end-diastolic volume index. Main aim was to assess the prognostic impact of CRC in stage A and B HF. A total of 1,750 asymptomatic subjects underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors. LV dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated, together with LV remodeling. We considered a composite end point: all-cause death, myocardial infarction, coronary revascularizations, cerebrovascular events, and acute pulmonary edema. CRC was suitable for 1,729 patients (men 53.6%; age 58.3 ± 13 years). Two hundred thirty-eight patients presented systolic dysfunction (ejection fraction <50%) and 483 diastolic dysfunction. According to the CRC, 891 patients were normals or presented with physiologic hypertrophy, 273 concentric remodeling, 47 eccentric remodeling, 350 concentric hypertrophy, 29 mixed hypertrophy, 86 dilated hypertrophy, and 53 eccentric hypertrophy. Age and gender distribution was noticed (p <0.001). After a median follow-up of 21 months, Kaplan-Meier analysis showed different survival distribution (p <0.001) of the CRC patterns. In multivariate Cox regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification, systolic, and diastolic dysfunction), CRC was independent predictor of primary end point (p = 0.044, hazard ratio 1.101, 95% CI 1.003 to 1.21), confirmed in a logistic regression (p <0.03). In conclusion, CRC could help physicians in prognostic stratification of patients in stage A and B HF.

  8. Cigarette smoke exacerbates ventricular remodeling and dysfunction in the volume overloaded heart.

    PubMed

    Bradley, Jessica M; Nguyen, Jonathan B; Fournett, Alyssa C; Gardner, Jason D

    2012-02-01

    Cigarette smoking is an independent risk factor for heart disease and is linked to sudden cardiac death. In this study, we examined the effects of cigarette smoke (CS) on the volume overload stressed heart. Our hypothesis was that CS exacerbates volume overload (VO)-induced cardiac dysfunction by accelerating ventricular remodeling. VO stress was surgically induced in male Sprague-Dawley rats by abdominal aortocaval fistula (ACF). Rats, with and without ACF, were exposed to either room air or CS (6 cigarettes/day) for 6 weeks. Temporal echocardiogram measurements indicated that CS significantly increased VO-induced left ventricular dilatation, prevented compensatory wall thickening, and depressed fractional shortening. Morphological analysis of ventricular collagen revealed that CS blunted compensatory collagen expression (45% decrease versus ACF alone). CS exacerbated the VO-induced increase of MMP-9 and TIMP-1 expression in the heart. CS also blocked the compensatory increases of HIF-1α, VEGF, and TGF-β in the VO-stressed heart. These data indicate that CS worsens VO remodeling by disrupting compensatory mechanisms, thereby promoting eccentric dilation and dysfunction.

  9. Reverse ventricular remodeling and improved ventricular compliance after heart transplantation in infants and young children.

    PubMed

    Farooqi, Kanwal M; Lopez, Leo; Pass, Robert H; Hsu, Daphne T; Lamour, Jacqueline M

    2014-08-01

    After heart transplantation (HT) in infants and young children, environmental and intrinsic factors may lead to changes in the geometry and compliance of the donor heart. Serial demographic, clinical, hemodynamic, and echocardiographic data were obtained from HT recipients younger than 4 years of age. Echocardiographic chamber measurement z-scores were compared using recipient body surface area from the time of HT to 1 week, 3 months, and last follow-up visit. Left ventricular end-diastolic volume (LVEDV) z-scores were correlated with pulmonary capillary wedge pressure (PCWP) at each time point. Heart transplantation was performed for 13 children between March 2009 and December 2012, 9 of whom (69%) were boys. The median age at HT was 8 months (range, 4-43 months), and the mean follow-up period was 13 ± 7 months. Left ventricular end-diastolic dimension z-scores decreased significantly (p = 0.03) between HT and 1 week, then increased from 1 week to 3 and 12 months. (-1.32 ± 1.7, -0.71 ± 1.8, 0.41 ± 2.1, 0.79 ± 2.3, respectively). A positive relationship (R(2) = 0.48) between the LVEDV z-score and PCPW was present at the last follow-up visit. For infants and young children, the allograft demonstrates appropriate growth by 1 year after HT. Left ventricular compliance improves over time.

  10. Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: heart failure causes severe lung disease.

    PubMed

    Chen, Yingjie; Guo, Haipeng; Xu, Dachun; Xu, Xin; Wang, Huan; Hu, Xinli; Lu, Zhongbing; Kwak, Dongmin; Xu, Yawei; Gunther, Roland; Huo, Yuqing; Weir, E Kenneth

    2012-06-01

    Chronic left ventricular failure causes pulmonary congestion with increased lung weight and type 2 pulmonary hypertension. Understanding the molecular mechanisms for type 2 pulmonary hypertension and the development of novel treatments for this condition requires a robust experimental animal model and a good understanding of the nature of the resultant pulmonary remodeling. Here we demonstrate that chronic transverse aortic constriction causes massive pulmonary fibrosis and remodeling, as well as type 2 pulmonary hypertension, in mice. Thus, aortic constriction-induced left ventricular dysfunction and increased left ventricular end-diastolic pressure are associated with a ≤5.3-fold increase in lung wet weight and dry weight, pulmonary hypertension, and right ventricular hypertrophy. Interestingly, the aortic constriction-induced increase in lung weight was not associated with pulmonary edema but resulted from profound pulmonary remodeling with a dramatic increase in the percentage of fully muscularized lung vessels, marked vascular and lung fibrosis, myofibroblast proliferation, and leukocyte infiltration. The aortic constriction-induced left ventricular dysfunction was also associated with right ventricular hypertrophy, increased right ventricular end-diastolic pressure, and right atrial hypertrophy. The massive lung fibrosis, leukocyte infiltration, and pulmonary hypertension in mice after transverse aortic constriction clearly indicate that congestive heart failure also causes severe lung disease. The lung fibrosis and leukocyte infiltration may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. Thus, the effective treatment of left ventricular failure may require additional efforts to reduce lung fibrosis and the inflammatory response.

  11. Onset of hypertension during pregnancy is associated with long-term worse blood pressure control and adverse cardiac remodeling.

    PubMed

    Mesquita, Roberto F; Reis, Muriel; Beppler, Ana Paula; Bellinazzi, Vera Regina; Mattos, Sandra S; Lima-Filho, José L; Cipolli, José A; Coelho-Filho, Otavio R; Pio-Magalhães, José A; Sposito, Andrei C; Matos-Souza, José R; Nadruz, Wilson

    2014-11-01

    Up to 20% of women with hypertensive pregnancy disorders might persist with chronic hypertension. This study compared clinical and echocardiographic features between women whose hypertension began as hypertensive pregnancy disorders (PH group) and women whose diagnosis of hypertension did not occur during pregnancy (NPH group). Fifty PH and 100 NPH women were cross-sectionally evaluated by clinical, laboratory, and echocardiography analysis, and the groups were matched by duration of hypertension. PH exhibited lower age (46.6 ± 1.4 vs. 65.3 ± 1.1 years; P < .001), but higher systolic (159.8 ± 3.9 vs. 148.0 ± 2.5 mm Hg; P = .009) and diastolic (97.1 ± 2.4 vs. 80.9 ± 1.3 mm Hg; P < .001) blood pressure than NPH, although used more antihypertensive classes (3.4 ± 0.2 vs. 2.6 ± 0.1; P < .001). Furthermore, PH showed higher left ventricular wall thickness and increased prevalence of concentric hypertrophy than NPH after adjusting for age and blood pressure. In conclusion, this study showed that PH may exhibit worse blood pressure control and adverse left ventricular remodeling compared with NPH.

  12. Diacerein Improves Left Ventricular Remodeling and Cardiac Function by Reducing the Inflammatory Response after Myocardial Infarction

    PubMed Central

    Torina, Anali Galluce; Reichert, Karla; Lima, Fany; de Souza Vilarinho, Karlos Alexandre; de Oliveira, Pedro Paulo Martins; do Carmo, Helison Rafael Pereira; de Carvalho, Daniela Diógenes; Saad, Mário José Abdalla; Sposito, Andrei Carvalho; Petrucci, Orlando

    2015-01-01

    Background The inflammatory response has been implicated in the pathogenesis of left ventricular (LV) remodeling after myocardial infarction (MI). An anthraquinone compound with anti-inflammatory properties, diacerein inhibits the synthesis and activity of pro-inflammatory cytokines, such as tumor necrosis factor and interleukins 1 and 6. The purpose of this study was to investigate the effects of diacerein on ventricular remodeling in vivo. Methods and Results Ligation of the left anterior descending artery was used to induce MI in an experimental rat model. Rats were divided into two groups: a control group that received saline solution (n = 16) and a group that received diacerein (80 mg/kg) daily (n = 10). After 4 weeks, the LV volume, cellular signaling, caspase 3 activity, and nuclear factor kappa B (NF-κB) transcription were compared between the two groups. After 4 weeks, end-diastolic and end-systolic LV volumes were reduced in the treatment group compared to the control group (p < .01 and p < .01, respectively). Compared to control rats, diacerein-treated rats exhibited less fibrosis in the LV (14.65%± 7.27% vs. 22.57%± 8.94%; p < .01), lower levels of caspase-3 activity, and lower levels of NF-κB p65 transcription. Conclusions Treatment with diacerein once a day for 4 weeks after MI improved ventricular remodeling by promoting lower end-systolic and end-diastolic LV volumes. Diacerein also reduced fibrosis in the LV. These effects might be associated with partial blockage of the NF-κB pathway. PMID:25816098

  13. Dilation and Hypertrophy: A Cell-Based Continuum Mechanics Approach Towards Ventricular Growth and Remodeling

    NASA Astrophysics Data System (ADS)

    Ulerich, J.; Göktepe, S.; Kuhl, E.

    This manuscript presents a continuum approach towards cardiac growth and remodeling that is capable to predict chronic maladaptation of the heart in response to changes in mechanical loading. It is based on the multiplicative decomposition of the deformation gradient into and elastic and a growth part. Motivated by morphological changes in cardiomyocyte geometry, we introduce an anisotropic growth tensor that can capture both hypertrophic wall thickening and ventricular dilation within one generic concept. In agreement with clinical observations, we propose wall thickening to be a stress-driven phenomenon whereas dilation is introduced as a strain-driven process. The features of the proposed approach are illustrated in terms of the adaptation of thin heart slices and in terms overload-induced dilation in a generic bi-ventricular heart model.

  14. Atorvastatin therapy associated with improvement in left ventricular remodeling in a case of idiopathic dilated cardiomyopathy.

    PubMed

    Yamada, Takahisa; Node, Koichi; Mine, Takanao; Morita, Takashi; Kioka, Hidetaka; Tamaki, Shunsuke; Tsukamoto, Yasumasa; Masuda, Masaharu; Okuda, Keiji; Fukunami, Masatake

    2006-12-01

    Statins have pleiotropic effects such as anti-inflammatory and vascular protective effects that would be beneficial for patients with chronic heart failure. This report describes a patient with idiopathic dilated cardiomyopathy and a long-standing history of heart failure that was treated with atorvastatin in addition to conventional therapy that included beta-blockers. Atorvastatin therapy for 12 months was associated with an improvement in cardiac function and improved left ventricular remodeling and peak oxygen consumption. This result suggests that statin therapy may be a potential novel treatment strategy for patients with chronic heart failure.

  15. Right ventricular reverse remodelling in Idiopathic Pulmonary Arterial Hypertension diagnosed during pregnancy: Is it possible?

    PubMed

    Paciocco, Giuseppe; Lombi, Andrea; Vincenzi, Antonella; Pesci, Alberto; Achilli, Felice

    2017-01-01

    We present a case of a 36-year-old woman who developed a severe form of Idiopathic Pulmonary Arterial Hypertension (IPAH) during pregnancy and after emergency delivery. The management of IPAH during or after pregnancy is complex. Due to the severity of her IPAH, an upfront triple combination therapy, including i.v. epoprostenol, was started. The rapid institution of this treatment regimen allowed a complete right ventricular reverse remodelling after 1 year of therapy, leading to a down-titration until complete suspension of epoprostenol from the treatment regimen.

  16. Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model

    PubMed Central

    Ishikawa, Kiyotake; Hadri, Lahouaria; Santos-Gallego, Carlos; Fish, Kenneth; Hammoudi, Nadjib; Chaanine, Antoine; Torquato, Samantha; Naim, Charbel; Ibanez, Borja; Pereda, Daniel; García-Alvarez, Ana; Fuster, Valentin; Sengupta, Partho P.; Leopold, Jane A.; Hajjar, Roger J.

    2014-01-01

    In pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure is the main determinant of a poor prognosis. We aimed to characterize RV structural and functional differences during adaptive RV remodeling and progression to RV failure in a large animal model of chronic PH. Postcapillary PH was created surgically in swine (n = 21). After an 8- to 14-wk follow-up, two groups were identified based on the development of overt heart failure (HF): PH-NF (nonfailing, n = 12) and PH-HF (n = 8). In both groups, invasive hemodynamics, pressure-volume relationships, and echocardiography confirmed a significant increase in pulmonary pressures and vascular resistance consistent with PH. Histological analysis also demonstrated distal pulmonary arterial (PA) remodeling in both groups. Diastolic dysfunction, defined by a steeper RV end-diastolic pressure-volume relationship and longitudinal strain, was found in the absence of HF as an early marker of RV remodeling. RV contractility was increased in both groups, and RV-PA coupling was preserved in PH-NF animals but impaired in the PH-HF group. RV hypertrophy was present in PH-HF, although there was evidence of increased RV fibrosis in both PH groups. In the PH-HF group, RV sarcoplasmic reticulum Ca2+-ATPase2a expression was decreased, and endoplasmic reticulum stress was increased. Aldosterone levels were also elevated in PH-HF. Thus, in the swine pulmonary vein banding model of chronic postcapillary PH, RV remodeling occurs at the structural, histological, and molecular level. Diastolic dysfunction and fibrosis are present in adaptive RV remodeling, whereas the onset of RV failure is associated with RV-PA uncoupling, defective calcium handling, and hyperaldosteronism. PMID:25158063

  17. Effect of Wenxin Granule on Ventricular Remodeling and Myocardial Apoptosis in Rats with Myocardial Infarction

    PubMed Central

    Wu, Aiming; Zhai, Jianying; Zhang, Dongmei; Lou, Lixia; Zhu, Haiyan; Gao, Yonghong; Chai, Limin; Xing, Yanwei; Lv, Xiying; Zhu, Lingqun; Zhao, Mingjing; Wang, Shuoren

    2013-01-01

    Aim. To determine the effect of a Chinese herbal compound named Wenxin Granule on ventricular remodeling and myocardial apoptosis in rats with myocardial infarction (MI). Methods. Male Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the model group, the metoprolol group, and the Wenxin Granule group (WXKL group) with sample size (n) of 7 rats in each group. An MI model was established in all rats by occlusion of the left anterior descending coronary artery (the control group was without occlusion). Wenxin Granule (1.35 g/kg/day), metoprolol (12 mg/kg/day), and distilled water (5 mL/kg/day for the control and model groups) were administered orally for 4 weeks. Ultrasonic echocardiography was used to examine cardiac structural and functional parameters. Myocardial histopathological changes were observed using haematoxylin and eosin (H&E) dyeing. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Serum angiotensin II (Ang II) concentration was measured using the enzyme-linked immunosorbent assay (ELISA). Results. It was found that Wenxin Granule could partially reverse ventricular remodeling, improve heart function, alleviate the histopathological damage, inhibit myocardial apoptosis, and reduce Ang II concentration in rats with MI. Conclusions. The results of the current study suggest that Wenxin Granule may be a potential alternative and complementary medicine for the treatment of MI. PMID:23997803

  18. Myocardial infarction and left ventricular remodeling: results of the CEDIM trial. Carnitine Ecocardiografia Digitalizzata Infarto Miocardico.

    PubMed

    Colonna, P; Iliceto, S

    2000-02-01

    Left ventricular dilatation after acute myocardial infarction (MI) is a powerful predictor of progressive functional deterioration, culminating in heart failure and death. The most important determinants of post-MI left ventricular remodeling are the size of the infarct, the degree of residual stenosis in the infarct-related artery, and the viability of the infarct zone. In addition to reperfusion therapy and angiotensin-converting enzyme inhibition, metabolic intervention with L-carnitine may represent a therapeutic approach for preventing left ventricular dilatation and preserving cardiac function. Ongoing studies with early metabolic intervention with carnitine in the acute phase of infarction may prove successful in protecting the microcirculation against ischemic damage and enhancing its ability to respond to blood flow resumption. The results of the multicenter, randomized, double-blind Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial suggest that the early and long-term administration of L-carnitine attenuates progressive left ventricular dilatation after acute anterior MI. Results show significant, consistent reductions in end-diastolic volume and end-systolic volume in patients who received L-carnitine compared with placebo. The ongoing CEDIM-2 trial (projected 4000 patients with acute MI) will assess the efficacy of L-carnitine in reducing the combined incidence of death and heart failure at 6 months. In addition to standard reperfusion therapy and angiotensin-converting enzyme inhibition, metabolic intervention with L-carnitine may be a therapeutic approach for preventing left ventricular dilatation and preserving cardiac function by limiting infarct size, decreasing residual stenosis in the infarct-related artery, and increasing viability of the infarct zone.

  19. Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction.

    PubMed

    Lassen, Thomas Ravn; Nielsen, Jan Møller; Johnsen, Jacob; Ringgaard, Steffen; Bøtker, Hans Erik; Kristiansen, Steen Buus

    2017-05-01

    Left ventricular (LV) remodeling following a myocardial infarction (MI) involves formation of reactive oxygen species (ROS). Paroxetine, a selective serotonin reuptake inhibitor, has an antioxidant effect in the vascular wall. We investigated whether paroxetine reduces myocardial ROS formation and LV remodeling following a MI. In a total of 32 Wistar rats, MI was induced by a 30-min ligation of the left anterior descending artery followed by 7- or 28-day reperfusion. During the 28 days of reperfusion, LV remodeling was evaluated by magnetic resonance imaging (MRI) and echocardiography (n = 20). After 28 days of reperfusion, the susceptibility to ventricular tachycardia was evaluated prior to sacrifice and histological assessment of myocyte cross-sectional area, fibrosis, and presence of myofibroblasts. Myocardial ROS formation was measured with dihydroethidium after 7 days of reperfusion in separate groups (n = 12). Diastolic LV volume, evaluated by MRI (417 ± 60 vs. 511 ± 64 µL, p < 0.05), and echocardiography (515 ± 80 vs. 596 ± 83 µL, p < 0.05) as well as diastolic LV internal diameter evaluated with echocardiography (7.2 ± 0.6 vs. 8.1 ± 0.7 mm, p < 0.05) were lower in the paroxetine group than in controls. Furthermore, myocyte cross-sectional area was reduced in the paroxetine group compared with controls (277 ± 26 vs. 354 ± 23 mm(3), p < 0.05) and ROS formation was reduced in the remote myocardium (0.415 ± 0.19 normalized to controls, p < 0.05). However, no differences in the presence of fibrosis or myofibroblasts were observed. Finally, paroxetine reduced the susceptibility to ventricular tachycardia (induced in 2/11 vs. 6/8 rats, p < 0.05). Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probably by reducing ROS formation.

  20. 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

  1. 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.

  2. Temporal pattern of left ventricular structural and functional remodeling following reversal of volume overload heart failure

    PubMed Central

    Hutchinson, Kirk R.; Guggilam, Anuradha; Cismowski, Mary J.; Galantowicz, Maarten L.; West, Thomas A.; Stewart, James A.; Zhang, Xiaojin; Lord, Kevin C.

    2011-01-01

    Current surgical management of volume overload-induced heart failure (HF) leads to variable recovery of left ventricular (LV) function despite a return of LV geometry. The mechanisms that prevent restoration of function are unknown but may be related to the timing of intervention and the degree of LV contractile impairment. This study determined whether reduction of aortocaval fistula (ACF)-induced LV volume overload during the compensatory stage of HF results in beneficial LV structural remodeling and restoration of pump function. Rats were subjected to ACF for 4 wk; a subset then received a load-reversal procedure by closing the shunt using a custom-made stent graft approach. Echocardiography or in vivo pressure-volume analysis was used to assess LV morphology and function in sham rats; rats subjected to 4-, 8-, or 15-wk ACF; and rats subjected to 4-wk ACF followed by 4- or 11-wk reversal. Structural and functional changes were correlated to LV collagen content, extracellular matrix (ECM) proteins, and hypertrophic markers. ACF-induced volume overload led to progressive LV chamber dilation and contractile dysfunction. Rats subjected to short-term reversal (4-wk ACF + 4-wk reversal) exhibited improved chamber dimensions (LV diastolic dimension) and LV compliance that were associated with ECM remodeling and normalization of atrial and brain natriuretic peptides. Load-independent parameters indicated LV systolic (preload recruitable stroke work, Ees) and diastolic dysfunction (tau, arterial elastance). These changes were associated with an altered α/β-myosin heavy chain ratio. However, these changes were normalized to sham levels in long-term reversal rats (4-wk ACF + 11-wk reversal). Acute hemodynamic changes following ACF reversal improve LV geometry, but LV dysfunction persists. Gradual restoration of function was related to normalization of eccentric hypertrophy, LV wall stress, and ECM remodeling. These results suggest that mild to moderate LV systolic

  3. UM206, a selective Frizzled antagonist, attenuates adverse remodeling after myocardial infarction in swine.

    PubMed

    Uitterdijk, André; Hermans, Kevin C M; de Wijs-Meijler, Daphne P M; Daskalopoulos, Evangelos P; Reiss, Irwin K; Duncker, Dirk J; Matthijs Blankesteijn, W; Merkus, Daphne

    2016-02-01

    Modulation of Wnt/Frizzled signaling with UM206 reduced infarct expansion and prevented heart failure development in mice, an effect that was accompanied by increased myofibroblast presence in the infarct, suggesting that Wnt/Frizzled signaling has a key role in cardiac remodeling following myocardial infarction (MI). This study investigated the effects of modulation of Wnt/Frizzled signaling with UM206 in a swine model of reperfused MI. For this purpose, seven swine with MI were treated with continuous infusion of UM206 for 5 weeks. Six control swine were treated with vehicle. Another eight swine were sham-operated. Cardiac function was determined by echo in awake swine. Infarct mass was estimated at baseline by heart-specific fatty acid-binding protein ELISA and at follow-up using planimetry. Components of Wnt/Frizzled signaling, myofibroblast presence, and extracellular matrix were measured at follow-up with qPCR and/or histology. Results show that UM206 treatment resulted in a significant decrease in infarct mass compared with baseline (-41±10%), whereas infarct mass remained stable in the Control-MI group (+3±17%). Progressive dilation of the left ventricle occurred in the Control-MI group between 3 and 5 weeks after MI, while adverse remodeling was halted in the UM206-treated group. mRNA expression for Frizzled-4 and the Frizzled co-receptor LRP5 was increased in UM206-treated swine as compared with Control-MI swine. Myofibroblast presence was significantly lower in infarcted tissue of the UM206-treated animals (1.53±0.43% vs 3.38±0.61%) at 5 weeks follow-up. This study demonstrates that UM206 treatment attenuates adverse remodeling in a swine model of reperfused MI, indicating that Wnt/Frizzled signaling is a promising target to improve infarct healing and limit post-MI remodeling.

  4. Fibroblast Growth Factor-9 Enhances M2 Macrophage Differentiation and Attenuates Adverse Cardiac Remodeling in the Infarcted Diabetic Heart

    PubMed Central

    Singla, Dinender K.; Singla, Reetu D.; Abdelli, Latifa S.; Glass, Carley

    2015-01-01

    Inflammation has been implicated as a perpetrator of diabetes and its associated complications. Monocytes, key mediators of inflammation, differentiate into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages upon infiltration of damaged tissue. However, the inflammatory cell types, which propagate diabetes progression and consequential adverse disorders, remain unclear. The current study was undertaken to assess monocyte infiltration and the role of fibroblast growth factor-9 (FGF-9) on monocyte to macrophage differentiation and cardioprotection in the diabetic infarcted heart. Db/db diabetic mice were assigned to sham, myocardial infarction (MI), and MI+FGF-9 groups. MI was induced by permanent coronary artery ligation and animals were subjected to 2D transthoracic echocardiography two weeks post-surgery. Immunohistochemical and immunoassay results from heart samples collected suggest significantly increased infiltration of monocytes (Mean ± SEM; MI: 2.02% ± 0.23% vs. Sham 0.75% ± 0.07%; p<0.05) and associated pro-inflammatory cytokines (TNF-α, MCP-1, and IL-6), adverse cardiac remodeling (Mean ± SEM; MI: 33% ± 3.04% vs. Sham 2.2% ± 0.33%; p<0.05), and left ventricular dysfunction (Mean ± SEM; MI: 35.4% ± 1.25% vs. Sham 49.19% ± 1.07%; p<0.05) in the MI group. Importantly, treatment of diabetic infarcted myocardium with FGF-9 resulted in significantly decreased monocyte infiltration (Mean ± SEM; MI+FGF-9: 1.39% ± 0.1% vs. MI: 2.02% ± 0.23%; p<0.05), increased M2 macrophage differentiation (Mean ± SEM; MI+FGF-9: 4.82% ± 0.86% vs. MI: 0.85% ± 0.3%; p<0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean ± SEM; MI+FGF-9: 11.59% ± 1.2% vs. MI: 33% ± 3.04%; p<0.05), and improved cardiac function (Fractional shortening, Mean ± SEM; MI+FGF-9: 41.51% ± 1.68% vs. MI: 35.4% ± 1.25%; p<0.05). In conclusion, our data suggest FGF-9 possesses novel therapeutic potential in its ability to

  5. Aldehyde dehydrogenase 2 activation in heart failure restores mitochondrial function and improves ventricular function and remodelling

    PubMed Central

    Gomes, Katia M.S.; Campos, Juliane C.; Bechara, Luiz R.G.; Queliconi, Bruno; Lima, Vanessa M.; Disatnik, Marie-Helene; Magno, Paulo; Chen, Che-Hong; Brum, Patricia C.; Kowaltowski, Alicia J.; Mochly-Rosen, Daria; Ferreira, Julio C.B.

    2014-01-01

    Aims We previously demonstrated that pharmacological activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) protects the heart against acute ischaemia/reperfusion injury. Here, we determined the benefits of chronic activation of ALDH2 on the progression of heart failure (HF) using a post-myocardial infarction model. Methods and results We showed that a 6-week treatment of myocardial infarction-induced HF rats with a selective ALDH2 activator (Alda-1), starting 4 weeks after myocardial infarction at a time when ventricular remodelling and cardiac dysfunction were present, improved cardiomyocyte shortening, cardiac function, left ventricular compliance and diastolic function under basal conditions, and after isoproterenol stimulation. Importantly, sustained Alda-1 treatment showed no toxicity and promoted a cardiac anti-remodelling effect by suppressing myocardial hypertrophy and fibrosis. Moreover, accumulation of 4-hydroxynonenal (4-HNE)-protein adducts and protein carbonyls seen in HF was not observed in Alda-1-treated rats, suggesting that increasing the activity of ALDH2 contributes to the reduction of aldehydic load in failing hearts. ALDH2 activation was associated with improved mitochondrial function, including elevated mitochondrial respiratory control ratios and reduced H2O2 release. Importantly, selective ALDH2 activation decreased mitochondrial Ca2+-induced permeability transition and cytochrome c release in failing hearts. Further supporting a mitochondrial mechanism for ALDH2, Alda-1 treatment preserved mitochondrial function upon in vitro aldehydic load. Conclusions Selective activation of mitochondrial ALDH2 is sufficient to improve the HF outcome by reducing the toxic effects of aldehydic overload on mitochondrial bioenergetics and reactive oxygen species generation, suggesting that ALDH2 activators, such as Alda-1, have a potential therapeutic value for treating HF patients. PMID:24817685

  6. Characterizing the spectrum of right ventricular remodelling in response to chronic training.

    PubMed

    Sitges, Marta; Merino, Beatriz; Butakoff, Constatine; de la Garza, Maria Sanz; Paré, Carles; Montserrat, Silvia; Vidal, Barbara; Azqueta, Manel; Sarquella, Georgia; Gutierrez, Josep Antoni; Canal, Ramon; Brugada, Josep; Bijnens, Bart H

    2016-11-15

    The significance and spectrum of reduced right ventricular (RV) deformation, reported in endurance athletes, is unclear. To comprehensively analyze the cardiac performance at rest of athletes, especially focusing on integrating RV size and deformation to unravel the underlying triggers of this ventricular remodelling. Hundred professional male athletes and 50 sedentary healthy males of similar age were prospectively studied. Conventional echocardiographic parameters of all four chambers were obtained, as well as 2D echo-derived strain (2DSE) in the left (LV) and in the RV free wall with separate additional analysis of the RV basal and apical segments. Left and right-sided dimensions were larger in athletes than in controls, but with a disproportionate RA enlargement. RV global strain was lower in sportsmen (-26.8 ± 2.8% vs -28.5 ± 3.4%, p < 0.001) due to a decrease in the basal segment (-22.8 ± 3.5% vs -25.8 ± 4.0%, p < 0.001) resulting in a marked gradient of deformation from the RV inlet towards the apex. By integrating size, deformation and stroke volume, we observed that the LV working conditions were similar in all sportsmen while a wider variability existed in the RV. Cardiac remodelling in athletes is more pronounced in the right heart cavities with specific regional differences within the right ventricle, but with a wide variability among individuals. The large inter-individual differences, as well as its acute and chronic relevance warrant further investigation.

  7. Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction.

    PubMed

    Beaumont, Eric; Southerland, Elizabeth M; Hardwick, Jean C; Wright, Gary L; Ryan, Shannon; Li, Ying; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

    2015-10-01

    This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions.

  8. The Homeostatic Chemokine CCL21 Predicts Mortality in Aortic Stenosis Patients and Modulates Left Ventricular Remodeling

    PubMed Central

    Finsen, Alexandra Vanessa; Ueland, Thor; Sjaastad, Ivar; Ranheim, Trine; Ahmed, Mohammed S.; Dahl, Christen P.; Askevold, Erik T.; Aakhus, Svend; Husberg, Cathrine; Fiane, Arnt E.; Lipp, Martin; Gullestad, Lars; Christensen, Geir; Aukrust, Pål; Yndestad, Arne

    2014-01-01

    Background CCL21 acting through CCR7, is termed a homeostatic chemokine. Based on its role in concerting immunological responses and its proposed involvement in tissue remodeling, we hypothesized that this chemokine could play a role in myocardial remodeling during left ventricular (LV) pressure overload. Methods and Results Our main findings were: (i) Serum levels of CCL21 were markedly raised in patients with symptomatic aortic stenosis (AS, n = 136) as compared with healthy controls (n = 20). (ii) A CCL21 level in the highest tertile was independently associated with all-cause mortality in these patients. (iii) Immunostaining suggested the presence of CCR7 on macrophages, endothelial cells and fibroblasts within calcified human aortic valves. (iv). Mice exposed to LV pressure overload showed enhanced myocardial expression of CCL21 and CCR7 mRNA, and increased CCL21 protein levels. (v) CCR7−/− mice subjected to three weeks of LV pressure overload had similar heart weights compared to wild type mice, but increased LV dilatation and reduced wall thickness. Conclusions Our studies, combining experiments in clinical and experimental LV pressure overload, suggest that CCL21/CCR7 interactions might be involved in the response to pressure overload secondary to AS. PMID:25398010

  9. Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction

    PubMed Central

    Huang, Yan; Wang, Dandan; Wang, Xin; Zhang, Yijie; Liu, Tao; Chen, Yuting; Tang, Yanhong; Wang, Teng; Hu, Dan; Huang, Congxin

    2016-01-01

    CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism. MI was induced by surgical ligation of the left anterior descending coronary artery in CCR9 knockout mice and their CCR9+/+ littermates. Our results showed that the CCR9 expression levels were up-regulated in the hearts of the MI mice. Abrogation of CCR9 improved the post-MI survival rate and left ventricular (LV) dysfunction and decreased the infarct size. In addition, the CCR9 knockout mice exhibited attenuated inflammation, apoptosis, structural and electrical remodeling compared with the CCR9+/+ MI mice. Mechanistically, CCR9 mainly regulated the pathological response by interfering with the NF-κB and MAPK signaling pathways. In conclusion, the data reveal that CCR9 serves as a novel modulator of pathological progression following MI through NF-κB and MAPK signaling. PMID:27585634

  10. Temporal evaluation of left ventricular remodeling and function in rats with chronic volume overload.

    PubMed

    Brower, G L; Henegar, J R; Janicki, J S

    1996-11-01

    The left ventricle (LV) significantly dilates and hypertrophies in response to chronic volume overload. However, the temporal responses in LV mass, volume, and systolic/diastolic function secondary to chronic volume overload induced by an infrarenal arteriovenous (A-V) fistula in rats have not been well characterized. To this end, LV end-diastolic pressure, size, and function (i.e., isovolumetric pressure-volume relationships in the blood-perfused isolated heart) were assessed at 1, 2, 3, 5, and 8 wk post-A-V fistula and compared with age-matched control animals. Progressive hypertrophy (192% at 8 wk), ventricular dilatation (172% at 8 wk), and a decrease in ventricular stiffness (257% at 8 wk) occurred in the fistula groups. LV end-diastolic pressure increased from a control value of 4.2 +/- 3.1 mmHg to a peak value of 15.7 +/- 3.6 mmHg after 3 wk of volume overload. A subsequent decline in LVEDP to 11.0 +/- 6.0 mmHg together with further LV dilation (169%) corresponded to a significant decrease in LV stiffness (222%) at 5 wk post-A-V fistula. Myocardial contractility, as assessed by the isovolumetric pressure-volume relationship, was significantly reduced in all A-V fistula groups; however, the compensatory remodeling induced by 8 wk of chronic biventricular volume overload tended to preserve systolic function.

  11. ET-receptor antagonism, myocardial gene expression, and ventricular remodeling during CHF in rats.

    PubMed

    Oie, E; Bjønerheim, R; Grogaard, H K; Kongshaug, H; Smiseth, O A; Attramadal, H

    1998-09-01

    Both myocardial and plasma endothelin-1 (ET-1) are elevated in congestive heart failure (CHF). However, the role played by endogenous ET-1 in the progression of CHF remains unknown. The aim of the present study was to investigate and correlate myocardial gene expression programs and left ventricular (LV) remodeling during chronic ET-receptor antagonism in CHF rats. After ligation of the left coronary artery, rats were randomized to oral treatment with a nonselective ET-receptor antagonist (bosentan, 100 mg . kg-1 . day-1, n = 11) or vehicle (saline, n = 13) for 15 days, starting 24 h after induction of myocardial infarction. Bosentan substantially attenuated LV dilatation during postinfarction failure as evaluated by echocardiography. Furthermore, bosentan decreased LV systolic and end-diastolic pressures and increased fractional shortening. Myocardial expression of preproET-1 mRNA and a fetal gene program characteristic of myocardial hypertrophy were increased in the CHF rats and were not affected by bosentan. Consistently, right ventricular-to-body weight ratios, diameters of cardiomyocytes, and echocardiographic analysis demonstrated a sustained hypertrophic response and a normalized relative wall thickness after intervention with bosentan. Thus the modest reduction of preload and afterload provided by bosentan substantially attenuates LV dilatation, causing improved pressure-volume relationships. However, the compensatory hypertrophic response was not altered by ET-receptor antagonism. Therefore, ET-1 does not appear to play a crucial role in the mechanisms of myocardial hypertrophy during the early phase of postinfarction failure.

  12. Regulatory role of CARD3 in left ventricular remodelling and dysfunction after myocardial infarction.

    PubMed

    Li, Liangpeng; Wang, Xiaodi; Chen, Wen; Qi, Haoyu; Jiang, Ding-Sheng; Huang, Ling; Huang, Fuhua; Wang, Liming; Li, Hongliang; Chen, Xin

    2015-11-01

    Caspase activation and recruitment domain 3 (CARD3) is a caspase recruitment domain (CARD)-containing serine/threonine kinase and plays a pivotal role in apoptosis, immunity, tissue development and proliferation. To date, the causal relationship between CARD3 and myocardial infarction (MI) remains largely unexplored. This study aimed to identify the functional significance of CARD3 in the regulation of cardiac remodelling after MI and the underlying mechanisms of its effects. The levels of CARD3 expression were up-regulated in failing human and mouse post-infarction hearts. In addition, CARD3-knockout (KO) mice and transgenic mice overexpressing CARD3 in the heart were then generated and subjected to MI. Compared with wild-type (WT) control mice, CARD3-KO mice developed smaller infarct sizes, improved survival rates, and preserved left ventricle (LV) function after MI. Significantly, CARD3-KO hearts had less cardiomyocyte apoptosis and inflammatory cell infiltration in the infarct border zone. Attenuated LV remodelling was also observed in the KO hearts following MI, with reduced cardiac hypertrophy and fibrosis. Conversely, CARD3 overexpression resulted in the opposite MI-induced phenotype. Similar results were observed in ex vivo-cultured neonatal rat cardiomyocytes exposed to hypoxia. Mechanistically, we discovered that the CARD3-mediated detrimental effects of MI were associated with the activation of the NF-κB and p38 signalling cascades. Taken together, these data demonstrate that CARD3 serves as a novel positive modulator of ventricular remodelling after MI via the regulation of the NF-κB and p38 signalling. Thus, CARD3 may be a promising therapeutic target for the treatment of heart failure after MI.

  13. Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure

    PubMed Central

    Lou, Qing; Fedorov, Vadim V.; Glukhov, Alexey V.; Moazami, Nader; Fast, Vladimir G.; Efimov, Igor R.

    2011-01-01

    Background Excitation-contraction (EC) coupling is altered in the end-stage heart failure (HF). However, spatial heterogeneity of this remodeling has not been established at the tissue level in failing human heart. The objective is to study functional remodeling of EC coupling and calcium handling in failing and nonfailing human hearts. Methods and Results We simultaneously optically mapped action potentials (AP) and calcium transients (CaT) in coronary-perfused left ventricular wedge preparations from nonfailing (n = 6) and failing (n = 5) human hearts. Our major findings are: (1) CaT duration minus AP duration was longer at sub-endocardium in failing compared to nonfailing hearts during bradycardia (40 beats/min). (2) The transmural gradient of CaT duration was significantly smaller in failing hearts compared with nonfailing hearts at fast pacing rates (100 beats/min). (3) CaT in failing hearts had a flattened plateau at the midmyocardium; and exhibited a “two-component” slow rise at sub-endocardium in three failing hearts. (4) CaT relaxation was slower at sub-endocardium than that at sub-epicardium in both groups. Protein expression of sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) was lower at sub-endocardium than that at sub-epicardium in both nonfailing and failing hearts. SERCA2a protein expression at sub-endocardium was lower in hearts with ischemic cardiomyopathy compared with nonischemic cardiomyopathy. Conclusions For the first time, we present direct experimental evidence of transmural heterogeneity of EC coupling and calcium handling in human hearts. End-stage HF is associated with the heterogeneous remodeling of EC coupling and calcium handling. PMID:21502574

  14. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    PubMed

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values < 0.05). For every reduction of 5% in left ventricular ejection fraction induced by mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  15. Effects of ACE-inhibitors and beta-blockers on left ventricular remodeling in chronic heart failure.

    PubMed

    Khattar, R S

    2003-04-01

    In recent years, it has become increasingly recognised that a central feature of the disease progression associated with heart failure is the process of left ventricular remodeling. The remodeling process manifests as an increase in left ventricular volumes, leading to a rise in wall stress and a compensatory increase in myocardial mass. The left ventricle also gradually assumes a more spherical shape, resulting in functional mitral regurgitation leading to further haemodynamic overload, worsening myocardial function and an unfavourable clinical course. Accumulating clinical data support the hypothesis that the benefits in clinical outcome with ACE-inhibitors and beta-blockers may relate to modification of the remodeling process resulting in slowing of disease progression and preservation of contractile function. The general trend from a number of clinical studies indicates that whereas ACE-inhibitors seem to prevent progressive left ventricular dilatation, the third generation beta-blocker, carvedilol, may actually reverse the remodelling process by reducing left ventricular volumes and improving systolic function. Direct comparisons indicate that carvedilol has a similar safety and tolerability profile to ACE-inhibitors and thereby support the feasibility of administering this drug as first-line therapy in selected patients with mild to moderate chronic heart failure. Therefore, the decision to initiate treatment with carvedilol or an ACE-inhibitor might in future be tailored on an individual basis and followed thereafter by combination therapy at the earliest and safest opportunity. Finally, the possible development of treatment strategies addressing the cellular and molecular mechanisms responsible for the remodeling process and the recently published benefits of device therapies herald a combined, synergistic approach to the future management of heart failure.

  16. Two-Dimensional Speckle Tracking Echocardiography Predict Left Ventricular Remodeling after Acute Myocardial Infarction in Patients with Preserved Ejection Fraction

    PubMed Central

    Hsiao, Ju-Feng; Chung, Chang-Min; Chu, Chi-Ming; Lin, Yu-Shen; Pan, Kuo-Li; Chang, Shih-Tai

    2016-01-01

    Objectives Left ventricular remodeling after acute myocardial infarction increases cardiovascular events and mortality. But few study was done in patients with preserved ejection fraction (EF > 40%). We investigate whether the strain and strain rate by 2D speckle tracking echocardiography could predict left ventricular remodeling after acute myocardial infarction in this cohort. Methods The 83 patients (average age 60.7 ± 12.3 y, 75 [90.4%] male) with new-onset acute myocardial infarction receiving echocardiography immediately, and 6 months after admission were grouped by the presence or absence of left ventricular remodeling. Strain and strain rate including longitudinal, circumferential, and radial direction were calculated. The average of strain and strain rate of which segmental longitudinal strains > – 15% were defined as the injury longitudinal strain (InjLS). Results Left ventricular remodeling occurred in 24 of 83 patients (28.9%). In univariate logistic regression analyses, gender, peak CK-MB, log BNP, use of statin before discharge, wall motion score index, and InjLS were significantly associated with left ventricular remodeling (p < 0.05). In multivariate analysis using the forward stepwise method, gender, CK-MB, and InjLS were independent predictors. The hazard ratio for InjLS was 1.48 (p = 0.04). Receiver operating characteristic curve (ROC) analyses showed the area under the curve (AUC) of InjLS was largest (AUC = 0.75, cut-off value = –11.7%, sensitivity = 81%, specificity = 71%, p < 0.01). In ST-segment elevation myocardial infarction subgroup, InjLS was the only predictor according to ROC analysis (AUC = 0.79, p < 0.01, cut-off value = –11.4%, sensitivity = 88%, specificity = 77%) and multivariate logistic regression analysis (hazard ratio = 1.88, 95% CI: 1.22–2.88, p < 0.01). Conclusions InjLS was an excellent predictor for left ventricular remodeling after acute myocardial infarction in patient with preserved ejection fraction. PMID

  17. A Meta-analysis of the effects of Exercise Training on Left Ventricular Remodeling Following Myocardial Infarction: Start early and go longer for greatest exercise benefits on remodeling

    PubMed Central

    2011-01-01

    Background The effects of variations in exercise training on Left ventricular (LV) remodeling in patients shortly after Myocardial Infarction (MI) are important but poorly understood. Methods Systematic review incorporating meta-analysis using meta-regression. Studies were identified via systematic searches of: OVID MEDLINE (1950 to 2009), Cochrane Central Register of Controlled Trials (1991 to 2009), AMED (1985 to 2009), EMBASE (1988 to 2009), PUBMED (1966 to 2009), SPORT DISCUS (1975 to 2009), SCOPUS (1950 to 2009) and WEB OF SCIENCE (1950 to 2009) using the medical subject headings: myocardial infarction, post myocardial infarction, post infarction, heart attack, ventricular remodeling, ventricular volumes, ejection fraction, left ventricular function, exercise, exercise therapy, kinesiotherapy, exercise training. Reference lists of all identified studies were also manually searched for further relevant studies. Studies selected were randomized controlled trials of exercise training interventions reporting ejection fraction (EF) and/or ventricular volumes in patients following recent MI (≤ 3 months) post-MI patients involving control groups. Studies were excluded if they were not randomized, did not have a 'usual-care' control (involving no exercise), evaluated a non-exercise intervention, or did not involve human subjects. Non-English studies were also excluded. Results After screening of 1029 trials, trials were identified that reported EF (12 trials, n = 647), End Systolic Volumes (ESV) (9 trials, n = 475) and End Diastolic Volumes (EDV) (10 trials, n = 512). Meta-regression identified that changes in EF effect size difference decreased as the time between MI and initiation of the exercise program lengthened, and increased as the duration of the program increased (Q = 25.48, df = 2, p < 0.01, R2 = 0.76). Greater reductions in ESV and EDV (as indicated by effect size decreases) occurred with earlier initiation of exercise training and with longer training

  18. Long-acting calcium channel antagonist pranidipine prevents ventricular remodeling after myocardial infarction in rats.

    PubMed

    Takeuchi, K; Omura, T; Yoshiyama, M; Yoshida, K; Otsuka, R; Shimada, Y; Ujino, K; Yoshikawa, J

    1999-01-01

    The purpose of this study was to examine the effects of the long-acting calcium channel antagonist pranidipine on ventricular remodeling, systolic and diastolic cardiac function, circulating humoral factors, and cardiac mRNA expression in myocardial infarcted rats. Myocardial infarction (MI) was produced by ligation of the coronary artery in Wistar rats. Three mg/kg per day of pranidipine was randomly administered to the infarcted rats. Hemodynamic measurements, Doppler echocardiographic examinations, analyses of the plasma levels of humoral factors, and myocardial mRNA expression were performed at 4 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 24.2 +/- 1.2mmHg and 5.4 +/- 0.6 mmHg. Pranidipine reduced LVEDP and CVP to 13.6 +/- 1.4mmHg (P < 0.01) and 2.5 +/- 0.4mmHg (P < 0.01). The weight of the left and right ventricles in MI was significantly higher than in the sham-operated rats (sham, 2.02 +/- 0.04 and 0.47 +/- 0.02g/kg; MI, 2.18 +/- 0.05 and 0.79 +/- 0.04g/ kg; P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3mm (P < 0.01) (sham, 6.4 +/- 0.3mm). Pranidipine prevented an increase in the weight of the left and right ventricles (2.02 +/- 0.04 and 0.6 +/- 0.03g/kg, P < 0.01) and LVDd (7.9 +/-0.2mm, P < 0.01 to MI). Plasma renin activity (PRA), and plasma epinephrine, norepinephrine, and dopamine concentrations in MI were higher than those of the sham-operated rats. Pranidipine decreased the PRA and plasma cathecolamine levels of the myocardial infarcted rats to the level of the sham-operated rats. Moreover, the rats in MI showed systolic dysfunction, shown by decreased fractional shortening (sham, 31 +/- 2% vs MI, 15 +/- 1%; P < 0.01) and diastolic dysfunction shown by the E-wave deceleration rate (sham, 12.8 +/- 1.1 m/s2; MI, 32.6 +/- 2.1 m/s2; P < 0.01). Pranidipine significantly prevented systolic and diastolic dysfunction. The increases

  19. Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling

    PubMed Central

    Pavo, Noemi; Lukovic, Dominika; Zlabinger, Katrin; Zimba, Abelina; Lorant, David; Goliasch, Georg; Winkler, Johannes; Pils, Dietmar; Auer, Katharina; Jan Ankersmit, Hendrik; Giricz, Zoltán; Baranyai, Tamas; Sárközy, Márta; Jakab, András; Garamvölgyi, Rita; Emmert, Maximilian Y.; Hoerstrup, Simon P.; Hausenloy, Derek J.; Ferdinandy, Péter; Maurer, Gerald; Gyöngyösi, Mariann

    2017-01-01

    We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adverse remodeling. Domestic pigs underwent three cycles of 10/10 min r-I/R by percutaneous intracoronary balloon inflation/deflation in the mid left anterior descending artery, without consecutive MI. Sham interventions (n = 8) served as controls. Hearts were explanted at 5 h (n = 6) and 24 h (n = 6), and transcriptomic profiling of the distal (ischemia-affected) and proximal (non-affected) anterior myocardial regions were analyzed by next generation sequencing (NGS) and post-processing with signaling pathway impact and pathway network analyses. In ischemic region, r-I/R induced early activation of Ca-, adipocytokine and insulin signaling pathways with key regulator STAT3, which was also upregulated in the remote areas together with clusterin (CLU) and TNF-alpha. During the late phase of cardioprotection, antigen immunomodulatory pathways were activated with upregulation of STAT1 and CASP3 and downregulation of neprilysin in both zones, suggesting r-I/R induced intrinsic remote conditioning. The temporo-spatially differently activated pathways revealed a global myocardial response, and neprilysin and the STAT family as key regulators of intrinsic remote conditioning for prevention of adverse remodeling. PMID:28266659

  20. Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure.

    PubMed

    Ashikaga, Hiroshi; Omens, Jeffrey H; Covell, James W

    2004-11-01

    To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 +/- 2 wk (means +/- SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 +/- 0.030; P <0.05), whereas the apical site did not [P=not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 +/- 0.003 at 2 wk and 0.054 +/- 0.021 at final; both P <0.05), which contributed to a significant increase in wall thickness at the final study (0.181 +/- 0.047; P < 0.05), whereas the apical site did not (P=NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.

  1. IGF-1 degradation by mouse mast cell protease 4 promotes cell death and adverse cardiac remodeling days after a myocardial infarction

    PubMed Central

    Tejada, Thor; Tan, Lin; Torres, Rebecca A.; Calvert, John W.; Lambert, Jonathan P.; Zaidi, Madiha; Husain, Murtaza; Berce, Maria D.; Naib, Hussain; Pejler, Gunnar; Abrink, Magnus; Graham, Robert M.; Lefer, David J.; Naqvi, Nawazish; Husain, Ahsan

    2016-01-01

    Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in postischemic heart disease. PMID:27274047

  2. Evaluation of remodeling in left and right ventricular myocytes from heterozygous (mRen2)27 transgenic rats.

    PubMed

    Chouabe, Christophe; Ricci, Estelle; Kurdi, Mazen; Legrand, Claude; Bricca, Giampiero; Bonvallet, Robert

    2009-03-01

    Cardiac remodeling was assessed both in the pressure-overloaded left ventricle and in the normotensive right ventricle of hypertensive transgenic rats (mRen2)27 (TGR27). The present study combined histology, electrophysiology, molecular biology and biochemistry techniques. A significant increase in action potential (AP) duration was recorded both in right and left ventricular myocytes wheareas only in the latter ones were hypertrophic. The increase in AP duration is mainly supported by the reduction of the transient outward K current (I(to)) density since no significant modification was observed for the L-type calcium current (I(Ca,L)), the sodium-calcium exchange current (I(NCX)), the delayed rectifier current (I(K)) and the inward rectifier current (I(K1)). The lower amplitude of I(to) current was associated with a lower Kv4.3 protein expression both in right and left ventricles while Kv4.3 mRNA levels was decreased only in left ventricle. Thus, a differential ventricular remodeling takes place in the TGR27 model. The possible cause of electrical remodeling in right ventricular myocytes of TGR27 is discussed.

  3. Connective tissue growth factor inhibition attenuates left ventricular remodeling and dysfunction in pressure overload-induced heart failure.

    PubMed

    Szabó, Zoltán; Magga, Johanna; Alakoski, Tarja; Ulvila, Johanna; Piuhola, Jarkko; Vainio, Laura; Kivirikko, Kari I; Vuolteenaho, Olli; Ruskoaho, Heikki; Lipson, Kenneth E; Signore, Pierre; Kerkelä, Risto

    2014-06-01

    Connective tissue growth factor (CTGF) is involved in the pathogenesis of various fibrotic disorders. However, its role in the heart is not clear. To investigate the role of CTGF in regulating the development of cardiac fibrosis and heart failure, we subjected mice to thoracic aortic constriction (TAC) or angiotensin II infusion, and antagonized the function of CTGF with CTGF monoclonal antibody (mAb). After 8 weeks of TAC, mice treated with CTGF mAb had significantly better preserved left ventricular (LV) systolic function and reduced LV dilatation compared with mice treated with control immunoglobulin G. CTGF mAb-treated mice exhibited significantly smaller cardiomyocyte cross-sectional area and reduced expression of hypertrophic marker genes. CTGF mAb treatment reduced the TAC-induced production of collagen 1 but did not significantly attenuate TAC-induced accumulation of interstitial fibrosis. Analysis of genes regulating extracellular matrix proteolysis showed decreased expression of plasminogen activator inhibitor-1 and matrix metalloproteinase-2 in mice treated with CTGF mAb. In contrast to TAC, antagonizing the function of CTGF had no effect on LV dysfunction or LV hypertrophy in mice subjected to 4-week angiotensin II infusion. Further analysis showed that angiotensin II-induced expression of hypertrophic marker genes or collagens was not affected by treatment with CTGF mAb. In conclusion, CTGF mAb protects from adverse LV remodeling and LV dysfunction in hearts subjected to pressure overload by TAC. Antagonizing the function of CTGF may offer protection from cardiac end-organ damage in patients with hypertension.

  4. Darbepoetin-α prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure

    PubMed Central

    Rastogi, Sharad; Imai, Makoto; Sharov, Victor G.; Mishra, Sudhish; Sabbah, Hani N.

    2008-01-01

    In anemic patients with heart failure (HF), erythropoietin-type drugs can elicit clinical improvement. This study examined the effects of chronic monotherapy with darbepoetin-α (DARB) on left ventricular (LV) function and remodeling in nonanemic dogs with advanced HF. HF [LV ejection fraction (EF) ∼25%] was produced in 14 dogs by intracoronary microembolizations. Dogs were randomized to once a week subcutaneous injection of DARB (1.0 μg/kg, n = 7) or to no therapy (HF, n = 7). All procedures were performed during cardiac catheterization under general anesthesia and under sterile conditions. LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were measured before the initiation of therapy and at the end of 3 mo of therapy. mRNA and protein expression of caspase-3, hypoxia inducible factor-1α, and the bone marrow-derived stem cell marker c-Kit were determined in LV tissue. In HF dogs, EDV and ESV increased and EF decreased after 3 mo of followup. Treatment with DARB prevented the increase in EDV, decreased ESV, and increased EF. DARB therapy also normalized the expression of HIF-1α and active caspase-3 and enhanced the expression of c-Kit. We conclude that chronic monotherapy with DARB prevents progressive LV dysfunction and dilation in nonanemic dogs with advanced HF. These results suggest that DARB elicits beneficial effects in HF that are independent of the presence of anemia. PMID:18952719

  5. Long-term intake of sesamin improves left ventricular remodelling in spontaneously hypertensive rats.

    PubMed

    Li, Wen-xing; Kong, Xiang; Zhang, Jun-xiu; Yang, Jie-ren

    2013-02-26

    This study was designed to evaluate the in vivo cardioprotective effects of food-derived sesamin in spontaneously hypertensive rats (SHR). The study was performed with 17-week-old male normotensive Wistar-Kyoto rats (WKY) and SHR which are untreated or treated with orally administered sesamin for 16 weeks before they were sacrificed. Long-term treatment with sesamin obviously improved left ventricular (LV) hypertrophy and fibrosis in SHR, as indicated by the decrease of LV weight/body weight, myocardial cell size, cardiac fibrosis and collagen type I expression as well as the amelioration of the LV ultrastructure. These effects were associated with reduced systolic blood pressure, enhanced cardiac total antioxidant capability and decreased malondialdehyde content, nitrotyrosine level and transforming growth factor β1 (TGF-β1) expression. All these results suggest that chronic treatment with sesamin improves LV remodeling in SHR through alleviation of oxidative and nitrative stress, reduction of blood pressure and downregulation of TGF-β1 expression.

  6. Low Carbohydrate/High Fat Diet Attenuates Pressure Overload Induced Ventricular Remodeling and Dysfunction

    PubMed Central

    Duda, Monika K.; O’Shea, Karen M.; Lei, Biao; Barrows, Brian R.; Azimzadeh, Agnes M.; McElfresh, Tracy E.; Hoit, Brian D.; Kop, Willem J.; Stanley, William C.

    2009-01-01

    Background It is not known how carbohydrate and fat intake impact the development of left ventricular (LV) hypertrophy and contractile dysfunction in response to pressure overload. We hypothesized that a low carbohydrate/high fat diet prevents LV hypertrophy and dysfunction compared to high carbohydrate diets. Methods and Results Rats were fed high carbohydrate diets comprised of either starch or sucrose, or a low carbohydrate/high fat diet, and underwent abdominal aortic banding (AAB) for two months. AAB increased LV mass with all diets. LV end diastolic and systolic volumes, and the ratio of the mRNA for myosin heavy chainβ/α were increased with both high carbohydrate diets, but not with the low carbohydrate/high fat diet. Circulating levels of insulin and leptin, both stimulants for cardiac growth, were lower, and free fatty acids higher, with the low carbohydrate/high fat diet compared to high carbohydrate diets. Among AAB animals LV volumes were positively correlated with insulin, and LV mass correlated with leptin. Conclusion A low carbohydrate/high fat diet attenuated pressure overload-induced LV remodeling compared to high carbohydrate diets. This effect corresponded to lower insulin and leptin concentrations, suggesting they may contribute to the development of LV hypertrophy and dysfunction under conditions of pressure overload. PMID:18474346

  7. RELATION OF LEFT VENTRICULAR MASS AND CONCENTRIC REMODELING TO EXTENT OF CORONARY ARTERY DISEASE BY COMPUTED TOMOGRAPHY IN PATIENTS WITHOUT LEFT VENTRICULAR HYPERTROPHY: ROMICAT STUDY

    PubMed Central

    Truong, Quynh A.; Toepker, Michael; Mahabadi, Amir A.; Bamberg, Fabian; Rogers, Ian S.; Blankstein, Ron; Brady, Thomas J.; Nagurney, John T.; Hoffmann, Udo

    2010-01-01

    Objective Cardiac computed tomography (CT) allows for simultaneous assessment of left ventricular mass (LVM) and coronary artery disease (CAD). We aimed to determine whether LVM, LVM index (LVMi), and the left ventricular (LV) geometric pattern of concentric remodeling are associated with the extent of CAD in patients without left ventricular hypertrophy (LVH). Methods In 348 patients from the ROMICAT trial, 64-slice CT was performed and LVM measured at end-diastole. We used 3 LVM indexation criteria to obtain 3 cohorts: LVM indexed to body surface area by echocardiography (n=337) and CT criteria (n=325), and by height2.7 (n=326). The cohorts were subdivided into concentric remodeling and normal geometry. Extent of coronary plaque was classified based on a 17-segment model, treated as a continuous variable, and stratified into 3 groups: 0 segments, 1–4 segments, >4 segments. Results Patients with >4 segments of coronary plaque had higher LVM (Δ12.8–15.1g) and LVMi (Δ4.0–5.5g/m2 and Δ2.2g/m2.7) than those without CAD (all p≤0.03). After multivariable adjustment, LVM and LVMi remained independent predictors of extent of coronary plaque, with 0.27–0.29 segments more plaque per 20 g increase of LVM (all p=0.02), 0.32–0.34 segments more plaque per 10 g/m2 increase of LVMi (both p=0.02), and 0.80 segments more plaque per 10 g/m2.7 increase of LVMi (p=0.008). Concentric remodeling patients had 1.1–1.3 segments more plaque than those with normal geometry (all p≤0.05). Patients with >4 segments of plaque had 2-fold increase odds (all p≤0.05) of having concentric remodeling as compared to those without CAD. Conclusion Increased LVM, LVMi, and concentric remodeling are associated with a greater degree of coronary plaque burden in patients without LVH. These findings could provide an indication to intensify medical therapy in patients with subclinical CAD and hypertension. PMID:19696685

  8. Overexpression of TIMP-1 in embryonic stem cells attenuates adverse cardiac remodeling following myocardial infarction.

    PubMed

    Glass, Carley; Singla, Dinender K

    2012-01-01

    Transplanted embryonic stem (ES) cells, following myocardial infarction (MI), contribute to limited cardiac repair and regeneration with improved function. Therefore, novel strategies are still needed to understand the effects of genetically modified transplanted stem cells on cardiac remodeling. The present study evaluates whether transplanted mouse ES cells overexpressing TIMP-1, an antiapoptotic and antifibrotic protein, can enhance cardiac myocyte differentiation, inhibit native cardiac myocyte apoptosis, reduce fibrosis, and improve cardiac function in the infarcted myocardium. MI was produced in C57BL/6 mice by coronary artery ligation. TIMP-1-ES cells, ES cells, or culture medium (control) were transplanted into the peri-infarct region of the heart. Immunofluorescence, TUNEL staining, caspase-3 activity, ELISAs, histology, and echocardiography were used to identify newly differentiated cardiac myocytes and assess apoptosis, fibrosis, and heart function. Two weeks post-MI, significantly (p < 0.05) enhanced engraftment and cardiac myocyte differentiation was observed in TIMP-1-ES cell-transplanted hearts compared with hearts transplanted with ES cells and control. Hearts transplanted with TIMP-1-ES cells demonstrated a reduction in apoptosis as well as an increase (p< 0.05) in p-Akt activity compared with ES cells or culture media controls. Infarct size and interstitial and vascular fibrosis were significantly (p< 0.05) decreased in the TIMP-1-ES cell group compared to controls. Furthermore, MMP-9, a key profibrotic protein, was significantly (p < 0.01) reduced following TIMP-1-ES cell transplantation. Echocardiography data showed fractional shortening and ejection fraction were significantly (p< 0.05) improved in the TIMP-1-ES cell group compared with respective controls. Our data suggest that transplanted ES cells overexpressing TIMP-1 attenuate adverse myocardial remodeling and improve cardiac function compared with ES cells that may have therapeutic

  9. Metabolic stress in isolated mouse ventricular myocytes leads to remodeling of t tubules.

    PubMed

    Cheng, Lu-Feng; Wang, Fuzhen; Lopatin, Anatoli N

    2011-11-01

    Cardiac ventricular myocytes possess an extensive t-tubular system that facilitates the propagation of membrane potential across the cell body. It is well established that ionic currents at the restricted t-tubular space may lead to significant changes in ion concentrations, which, in turn, may affect t-tubular membrane potential. In this study, we used the whole cell patch-clamp technique to study accumulation and depletion of t-tubular potassium by measuring inward rectifier potassium tail currents (I(K1,tail)), and inward rectifier potassium current (I(K1)) "inactivation". At room temperatures and in the absence of Mg(2+) ions in pipette solution, the amplitude of I(K1,tail) measured ~10 min after the establishment of whole cell configuration was reduced by ~18%, but declined nearly twofold in the presence of 1 mM cyanide. At ~35°C I(K1,tail) was essentially preserved in intact cells, but its amplitude declined by ~85% within 5 min of cell dialysis, even in the absence of cyanide. Intracellular Mg(2+) ions played protective role at all temperatures. Decline of I(K1,tail) was accompanied by characteristic changes in its kinetics, as well as by changes in the kinetics of I(K1) inactivation, a marker of depletion of t-tubular K(+). The data point to remodeling of t tubules as the primary reason for the observed effects. Consistent with this, detubulation of myocytes using formamide-induced osmotic stress significantly reduced I(K1,tail), as well as the inactivation of inward I(K1). Overall, the data provide strong evidence that changes in t tubule volume/structure may occur on a short time scale in response to various types of stress.

  10. Conduction Remodeling in Human End-Stage Non-Ischemic Left Ventricular Cardiomyopathy

    PubMed Central

    Glukhov, Alexey V.; Fedorov, Vadim V.; Kalish, Paul W.; Ravikumar, Vinod K.; Lou, Qing; Janks, Deborah; Schuessler, Richard B.; Moazami, Nader; Efimov, Igor R.

    2012-01-01

    Background Several arrhythmogenic mechanisms have been inferred from animal heart failure (HF) models. However, the translation of these hypotheses is difficult due to lack of functional human data. We aimed to investigate the electrophysiological substrate for arrhythmia in human end-stage non-ischemic cardiomyopathy. Methods and Results We optically mapped the coronary-perfused left ventricular wedge preparations from human hearts with end-stage non-ischemic cardiomyopathy (HF, n=10) and non-failing hearts (NF, n=10). Molecular remodeling was studied with immunostaining, Western blotting, and histological analyses. HF produced heterogeneous prolongation of action potential duration (APD) resulting in the decrease of transmural APD dispersion (64±12 ms vs 129±15 ms in NF, P<0.005). In the failing hearts, transmural activation was significantly slowed from the endocardium (39±3 cm/s versus 49±2 cm/s in NF, P=0.008) to the epicardium (28±3 cm/s versus 40±2 cm/s in NF, P=0.008). Conduction slowing was likely due to Cx43 downregulation, decreased colocalization of Cx43 with N-cadherin (40±2% versus 52±5% in NF, P=0.02), and an altered distribution of phosphorylated Cx43 isoforms by the upregulation of the dephosphorylated Cx43 in both the subendocardium and subepicardium layers. Failing hearts further demonstrated spatially discordant conduction velocity alternans which resulted in nonuniform propagation discontinuities and wavebreaks conditioned by strands of increased interstitial fibrosis (fibrous tissue content in HF 16.4±7.7 versus 9.9±1.4% in NF, P=0.02). Conclusions Conduction disorder resulting from the anisotropic downregulation of Cx43 expression, the reduction of Cx43 phosphorylation, and increased fibrosis is likely to be a critical component of arrhythmogenic substrate in patients with non-ischemic cardiomyopathy. PMID:22412072

  11. Effects of rotigaptide (ZP123) on connexin43 remodeling in canine ventricular fibrillation

    PubMed Central

    SU, GUO-YING; WANG, JING; XU, ZHEN-XING; QIAO, XIAO-JUN; ZHONG, JING-QUAN; ZHANG, YUN

    2015-01-01

    The present study investigated the effects of rotigaptide (ZP123) on the expression, distribution and phosphorylation of connexin43 (Cx43) in myocardial cell membranes in cardioversion of ventricular fibrillation (VF). A model of prolonged VF (8, 12 and 30 min) was established in mongrel dogs (n=8/group), following treatment with ZP123 or normal saline (NS control). A sham control was included. Cardiopulmonary resuscitation was begun at the start of VF followed by defibrillation. Animals received a maximum of three defibrillations of increasing energy (70, 100 and 150 J biphasic shock) as required. The average defibrillation energy, defibrillation success rate, return of spontaneous circulation and survival rate were recorded. Cx43 and phosphorylated (p-) Cx43 expression in cardiomyocyte membranes was detected by western blot and immunofluorescence analyses. Compared with the NS-treated control groups, the success defibrillation rate in the 8-min and 12-min ZP123 groups was significantly higher (P<0.05), while the average defibrillation energy was significantly lower (P<0.05). Cx43 expression in the VF groups was significantly lower than that in the sham control group (P<0.05). Cx43 expression was higher in the 12-min and 30-min ZP123 groups than that in the NS control group (P<0.05), while p-Cx43 expression decreased, although the levels were significantly higher than those in the control groups (P<0.05). Cx43 expression was positively correlated with the defibrillation success rate (r=0.91; P<0.01) and negatively with the mean defibrillation energy (r=−0.854; P<0.01), while p-Cx43 expression was positively correlated with the success rate of the previous three defibrillations (r=0.926; P<0.01). In conclusion, ZP123 reduced Cx43 remodeling through regulating the expression, distribution and phosphorylation of Cx43, thereby reducing the defibrillation energy required for successful cardioversion. PMID:26252617

  12. Angiotensin receptor blockade and angiotensin-converting-enzyme inhibition limit adverse remodeling of infarct zone collagens and global diastolic dysfunction during healing after reperfused ST-elevation myocardial infarction.

    PubMed

    Jugdutt, Bodh I; Idikio, Halliday; Uwiera, Richard R E

    2007-09-01

    To determine whether therapy with the angiotensin II type 1 receptor blocker (ARB) candesartan and the comparator angiotensin-converting-enzyme inhibitor (ACEI) enalapril during healing after reperfused ST-elevation myocardial infarction (RSTEMI) limit adverse remodeling of infarct zone (IZ) collagens and left ventricular (LV) diastolic dysfunction, we randomized 24 dogs surviving anterior RSTEMI (90-min coronary occlusion) to placebo, candesartan, and enalapril therapy between day 2 and 42. Six other dogs were sham. We measured regional IZ and non-infarct zone (NIZ) collagens (hydroxyproline; types I/III; cross-linking), transforming growth factor-beta (TGF-beta) and topography at 6 weeks, and hemodynamics, LV diastolic and systolic function, and remodeling over 6 weeks. Compared to sham, placebo-RSTEMI differentially altered regional collagens, with more pronounced increase in TGF-beta, hydroxyproline, and type I, insoluble, and cross-linked collagens in the IZ than NIZ, and increased IZ soluble and type III collagens at 6 weeks, and induced persistent LV filling pressure elevation, diastolic and systolic dysfunction, and LV remodeling over 6 weeks. Compared to placebo-RSTEMI, candesartan and enalapril limited adverse regional collagen remodeling, with normalization of type III, soluble and insoluble collagens and decrease in pyridinoline cross-linking in the IZ at 6 weeks, and attenuation of LV filling pressure, diastolic dysfunction, and remodeling over 6 weeks. The results suggest that candesartan and enalapril during healing after RSTEMI prevent rather than worsen adverse remodeling of IZ collagens and LV diastolic dysfunction, supporting the clinical use of ARBs and ACEIs during subacute RSTEMI.

  13. Exercise Training Attenuates Right Ventricular Remodeling in Rats with Pulmonary Arterial Stenosis

    PubMed Central

    de Melo, Brunno Lemes; Vieira, Stella S.; Antônio, Ednei L.; dos Santos, Luís F. N.; Portes, Leslie A.; Feliciano, Regiane S.; de Oliveira, Helenita A.; Silva, José A.; de Carvalho, Paulo de Tarso C.; Tucci, Paulo J. F.; Serra, Andrey J.

    2016-01-01

    Introduction: Pulmonary arterial stenosis (PAS) is a congenital defect that causes outflow tract obstruction of the right ventricle (RV). Currently, negative issues are reported in the PAS management: not all patients may be eligible to surgeries; there is often the need for another surgery during passage to adulthood; patients with mild stenosis may have later cardiac adverse repercussions. Thus, the search for approaches to counteract the long-term PAS effects showed to be a current target. At the study herein, we evaluated the cardioprotective role of exercise training in rats submitted to PAS for 9 weeks. Methods and Results: Exercise resulted in improved physical fitness and systolic RV function. Exercise also blunted concentric cavity changes, diastolic dysfunction, and fibrosis induced by PAS. Exercise additional benefits were also reported in a pro-survival signal, in which there were increased Akt1 activity and normalized myocardial apoptosis. These findings were accompanied by microRNA-1 downregulation and microRNA-21 upregulation. Moreover, exercise was associated with a higher myocardial abundance of the sarcomeric protein α-MHC and proteins that modulate calcium handling—ryanodine receptor and Serca 2, supporting the potential role of exercise in improving myocardial performance. Conclusion: Our results represent the first demonstration that exercise can attenuate the RV remodeling in an experimental PAS. The cardioprotective effects were associated with positive modulation of RV function, survival signaling pathway, apoptosis, and proteins involved in the regulation of myocardial contractility. PMID:27994552

  14. Rheumatoid Arthritis is Associated with Left Ventricular Concentric Remodeling: Results of a Population-based Cross-sectional Study

    PubMed Central

    Myasoedova, Elena; Davis, John M.; Crowson, Cynthia S.; Roger, Véronique L.; Karon, Barry L.; Borgeson, Daniel D.; Therneau, Terry M.; Matteson, Eric L.; Rodeheffer, Richard J.; Gabriel, Sherine E.

    2014-01-01

    Objective To study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) who have no heart failure (HF) versus subjects without either RA or HF, and to determine the impact of RA on LV remodeling. Methods A cross-sectional, community-based study was conducted among adult (≥50 years) RA patients and age- and sex-matched non-RA subjects without a history of HF. All participants underwent a standard 2D/Doppler echocardiography. LV geometry was classified into four categories based on relative wall thickness and sex-specific cut-offs for LV mass index: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal geometry. Results The study included 200 RA patients and 600 matched non-RA subjects (mean age 65; 74% female in both cohorts). RA patients were significantly more likely to have abnormal LV geometry than non-RA subjects (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.03, 2.00), adjusting for cardiovascular risk factors and comorbidities. Among those with abnormal LV geometry, RA patients had significantly increased odds of concentric LV remodeling (OR 4.73; 95% CI 2.85, 7.83). In linear regression analyses, LV mass index appeared to be lower in RA patients currently using corticosteroids (Beta +/− standard error: −0.082 +/− 0.027; p=0.002), adjusting for cardiovascular risk factors and comorbidities. Conclusion RA was strongly associated with abnormal LV remodeling, particularly, with concentric LV remodeling, among patients without HF. This association was significant beyond adjustment for cardiovascular risk factors and comorbidities. RA disease related factors may promote changes in LV geometry. The biological mechanisms underlying LV remodeling warrant further investigation. PMID:23553738

  15. Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation.

    PubMed

    Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G; Stöhr, Eric J; Cotter, James D; Nio, Amanda Q X; Shave, Rob

    2014-08-01

    Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function.

  16. Asiatic acid inhibits left ventricular remodeling and improves cardiac function in a rat model of myocardial infarction

    PubMed Central

    HUO, LIANYING; SHI, WENBING; CHONG, LING; WANG, JINLONG; ZHANG, KAI; LI, YUFENG

    2016-01-01

    Left ventricular remodeling results in cardiac dysfunction and accounts for the majority of the morbidity and mortality following myocardial infarction (MI). The aim of the present study was to investigate the effect of asiatic acid (AA) on cardiac function and left ventricular remodeling in a rat model of MI and explore the underlying mechanisms. Rats were subjected to coronary artery ligation to model MI and orally treated with AA. After 4 weeks, cardiac function was assessed by echocardiography. Cardiomyocyte cross-sectional area was recorded, and the expression levels of a number of inflammatory cytokines were detected using ELISA. The degree of interstitial fibrosis was determined by evaluating the mRNA expression levels of collagen II and III. Western blot analysis was performed to detect the expression levels of total and phosphorylated p38 MAPK and ERK1/2, to investigate whether they are involved in the mechanism underlying the effect of AA on the heart. Rats subjected to MI displayed significantly impaired cardiac function compared with those subjected to a sham procedure, while this change was reversed by treatment with AA. Furthermore, AA markedly inhibited cardiac hypertrophy, reduced the mRNA expression levels of inflammatory cytokines and decreased interstitial fibrosis in the infarct border zone of MI model rats compared with those in vehicle-treated MI model rats. Furthermore, the phosphorylation of p38 MAPK and ERK1/2 was blocked by AA in the MI rats but not in the sham rats. In summary, AA treatment preserved cardiac function and inhibited left ventricular remodeling, potentially by blocking the phosphorylation of p38 MAPK and ERK1/2 in the infarct border zone of the ischemic myocardium, indicating that AA may be a novel candidate for development as a therapy for MI. PMID:26889217

  17. Comparison of Macitentan and Bosentan on Right Ventricular Remodeling in a Rat Model of Non-vasoreactive Pulmonary Hypertension

    PubMed Central

    Landskroner, Kyle; Bauer, Yasmina; Vercauteren, Magali; Rey, Markus; Renault, Berengère; Studer, Rolf; Vezzali, Enrico; Freti, Diego; Hadana, Hakim; Schläpfer, Manuela; Cattaneo, Christophe; Bortolamiol, Céline; Weber, Edgar; Whitby, Brian R.; Delahaye, Stéphane; Wanner, Daniel; Steiner, Pauline; Nayler, Oliver; Hess, Patrick; Clozel, Martine

    2015-01-01

    Aims: We compared the efficacy of macitentan, a novel dual endothelin A/endothelin B receptor antagonist, with that of another dual endothelin receptor antagonist, bosentan, in a rat model of non-vasoreactive pulmonary hypertension (PH) with particular emphasis on right ventricular (RV) remodeling. Methods and Results: Unlike monocrotaline or hypoxic/sugen rats, bleomycin-treated rats presented a non-vasoreactive PH characterized by the absence of pulmonary dilatation to adenosine. We therefore chose the bleomycin rat model to compare the effects of the maximally effective doses of macitentan and bosentan on pulmonary vascular and RV remodeling. Macitentan (100 mg·kg−1·d−1), but not bosentan (300 mg·kg−1·d−1), significantly prevented pulmonary vascular remodeling, RV hypertrophy, and cardiomyocyte diameter increase. Cardiac protection by macitentan was associated with a significant attenuation of genes related to cell hypertrophy and extracellular matrix remodeling. Microautoradiography and high performance liquid chromatography analysis showed greater distribution of macitentan than bosentan in the RV and pulmonary tissue. Conclusions: Macitentan was more efficacious than bosentan in preventing the development of pulmonary and RV hypertrophies in a model of non-vasoreactive PH. Greater ability to distribute into the tissue could contribute to the greater structural improvement by macitentan compared with bosentan. PMID:26230396

  18. Combined biomarker testing for the prediction of left ventricular remodelling in ST-elevation myocardial infarction

    PubMed Central

    Reinstadler, Sebastian Johannes; Feistritzer, Hans-Josef; Reindl, Martin; Klug, Gert; Mayr, Agnes; Mair, Johannes; Jaschke, Werner; Metzler, Bernhard

    2016-01-01

    Objective The utility of different biomarkers for the prediction of left ventricular remodelling (LVR) following ST-elevation myocardial infarction (STEMI) has been evaluated in several studies. However, very few data exist on the prognostic value of combined biomarkers. The aim of this study was to comprehensively investigate the prognostic value for LVR of routinely available biomarkers measured after reperfused STEMI. Methods Serial measurements of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and high-sensitivity C reactive protein (hs-CRP) were performed in 123 patients with STEMI treated with primary percutaneous coronary intervention in this prospective observational study. Patients underwent cardiac MRI at 2 (1–4) and 125 (121–146) days after infarction. An increase in end-diastolic volume of ≥20% was defined as LVR. Results LVR occurred in 16 (13%) patients. Peak concentrations of the following biomarkers showed significant areas under the curves (AUCs) for the prediction of LVR—NT-proBNP: 0.68 (95% CI 0.59 to 0.76, p=0.03), hs-cTnT: 0.75 (95% CI 0.66 to 0.82, p<0.01), AST: 0.72 (95% CI 0.63 to 0.79, p<0.01), ALT: 0.66 (95% CI 0.57 to 0.75, p=0.03), LDH: 0.78 (95% CI 0.70 to 0.85, p<0.01) and hs-CRP: 0.63 (95% CI 0.54 to 0.72, p=0.05). The combination of all biomarkers yielded a significant increase in AUC to 0.85 (95% CI 0.77 to 0.91) (all vs NT-proBNP: p=0.02, all vs hs-cTnT: p=0.02, all vs AST: p<0.01, all vs ALT: p<0.01, all vs hs-CRP: p<0.01 and all vs LDH: p=0.04). Conclusions In patients with reperfused STEMI, the combined assessment of peak NT-proBNP, hs-cTnT, AST, ALT, hs-CRP and LDH provide incremental prognostic information for the prediction of LVR when compared with single-biomarker measurement. PMID:27738517

  19. Surgical Ventricular Restoration: An Operation to Reverse Remodeling - Clinical Application (Part II)

    PubMed Central

    Shanmugam, Ganesh; Ali, Imtiaz S.

    2009-01-01

    The first part of the article dealt with the basic science behind the evolution of ventricular restoration procedures and the rationale for the use of novel surgical techniques. The second part describes the preoperative workup of patients in advanced heart failure, the core information required to determine the surgical approach and the essential principles and techniques of ventricular restoration. It then examines the effects of ventricular restorative procedures on pump function and clinical outcomes, the results of the worldwide experience with ventricular restoration and concludes with more recent advances in this field. PMID:21037852

  20. Left Ventricular Remodeling and Function in Children with Biventricular Circulation After Fetal Aortic Valvuloplasty.

    PubMed

    Friedman, Kevin G; Freud, Lindsay; Escobar-Diaz, Maria; Banka, Puja; Emani, Sitaram; Tworetzky, Wayne

    2015-10-01

    Fetal aortic valvuloplasty (FAV) has shown promise in averting the progression of fetal aortic stenosis to hypoplastic left-heart syndrome. Altered loading conditions due to valvar disease, intrinsic endomyocardial abnormalities, and procedures that alter endomyocardial mechanics may place patients with biventricular circulation (BiV) after FAV at risk of abnormal LV remodeling and function. Using the most recent echo data on BiV patients after technically successful FAV (n = 34), we evaluated LV remodeling pattern, risk factors for pathologic LV remodeling, and the association between LV remodeling pattern and LV function. Median age at follow-up was 4.7 years (range 1.0-12.5). Cardiac interventions were common. At latest follow-up, no patient had hypoplastic LV. Nineteen patients (55 %) had dilated LV, and five (16 %) patients had severely dilated LV. LV remodeling patterns were as follows: 12 (35 %) normal ventricle, 11 (32 %) mixed hypertrophy, 8 (24 %) eccentric hypertrophy or remodeling, and 3 (9 %) concentric hypertrophy. Univariate factors associated with pathologic LV remodeling were long-standing AR, ≥2 cardiac interventions, EFE resection, and aortic or mitral regurgitation ≥ moderate at most recent follow-up. In multivariate analysis, only long-standing AR fraction remained associated with pathologic remodeling. Pathologic LV remodeling was associated with depressed ejection fraction, lower septal E´, and higher E/E´. Pathologic LV remodeling, primarily eccentric or mixed hypertrophy, is common in BiV patients after FAV and is related to LV loading conditions imposed by valvar disease. Pathologic remodeling is associated with both systolic and diastolic dysfunction in this population.

  1. Intramyocardial Delivery of Mesenchymal Stem Cell-Seeded Hydrogel Preserves Cardiac Function and Attenuates Ventricular Remodeling after Myocardial Infarction

    PubMed Central

    Mathieu, Eva; Lamirault, Guillaume; Toquet, Claire; Lhommet, Pierre; Rederstorff, Emilie; Sourice, Sophie; Biteau, Kevin; Hulin, Philippe; Forest, Virginie; Weiss, Pierre

    2012-01-01

    Background To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC) therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) hydrogel seeded with MSC (MSC+hydrogel) could preserve cardiac function and attenuate left ventricular (LV) remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI). Methodology/Principal Finding Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. Conclusion/Significance These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium. PMID:23284842

  2. Resveratrol Treatment Reduces Cardiac Progenitor Cell Dysfunction and Prevents Morpho-Functional Ventricular Remodeling in Type-1 Diabetic Rats

    PubMed Central

    Delucchi, Francesca; Berni, Roberta; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Sala, Roberto; Chaponnier, Christine; Gabbiani, Giulio; Calani, Luca; Rio, Daniele Del; Bocchi, Leonardo; Lagrasta, Costanza; Quaini, Federico; Stilli, Donatella

    2012-01-01

    Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n = 128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n = 54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n = 64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic “milieu” on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing

  3. Preventive Effect of Yuzu and Hesperidin on Left Ventricular Remodeling and Dysfunction in Rat Permanent Left Anterior Descending Coronary Artery Occlusion Model

    PubMed Central

    Yu, Hye Yon; Ahn, Ji Hun; Park, Se Won; Jung, Yi-Sook

    2015-01-01

    Left ventricular (LV) remodeling, which includes ventricular dilatation and increased interstitial fibrosis after myocardial infarction (MI), is the critical process underlying the progression to heart failure. Therefore, a novel approach for preventing LV remodeling after MI is highly desirable. Yuzu is a citrus plant originating in East Asia, and has a number of cardioprotective properties such as hesperidin. However, no study has proved whether yuzu can prevent LV remodeling. The aim of this study was to determine the effects of yuzu on heart failure (HF) and its potential impact on the LV remodeling process after MI. Our in vivo study using the permanent left anterior descending coronary artery (LAD) occlusion model demonstrate that one week pre-treatment with yuzu or its major metabolite hesperidin before LAD occlusion significantly attenuated cardiac dysfunction, myocyte apoptosis and inflammation. Not only yuzu but also hesperidin inhibited caspase-3 activity, myeloperoxidase expression, α-smooth muscle actin expression, and matrix metalloproteinase-2 activity in a permanent LAD occlusion rat model. To our knowledge, our findings provide the first evidence that yuzu and hesperidin prevent MI-induced ventricular dysfunction and structural remodeling of myocardium. PMID:25559243

  4. Preventive effect of yuzu and hesperidin on left ventricular remodeling and dysfunction in rat permanent left anterior descending coronary artery occlusion model.

    PubMed

    Yu, Hye Yon; Ahn, Ji Hun; Park, Se Won; Jung, Yi-Sook

    2015-01-01

    Left ventricular (LV) remodeling, which includes ventricular dilatation and increased interstitial fibrosis after myocardial infarction (MI), is the critical process underlying the progression to heart failure. Therefore, a novel approach for preventing LV remodeling after MI is highly desirable. Yuzu is a citrus plant originating in East Asia, and has a number of cardioprotective properties such as hesperidin. However, no study has proved whether yuzu can prevent LV remodeling. The aim of this study was to determine the effects of yuzu on heart failure (HF) and its potential impact on the LV remodeling process after MI. Our in vivo study using the permanent left anterior descending coronary artery (LAD) occlusion model demonstrate that one week pre-treatment with yuzu or its major metabolite hesperidin before LAD occlusion significantly attenuated cardiac dysfunction, myocyte apoptosis and inflammation. Not only yuzu but also hesperidin inhibited caspase-3 activity, myeloperoxidase expression, α-smooth muscle actin expression, and matrix metalloproteinase-2 activity in a permanent LAD occlusion rat model. To our knowledge, our findings provide the first evidence that yuzu and hesperidin prevent MI-induced ventricular dysfunction and structural remodeling of myocardium.

  5. Exploring susceptibility to atrial and ventricular arrhythmias resulting from remodeling of the passive electrical properties in the heart: a simulation approach

    PubMed Central

    Trayanova, Natalia A.; Boyle, Patrick M.; Arevalo, Hermenegild J.; Zahid, Sohail

    2014-01-01

    Under diseased conditions, remodeling of the cardiac tissue properties (“passive properties”) takes place; these are aspects of electrophysiological behavior that are not associated with active ion transport across cell membranes. Remodeling of the passive electrophysiological properties most often results from structural remodeling, such as gap junction down-regulation and lateralization, fibrotic growth infiltrating the myocardium, or the development of an infarct scar. Such structural remodeling renders atrial or ventricular tissue as a major substrate for arrhythmias. The current review focuses on these aspects of cardiac arrhythmogenesis. Due to the inherent complexity of cardiac arrhythmias, computer simulations have provided means to elucidate interactions pertinent to this spatial scale. Here we review the current state-of-the-art in modeling atrial and ventricular arrhythmogenesis as arising from the disease-induced changes in the passive tissue properties, as well as the contributions these modeling studies have made to our understanding of the mechanisms of arrhythmias in the heart. Because of the rapid advance of structural imaging methodologies in cardiac electrophysiology, we chose to present studies that have used such imaging methodologies to construct geometrically realistic models of cardiac tissue, or the organ itself, where the regional remodeling properties of the myocardium can be represented in a realistic way. We emphasize how the acquired knowledge can be used to pave the way for clinical applications of cardiac organ modeling under the conditions of structural remodeling. PMID:25429272

  6. Endocardial Remodeling in Heart Failure Patients with Impaired and Preserved Left Ventricular Systolic Function--A Magnetic Resonance Image Study.

    PubMed

    Lin, Lian-Yu; Su, Mao-Yuan M; Pham, Van-Truong; Tran, Thi-Thao; Wang, Yung-Hung; Tseng, Wen-Yih I; Lo, Men-Tzung; Lin, Jiunn-Lee

    2016-02-15

    Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function.

  7. MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction.

    PubMed

    Dorsey, Shauna M; McGarvey, Jeremy R; Wang, Hua; Nikou, Amir; Arama, Leron; Koomalsingh, Kevin J; Kondo, Norihiro; Gorman, Joseph H; Pilla, James J; Gorman, Robert C; Wenk, Jonathan F; Burdick, Jason A

    2015-11-01

    Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine magnetic resonance imaging (MRI) assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI.

  8. MRI Evaluation of Injectable Hyaluronic Acid-Based Hydrogel Therapy to Limit Ventricular Remodeling after Myocardial Infarction

    PubMed Central

    Dorsey, Shauna M.; McGarvey, Jeremy R.; Wang, Hua; Nikou, Amir; Arama, Leron; Koomalsingh, Kevin J.; Kondo, Norihiro; Gorman, Joseph H.; Pilla, James J.; Gorman, Robert C.; Wenk, Jonathan F.; Burdick, Jason A.

    2015-01-01

    Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine MRI assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI. PMID:26280951

  9. Value of three-dimensional strain parameters for predicting left ventricular remodeling after ST-elevation myocardial infarction.

    PubMed

    Xu, Lin; Huang, Xiaomin; Ma, Jun; Huang, Jiangming; Fan, Yongwang; Li, Huidi; Qiu, Jian; Zhang, Heye; Huang, Wenhua

    2017-02-01

    This study was to evaluate the value of multi-directional strain parameters derived from three-dimensional (3D) speckle tracking echocardiography (STE) for predicting left ventricular (LV) remodeling after ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) compared with that of two-dimensional (2D) global longitudinal strain (GLS). A total of 110 patients (mean age, 54 ± 9 years) after STEMI treated with primary PCI were enrolled in our study. At baseline (within 24 h after PCI), standard 2D echocardiography, 2D STE and 3D STE were performed to acquire the conventional echocardiographic parameters and strain parameters. At 3-month follow-up, standard 2D echocardiography was repeated to all the patients to determine LV remodeling, which was defined as a 20% increase in LV end-diastolic volume. At 3-month follow-up, LV remodeling occurred in 26 patients (24%). Compared with patients without LV remodeling, patients with remodeling had significantly reduced 2D GLS (-12.5 ± 3.2% vs -15.0 ± 3.1%, p < 0.001), 3D GLS (-9.9 ± 2.2% vs -13.1 ± 2.7%, p < 0.001), 3D global area strain (GAS) (-20.3 ± 3.9% vs -23.3 ± 4.8%, p = 0.005) and 3D global radial strain (GRS) (29.0 ± 7.4% vs 34.3 ± 8.5%, p = 0.007) at baseline, but there is no significant difference in 3D global circumferential strain (GCS) (-12.7 ± 2.9% vs -13.0 ± 3.2%, p = 0.822). Separated multivariate analysis shows that 2D GLS, 3D GLS, 3D GAS and 3D GRS all can be independent predictors of LV remodeling. However, receiver-operating characteristic curve analysis showed that the area under the curve of 3D GLS (0.82) for predicting LV remodeling was significantly higher than that of 2D GLS (0.72, p = 0.034), 3D GAS (0.68, p < 0.001) and 3D GRS (0.68, p < 0.001). In patients after STEMI, 2D GLS, 3D GLS, 3D GAS and 3D GRS but not 3D GCS measured after primary PCI are independent

  10. Effect of lithium on ventricular remodelling in infarcted rats via the Akt/mTOR signalling pathways.

    PubMed

    Lee, Tsung-Ming; Lin, Shinn-Zong; Chang, Nen-Chung

    2017-04-28

    Activation of phosphoinositide 3-kinase (PI3K)/Akt signalling is the molecular pathway driving physiological hypertrophy. As lithium, a PI3K agonist, is highly toxic at regular doses, we assessed the effect of lithium at a lower dose on ventricular hypertrophy after myocardial infarction (MI). Male Wistar rats after induction of MI were randomized to either vehicle or lithium (1 mmol/kg per day) for 4 weeks. The dose of lithium led to a mean serum level of 0.39 mM, substantially lower than the therapeutic concentrations (0.8-1.2 mM). Infarction in the vehicle was characterized by pathological hypertrophy in the remote zone; histologically, by increased cardiomyocyte sizes, interstitial fibrosis and left ventricular dilatation; functionally, by impaired cardiac contractility; and molecularly, by an increase of p-extracellular-signal-regulated kinase (ERK) levels, nuclear factor of activated T cells (NFAT) activity, GATA4 expression and foetal gene expressions. Lithium administration mitigated pathological remodelling. Furthermore, lithium caused increased phosphorylation of eukaryotic initiation factor 4E binding protein 1 (p-4E-BP1), the downstream target of mammalian target of rapamycin (mTOR). Blockade of the Akt and mTOR signalling pathway with deguelin and rapamycin resulted in markedly diminished levels of p-4E-BP1, but not ERK. The present study demonstrated that chronic lithium treatment at low doses mitigates pathological hypertrophy through an Akt/mTOR dependent pathway.

  11. Relation of the ischaemic substrate to left ventricular remodelling by cardiac magnetic resonance at 1.5 T in rabbits

    PubMed Central

    Mansencal, Nicolas; Tissier, Renaud; Deux, Jean-François; Ghaleh, Bijan; Couvreur, Nicolas; Rienzo, Mario; Guéret, Pascal; Rahmouni, Alain; Berdeaux, Alain; Garot, Jérôme

    2010-01-01

    Objectives Contrast-enhanced cardiac magnetic resonance (CMR) for infarct sizing has been validated in large animals, but studies and follow-up are restricted. We sought to 1) validate CMR for assessment of myocardial area at risk (MAR) and infarct size (IS) in a rabbit model of reperfused myocardial infarction (MI); 2) analyse the relation between ischaemic substrates and subsequent left ventricular (LV) remodelling. Methods Experimental reperfused acute MI was induced in 16 rabbits. Ten animals underwent cross-registered cine and contrast-enhanced CMR and histopathology at day 3 for assessment of MAR and IS (group#1). The remaining 6 rabbits had serial CMR for the study of LV remodelling (group#2). Results In group#1, mean IS was 12.7±6.4% and 12.7±6.9% of total LV myocardial mass on CMR (late-enhancement technique) and histopathology (P=0.52; r=0.93). No significant difference occurred between CMR and histopathology for the calculation of MAR and IS/MAR ratio (P=0.18 and P=0.17), whereas correlations were strong (r=0.92 and r=0.95). In group#2, mean LV end-diastolic, end-systolic volumes and LV mass were significantly increased at 3 weeks compared with measurements at day 3 (P<0.01). Significant correlations between initial IS and the increase in LV end-diastolic volume (r=0.66) and the increase in LV mass (r=0.48) were observed, as well as correlations between initial MAR and the increase in LV end-diastolic volume (r=0.70) and the increase in LV mass (r=0.37). Conclusions Comprehensive CMR provides accurate assessment of IS and MAR in reperfused rabbit MI. Infarct size is closely related to LV remodelling. Through the infarct size/MAR ratio, this approach has great potential for assessing interventions aimed at cardioprotection. PMID:19936756

  12. Low coronary driving pressure early in the course of myocardial infarction is associated with subendocardial remodelling and left ventricular dysfunction

    PubMed Central

    Koike, Marcia Kiyomi; De Carvalho Frimm, Clovis; Cúri, Mariana

    2007-01-01

    Subendocardial remodelling of the left ventricular (LV) non-infarcted myocardium has been poorly investigated. Previously, we have demonstrated that low coronary driving pressure (CDP) early postinfarction was associated with the subsequent development of remote subendocardial fibrosis. The present study aimed at examining the role of CDP in LV remodelling and function following infarction. Haemodynamics were performed in Wistar rats immediately after myocardial infarction (MI group) or sham surgery (SH group) and at days 1, 3, 7 and 28. Heart tissue sections were stained with HE, Sirius red and immunostained for α-actin. Two distinct LV regions remote to infarction were examined: subendocardium (SE) and interstitium (INT). Myocyte necrosis, leucocyte infiltration, myofibroblasts and collagen volume fraction were determined. Compared with SH, MI showed lower CDP and LV systolic and diastolic dysfunction. Necrosis was evident in SE at day 1. Inflammation and fibroplasia predominated in SE as far as day 7. Fibrosis was restricted to SE from day 3 on. Inflammation occurred in INT at days 1 and 3, but at a lower grade than in SE. CDP correlated inversely with SE necrosis (r = −0.65, P = 0.003, at day 1), inflammation (r = −0.76, P < 0.001, at day 1), fibroplasia (r = −0.47, P = 0.04, at day 7) and fibrosis (r = −0.83, P < 0.001, at day 28). Low CDP produced progressive LV expansion. Necrosis at day 1, inflammation at days 3 and 7, and fibroplasia at day 7 correlated inversely with LV function. CDP is a key factor to SE integrity and affects LV remodelling and function following infarction. PMID:17696909

  13. Early intervention with a potent endothelin-A/endothelin-B receptor antagonist aggravates left ventricular remodeling after myocardial infarction in rats.

    PubMed

    Oie, Erik; Yndestad, Arne; Robins, Simon P; Børnerheim, Reidar; Asberg, Anders; Attramadal, Håvard

    2002-05-01

    Intervention with selective endothelin (ET)A receptor antagonists within 24h after myocardial infarction (MI) in rats has been reported to aggravate left ventricular (LV) remodeling. In contrast, beneficial effects are reported when initiation of treatment is delayed 7 days or more after MI. However, bosentan, a mixed ET(A)/ET(B) receptor antagonist with low affinity for the ET receptors, has been shown to exert beneficial effects independent of the time point of initiation of treatment after MI. The aim of the present study was to investigate to what extent early intervention with a mixed ET(A)/ET(B) receptor antagonist with higher affinity at the ET receptors (SB 209670) would also exert beneficial effects on postinfarction LV remodeling. After ligation of the left coronary artery, rats were randomized to treatment with SB 209670 (6.25 mg x kg(-1) SC b.i.d., n = 10) or vehicle (n = 12) for 26 days, starting 48h after MI. Treatment with SB 209670 adversely affected the postinfarction remodeling process causing further dilatation of the LV (LV end-diastolic diameter: 10.4+/-0.5 vs 9.1+/-0.2 mm; LV end-systolic diameter: 8.5+/-0.4 vs 7.2+/-0.2 mm, P < 0.05). However, SB 209670 did not significantly affect infarct size, compensatory cardiac hypertrophy, nor the myocardial mRNA levels of procollagen type I and III, and prolyl 4-hydroxylase and lysyl oxidase, 2 important enzymes affecting collagen secretion, stability and functionality. In addition, SB 209670 had no significant effects on LV collagen cross-linking or extent of fibrosis. Thus, our data demonstrate that early intervention with a potent, mixed ET(A)/ET(B) receptor antagonist after MI may promote dilatation of the LV without significant alterations of infarct size and extracellular matrix composition. Our data support the notion that the timing of initiation of ET receptor antagonism after MI is critical and that potent ET receptor antagonists may be harmful during the first few days after MI.

  14. Tumor Necrosis Factor Receptor Associated Factor 2 Signaling Provokes Adverse Cardiac Remodeling in the Adult Mammalian Heart

    PubMed Central

    Divakaran, Vijay G.; Evans, Sarah; Topkara, Veli K.; Diwan, Abhinav; Burchfield, Jana; Gao, Feng; Dong, Jianwen; Tzeng, Huei-Ping; Sivasubramanian, Natarajan; Barger, Philip M.; Mann, Douglas L.

    2013-01-01

    Background Tumor necrosis factor (TNF) superfamily ligands that provoke a dilated cardiac phenotype signal through a common scaffolding protein termed TNF receptor associated factor 2 (TRAF2); however, virtually nothing is known with regard to TRAF2 signaling in the adult mammalian heart. Methods and Results We generated multiple founder lines of mice with cardiac restricted overexpression of TRAF2 and characterized the phenotype of mice with higher expression levels of TRAF2 (MHC-TRAF2HC). MHC-TRAF2HC transgenic mice developed a time-dependent increase in cardiac hypertrophy, LV dilation and adverse LV remodeling, and a significant decrease in LV +dP/dt and −dP/dt when compared to littermate (LM) controls (p < 0.05 compared to LM). During the early phases of LV remodeling there was a significant increase in total matrix metalloproteinase (MMP) activity that corresponded with a decrease in total myocardial fibrillar collagen content. As the MHC-TRAF2HC mice aged, there was a significant decrease in total MMP activity accompanied by an increase in total fibrillar collagen content and an increase in myocardial tissue inhibitor of metalloproteinase-1 levels. There was a significant increase in NF-κB activation at 4 – 12 weeks and JNK activation at 4 weeks in the MHCs TRAF2HC mice. Transciptional profiling revealed that > 95% of the hypertrophic/dilated cardiomyopathy-related genes that were significantly upregulated genes in the MHC-TRAF2HC hearts contained κB elements in their promoters. Conclusions These results show for the first time that targeted overexpression of TRAF2 is sufficient to mediate adverse cardiac remodeling in the heart. PMID:23493088

  15. Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2-mediated degradation of acetylated LKB1

    PubMed Central

    Bai, Bo; Man, Andy W.C.; Yang, Kangmin; Guo, Yumeng; Xu, Cheng; Tse, Hung-Fat; Han, Weiping; Bloksgaard, Maria; De Mey, Jo G.R.; Vanhoutte, Paul M.; Xu, Aimin; Wang, Yu

    2016-01-01

    Aims-SIRT1 exerts potent activity against cellular senescence and vascular ageing. By decreasing LKB1 protein levels, it promotes the survival and regeneration of endothelial cells. The present study aims to investigate the molecular mechanisms underlying SIRT1-mediated LKB1 degradation for the prevention of vascular ageing. Methods and Results-Co-immunoprecipitation assay demonstrated that SIRT1, via its amino-terminus, binds to the DOC domain of HERC2 [HECT and RLD domain containing E3 ubiquitin protein ligase 2], which then ubiquitinates LKB1 in the nuclear compartment of endothelial cells. Site-directed mutagenesis revealed that acetylation at lysine (K) 64 of LKB1 triggers the formation of SIRT1/HERC2/LKB1 protein complex and subsequent proteasomal degradation. In vitro cellular studies suggested that accumulation of acetylated LKB1 in the nucleus leads to endothelial activation, in turn stimulating the proliferation of vascular smooth muscle cells and the production of extracellular matrix proteins. Chromatin immunoprecipitation quantitative PCR confirmed that acetylated LKB1 interacts with and activates TGFβ1 promoter, which is inhibited by SIRT1. Knocking down either SIRT1 or HERC2 results in an increased association of LKB1 with the positive regulatory elements of TGFβ1 promoter. In mice without endothelial nitric oxide synthase, selective overexpression of human SIRT1 in endothelium prevents hypertension and age-related adverse arterial remodeling. Lentiviral-mediated knockdown of HERC2 abolishes the beneficial effects of endothelial SIRT1 on both arterial remodeling and arterial blood pressure control. Conclusion-By downregulating acetylated LKB1 protein via HERC2, SIRT1 fine-tunes the crosstalk between endothelial and vascular smooth muscle cells to prevent adverse arterial remodeling and maintain vascular homeostasis. PMID:27259994

  16. Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2-mediated degradation of acetylated LKB1.

    PubMed

    Bai, Bo; Man, Andy W C; Yang, Kangmin; Guo, Yumeng; Xu, Cheng; Tse, Hung-Fat; Han, Weiping; Bloksgaard, Maria; De Mey, Jo G R; Vanhoutte, Paul M; Xu, Aimin; Wang, Yu

    2016-06-28

    Aims-SIRT1 exerts potent activity against cellular senescence and vascular ageing. By decreasing LKB1 protein levels, it promotes the survival and regeneration of endothelial cells. The present study aims to investigate the molecular mechanisms underlying SIRT1-mediated LKB1 degradation for the prevention of vascular ageing.Methods and Results-Co-immunoprecipitation assay demonstrated that SIRT1, via its amino-terminus, binds to the DOC domain of HERC2 [HECT and RLD domain containing E3 ubiquitin protein ligase 2], which then ubiquitinates LKB1 in the nuclear compartment of endothelial cells. Site-directed mutagenesis revealed that acetylation at lysine (K) 64 of LKB1 triggers the formation of SIRT1/HERC2/LKB1 protein complex and subsequent proteasomal degradation. In vitro cellular studies suggested that accumulation of acetylated LKB1 in the nucleus leads to endothelial activation, in turn stimulating the proliferation of vascular smooth muscle cells and the production of extracellular matrix proteins. Chromatin immunoprecipitation quantitative PCR confirmed that acetylated LKB1 interacts with and activates TGFβ1 promoter, which is inhibited by SIRT1. Knocking down either SIRT1 or HERC2 results in an increased association of LKB1 with the positive regulatory elements of TGFβ1 promoter. In mice without endothelial nitric oxide synthase, selective overexpression of human SIRT1 in endothelium prevents hypertension and age-related adverse arterial remodeling. Lentiviral-mediated knockdown of HERC2 abolishes the beneficial effects of endothelial SIRT1 on both arterial remodeling and arterial blood pressure control.Conclusion-By downregulating acetylated LKB1 protein via HERC2, SIRT1 fine-tunes the crosstalk between endothelial and vascular smooth muscle cells to prevent adverse arterial remodeling and maintain vascular homeostasis.

  17. Antioxidant effects of hydrogen sulfide on left ventricular remodeling in smoking rats are mediated via PI3K/Akt-dependent activation of Nrf2.

    PubMed

    Zhou, Xiang; Zhao, Liangping; Mao, Jinning; Huang, Jian; Chen, Jianchang

    2015-03-01

    There is growing evidence that oxidative stress plays critical roles in the pathogenesis of cardiac remodeling. In the present study, we established a rat model of passive smoking and investigated the antioxidant effects of hydrogen sulfide (H2S) on smoking-induced left ventricular remodeling. Cardiac structure and function were evaluated using 2-dimensional echocardiography. Myocardial fibrosis was detected by Masson's trichrome staining and immunohistochemistry. Oxidative stress was assessed by measuring malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities, and reactive oxygen species generation in the myocardium. Neonatal rat cardiomyocytes transfected with specific siRNA and exposed to cigarette smoke condensate and H2S donor sodium hydrosulfide were used to confirm the involvement of Nrf2 and PI3K/Akt signaling in the antioxidant effects of H2S. Our results indicated that H2S could protect against left ventricular remodeling in smoking rats via attenuation of oxidative stress. Moreover, H2S was also found to increase the phosphorylation of Akt and GSK3β and decrease the nuclear expression of Fyn, which consequently leads to nuclear translocation of Nrf2 and elevated expression of HO-1 and NQO1. In conclusion, H2S may exert antioxidant effects on left ventricular remodeling in smoking rats via PI3K/Akt-dependent activation of Nrf2 signaling.

  18. Assessment of the Utility of the Septal E/(E′ × S′) Ratio and Tissue Doppler Index in Predicting Left Ventricular Remodeling after Acute Myocardial Infarction

    PubMed Central

    Kenar Tiryakioglu, Selma; Yalin, Kıvanc; Coskun, Senol

    2016-01-01

    Background. The aim of this study is to show whether the septal E/(E′ × S′) ratio assessed by tissue Doppler echocardiography can predict left ventricular remodeling after first ST segment elevation myocardial infarction treated successfully with primary percutaneous intervention. Methods. Consecutive patients (n = 111) presenting with acute anterior myocardial infarction for the first time in their life were enrolled. All patients underwent successful primary percutaneous coronary intervention. Standard and tissue Doppler echocardiography were performed in the first 24-36 hours of admission. Echocardiographic examination was repeated after 6 months to reassess left ventricular volumes. Septal E/(E′ × S′) ratio was assessed by pulsed Doppler echocardiography. Results. Group 1 consisted of 33 patients with left ventricular (LV) remodeling, and Group 2 had 78 patients without LV remodeling. E/(E′ × S′) was significantly higher in Group 1 (4.1 ± 1.9 versus 1.65 ± 1.32, p = 0.001). The optimal cutoff value for E/(E′ × S′) ratio was 2.34 with 87.0% sensitivity and 82.1% specificity. Conclusion. Septal E/(E′ × S′) values measured after the acute anterior myocardial infarction can strongly predict LV remodeling in the 6-month follow-up. In the risk assessment, the septal E/(E′ × S′) can be evaluated together with the conventional echocardiographic techniques. PMID:27703973

  19. Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions.

    PubMed

    Sedmera, D; Pexieder, T; Rychterova, V; Hu, N; Clark, E B

    1999-02-01

    Adult myocardium adapts to changing functional demands by hyper- or hypotrophy while the developing heart reacts by hyper- or hypoplasia. How embryonic myocardial architecture adjusts to experimentally altered loading is not known. We subjected the chick embryonic hearts to mechanically altered loading to study its influence upon ventricular myoarchitecture. Chick embryonic hearts were subjected to conotruncal banding (increased afterload model), or left atrial ligation or clipping, creating a combined model of increased preload in right ventricle and decreased preload in left ventricle. Modifications of myocardial architecture were studied by scanning electron microscopy and histology with morphometry. In the conotruncal banded group, there was a mild to moderate ventricular dilatation, thickening of the compact myocardium and trabeculae, and spiraling of trabecular course in the left ventricle. Right atrioventricular valve morphology was altered from normal muscular flap towards a bicuspid structure. Left atrial ligation or clipping resulted in hypoplasia of the left heart structures with compensatory overdevelopment on the right side. Hypoplastic left ventricle had decreased myocardial volume and showed accelerated trabecular compaction. Increased volume load in the right ventricle was compensated primarily by chamber dilatation with altered trabecular pattern, and by trabecular proliferation and thickening of the compact myocardium at the later stages. A ventricular septal defect was noted in all conotruncal banded, and 25% of left atrial ligated hearts. Increasing pressure load is a main stimulus for embryonic myocardial growth, while increased volume load is compensated primarily by dilatation. Adequate loading is important for normal cardiac morphogenesis and the development of typical myocardial patterns.

  20. Interleukin-1 Blockade With Anakinra to Prevent Adverse Cardiac Remodeling After Acute Myocardial Infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot Study)

    PubMed Central

    Abbate, Antonio; Kontos, Michael C.; Grizzard, John D.; Biondi-Zoccai, Giuseppe G. L.; Van Tassell, Benjamin W.; Robati, Roshanak; Roach, Lenore M.; Arena, Ross A.; Roberts, Charlotte S.; Varma, Amit; Gelwix, Christopher C.; Salloum, Fadi N.; Hastillo, Andrea; Dinarello, Charles A.; Vetrovec, George W.

    2013-01-01

    Acute myocardial infarction (AMI) initiates an intense inflammatory response in which interleukin-1 (IL-1) plays a central role. The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m2 median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a –3.2 ml/m2 median decrease (interquartile range –4.5, –1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m2. On echocardiography, the median difference in the LVESVi change was 13.4 ml/m2 (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m2, p = 0.033) and echocardiography (9.4 ml/m2, p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R =+0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI. PMID:23453459

  1. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study).

    PubMed

    Abbate, Antonio; Kontos, Michael C; Grizzard, John D; Biondi-Zoccai, Giuseppe G L; Van Tassell, Benjamin W; Robati, Roshanak; Roach, Lenore M; Arena, Ross A; Roberts, Charlotte S; Varma, Amit; Gelwix, Christopher C; Salloum, Fadi N; Hastillo, Andrea; Dinarello, Charles A; Vetrovec, George W

    2010-05-15

    Acute myocardial infarction (AMI) initiates an intense inflammatory response in which interleukin-1 (IL-1) plays a central role. The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m(2) median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a -3.2 ml/m(2) median decrease (interquartile range -4.5, -1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m(2). On echocardiography, the median difference in the LVESVi change was 13.4 ml/m(2) (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m(2), p = 0.033) and echocardiography (9.4 ml/m(2), p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R = +0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI.

  2. Ethnicity-related variations of left ventricular remodeling in adolescent amateur football players.

    PubMed

    Pelà, G; Li Calzi, M; Crocamo, A; Pattoneri, P; Goldoni, M; Anedda, A; Musiari, L; Biggi, A; Bonetti, A; Montanari, A

    2015-06-01

    Adult and adolescent elite black athletes display - as compared with their white counterparts - excessively increased left ventricle (LV) wall thickness (LVWT), mass (LVM), and relative wall thickness (RWT). To investigate such ethnicity-related differences in non-professional adolescent athletes, 138 male, amateur football players [age 14.0 ± 1.7 years, 42 West-African blacks (BA) and 96 Italian whites (WA)] underwent an echocardiographic study of LV diameters, LVWT, maximal wall thickness (MWT), LVM, and RWT as remodeling index. BA vs WA exhibited greater thickness of septum and posterior wall, higher MWT (10.3 ± 1.7 vs 8.8 ± 1.1 mm), and higher LVM (117 ± 27 vs 101 ± 20 g/m(2)) and RWT (0.44 ± 0.07 vs 0.35 ± 0.04). Age, systolic blood pressure, body mass index, and ethnicity predicted MWT and LVM, whereas ethnicity was the sole strong predictor of RWT. The greater MWT, LVWT, and LVM of 14-year-old, amateur-level BA vs WA indicates that ethnicity substantially affects LV structure in adolescent, non-professional athletes. In contrast with MWT and LVM, elevated RWT was predicted by black ethnicity only. We suggest that concentric-type LV remodeling is a peculiar LV phenotype in adolescent African athletes.

  3. Two-dimensional speckle-tracking echocardiography assessment of left ventricular remodeling in patients after myocardial infarction and primary reperfusion

    PubMed Central

    Haberka, Maciej; Tabor, Zbigniew; Finik, Maciej; Gąsior, Zbigniew

    2014-01-01

    Introduction Left ventricular remodeling (LVR) is the most prognostically important consequence of acute myocardial infarction (AMI). The aim of the study was to assess the value of speckle tracking echocardiography in the prediction of left ventricular remodeling in patients after AMI and primary coronary angioplasty (PCI). Material and methods Eighty-eight patients (F/M = 31/57 patients; 63.6 ±11 years old) with coronary artery disease (CAD) and successful PCI were enrolled and divided into group I with ST-elevation myocardial infarction or non-ST elevation myocardial infarction and group II with stable angina pectoris. Conventional and speckle tracking echocardiography was performed 3 days (baseline), 30 days and 90 days after PCI. Patients were divided into 2 groups based on the presence of LVR (increase of LV end-diastolic and/or end-systolic volume > 20%) at 3 months follow-up. Results At initial presentation, 2-chamber longitudinal strain (9.4 ±3.5% vs. –11.6 ±3.6%, p < 0.04) and 4-chamber transverse strain (10.4 ±8.2% vs. 15.6 ±8%, p < 0.003) were lower in the LVR+ group compared to the LVR– group. LV wall motion score index did not differ between the two groups. After 30 days, circumferential apical and basal strain (–15.58 ±8.9% vs. –25.53 ±8.8%, p < 0.001; –15.02 ±5.6 vs. –19.78 ±6.3, p < 0.008), radial apical strain (9.96 ±8.4% vs. 14.15 ±5.5%, p < 0.03), 4-chamber longitudinal strain (–8.7 ±5.8% vs. –13.47 ±3.9%, p < 0.005), 4-chamber transverse strain (10.5 ±8.1% vs. 16.7 ±8.3%, p < 0.03), apical rotation (3.84 ±2.5° vs, 5.66 ±3.2°, p < 0.04) and torsion (6.15 ±4.1° vs. 8.98 ±4.6°, p < 0.03) were significantly decreased in the LVR+ group compared to the LVR– group. According to ROC analysis, circumferential apical strain > –15.92% (sensitivity 93%, specificity 59%, positive predictive value 90%) was the most powerful predictor of remodeling after primary PCI in AMI. Conclusions Our results suggest that

  4. Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Shida, Takuya; Ohori, Takashi; Suzuki, Takayuki; Matsuki, Akira; Inoue, Hiroshi

    2011-08-01

    Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

  5. Hypertension-induced remodeling of cardiac excitation-contraction coupling in ventricular myocytes occurs prior to hypertrophy development.

    PubMed

    Chen-Izu, Ye; Chen, Ling; Bányász, Tamás; McCulle, Stacey L; Norton, Byron; Scharf, Steven M; Agarwal, Anuj; Patwardhan, Abhijit; Izu, Leighton T; Balke, C William

    2007-12-01

    Hypertension is a major risk factor for developing cardiac hypertrophy and heart failure. Previous studies show that hypertrophied and failing hearts display alterations in excitation-contraction (E-C) coupling. However, it is unclear whether remodeling of the E-C coupling system occurs before or after heart disease development. We hypothesized that hypertension might cause changes in the E-C coupling system that, in turn, induce hypertrophy. Here we tested this hypothesis by utilizing the progressive development of hypertensive heart disease in the spontaneously hypertensive rat (SHR) to identify a window period when SHR had just developed hypertension but had not yet developed hypertrophy. We found the following major changes in cardiac E-C coupling during this window period. 1) Using echocardiography and hemodynamics measurements, we found a decrease of left ventricular ejection fraction and cardiac output after the onset of hypertension. 2) Studies in isolated ventricular myocytes showed that myocardial contraction was also enhanced at the same time. 3) The action potential became prolonged. 4) The E-C coupling gain was increased. 5) The systolic Ca(2+) transient was augmented. These data show that profound changes in E-C coupling already occur at the onset of hypertension and precede hypertrophy development. Prolonged action potential and increased E-C coupling gain synergistically increase the Ca(2+) transient. Functionally, augmented Ca(2+) transient causes enhancement of myocardial contraction that can partially compensate for the greater workload to maintain cardiac output. The increased Ca(2+) signaling cascade as a molecular mechanism linking hypertension to cardiac hypertrophy development is also discussed.

  6. Short-Term Left Ventricular Remodeling After Revascularization in Subacute Total and Subtotal Occlusion With the Infarct-Related Left Anterior Descending Artery

    PubMed Central

    Celik, Ahmet; Kalay, Nihat; Korkmaz, Hasan; Dogdu, Orhan; Sahin, Omer; Elcik, Deniz; Karacavus, Seyhan; Dogan, Ali; Inanc, Tugrul; Ozdogru, Ibrahim; Oguzhan, Abdurrahman; Topsakal, Ramazan

    2011-01-01

    Background Large randomized studies revealed that percutaneous coronary intervention has no clinical benefit in patients with total occlusion. The purpose of this study is to evaluate left ventricular remodelling after PCI for total and subtotal infarct-related left anterior desending artery in stable patients who have not received trombolytic theraphy. Methods Sixty stable patients with subacute anterior myocardial infarction who have total or subtotal occlusion in the infarct-related left anterior descending artery were enrolled the study (20 patient in the total-medical group, 20 patient in the total-PCI group and 20 patient in the subtotal-PCI group). All patients’ left ventricular diameters, volumes and ejection fractions measured at admission and after a month. Results The necrotic segment number in scintigraphy were similar in three groups. In the total-PCI group, there were significant increases in left ventricular diastolic diameter, left ventricular end-diastolic volume and left ventricular end-systolic volume at first month. A borderline significant increase was observed in LVEDV in the total-medical group at first month. No significant difference was seen in all echocardiographic parameters in the subtotal-PCI group at a month after discharge. The percentage of increase in LVEDV was significantly higher and the percentage of increase in LVESV was borderline significantly higher in the total-PCI group than the other groups. Conclusions In stable patients, PCI for total occlusion in the subacute phase of anterior MI causes an increase in LV remodeling. Nevertheless PCI for subtotal occlusion in the subacute phase of anterior MI may prevent LV remodeling.

  7. A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

    PubMed Central

    Zhang, Xinlu; Wang, Xu; Hu, Feng; Zhou, Boda; Chen, Hai-Bin; Zha, Daogang; Liu, Yili; Guo, Yansong; Zheng, Lemin; Xiu, Jiancheng

    2016-01-01

    Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension. PMID:28008249

  8. A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats.

    PubMed

    Zhang, Xinlu; Wang, Xu; Hu, Feng; Zhou, Boda; Chen, Hai-Bin; Zha, Daogang; Liu, Yili; Guo, Yansong; Zheng, Lemin; Xiu, Jiancheng

    Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension.

  9. Targeting TRAF3IP2 by Genetic and Interventional Approaches Inhibits Ischemia/Reperfusion-induced Myocardial Injury and Adverse Remodeling.

    PubMed

    Erikson, John M; Valente, Anthony J; Mummidi, Srinivas; Kandikattu, Hemanth Kumar; DeMarco, Vincent G; Bender, Shawn B; Fay, William P; Siebenlist, Ulrich; Chandrasekar, Bysani

    2017-02-10

    Re-establishing blood supply is the primary goal for reducing myocardial injury in subjects with ischemic heart disease. Paradoxically, reperfusion results in nitroxidative stress and a marked inflammatory response in the heart. TRAF3IP2 (TRAF3 Interacting Protein 2; previously known as CIKS or Act1) is an oxidative stress-responsive cytoplasmic adapter molecule that is an upstream regulator of both IκB kinase (IKK) and c-Jun N-terminal kinase (JNK), and an important mediator of autoimmune and inflammatory responses. Here we investigated the role of TRAF3IP2 in ischemia/reperfusion (I/R)-induced nitroxidative stress, inflammation, myocardial dysfunction, injury, and adverse remodeling. Our data show that I/R up-regulates TRAF3IP2 expression in the heart, and its gene deletion, in a conditional cardiomyocyte-specific manner, significantly attenuates I/R-induced nitroxidative stress, IKK/NF-κB and JNK/AP-1 activation, inflammatory cytokine, chemokine, and adhesion molecule expression, immune cell infiltration, myocardial injury, and contractile dysfunction. Furthermore, Traf3ip2 gene deletion blunts adverse remodeling 12 weeks post-I/R, as evidenced by reduced hypertrophy, fibrosis, and contractile dysfunction. Supporting the genetic approach, an interventional approach using ultrasound-targeted microbubble destruction-mediated delivery of phosphorothioated TRAF3IP2 antisense oligonucleotides into the LV in a clinically relevant time frame significantly inhibits TRAF3IP2 expression and myocardial injury in wild type mice post-I/R. Furthermore, ameliorating myocardial damage by targeting TRAF3IP2 appears to be more effective to inhibiting its downstream signaling intermediates NF-κB and JNK. Therefore, TRAF3IP2 could be a potential therapeutic target in ischemic heart disease.

  10. Serial magnetic resonance imaging of global and regional left ventricular remodeling during 1 year after acute myocardial infarction.

    PubMed

    Schroeder, A P; Houlind, K; Pedersen, E M; Nielsen, T T; Egeblad, H

    2001-01-01

    Biplane long-axis cine MRI was performed in 51 patients 1, 13, 26, and 52 weeks after their first AMI. LV mass index (LVMI) was significantly increased 1 week after AMI (84.3 +/- 16.9 vs. 68.1 +/- 11.4 g/m(2) controls, n = 48, p < 0.001), presumably owing to edema of the infarcted myocardium. Six months after AMI, LVMI decreased to 76.5 +/- 16.4 g/m(2), but had again augmented after 1 year (81.8 +/- 17.3 g/m(2), p < 0.05), suggesting late, compensatory left ventricular hypertrophy. In patients treated with primary percutaneous transluminal coronary angioplasty, LVMI decreased 5% over 1 year, while LVMI increased 10% in patients receiving thrombolysis (p < 0.05). In the entire population, the global increase in LVMI 1 year after AMI seemed to reflect global cavity dilatation with unchanged thickness of the vital myocardium. In conclusion, in patients receiving contemporary treatment, LV remodeling only partially complied with the classical patho-anatomical concept.

  11. Effect of Exercise Training on Left Ventricular Remodeling in Diabetic Patients with Diastolic Dysfunction: Rationale and Design

    PubMed Central

    Asrar ul Haq, Muhammad; Wong, Chiew; Levinger, Itamar; Srivastava, Piyush M.; Sbaraglia, Melissa; Toia, Deidre; Jerums, George; Selig, Steve; Hare, David L.

    2014-01-01

    INTRODUCTION This study will examine the effects of combined aerobic and resistance training on left ventricular remodeling in diabetic patients with diastolic dysfunction. This is the first randomized controlled trial to look for effects of combined strength training and aerobic exercise on myocardial function as well as other clinical, functional, or psychological parameters in diabetic patients with isolated diastolic dysfunction, and will provide important insights into the potential management strategies for heart failure with preserved ejection fraction. METHODS AND ANALYSIS This is a prospective, randomized controlled investigator initiated single center trial. Diabetic patients with LV diastolic dysfunction suitable for exercise training intervention will be randomized to three months of a supervised combination of aerobic and strength training exercises, or supervised light stretching (control arm). Pre and post intervention assessment will include stress echocardiography, peak aerobic power with 12-lead ECG, dual-energy X-ray absorptiometry, muscle strength, the capacity to perform activities of daily living (ADLs), and questionnaires to assess self-perceived quality of life and symptoms of depression. The primary endpoint is to compare any change in tissue Doppler-derived LV systolic and early diastolic velocities. ETHICS AND DISSEMINATION The current trial protocol has been approved by the Human Research Ethics Committee of Austin Health and the University of Melbourne, Melbourne. The study will be performed in accordance with the Declaration of Helsinki. The investigator, regardless of the outcome, will publish the results of the study. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry: ACTRN12610000943044. PMID:24653649

  12. Evaluation of right ventricular remodeling using cardiac magnetic resonance imaging in co-existent chronic obstructive pulmonary disease and obstructive sleep apnea.

    PubMed

    Sharma, Bhavneesh; Neilan, Tomas G; Kwong, Raymond Y; Mandry, Damien; Owens, Robert L; McSharry, David; Bakker, Jessie P; Malhotra, Atul

    2013-02-01

    Untreated chronic obstructive pulmonary disease (COPD) co-existing with obstructive sleep apnea (OSA), also known as overlap syndrome, has higher cardiovascular mortality than COPD alone but its underlying mechanism remains unclear. We hypothesize that the presence of overlap syndrome is associated with more extensive right ventricular (RV) remodeling compared to patients with COPD alone. Adult COPD patients (GOLD stage 2 or higher) with at least 10 pack-years of smoking history were included. Overnight laboratory-based polysomnography was performed to test for OSA. Subjects with an apnea-hypopnea index (AHI) >10/h were classified as having overlap syndrome (n = 7), else classified as having COPD-only (n = 11). A cardiac MRI was performed to assess right and left cardiac chambers sizes, ventricular masses, and cine function. RV mass index (RVMI) was markedly higher in the overlap group than the COPD-only group (19 ± 6 versus 11 ± 6; p = 0.02). Overlap syndrome subjects had a reduced RV remodeling index (defined as the ratio between RVMI and RV end-diastolic volume index) compared to the COPD-only group (0.27 ± 0.06 versus 0.18 ± 0.08; p = 0.02). In the overlap syndrome subjects, the extent of RV remodeling was associated with severity of oxygen desaturation (R(2) = 0.65, p = 0.03). Our pilot results suggest that untreated overlap syndrome may cause more extensive RV remodeling than COPD alone.

  13. Effect of telmisartan and enalapril on ventricular remodeling and kidney prognosis of patients with coronary artery disease complicated with diabetic nephropathy

    PubMed Central

    Hou, Yuyan; Zhang, Fucheng; Liu, Zhiqiang; Su, Shuhong; Wu, Xiao; Wang, Zhifang

    2017-01-01

    The aim of the present study was to compare the value of telmisartan and enalapril on ventricular remodeling and kidney prognosis of patients with coronary artery disease complicated with diabetic nephropathy, and provide discussion on clinical reasonably chosen medicine. A total of 60 cases of coronary artery disease complicated with diabetic nephropathy were randomly divided for telmisartan (80 mg/day) treatment (n=32), enalapril (10 mg/day) treatment (n=28), while the rest of the therapy was kept the same. After 12 weeks, the clinical effects were compared between different groups. It was found that in comparison with enalapril group, the left ventricular ejection fraction of telmisartan group was significantly higher, and left ventricular end-diastolic diameter was significantly lower (P<0.05). The serum creatinine level and 24-h protein of telmisartan group were significantly lower than that for the enalapril group (P<0.05). In conclusion, the regular telmisartan treatment for patients with coronary artery disease complicated with diabetic nephropathy is better than enalapril on ventricular remodeling and kidney prognosis. PMID:28123481

  14. Comparison of the usefulness of Doppler-derived deceleration time versus plasma brain natriuretic peptide to predict left ventricular remodeling after mechanical revascularization in patients with ST-elevation acute myocardial infarction and left ventricular systolic dysfunction.

    PubMed

    Cerisano, Giampaolo; Pucci, Paolo Domenico; Valenti, Renato; Boddi, Vieri; Migliorini, Angela; Tommasi, Maria Silvia; Raspanti, Silvia; Parodi, Guido; Antoniucci, David

    2005-04-15

    The correlation between Doppler deceleration time (DT) and brain natriuretic peptide (BNP) and their predictive value for detecting left ventricular (LV) remodeling in patients who are treated with primary percutaneous intervention for infarction and LV dysfunction are unknown. Fifty-six patients (64 +/- 12 years of age; 11 women) who had a first ST-segment elevation myocardial infarction and systolic dysfunction that was successfully treated with direct primary coronary intervention underwent 2-dimensional Doppler echocardiographic and plasma BNP evaluation at days 1 and 3 and 1 and 6 months after the index infarction. Repeat coronary angiograms were obtained at 1 and 6 months. Because of previous consistent evidence, 3 days after the index infarction was the time point of comparison between BNP and DT values. Echocardiographic LV remodeling was defined as an increase in end-diastolic volume index above baseline values of 2 x SD. Ventricular remodeling occurred in 20 patients (36%). Multivariate analyses that included BNP level, Doppler DT, echocardiographic measurements of systolic function, peak creatine kinase, and anterior infarct location showed Doppler DT to be the only predictor of LV remodeling (odds ratio 0.963, 95% confidence interval 0.936 to 0.990, p = 0.008). The optimal cutoff for DT in the prediction of 6-month LV remodeling was <136 ms (sensitivity 75%, specificity 97%, accuracy 81%, area under receiver-operating characteristic curve 0.90). Thus, in patients who have a first ST-segment elevation myocardial infarction and LV systolic dysfunction that is successfully treated with primary percutaneous coronary intervention, Doppler-derived DT 3 days after index infarction is more effective than BNP level in detecting patients who are at higher risk for 6-month LV remodeling.

  15. Increased systolic load causes adverse remodeling of fetal aortic and mitral valves

    PubMed Central

    Louey, Samantha; Espinoza, Herbert; Chattergoon, Natasha; You, Fanglei; Thornburg, Kent L.; Giraud, George

    2015-01-01

    While abnormal hemodynamic forces alter fetal myocardial growth, little is known about whether such insults affect fetal cardiac valve development. We hypothesized that chronically elevated systolic load would detrimentally alter fetal valve growth. Chronically instrumented fetal sheep received either a continuous infusion of adult sheep plasma to increase fetal blood pressure, or a lactated Ringer's infusion as a volume control beginning on day 126 ± 4 of gestation. After 8 days, mean arterial pressure was higher in the plasma infusion group (63.0 mmHg vs. 41.8 mmHg, P < 0.05). Mitral annular septal-lateral diameter (11.9 mm vs. 9.1 mm, P < 0.05), anterior leaflet length (7.7 mm vs. 6.4 mm, P < 0.05), and posterior leaflet length (P2; 4.0 mm vs. 3.0 mm, P < 0.05) were greater in the elevated load group. mRNA levels of Notch-1, TGF-β2, Wnt-2b, BMP-1, and versican were suppressed in aortic and mitral valve leaflets; elastin and α1 type I collagen mRNA levels were suppressed in the aortic valves only. We conclude that sustained elevated arterial pressure load on the fetal heart valve leads to anatomic remodeling and, surprisingly, suppression of signaling and extracellular matrix genes that are important to valve development. These novel findings have important implications on the developmental origins of valve disease and may have long-term consequences on valve function and durability. PMID:26354842

  16. Posterior ventricular anchoring neochordal repair of degenerative mitral regurgitation efficiently remodels and repositions posterior leaflet prolapse†

    PubMed Central

    Woo, Y. Joseph; MacArthur, John W.

    2013-01-01

    OBJECTIVES Mitral valve repair techniques for degenerative disease typically entail leaflet resection or neochordal construction, which may require extensive resection, leaflet detachment/reattachment, reliance on diseased native chords or precise neochordal measuring. Occasionally, impaired leaflet mobility, reduced coaptation surface and systolic anterior motion (SAM) may result. We describe a novel technique for addressing posterior leaflet prolapse/flail, which both simplifies repair and addresses these issues. METHODS Fifty-four patients (age 62 ± 11 years) with degenerative MR underwent this new repair, 36 of whom minimally-invasively. A CV5 Gore-Tex suture was placed into the posterior left ventricular myocardium underneath the prolapsing segment as an anchor. This suture was then used to imbricate a portion of the prolapsed segment into the ventricle, creating a smooth, broad, non-prolapsed coapting surface on a leaflet with preserved mobility, additional neochordal support and posteriorly positioned enough to preclude SAM. RESULTS Repair was successful in all patients. The mean MR grade was reduced from +3.8 to +0.1 with 50 of 54 patients having zero MR and 4 of the 54 having trace or mild MR. All patients had proper antero-posterior location of the coaptation line of a mean length of 10.2 mm, and preserved posterior leaflet mobility. No patients had SAM or mitral stenosis. All patients were discharged and are currently doing well. CONCLUSION This new technique facilitated efficient single-suture repair of the prolapsed posterior leaflet mitral regurgitation without the need for resection or sliding annuloplasty. It precluded the need for precise neochordal measurement and preserved the leaflet coaptation surface. PMID:23449863

  17. Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

    PubMed Central

    Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.

    2015-01-01

    The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

  18. Left ventricular remodeling during and after 60 days of sedentary head-down bed rest.

    PubMed

    Westby, Christian M; Martin, David S; Lee, Stuart M C; Stenger, Michael B; Platts, Steven H

    2016-04-15

    Short periods of weightlessness are associated with reduced stroke volume and left ventricular (LV) mass that appear rapidly and are thought to be largely dependent on plasma volume. The magnitude of these cardiac adaptations are even greater after prolonged periods of simulated weightlessness, but the time course during and the recovery from bed rest has not been previously described. We collected serial measures of plasma volume (PV, carbon monoxide rebreathing) and LV structure and function [tissue Doppler imaging, three-dimensional (3-D) and 2-D echocardiography] before, during, and up to 2 wk after 60 days of 6° head down tilt bed rest (HDTBR) in seven healthy subjects (four men, three women). By 60 days of HDTBR, PV was markedly reduced (2.7 ± 0.3 vs. 2.3 ± 0.3 liters,P< 0.001). Resting measures of LV volume and mass were ∼15% (P< 0.001) and ∼14% lower (P< 0.001), respectively, compared with pre-HDTBR values. After 3 days of reambulation, both PV and LV volumes were not different than pre-HDTBR values. However, LV mass did not recover with normalization of PV and remained 12 ± 4% lower than pre-bed rest values (P< 0.001). As previously reported, decreased PV and LV volume precede and likely contribute to cardiac atrophy during prolonged LV unloading. Although PV and LV volume recover rapidly after HDTBR, there is no concomitant normalization of LV mass. These results demonstrate that reduced LV mass in response to prolonged simulated weightlessness is not a simple effect of tissue dehydration, but rather true LV muscle atrophy that persists well into recovery.

  19. Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy.

    PubMed

    Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J; Lipskaia, Larissa; Chemaly, Elie R

    2015-11-01

    The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy.

  20. Right ventricular arrhythmogenesis in failing human heart: the role of conduction and repolarization remodeling.

    PubMed

    Lou, Qing; Janks, Deborah L; Holzem, Katherine M; Lang, Di; Onal, Birce; Ambrosi, Christina M; Fedorov, Vadim V; Wang, I-Wen; Efimov, Igor R

    2012-12-15

    Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ∼6.3 × 6.3 cm(2) field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 ± 44 vs. 448 ± 39 ms, at BCL = 2,000 ms, P < 0.05). Dispersion of APD was increased in three failing hearts (161 ± 5 vs. 86 ± 19 ms, at BCL = 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 ± 11 vs. 98 ± 8 cm/s, at BCL = 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF.

  1. Right ventricular arrhythmogenesis in failing human heart: the role of conduction and repolarization remodeling

    PubMed Central

    Lou, Qing; Janks, Deborah L.; Holzem, Katherine M.; Lang, Di; Onal, Birce; Ambrosi, Christina M.; Fedorov, Vadim V.; Wang, I-Wen

    2012-01-01

    Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ∼6.3 × 6.3 cm2 field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 ± 44 vs. 448 ± 39 ms, at BCL = 2,000 ms, P < 0.05). Dispersion of APD was increased in three failing hearts (161 ± 5 vs. 86 ± 19 ms, at BCL = 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 ± 11 vs. 98 ± 8 cm/s, at BCL = 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF. PMID:23042951

  2. Hydrogen gas attenuates embryonic gene expression and prevents left ventricular remodeling induced by intermittent hypoxia in cardiomyopathic hamsters.

    PubMed

    Kato, Ryuji; Nomura, Atsuo; Sakamoto, Aiji; Yasuda, Yuki; Amatani, Koyuha; Nagai, Sayuri; Sen, Yoko; Ijiri, Yoshio; Okada, Yoshikatsu; Yamaguchi, Takehiro; Izumi, Yasukatsu; Yoshiyama, Minoru; Tanaka, Kazuhiko; Hayashi, Tetsuya

    2014-12-01

    The prevalence of sleep apnea is very high in patients with heart failure (HF). The aims of this study were to investigate the influence of intermittent hypoxia (IH) on the failing heart and to evaluate the antioxidant effect of hydrogen gas. Normal male Syrian hamsters (n = 22) and cardiomyopathic (CM) hamsters (n = 33) were exposed to IH (repeated cycles of 1.5 min of 5% oxygen and 5 min of 21% oxygen for 8 h during the daytime) or normoxia for 14 days. Hydrogen gas (3.05 vol/100 vol) was inhaled by some CM hamsters during hypoxia. IH increased the ratio of early diastolic mitral inflow velocity to mitral annulus velocity (E/e', 21.8 vs. 16.9) but did not affect the LV ejection fraction (EF) in normal Syrian hamsters. However, IH increased E/e' (29.4 vs. 21.5) and significantly decreased the EF (37.2 vs. 47.2%) in CM hamsters. IH also increased the cardiomyocyte cross-sectional area (672 vs. 443 μm(2)) and interstitial fibrosis (29.9 vs. 9.6%), along with elevation of oxidative stress and superoxide production in the left ventricular (LV) myocardium. Furthermore, IH significantly increased the expression of brain natriuretic peptide, β-myosin heavy chain, c-fos, and c-jun mRNA in CM hamsters. Hydrogen gas inhalation significantly decreased both oxidative stress and embryonic gene expression, thus preserving cardiac function in CM hamsters. In conclusion, IH accelerated LV remodeling in CM hamsters, at least partly by increasing oxidative stress in the failing heart. These findings might explain the poor prognosis of patients with HF and sleep apnea.

  3. Left ventricular remodelling, and systolic and diastolic function in young adults with β thalassaemia major: a Doppler echocardiographic assessment and correlation with haematological data

    PubMed Central

    Bosi, G; Crepaz, R; Gamberini, M R; Fortini, M; Scarcia, S; Bonsante, E; Pitscheider, W; Vaccari, M

    2003-01-01

    Objective: To evaluate left ventricular morphology and function in a large population of patients with β thalassaemia. Design: Echo Doppler assessment of left ventricular function and correlation of cardiovascular data with haematological data. Setting: Thalassaemia unit in a tertiary referral centre. Patients: 197 young adults with β thalassaemia, following an adequate transfusional and chelation treatment regimen, without clinical signs of cardiopulmonary involvement. The control group consisted of 213 healthy subjects. Results: Left ventricular volumes, mass index, and mass/volume ratio were increased. Diastolic and systolic shapes were different, the left ventricle maintaining an ellipsoidal shape. The ejection fraction was reduced, and was < 50% in 33 patients. Stroke volume and cardiac index were increased, and systemic vascular resistance was decreased. Fractional shortening and mean velocity of circumferential shortening were decreased. Meridional end systolic and peak systolic stress were increased, as was circumferential end systolic stress. The contractile state was reduced while the functional preload index did not differ. Left ventricular diastolic function, evaluated from the mitral inflow, showed a slightly prolonged isovolumic relaxation time, increased flow velocity integrals, and an increased E/A ratio. Among the haematological data, only serum ferritin showed a weak negative correlation with left ventricular ejection fraction. The patients with the highest serum ferritin (> 2500 ng/ml) had the lowest ejection fraction. Conclusions: Patients with β thalassaemia on an adequate transfusion and chelation treatment regimen show abnormal left ventricular remodelling with increased volumes, mass, and mass/volume ratio. Systolic chamber function and contractile state are reduced, with a slightly increased afterload. These findings seem mainly to be related to the increased cardiac output caused by chronic anaemia. Left ventricular performance is

  4. Ramipril attenuates left ventricular remodeling by regulating the expression of activin A-follistatin in a rat model of heart failure

    PubMed Central

    Wei, Qun; Liu, Haiyan; Liu, Miao; Yang, Chunyan; Yang, Jie; Liu, Zhonghui; Yang, Ping

    2016-01-01

    Prior studies have shown that overexpression of ACT A can lead to ventricular remodeling in rat models of heart failure. Furthermore, recently work studying demonstrated that stimulation of activin An expression in rat aortic smooth muscle (RASM) cells by angiotensin II (Ang II). Ramipril is a recently developed angiotensin converting enzyme (ACE) inhibitor. To investigate the effects of Ramipril on expression of ACT A-FS, we established the rat model of heart failure after myocardial infarction (MI), and divided into either a sham operation (SO), MI, or MI-Ramipril group. We found that Ramipril significantly attenuates collagen-I and III deposition (col-I and III). Notably, we determined that expression of ACT A and II activin receptor (ActRII) were significantly down-regulated in the non-infarcted area of the left ventricle in the Ramipril group, whereas the mRNA and protein levels of FS were markedly up-regulated. Our data suggested that Ramipril benefited left ventricular remodeling by reducing fibrosis and collagen accumulation in the left ventricle of rats after myocardial infarction. This observation was also associated with down-regulation of ACT A expression. This study elucidated a new protective mechanism of Ramipril and suggests a novel strategy for treatment of post-infarct remodeling and subsequent heart failure. PMID:27642098

  5. Prevention of AMI Induced Ventricular Remodeling: Inhibitory Effects of Heart-Protecting Musk Pill on IL-6 and TNF-Alpha

    PubMed Central

    Chen, Zhiliang; Hoppe, Ralph

    2017-01-01

    Heart-Protecting Musk Pill (HMP) is a Traditional Chinese Medicine (TCM) that has been used for the prevention and treatment of coronary heart disease in clinic. The current study investigated the effect of HMP on the concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and observed the relationship between level changes of inflammatory cytokines and ventricular remodeling in rats with acute myocardial infarction (AMI). Animal models of AMI were made by coronary artery ligation in Sprague-Dawley (SD) rats. AMI rats showed increased levels of IL-6 and TNF-α. Treatment with HMP decreases IL-6 and TNF-α concentrations in rats with AMI. Histopathological and transmission electron microscopic findings were also essentially in agreement with biochemical findings. The results of our study revealed that inflammatory cytokines IL-6 and TNF-α induce cardiac remodeling in rats after AMI; HMP improves cardiac function and ameliorates ventricular remodeling by downregulating the expression of IL-6 and TNF-α and further suppressing the ultrastructural changes of myocardial cells. PMID:28373886

  6. Involvement of Inflammation and Adverse Vascular Remodelling in the Blood Pressure Raising Effect of Repeatedly Heated Palm Oil in Rats

    PubMed Central

    Ng, Chun-Yi; Kamisah, Yusof; Faizah, Othman; Jubri, Zakiah; Qodriyah, Hj Mohd Saad; Jaarin, Kamsiah

    2012-01-01

    Oil thermoxidation during deep frying generates harmful oxidative free radicals that induce inflammation and increase the risk of hypertension. This study aimed to investigate the effect of repeatedly heated palm oil on blood pressure, aortic morphometry, and vascular cell adhesion molecule-1 (VCAM-1) expression in rats. Male Sprague-Dawley rats were divided into five groups: control, fresh palm oil (FPO), one-time-heated palm oil (1HPO), five-time-heated palm oil (5HPO), or ten-time-heated palm oil (10HPO). Feeding duration was six months. Blood pressure was measured at baseline and monthly using tail-cuff method. After six months, the rats were sacrificed and the aortic arches were dissected for morphometric and immunohistochemical analyses. FPO group showed significantly lower blood pressure than all other groups. Blood pressure was increased significantly in 5HPO and 10HPO groups. The aortae of 5HPO and 10HPO groups showed significantly increased thickness and area of intima-media, circumferential wall tension, and VCAM-1 than other groups. Elastic lamellae were disorganised and fragmented in 5HPO- and 10HPO-treated rats. VCAM-1 expression showed a significant positive correlation with blood pressure. In conclusion, prolonged consumption of repeatedly heated palm oil causes blood pressure elevation, adverse remodelling, and increased VCAM-1, which suggests a possible involvement of inflammation. PMID:22778962

  7. Impact of thermodilution-derived coronary blood flow patterns after percutaneous coronary intervention on mid-term left ventricular remodeling in patients with ST elevation myocardial infarction.

    PubMed

    Sumiyoshi, Akinori; Fujii, Kenichi; Fukunaga, Masashi; Shibuya, Masahiko; Imanaka, Takahiro; Kawai, Kenji; Miki, Kojiro; Tamaru, Hiroto; Horimatsu, Tetsuo; Saita, Ten; Nishimura, Machiko; Masuyama, Tohru; Ishihara, Masaharu

    2017-01-01

    We recently reported the coronary thermodilution curve can be evaluated by analyzing the thermodilution curve obtained from a pressure sensor/thermistor-tipped guidewire, and presence of a bimodal-shaped thermodilution curve following primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients was associated with worse outcomes. This study evaluated whether the bimodal-shaped thermodilution curve predicts left ventricular (LV) remodeling after STEMI. The coronary thermodilution curve patterns were evaluated for 75 patients treated by pPCI for their first STEMI using a pressure sensor/thermistor-tipped guidewire, and classified into the three groups according to the thermodilution curve shape: narrow unimodal (n = 39), wide unimodal (n = 26), and bimodal pattern (n = 10). Echocardiography was performed at baseline and 6 months after STEMI. LV remodeling was defined as a >20 % increase in LV end-diastolic volumes (LVEDV). LVEDV at 6-month follow-up was greater in the bimodal group than in the other groups (p < 0.001). The prevalence of LV remodeling was highest in the bimodal group than in the narrow and wide unimodal groups (60, 12, and 15 %, respectively; p = 0.003). Multivariate analysis revealed a bimodal-shaped thermodilution curve as an independent predictor of the prevalence of LV remodeling. A bimodal-shaped thermodilution curve is associated with LV remodeling after STEMI. This easily assessable coronary thermodilution curve pattern is useful to predict mid-term LV remodeling for STEMI patients at the catheterization laboratory.

  8. Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse RemodelingCLINICAL PERSPECTIVE

    SciTech Connect

    Kali, Avinash; Cokic, Ivan; Tang, Richard; Dohnalkova, Alice; Kovarik, Libor; Yang, Hsin-Jung; Kumar, Andreas; Prato, Frank S.; Wood, John C.; Underhill, David; Marbán, Eduardo; Dharmakumar, Rohan

    2016-11-01

    Emerging evidence now supports the notion that persistent microvascular obstruction (PMO) may be more predictive of major adverse cardiovascular events than MI size itself. But, how PMO, a phenomenon limited to the acute/sub-acute period of MI, imparts adverse remodeling throughout the post MI period, particularly after its resolution, is incompletely understood. We hypothesized that PMOs resolve into chronic iron crystals within MI territories and actively impart a proinflammatory burden and adverse remodeling of infarction and LV in the chronic phase of MI. Canine models reperfused (n=20) and non-reperfused (n=20) with and without PMO were studied with serial cardiac MRI to characterize the spatiotemporal relationships between PMO, iron deposition, and infarct and LV remodeling indices between acute (day 7, post MI) and chronic (week 8, post MI). Histopathology and immunohistochemistry were used to validate the iron deposition, microscopically map and quantify the relationship between iron-rich chronic MI regions against pro-inflammatory macrophages, proinflammatory cytokines and matrix metalloproteinase. Atomic resolution transmission electron microscopy (TEM) was used to determine the crystallinity of iron and assess the physical effects of iron on lysosomes within macrophages, and energy-dispersive X-ray spectroscopy (EDS) to identify the chemical composition of the iron composite. Results showed that PMOs lead to iron deposition within chronic MI and that the extent of chronic iron deposition is strongly related to PMO Volume (r>0.6, p<0.001). TEM and EDS analysis showed that iron within chronic MI is found within macrophages as aggregates of nanocrystals of ~2.5 nm diameter in ferric state. Correlative histological studies showed that iron content, proinflammatory burden and collagen degrading enzyme were highly correlated (r >0.7, p<0.001). Iron within chronic MI was significantly associated with infarct resorption (r>0.5, p<0.001) and adverse structural (r

  9. HCM-Linked Δ 160E Cardiac Troponin T Mutation Causes Unique Progressive Structural and Molecular Ventricular Remodeling in Transgenic Mice

    PubMed Central

    Moore, Rachel K.; Grinspan, Lauren Tal; Jimenez, Jesus; Guinto, Pia J.; Ertz-Berger, Briar; Tardiff, Jil C.

    2013-01-01

    Hypertrophic cardiomyopathy (HCM) is a primary disease of cardiac muscle, and one of the most common causes of sudden cardiac death (SCD) in young people. Many mutations in cardiac troponin T (cTnT) lead to a complex form of HCM with varying degrees of ventricular hypertrophy and ~65% of all cTnT mutations occur within or flanking the elongated N-terminal TNT1 domain. Biophysical studies have predicted that distal TNT1 mutations, including Δ160E, cause disease by a novel, yet unknown mechanism as compared to N-terminal mutations. To begin to address the specific effects of this commonly observed cTnT mutation we generated two independent transgenic mouse lines carrying variant doses of the mutant transgene. Hearts from the 30% and 70% cTnT Δ160E lines demonstrated a highly unique, dose-dependent disruption in cellular and sarcomeric architecture and a highly progressive pattern of ventricular remodeling. While adult ventricular myocytes isolated from Δ160E transgenic mice exhibited dosage-independent mechanical impairments, decreased sarcoplasmic reticulum calcium load and SERCA2a calcium uptake activity, the observed decreases in calcium transients were dosage-dependent. The latter findings were concordant with measures of calcium regulatory proteins abundance and phosphorylation state. Finally, studies of whole heart physiology in the isovolumic mode demonstrated dose-dependent differences in the degree of cardiac dysfuction. We conclude that the observed clinical severity of the cTnT Δ160E mutation is caused by a combination of direct sarcomeric disruption coupled to a profound disregulation of Ca2+ homeostasis at the cellular level that results in a unique and highly progressive pattern of ventricular remodeling. PMID:23434821

  10. Metformin and its effects on myocardial dimension and left ventricular hypertrophy in normotensive patients with coronary heart disease (the MET-REMODEL study): rationale and design of the MET-REMODEL study.

    PubMed

    Mohan, Mohapradeep; McSwiggan, Stephen; Baig, Fatima; Rutherford, Lynn; Lang, Chim C

    2015-02-01

    Left ventricular hypertrophy (LVH) is a common and independent risk factor for cardiovascular events in patients with coronary artery disease (CAD). Controlling blood pressure is the standard approach to the management of LVH, but this is only partially effective as LVH also persists in normotensive patients. Apart from blood pressure (BP), other main risk factors associated with LVH are insulin resistance (IR) and central obesity. The diabetic medication, Metformin, reduces IR and aids weight loss and may therefore regress LVH. The MET REMODEL study will investigate the ability of Metformin to regress LVH in 64 patients with CAD. The MET-REMODEL trial is a single-center, phase IV, double blind, randomized, placebo-controlled trial to investigate the efficacy of Metformin in regression of the independent cardiac risk factor of LVH in patients with CAD who are insulin resistant. A minimum of 64 adults with a history of CAD with LVH and IR will be randomized into two groups to receive, either Metformin XL or placebo. The primary endpoint of this trial is to investigate any change in left ventricular mass index. Secondary endpoints include changes to insulin resistance measured using fasting insulin resistance index (FIRI), obesity, LV size, and function and improvement in endothelial function. A positive result will assist clinicians to identify a new mechanism for LVH regression by administering Metformin XL. This may also lead to investigating the mortality benefit of Metformin in patients with CAD and LVH.

  11. Endothelial progenitor cells, microvascular obstruction, and left ventricular remodeling in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention.

    PubMed

    Porto, Italo; De Maria, Giovanni Luigi; Leone, Antonio Maria; Dato, Ilaria; D'Amario, Domenico; Burzotta, Francesco; Niccoli, Giampaolo; Trani, Carlo; Biasucci, Luigi Marzio; Bolognese, Leonardo; Crea, Filippo

    2013-09-15

    Endothelial progenitor cells (EPCs) are released from the bone marrow during cardiac ischemic events, potentially influencing vascular and myocardial repair. We assessed the clinical and angiographic correlates of EPC mobilization at the time of primary percutaneous coronary intervention in 78 patients with ST elevation myocardial infarction and the impact of both baseline and follow-up EPC levels on left ventricular (LV) remodeling. Blood samples were drawn from the aorta and the culprit coronary artery for cytofluorimetric EPC detection (CD34+CD45dimKDR+ cells, in percentage of cytofluorimetric counts). Area at risk was assessed by Bypass Angioplasty Revascularization Investigation myocardial jeopardy index, thrombotic burden as thrombus score and microvascular obstruction (MVO) as a combination of ST segment resolution and myocardial blush grade. Echocardiographic evaluation of LV remodeling was performed at 1-year follow-up in 54 patients, whereas peripheral EPC levels were reassessed in 40 patients. EPC levels during primary percutaneous coronary intervention were significantly higher in intracoronary than in aortic blood (0.043% vs 0.0006%, p <0.001). Both intracoronary and aortic EPC were related to area at risk extent, to intracoronary thrombus score (p <0.001), and inversely to MVO (p = 0.001). Peripheral EPC levels at 1-year follow-up were lower in patients with LV remodeling than in those without (0.001% [0.001 to 0.002] vs 0.003% [0.002 to 0.010]; p = 0.01) and independently predicted absence of remodeling at multivariate analysis. In conclusion, a rapid intracoronary EPC recruitment takes place in the early phases of ST elevation myocardial infarction, possibly reflecting an attempted reparative response. The extent of this mobilization seems to be correlated to the area at risk and to the amount of MVO. Persistently low levels of EPC are associated to LV remodeling.

  12. Relation of reduced preclinical left ventricular diastolic function and cardiac remodeling in overweight youth to insulin resistance and inflammation.

    PubMed

    Dahiya, Rachana; Shultz, Sarah P; Dahiya, Arun; Fu, Jinlin; Flatley, Christopher; Duncan, Danusia; Cardinal, John; Kostner, Karam M; Byrne, Nuala M; Hills, Andrew P; Harris, Mark; Conwell, Louise S; Leong, Gary M

    2015-05-01

    Insulin resistance (IR) and inflammation are associated with an increased risk of cardiovascular disease and may contribute to obesity cardiomyopathy. The earliest sign of obesity cardiomyopathy is impaired left ventricular (LV) diastolic function, which may be evident in obese children and adolescents. However, the precise metabolic basis of the impaired LV diastolic function remains unknown. The aims of this study were to evaluate cardiac structure and LV diastolic function by tissue Doppler imaging in overweight and obese (OW) youth and to assess the relative individual contributions of adiposity, IR, and inflammation to alterations in cardiac structure and function. We studied 35 OW (body mass index standard deviation score 2.0±0.8; non-IR n=19, IR n=16) and 34 non-OW youth (body mass index standard deviation score 0.1±0.7). LV diastolic function was reduced in OW youth compared with non-OW controls, as indicated by lower peak myocardial relaxation velocities (p<0.001) and greater filling pressures (p<0.001). OW youth also had greater LV mass index (p<0.001), left atrial volume index, and LV interventricular septal thickness (LV-IVS; both p=0.02). IR-OW youth had the highest LV filling pressures, LV-IVS, and relative wall thickness (all p<0.05). Homeostasis model of assessment-insulin resistance and C-reactive protein were negative determinants of peak myocardial relaxation velocity and positive predictors of filling pressure. Adiponectin was a negative determinant of LV-IVS, independent of obesity. In conclusion, OW youth with IR and inflammation are more likely to have adverse changes to cardiovascular structure and function which may predispose to premature cardiovascular disease in adulthood.

  13. Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Park, Jae-Hyeong; Park, Margaret M.; Farha, Samar; Sharp, Jacqueline; Lundgrin, Erika; Comhair, Suzy; Tang, Wai Hong; Erzurum, Serpil C.

    2015-01-01

    Background New 2-dimensional strain echocardiography enables quantification of right ventricular (RV) mechanics by assessing global longitudinal strain of RV (GLSRV) in patients with pulmonary arterial hypertension (PAH). However, the prognostic significance of impaired GLSRV is unclear in these patients. Methods Comprehensive echocardiography was performed in 51 consecutive PAH patients without atrial fibrillation (40 females, 48 ± 14 years old) with long-term follow-up. GLSRV was measured with off-line with velocity vector imaging (VVI, Siemens Medical System, Mountain View, CA, USA). Results GLSRV showed significant correlation with RV fractional area change (r = -0.606, p < 0.001), tricuspid annular plane systolic excursion (r = -0.579, p < 0.001), and RV Tei index (r = 0.590, p < 0.001). It showed significant correlations with pulmonary vascular resistance (r = 0.469, p = 0.001) and B-natriuretic peptide concentration (r = 0.351, p = 0.012). During a clinical followup time (45 ± 15 months), 20 patients experienced one or more adverse events (12 death, 2 lung transplantation, and 15 heart failure hospitalization). After multivariate analysis, age [hazard ratio (HR) = 2.343, p = 0.040] and GLSRV (HR = 2.122, p = 0.040) were associated with adverse clinical events. Age (HR = 3.200, p = 0.016) and GLSRV (HR = 2.090, p = 0.042) were also significant predictors of death. Impaired GLSRV (≥ -15.5%) was associated with lower event-free survival (HR = 4.906, p = 0.001) and increased mortality (HR = 8.842, p = 0.005). Conclusion GLSRV by VVI showed significant correlations with conventional echocardiographic parameters indicating RV systolic function. Lower GLSRV (≥ -15.5%) was significantly associated with presence of adverse clinical events and deaths in PAH patients. PMID:26140151

  14. Circulating long-non coding RNAs as biomarkers of left ventricular diastolic function and remodelling in patients with well-controlled type 2 diabetes.

    PubMed

    de Gonzalo-Calvo, D; Kenneweg, F; Bang, C; Toro, R; van der Meer, R W; Rijzewijk, L J; Smit, J W; Lamb, H J; Llorente-Cortes, V; Thum, T

    2016-11-22

    Contractile dysfunction is underdiagnosed in early stages of diabetic cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes. Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers were enrolled in the study. Left ventricular (LV) parameters were measured by magnetic resonance imaging. A panel of lncRNAs was quantified in serum by RT-qPCR. No differences in expression levels of lncRNAs were observed between type 2 diabetes patients and healthy volunteers. In patients with type 2 diabetes, long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) was inversely associated with diastolic function, measured as E/A peak flow (P < 0.050 for all linear models). LIPCAR was positively associated with grade I diastolic dysfunction (P < 0.050 for all logistic models). Myocardial infarction-associated transcript (MIAT) and smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA (SENCR) were directly associated with LV mass to LV end-diastolic volume ratio, a marker of cardiac remodelling (P < 0.050 for all linear models). These findings were validated in a sample of 30 patients with well-controlled type 2 diabetes. LncRNAs are independent predictors of diastolic function and remodelling in patients with type 2 diabetes.

  15. Circulating long-non coding RNAs as biomarkers of left ventricular diastolic function and remodelling in patients with well-controlled type 2 diabetes

    PubMed Central

    de Gonzalo-Calvo, D.; Kenneweg, F.; Bang, C.; Toro, R.; van der Meer, R. W.; Rijzewijk, L. J.; Smit, J. W.; Lamb, H. J.; Llorente-Cortes, V.; Thum, T.

    2016-01-01

    Contractile dysfunction is underdiagnosed in early stages of diabetic cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes. Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers were enrolled in the study. Left ventricular (LV) parameters were measured by magnetic resonance imaging. A panel of lncRNAs was quantified in serum by RT-qPCR. No differences in expression levels of lncRNAs were observed between type 2 diabetes patients and healthy volunteers. In patients with type 2 diabetes, long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) was inversely associated with diastolic function, measured as E/A peak flow (P < 0.050 for all linear models). LIPCAR was positively associated with grade I diastolic dysfunction (P < 0.050 for all logistic models). Myocardial infarction-associated transcript (MIAT) and smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA (SENCR) were directly associated with LV mass to LV end-diastolic volume ratio, a marker of cardiac remodelling (P < 0.050 for all linear models). These findings were validated in a sample of 30 patients with well-controlled type 2 diabetes. LncRNAs are independent predictors of diastolic function and remodelling in patients with type 2 diabetes. PMID:27874027

  16. Cardiac CaM Kinase II Genes δ and γ Contribute to Adverse Remodeling but Redundantly Inhibit Calcineurin-Induced Myocardial Hypertrophy

    PubMed Central

    Kreusser, Michael M.; Lehmann, Lorenz H.; Keranov, Stanislav; Hoting, Marc-Oscar; Oehl, Ulrike; Kohlhaas, Michael; Reil, Jan-Christian; Neumann, Kay; Schneider, Michael D.; Hill, Joseph A.; Dobrev, Dobromir; Maack, Christoph; Maier, Lars S.; Gröne, Hermann-Josef; Katus, Hugo A.; Olson, Eric N.; Backs, Johannes

    2014-01-01

    Background Ca2+-dependent signaling through CaM Kinase II (CaMKII) and calcineurin was suggested to contribute to adverse cardiac remodeling. However, the relative importance of CaMKII versus calcineurin for adverse cardiac remodeling remained unclear. Methods and Results We generated double-knockout mice (DKO) lacking the 2 cardiac CaMKII genes δ and γ specifically in cardiomyocytes. We show that both CaMKII isoforms contribute redundantly to phosphorylation not only of phospholamban, ryanodine receptor 2, and histone deacetylase 4, but also calcineurin. Under baseline conditions, DKO mice are viable and display neither abnormal Ca2+ handling nor functional and structural changes. On pathological pressure overload and β-adrenergic stimulation, DKO mice are protected against cardiac dysfunction and interstitial fibrosis. But surprisingly and paradoxically, DKO mice develop cardiac hypertrophy driven by excessive activation of endogenous calcineurin, which is associated with a lack of phosphorylation at the auto-inhibitory calcineurin A site Ser411. Likewise, calcineurin inhibition prevents cardiac hypertrophy in DKO. On exercise performance, DKO mice show an exaggeration of cardiac hypertrophy with increased expression of the calcineurin target gene RCAN1-4 but no signs of adverse cardiac remodeling. Conclusions We established a mouse model in which CaMKII’s activity is specifically and completely abolished. By the use of this model we show that CaMKII induces maladaptive cardiac remodeling while it inhibits calcineurin-dependent hypertrophy. These data suggest inhibition of CaMKII but not calcineurin as a promising approach to attenuate the progression of heart failure. PMID:25124496

  17. Incidence and Patterns of Adverse Event Onset During the First 60 Days After Ventricular Assist Device Implantation

    PubMed Central

    Genovese, Elizabeth A.; Dew, Mary Amanda; Teuteberg, Jeffrey J.; Simon, Marc A.; Kay, Joy; Siegenthaler, Michael P.; Bhama, Jay K.; Bermudez, Christian A.; Lockard, Kathleen L; Winowich, Steve; Kormos, Robert L.

    2009-01-01

    Background Although ventricular assist devices (VADs) provide effective treatment for end-stage heart failure, VAD support remains associated with significant risk for adverse events (AEs). To date there has been no detailed assessment of the incidence of a full range of AEs using standardized event definitions. We sought to characterize the frequency and timing of AE onset during the first 60 days of VAD support, a period during which clinical observation suggests the risk of incident AEs is high. Methods A retrospective analysis was performed utilizing prospectively collected data from a single-site clinical database including 195 patients aged ≥18 receiving VADs between 1996 and 2006. AEs were coded using standardized criteria. Cumulative incidence rates were determined, controlling for competing risks (death, transplantation, recovery/wean). Results During the first 60 days after implantation, the most common AEs were bleeding, infection, and arrhythmias (cumulative incidence rates, 36%–48%), followed by tamponade, respiratory events, reoperations, and neurologic events (24%–31%). Other events (e.g., hemolysis, renal, hepatic events) were less common (rates <15%). Some events (e.g., bleeding, arrhythmias) showed steep onset rates early after implantation. Others (e.g., infections, neurologic events) had gradual onsets during the 60-day period. Incidence of most events did not vary by implant era (1996–2000 vs. 2001–2006) or by left ventricular vs. biventricular support. Conclusions Understanding differential temporal patterns of AE onset will allow preventive strategies to be targeted to the time periods when specific AE risks are greatest. The AE incidence rates provide benchmarks against which future studies of VAD-related risks may be compared. PMID:19766801

  18. Association of a 4-tiered classification of left ventricular hypertrophy with adverse cardiovascular outcomes in the general population

    PubMed Central

    Garg, Sonia; de Lemos, James A.; Ayers, Colby; Khouri, Michel G.; Pandey, Ambarish; Berry, Jarett D.; Peshock, Ronald M.; Drazner, Mark H.

    2015-01-01

    Objectives This study was performed to determine whether a 4-tiered classification of left ventricular hypertrophy (LVH) defines subgroups in the general population which are at variable risk of adverse cardiovascular outcomes. Background We recently proposed a 4-tiered classification of LVH where eccentric LVH is subdivided into “indeterminate hypertrophy” and “dilated hypertrophy” and concentric LVH into “thick hypertrophy” and “both thick and dilated hypertrophy,” based on the presence of increased left ventricular end-diastolic volume. Methods Participants from the Dallas Heart study who underwent cardiac magnetic resonance imaging and did not have LV dysfunction or history of heart failure (HF) (n = 2,458) were followed for a median of 9 years for the primary outcome of HF or cardiovascular (CV) death. Multivariable Cox proportional hazard models were used to adjust for age, sex, African-American race, hypertension, diabetes, and history of cardiovascular disease (CVD). Results In the cohort, 70% had no LVH, 404 (16%) had indeterminate hypertrophy, 30 (1%) had dilated hypertrophy, 289 (12%) had thick hypertrophy, and 7 (0.2%) had both thick and dilated hypertrophy. The cumulative incidence of HF or CV death was 2% with no LVH, 1.7% with indeterminate, 16.7% with dilated, 11.1% with thick, and 42.9% with both thick and dilated hypertrophy (log rank p< 0.0001). Compared with participants without LVH, those with dilated (HR 7.3, 95% CI 2.8–18.8), thick (HR 2.4, 95% CI 1.4–4.0), and both thick and dilated (HR 5.8, 95% CI 1.7–19.5) hypertrophy remained at increased risk for HF or CV death after multivariable adjustment, whereas the group with indeterminate hypertrophy was not (HR 0.9, 95% CI 0.4–2.2). Conclusion In the general population, the 4-tiered classification system for LVH stratified LVH into subgroups with differential risk of adverse CV outcomes. Unstructured Abstract: Participants from the Dallas Heart Study were stratified using

  19. Increased Infarct Wall Thickness by a Bio-Inert Material Is Insufficient to Prevent Negative Left Ventricular Remodeling after Myocardial Infarction

    PubMed Central

    Rane, Aboli A.; Chuang, Joyce S.; Shah, Amul; Hu, Diane P.; Dalton, Nancy D.; Gu, Yusu; Peterson, Kirk L.; Omens, Jeffrey H.; Christman, Karen L.

    2011-01-01

    Background Several injectable materials have been shown to preserve or improve cardiac function as well as prevent or slow left ventricular (LV) remodeling post-myocardial infarction (MI). However, it is unclear as to whether it is the structural support or the bioactivity of these polymers that lead to beneficial effects. Herein, we examine how passive structural enhancement of the LV wall by an increase in wall thickness affects cardiac function post-MI using a bio-inert, non-degradable synthetic polymer in an effort to better understand the mechanisms by which injectable materials affect LV remodeling. Methods and Results Poly(ethylene glycol) (PEG) gels of storage modulus G′ = 0.5±0.1 kPa were injected and polymerized in situ one week after total occlusion of the left coronary artery in female Sprague Dawley rats. The animals were imaged using magnetic resonance imaging (MRI) at 7±1 day(s) post-MI as a baseline and again post-injection 49±4 days after MI. Infarct wall thickness was statistically increased in PEG gel injected vs. control animals (p<0.01). However, animals in the polymer and control groups showed decreases in cardiac function in terms of end diastolic volume, end systolic volume and ejection fraction compared to baseline (p<0.01). The cellular response to injection was also similar in both groups. Conclusion The results of this study demonstrate that passive structural reinforcement alone was insufficient to prevent post-MI remodeling, suggesting that bioactivity and/or cell infiltration due to degradation of injectable materials are likely playing a key role in the preservation of cardiac function, thus providing a deeper understanding of the influencing properties of biomaterials necessary to prevent post-MI negative remodeling. PMID:21731777

  20. Myocyte cellular hypertrophy and hyperplasia contribute to ventricular wall remodeling in anemia-induced cardiac hypertrophy in rats.

    PubMed Central

    Olivetti, G.; Quaini, F.; Lagrasta, C.; Ricci, R.; Tiberti, G.; Capasso, J. M.; Anversa, P.

    1992-01-01

    To determine the effects of chronic anemia on the functional and structural characteristics of the heart, 1-month-old male rats were fed a diet deficient in iron and copper, which led to a hemoglobin concentration of 4.63 g/dl, for 8 weeks. At sacrifice, under fentanyl citrate and droperidol anesthesia, systolic, diastolic, and mean arterial blood pressures were decreased, whereas differential pressure was increased. Left ventricular systolic pressure and the ventricular rate of pressure rise (mmHg/s) were reduced by 9% and 14%, respectively. Moreover, developed peak systolic ventricular pressure and maximal dP/dt diminished 14% and 12%. After perfusion fixation of the coronary vasculature and the myocardium, at a left ventricular intracavitary pressure equal to the in vivo measured end diastolic pressure, a 10% thickening of the left ventricular wall was measured in association with a 13% increase in the equatorial cavitary diameter and a 44% augmentation in ventricular mass. The 52% hypertrophy of the right ventricle was characterized by an 11% thicker wall and a 37% larger ventricular area. The 33% expansion in the aggregate myocyte volume of the left ventricle was found to be due to a 14% myocyte cellular hypertrophy and a 17% myocyte cellular hyperplasia. These cellular parameters were calculated from the estimation of the number of myocyte nuclei per unit volume of myocardium in situ and the evaluation of the distribution of nuclei per cell in enzymatically dissociated myocytes. Myocyte cellular hyperplasia provoked a 9% increase in the absolute number of cells across the left ventricular wall. In contrast, myocyte cellular hypertrophy (42%) was responsible for the increase in myocyte volume of the right ventricle. The proliferative response of left ventricular myocytes was not capable of restoring diastolic cell stress, which was enhanced by the changes in ventricular anatomy with anemia. In conclusion, chronic anemia induced an unbalanced load on the left

  1. Prognostic heterogeneity of diastolic abnormalities along left ventricular remodeling continuum according to survival rates and laser polarimetry of blood

    NASA Astrophysics Data System (ADS)

    Boychuk, T. M.; Ivashchuk, O. I.; Kolomoiets, M. Y.; Mikhaliev, K. O.; Chursina, T. Y.

    2011-09-01

    The results of examination of 35 arterial hypertension and coronary heart disease patients are presented. The clinical, paraclinical and echocardiographic examinations were performed, and the parameters of prognosis (survival) according to Seattle Heart Failure Model, as well as the optical (polarimetric) properties of erythrocytic suspension were determined. The group of patients under examination was stratified by patterns of remodeling of left ventricle (LV). It was determined that increasing of anisotropy of erythrocytic suspension along LV remodeling patterns continuum correlates with aggravation of structural and functional state of LV and is associated with unfavorable prognosis.

  2. Prognostic heterogeneity of diastolic abnormalities along left ventricular remodeling continuum according to survival rates and laser polarimetry of blood

    NASA Astrophysics Data System (ADS)

    Boychuk, T. M.; Ivashchuk, O. I.; Kolomoiets, M. Y.; Mikhaliev, K. O.; Chursina, T. Y.

    2012-01-01

    The results of examination of 35 arterial hypertension and coronary heart disease patients are presented. The clinical, paraclinical and echocardiographic examinations were performed, and the parameters of prognosis (survival) according to Seattle Heart Failure Model, as well as the optical (polarimetric) properties of erythrocytic suspension were determined. The group of patients under examination was stratified by patterns of remodeling of left ventricle (LV). It was determined that increasing of anisotropy of erythrocytic suspension along LV remodeling patterns continuum correlates with aggravation of structural and functional state of LV and is associated with unfavorable prognosis.

  3. Left Atrial Reverse Remodeling: Mechanisms, Evaluation, and Clinical Significance.

    PubMed

    Thomas, Liza; Abhayaratna, Walter P

    2017-01-01

    The left atrium is considered a biomarker for adverse cardiovascular outcomes, particularly in patients with left ventricular diastolic dysfunction and atrial fibrillation in whom left atrial (LA) enlargement is of prognostic importance. LA enlargement with a consequent decrease in LA function represents maladaptive structural and functional "remodeling" that in turn promotes electrical remodeling and a milieu conducive for incident atrial fibrillation. Medical and nonmedical interventions may arrest this pathophysiologic process to the extent that subsequent reverse remodeling results in a reduction in LA size and improvement in LA function. This review examines cellular and basic mechanisms involved in LA remodeling, evaluates the noninvasive techniques that can assess these changes, and examines potential mechanisms that may initiate reverse remodeling.

  4. 31P NMR 2D Mapping of Creatine Kinase Forward Flux Rate in Hearts with Postinfarction Left Ventricular Remodeling in Response to Cell Therapy

    PubMed Central

    Gao, Ling; Cui, Weina; Zhang, Pengyuan; Jang, Albert; Zhu, Wuqiang; Zhang, Jianyi

    2016-01-01

    Utilizing a fast 31P magnetic resonance spectroscopy (MRS) 2-dimensional chemical shift imaging (2D-CSI) method, this study examined the heterogeneity of creatine kinase (CK) forward flux rate of hearts with postinfarction left ventricular (LV) remodeling. Immunosuppressed Yorkshire pigs were assigned to 4 groups: 1) A sham-operated normal group (SHAM, n = 6); 2) A 60 minutes distal left anterior descending coronary artery ligation and reperfusion (MI, n = 6); 3) Open patch group; ligation injury plus open fibrin patch over the site of injury (Patch, n = 6); and 4) Cell group, hiPSCs-cardiomyocytes, -endothelial cells, and -smooth muscle cells (2 million, each) were injected into the injured myocardium pass through a fibrin patch (Cell+Patch, n = 5). At 4 weeks, the creatine phosphate (PCr)/ATP ratio, CK forward flux rate (Flux PCr→ATP), and k constant of CK forward flux rate (kPCr→ATP) were severely decreased at border zone myocardium (BZ) adjacent to MI. Cell treatment results in significantly increase of PCr/ATP ratio and improve the value of kPCr→ATP and Flux PCr→ATP in BZ myocardium. Moreover, the BZ myocardial CK total activity and protein expression of CK mitochondria isozyme and CK myocardial isozyme were significantly reduced, but recovered in response to cell treatment. Thus, cell therapy results in improvement of BZ bioenergetic abnormality in hearts with postinfarction LV remodeling, which is accompanied by significantly improvements in BZ CK activity and CK isozyme expression. The fast 2D 31P MR CSI mapping can reliably measure the heterogeneity of bioenergetics in hearts with post infarction LV remodeling. PMID:27606901

  5. Evaluation of Aortic Blood Flow and Wall Shear Stress in Aortic Stenosis and Its Association With Left Ventricular Remodeling

    PubMed Central

    von Knobelsdorff-Brenkenhoff, Florian; Karunaharamoorthy, Achudhan; Trauzeddel, Ralf Felix; Barker, Alex J; Blaszczyk, Edyta; Markl, Michael; Schulz-Menger, Jeanette

    2016-01-01

    Background Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. Study aim was to describe blood flow patterns in the ascending aorta of AS patients and determine their association with remodeling. Methods and Results Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age 63±13 years) and 37 healthy controls (age 60±10 years) underwent 4D-flow MRI. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress (WSSpeak) in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index (LVMI-I) and the ratio of LV mass to enddiastolic volume (relative wall mass; RWM). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and AS patients exhibited an asymmetric and elevated distribution of WSSpeak. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (p=0.0274), eccentricity (p=0.0070) and flow displacement (p=0.0021). Bicuspid aortic valve was associated with more intense helical (p=0.0098) and vortical flow formation (p=0.0536), higher flow displacement (p=0.11) and higher WSSpeak (p=0.0926). LVM-I and RWM were significantly associated with aortic orifice area (p=0.0611, p=0.0058) and flow displacement (p=0.0058, p=0.0283). Conclusions In this pilot study, AS leads to abnormal blood flow pattern and WSSpeak in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling. PMID:26917824

  6. Functional significance of the discordance between transcriptional profile and left ventricular structure/function during reverse remodeling

    PubMed Central

    Topkara, Veli K.; Chambers, Kari T.; Yang, Kai-Chien; Tzeng, Huei-Ping; Evans, Sarah; Weinheimer, Carla; Kovacs, Attila; Barger, Philip; Mann, Douglas L.

    2016-01-01

    To elucidate the mechanisms for reverse LV remodeling, we generated a conditional (doxycycline [dox] off) transgenic mouse tetracycline transactivating factor–TRAF2 (tTA-TRAF2) that develops a dilated heart failure (HF) phenotype upon expression of a proinflammatory transgene, TNF receptor–associated factor 2 (TRAF2), and complete normalization of LV structure and function when the transgene is suppressed. tTA-TRAF2 mice developed a significant increase in LV dimension with decreased contractile function, which was completely normalized in the tTA-TRAF2 mice fed dox for 4 weeks (tTA-TRAF2dox4W). Normalization of LV structure and function was accompanied by partial normalization (~60%) of gene expression associated with incident HF. Similar findings were observed in patients with dilated cardiomyopathy who underwent reverse LV remodeling following mechanical circulatory support. Persistence of the HF gene program was associated with an exaggerated hypertrophic response and increased mortality in tTA-TRAF2dox4W mice following transaortic constriction (TAC). These effects were no longer observed following TAC in tTA-TRAF2dox8W, wherein there was a more complete (88%) reversal of the incident HF genes. These results demonstrate that reverse LV remodeling is associated with improvements in cardiac myocyte biology; however, the persistence of the abnormal HF gene program may be maladaptive following perturbations in hemodynamic loading conditions. PMID:27158672

  7. New contribution to the study of ventricular remodeling and valve rings in dilated cardiomyopathy: anatomical and histological evaluation

    PubMed Central

    Dalva, Moise; Correia, Aristides Tadeu; Jatene, Natalia de Freitas; Saldiva, Paulo Hilário Nascimento; Jatene, Fabio Biscegli

    2014-01-01

    Introduction Idiopathic dilated cardiomyopathy causes great impact but many aspects of its pathophysiology remain unknown. Objective To evaluate anatomical and histological aspects of hearts with idiopathic dilated cardiomyopathy and compare them to a control group, evaluating the behavior of the perimeters of the atrioventricular rings and ventricles and to compare the percentage of collagen and elastic fibers of the atrioventricular rings. Methods Thirteen hearts with cardiomyopathy and 13 normal hearts were analysed. They were dissected keeping the ventricular mass and atrioventricular rings, with lamination of segments 20%, 50% and 80% of the distance between the atrioventricular groove and the ventricular apex. The sections were subjected to photo scanning, with measurement of perimeters. The atrioventricular rings were dissected and measured digitally to evaluate their perimeters, later being sent to the pathology laboratory, and stained by hematoxylin-eosin, picrosirius and oxidized resorcin fuccin. Results Regarding to ventricles, dilation occurs in all segments in the pathological group, and the right atrioventricular ring measurement was higher in idiopathic dilated cardiomyopathy group, with no difference in the left side. With respect to collagen, both sides had lower percentage of fibers in the pathological group. With respect to the elastic fibers, there was no difference between the groups. Conclusion There is a change in ventricular geometry in cardiomyopathy group. The left atrioventricular ring does not dilate, in spite of the fact that in both ventricles there is lowering of collagen. PMID:25714199

  8. Angiotensin-converting enzyme gene polymorphism, left ventricular remodeling, and exercise capacity in strength-trained athletes.

    PubMed

    Kasikcioglu, Erdem; Kayserilioglu, Abidin; Ciloglu, Figen; Akhan, Hulya; Oflaz, Huseyin; Yildiz, Safinaz; Peker, Ismail

    2004-11-01

    The mechanisms that regulate the development of human physiological cardiac hypertrophy remain poorly understood. The renin-angiotensin system, which is modulated by genetic polymorphism, plays an important role in the regulation of vascular tone and myocardial hypertrophy. Although a few studies have analyzed the association of angiotensin-converting enzyme (ACE) polymorphism and left ventricular (LV) hypertrophy in isotonic exercise-trained subjects who developed eccentric cardiac hypertrophy, there has been no research done in power athletes who developed concentric cardiac hypertrophy. We have hypothesized that ACE genotypic modulation characteristics may affect LV mass in power athletes. This study included 29 elite Caucasian wrestlers (mean age, 22.6 years) and 51 age-matched sedentary subjects. According to the absence or presence of the insertion segment in the polymerase chain reaction (PCR) product, the subjects were classified as homozygous deletion-deletion (DD), insertion-insertion (II), or heterozygous insertion-deletion (ID). The association of LV hypertrophy with ACE gene insertion/deletion (I/D) polymorphism was analyzed. Left ventricular mass and index were determined by echocardiography. Angiotensin-converting enzyme genotyping was performed on peripheral leukocytes using the polymerase chain reaction technique. The study and control group subjects were similar in height and weight. Left ventricular hypertrophy in the athletes was more apparent than in the controls. Angiotensin-converting enzyme genotype II frequency was 17.2% (5) in the athletes, 17.6% (9) in the controls; ID frequency was 51.7% (15) in the athletes, 56.8% (29) in the controls; and the DD frequency was 31% (9) in the athletes and 25.4% (13) in the controls. Left ventricular mass and mass index were found to be higher in genotype DD (126.2 +/- 2.9g/m2) than genotype II (85.5 +/- 4.0g/m2) or genotype ID (110.1 +/- 2.3g/m2) in the athletes (P < 0.001). Furthermore, maximal oxygen

  9. Time course of left ventricular reverse remodeling in response to pharmacotherapy: clinical implication for heart failure prognosis in patients with idiopathic dilated cardiomyopathy.

    PubMed

    Ikeda, Yuki; Inomata, Takayuki; Iida, Yuichiro; Iwamoto-Ishida, Miwa; Nabeta, Takeru; Ishii, Shunsuke; Sato, Takanori; Yanagisawa, Tomoyoshi; Mizutani, Tomohiro; Naruke, Takashi; Koitabashi, Toshimi; Takeuchi, Ichiro; Nishii, Mototsugu; Ako, Junya

    2016-04-01

    The present study aimed to identify the clinical significance of differences in detection timings of left ventricular reverse remodeling (LVRR) on heart failure (HF) prognosis in patients with idiopathic dilated cardiomyopathy (IDCM). We investigated 207 patients with IDCM who underwent pharmacotherapeutic treatment. LVRR was defined as improvements in both LV ejection fraction ≥10 % and indexed LV end-diastolic dimension (LVEDDi) ≥10 %. Patients were stratified into 3 groups by LVRR timing: patients with LVRR <24 months (Early LVRR), those with LVRR ≥24 months (Delayed LVRR), and those without LVRR during the entire follow-up period (No LVRR). The major endpoint was first detection of composite event including readmission for decompensated HF, major ventricular arrhythmias, or all-cause mortality. LVRR was recognized in 108 patients (52 %): Early LVRR in 83 (40 %), Delayed LVRR in 25 (12 %), and No LVRR in 99 (48 %). The survival rate for the major endpoint was significantly higher for Delayed LVRR than for No LVRR (P = 0.001); there was no significant difference between Early and Delayed LVRR. Among patients without LVRR <24 months (Delayed + No LVRR), receiver operating characteristic curve analysis showed that the area under the curve for improvement in LVEDDi during the first 6 months for predicting subsequent LVRR (Delayed LVRR) [0.822 (95 % confidence interval, 0.740-0.916; P = 0.038)] was greater than that for improvement in LVEF. In conclusion, LVRR was a favorable prognostic indicator in patients with IDCM irrespective of its detection timing. Reduced LVEDDi during the first 6 months was predictive for subsequent LVRR in the later phase.

  10. Integrative network analysis reveals time-dependent molecular events underlying left ventricular remodeling in post-myocardial infarction patients.

    PubMed

    Pinet, Florence; Cuvelliez, Marie; Kelder, Thomas; Amouyel, Philippe; Radonjic, Marijana; Bauters, Christophe

    2017-02-03

    To elucidate the time-resolved molecular events underlying the LV remodeling (LVR) process, we developed a large-scale network model that integrates the 24 molecular variables (plasma proteins and non-coding RNAs) collected in the REVE-2 study at four time points (baseline, 1month, 3months and 1year) after MI. The REVE-2 network model was built by extending the set of REVE-2 variables with their mechanistic context based on known molecular interactions (1310 nodes and 8639 edges). Changes in the molecular variables between the group of patients with high LVR (>20%) and low LVR (<20%) were used to identify active network modules within the clusters associated with progression of LVR, enabling assessment of time-resolved molecular changes. Although the majority of molecular changes occur at the baseline, two network modules specifically show an increasing number of active molecules throughout the post-MI follow up: one involved in muscle filament sliding, containing the major troponin forms and tropomyosin proteins, and the other associated with extracellular matrix disassembly, including matrix metalloproteinases, tissue inhibitors of metalloproteinases and laminin proteins. For the first time, integrative network analysis of molecular variables collected in REVE-2 patients with known molecular interactions allows insight into time-dependent mechanisms associated with LVR following MI, linking specific processes with LV structure alteration. In addition, the REVE-2 network model provides a shortlist of prioritized putative novel biomarker candidates for detection of LVR after MI event associated with a high risk of heart failure and is a valuable resource for further hypothesis generation.

  11. The Effects of Remodeling with Heart Failure on Mode of Initiation of Ventricular Fibrillation and its Spatiotemporal Organization

    PubMed Central

    Everett, Thomas H.; Hulley, George S.; Lee, Ken W.; Chang, Roger; Wilson, Emily E.; Olgin, Jeffrey E.

    2016-01-01

    Introduction The effect of the heart failure substrate on the initiation of ventricular fibrillation (VF), and its resulting mechanism is not known. The objective of this study was to determine the effects of substrate on VF initiation and its spatiotemporal organization in the heart failure model. Methods Optical action potentials were recorded from LV wedge preparations from either structurally normal hearts (control, n=11) or from congestive heart failure (CHF, n=7), at the epicardial surface, endocardial surface which included a papillary muscle, and a transmural cross section. Action potential duration (APD80) was determined, and VF was initiated. A fast Fourier-transform was calculated, and the dominant frequency (DF) was determined. Results The CHF group showed increased VF vulnerability (69% vs 26%, p<0.03), and every mapped surface showed an APD80 gradient which included islands of higher APDs on the transmural surface (M-cells) which was not observed in controls. VF in the CHF group was characterized by stable, discrete high DF areas that correlated to either foci or spiral waves located on the transmural surface at the site of the papillary muscle. Overall the top 10% of DFs correlated to an APD of 101 ms while the bottom 10% of DFs correlated to an APD of 126 ms (p<0.01). Conclusion In the CHF model, APD gradients correlated with an increased vulnerability to VF, and the highest stable DFs were located on the transmural surface which was not seen in Controls. This indicates that the CHF substrate creates unique APD and DF characteristics. PMID:26001644

  12. Predictive value of heart-type fatty acid-binding protein for left ventricular remodelling and clinical outcome of hypertensive patients with mild-to-moderate aortic valve diseases.

    PubMed

    Iida, M; Yamazaki, M; Honjo, H; Kodama, I; Kamiya, K

    2007-07-01

    Heart-type fatty acid-binding protein (H-FABP), a marker of acute myocardial infarction and a soluble cytosolic protein, may be released following left ventricular remodelling in cardiac overloaded hearts caused by hypertension, aortic regurgitation (AR) or aortic stenosis (AS). Our aim was to investigate if H-FABP levels are associated with left ventricular remodelling and clinical outcome in hypertensive patients with AR or AS. H-FABP and brain natriuretic peptide (BNP) were measured, glomerular filtration rate (GFR) was estimated using the modification of diet in renal disease (MDRD) equation, and left ventricular dimension at systole corrected for body surface area (LVDs/BSA) and relative wall thickness (RWT) were determined by echocardiography in hypertensive patients with mild-to-moderate AR (n=78), those with mild-to-moderate AS (n=73) and those without valvular heart diseases (HT) (n=50). H-FABP levels were significantly higher in AR (4.9+/-3 ng/ml) and in AS (4.5+/-3) than in HT (3.4+/-1) and BNP (65+/-73 pg/ml, 76+/-75, 35+/-22). H-FABP correlated with LVDs/BSA in AR (beta=0.23, P<0.05), and RWT in AS (beta=0.18, P<0.05) after adjustment for age, gender and all the other variables. AS and AR patients were prospectively followed up for cardiac events during 34+/-19 months. A multivariate Cox hazard analysis indicated H-FABP was an independent predictor of outcome both in AR (relative risk (RR)=7.61, 95% CI=2.39-25.3) and AS (RR=13.6, 95% CI=3.27-66.9). H-FABP, associated with left ventricular remodelling, is useful in predicting clinical outcome in hypertensive patients with mild-to-moderate aortic valve diseases.

  13. A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes.

    PubMed

    Wei, Hongguang; Jin, J-P

    2014-08-15

    We previously reported a point mutation substituting Cys for Arg(111) in the highly conserved troponin T (TnT)-contacting helix of cardiac troponin I (cTnI) in wild turkey hearts (Biesiadecki et al. J Biol Chem 279: 13825-13832, 2004). This dominantly negative TnI-TnT interface mutation decreases the binding affinity of cTnI for TnT, impairs diastolic function, and blunts the β-adrenergic response of cardiac muscle (Wei et al. J Biol Chem 285: 27806-27816, 2010). Here we further investigate cellular phenotypes of transgenic mouse cardiomyocytes expressing the equivalent mutation cTnI-K118C. Functional studies were performed on single adult cardiomyocytes after recovery in short-term culture from isolation stress. The amplitude of contraction and the velocities of shortening and relengthening were lower in cTnI-K118C cardiomyocytes than wild-type controls. The intracellular Ca(2+) transient was slower in cTnI-K118C cardiomyocytes than wild-type cells. cTnI-K118C cardiomyocytes also showed a weaker β-adrenergic response. The resting length of cTnI-K118C cardiomyocytes was significantly greater than that of age-matched wild-type cells, with no difference in cell width. The resting sarcomere was not longer, but slightly shorter, in cTnI-K118C cardiomyocytes than wild-type cells, indicating longitudinal addition of sarcomeres. More tri- and quadrinuclei cardiomyocytes were found in TnI-K118C than wild-type hearts, suggesting increased nuclear divisions. Whole-genome mRNA array and Western blots detected an increased expression of leukemia inhibitory factor receptor-β in the hearts of 2-mo-old cTnI-K118C mice, suggesting a signaling pathway responsible for the potent effect of cTnI-K118C mutation on early remodeling in cardiomyocytes.

  14. A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes

    PubMed Central

    Wei, Hongguang

    2014-01-01

    We previously reported a point mutation substituting Cys for Arg111 in the highly conserved troponin T (TnT)-contacting helix of cardiac troponin I (cTnI) in wild turkey hearts (Biesiadecki et al. J Biol Chem 279: 13825–13832, 2004). This dominantly negative TnI-TnT interface mutation decreases the binding affinity of cTnI for TnT, impairs diastolic function, and blunts the β-adrenergic response of cardiac muscle (Wei et al. J Biol Chem 285: 27806–27816, 2010). Here we further investigate cellular phenotypes of transgenic mouse cardiomyocytes expressing the equivalent mutation cTnI-K118C. Functional studies were performed on single adult cardiomyocytes after recovery in short-term culture from isolation stress. The amplitude of contraction and the velocities of shortening and relengthening were lower in cTnI-K118C cardiomyocytes than wild-type controls. The intracellular Ca2+ transient was slower in cTnI-K118C cardiomyocytes than wild-type cells. cTnI-K118C cardiomyocytes also showed a weaker β-adrenergic response. The resting length of cTnI-K118C cardiomyocytes was significantly greater than that of age-matched wild-type cells, with no difference in cell width. The resting sarcomere was not longer, but slightly shorter, in cTnI-K118C cardiomyocytes than wild-type cells, indicating longitudinal addition of sarcomeres. More tri- and quadrinuclei cardiomyocytes were found in TnI-K118C than wild-type hearts, suggesting increased nuclear divisions. Whole-genome mRNA array and Western blots detected an increased expression of leukemia inhibitory factor receptor-β in the hearts of 2-mo-old cTnI-K118C mice, suggesting a signaling pathway responsible for the potent effect of cTnI-K118C mutation on early remodeling in cardiomyocytes. PMID:24898585

  15. Quantitative Positron Emission Tomography Imaging Detects Early Metabolic Remodeling in a Mouse Model of Pressure Overload Left Ventricular Hypertrophy in vivo

    PubMed Central

    Zhong, Min; Alonso, Clayton E.; Taegtmeyer, Heinrich; Kundu, Bijoy K.

    2013-01-01

    We proposed that metabolic remodeling in the form of increased myocardial glucose analogue 2-[18F] fluoro-2deoxy-D-glucose (FDG) uptake precedes and triggers the onset of severe contractile dysfunction in pressure overload left ventricular hypertrophy (LVH) in vivo. To test this hypothesis we used a mouse model of transverse aortic constriction (TAC) together with Positron Emission Tomography (PET) and assessed serial changes in cardiac metabolism and function over 7 days. Methods PET scans of 16 C57BL/6 male mice were performed using a microPET scanner under sevofluorane anesthesia. A 10-minute transmission scan was followed by a 60-minute dynamic FDG-PET scan with cardiac and respiratory gating. Blood glucose levels were measured before and after the emission scan. Transverse aortic constriction (TAC) and sham surgeries were performed after baseline imaging. Osmotic mini-pumps containing either propranolol (5 mg/kg/day) or vehicle alone were implanted subcutaneously at the end of surgery. Subsequent scans were taken at days 1 and 7 after surgery. A compartment model, in which the blood input function with spill-over and partial volume corrections and the metabolic rate constants in a 3-compartment model are simultaneously estimated, was used to determine the net myocardial FDG influx constant, Ki. The rate of myocardial glucose use, rMGU, was also computed. Estimations of the ejection fractions (EF) were based on the high resolution gated PET images Results Mice undergoing TAC surgery exhibited an increase in the Ki (580%) and glucose usage the day after surgery indicating early adaptive response. On day 7 the EF had decreased by 24% indicating a maladaptive response. Average Ki increases were not linearly associated with increases in rMGU. Ki exceeded rMGU by 29% in the TAC mice. TAC Mice treated with propranolol attenuated rate of FDG uptake, diminished mismatch between Ki and rMGU (9%) and rescued cardiac function. Conclusions Metabolic maladaptation precedes

  16. Changes in ventricular remodelling and clinical status during the year following a single administration of stromal cell-derived factor-1 non-viral gene therapy in chronic ischaemic heart failure patients: the STOP-HF randomized Phase II trial

    PubMed Central

    Chung, Eugene S.; Miller, Leslie; Patel, Amit N.; Anderson, Russell David; Mendelsohn, Farrell O.; Traverse, Jay; Silver, Kevin H.; Shin, Julia; Ewald, Gregory; Farr, Mary Jane; Anwaruddin, Saif; Plat, Francis; Fisher, Scott J.; AuWerter, Alexander T.; Pastore, Joseph M.; Aras, Rahul; Penn, Marc S.

    2015-01-01

    Background Stromal cell-derived factor-1 (SDF-1) promotes tissue repair through mechanisms of cell survival, endogenous stem cell recruitment, and vasculogenesis. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure (STOP-HF) is a Phase II, double-blind, randomized, placebo-controlled trial to evaluate safety and efficacy of a single treatment of plasmid stromal cell-derived factor-1 (pSDF-1) delivered via endomyocardial injection to patients with ischaemic heart failure (IHF). Methods Ninety-three subjects with IHF on stable guideline-based medical therapy and left ventricular ejection fraction (LVEF) ≤40%, completed Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and 6-min walk distance (6 MWD), were randomized 1 : 1 : 1 to receive a single treatment of either a 15 or 30 mg dose of pSDF-1 or placebo via endomyocardial injections. Safety and efficacy parameters were assessed at 4 and 12 months after injection. Left ventricular functional and structural measures were assessed by contrast echocardiography and quantified by a blinded independent core laboratory. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure was powered based on change in 6 MWD and MLWHFQ at 4 months. Results Subject profiles at baseline were (mean ± SD): age 65 ± 9 years, LVEF 28 ± 7%, left ventricular end-systolic volume (LVESV) 167 ± 66 mL, N-terminal pro brain natriuretic peptide (BNP) (NTproBNP) 1120 ± 1084 pg/mL, MLWHFQ 50 ± 20 points, and 6 MWD 289 ± 99 m. Patients were 11 ± 9 years post most recent myocardial infarction. Study injections were delivered without serious adverse events in all subjects. Sixty-two patients received drug with no unanticipated serious product-related adverse events. The primary endpoint was a composite of change in 6 MWD and MLWHFQ from baseline to 4 months follow-up. The primary endpoint was not met (P = 0.89). For the patients treated with pSDF-1, there was a trend toward an

  17. Adipose-derived mesenchymal stem cells embedded in platelet-rich fibrin scaffolds promote angiogenesis, preserve heart function, and reduce left ventricular remodeling in rat acute myocardial infarction

    PubMed Central

    Chen, Yung-Lung; Sun, Cheuk-Kwan; Tsai, Tzu-Hsien; Chang, Li-Teh; Leu, Steve; Zhen, Yen-Yi; Sheu, Jiunn-Jye; Chua, Sarah; Yeh, Kuo-Ho; Lu, Hung-I; Chang, Hsueh-Wen; Lee, Fan-Yen; Yip, Hon-Kan

    2015-01-01

    Objective: This study tested the hypothesis that autologous adipose-derived mesenchymal stem cells (ADMSCs) embedded in platelet-rich fibrin (PRF) can significant promote myocardial regeneration and repair after acute myocardial infarction (AMI). Summary background: With avoiding the needle-related complications, PRF-embedded autologous ADMSCs graft provides a new effective stem cell-based therapeutic strategy for myocardial repair. Methods: Adult male Sprague-Dawley rats were equally divided (n = 8 per group) into group 1 (sham-operated), group 2 (AMI by ligating left coronary artery), group 3 (AMI+ PRF), and group 4 (AMI+PRF-embedded autologous ADMSCs). RPF with or without ADMSCs was patched on infarct area 1h after AMI induction. All animals were sacrificed on day 42 after echocardiography. Results: Left ventricular (LV) dimension and infarct/fibrotic areas were lowest in group 1, highest in group 2, in group 3 higher than in group 4, whereas LV performance and wall thickness exhibited a reversed pattern in all groups (all p < 0.001). Protein expressions of inflammatory (MMP-9, IL-1β), oxidative, apoptotic (Bax, cleaved PARP), fibrotic (Smad 3, TFG-β), hypertrophic (β-MHC), and heart failure (BNP) biomarkers displayed an identical pattern in infarct/fibrotic areas, whereas the protein expressions of anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), anti-fibrotic (Smad1/5, BMP-2) biomarkers and α-MHC showed an opposite pattern (all p < 0.01). Angiogenic activities (c-Kit+, Sca-1+, CD31+, SDF-1α+, CXCR4+ cells; protein expressions of SDF-1α, CXCR4, VEGF) were highest in group 4 and lowest in group 1 (all p < 0.001). Conclusion: ADMSCs embedded in PRF offered significant benefit in preserving LV function and limiting LV remodeling after AMI. PMID:26175843

  18. Low-level transcutaneous electrical stimulation of the auricular branch of vagus nerve ameliorates left ventricular remodeling and dysfunction by downregulation of matrix metalloproteinase 9 and transforming growth factor β1.

    PubMed

    Wang, Zhuo; Yu, Lilei; Huang, Bing; Wang, Songyun; Liao, Kai; Saren, Gaowa; Zhou, Xiaoya; Jiang, Hong

    2015-04-01

    Vagus nerve stimulation improves left ventricular (LV) remodeling by downregulation of matrix metalloproteinase 9 (MMP-9) and transforming growth factor β1 (TGF-β1). Our previous study found that low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve (LL-TS) could be substituted for vagus nerve stimulation to reverse cardiac remodeling. So, we hypothesize that LL-TS could ameliorate LV remodeling by regulation of MMP-9 and TGF-β1 after myocardial infarction (MI). Twenty-two beagle dogs were randomly divided into a control group (MI was induced by permanent ligation of the left coronary artery, n = 8), an LL-TS group (MI with long-term intermittent LL-TS, n = 8), and a normal group (sham ligation without stimulation, n = 6). At the end of 6 weeks follow-up, LL-TS significantly reduced LV end-systolic and end-diastolic dimensions, improved ejection fraction and ratio of early (E) to late (A) peak mitral inflow velocity. LL-TS attenuated interstitial fibrosis and collagen degradation in the noninfarcted myocardium compared with the control group. Elevated level of MMP-9 and TGF-β1 in LV tissue and peripheral plasma were diminished in the LL-TS treated dogs. LL-TS improves cardiac function and prevents cardiac remodeling in the late stages after MI by downregulation of MMP-9 and TGF-β1 expression.

  19. Estrogen attenuates chronic volume overload induced structural and functional remodeling in male rat hearts.

    PubMed

    Gardner, Jason D; Murray, David B; Voloshenyuk, Tetyana G; Brower, Gregory L; Bradley, Jessica M; Janicki, Joseph S

    2010-02-01

    We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload.

  20. Prognosis parameters and polarimetric properties of erythrocytes of the patients suffering from arterial hypertension and coronary heart disease at various patterns of left ventricular remodeling

    NASA Astrophysics Data System (ADS)

    Ivaschuk, Oleg I.; Kolomoiets, M. Y.; Mikhaliev, K. O.; Chursina, T. Ya.

    2012-01-01

    The results of examination of 35 arterial hypertension and coronary heart disease patients are presented. The clinical, paraclinical and echocardiographic examinations were performed, and the parameters of prognosis (survival) according to Seattle Heart Failure Model, as well as the optical (polarimetric) properties of erythrocytic suspension were determined. The group of patients under examination was stratified by patterns of remodeling of left ventricle (LV). It was determined that increasing of anisotropy of erythrocytic suspension along LV remodeling patterns continuum correlates with aggravation of structural and functional state of LV and is associated with unfavorable prognosis.

  1. Prognosis parameters and polarimetric properties of erythrocytes of the patients suffering from arterial hypertension and coronary heart disease at various patterns of left ventricular remodeling

    NASA Astrophysics Data System (ADS)

    Ivaschuk, Oleg I.; Kolomoiets, M. Y.; Mikhaliev, K. O.; Chursina, T. Ya.

    2011-09-01

    The results of examination of 35 arterial hypertension and coronary heart disease patients are presented. The clinical, paraclinical and echocardiographic examinations were performed, and the parameters of prognosis (survival) according to Seattle Heart Failure Model, as well as the optical (polarimetric) properties of erythrocytic suspension were determined. The group of patients under examination was stratified by patterns of remodeling of left ventricle (LV). It was determined that increasing of anisotropy of erythrocytic suspension along LV remodeling patterns continuum correlates with aggravation of structural and functional state of LV and is associated with unfavorable prognosis.

  2. Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial

    PubMed Central

    Tuñón, José; González-Hernández, Ignacio; Llanos-Jiménez, Lucía; Alonso-Martín, Joaquín; Escudier-Villa, Juan M; Tarín, Nieves; Cristóbal, Carmen; Sanz, Petra; Pello, Ana M; Aceña, Álvaro; Carda, Rocío; Orejas, Miguel; Tomás, Marta; Beltrán, Paula; Calero Rueda, Marta; Marcos, Esther; Serrano-Antolín, José María; Gutiérrez-Landaluce, Carlos; Jiménez, Rosa; Cabezudo, Jorge; Curcio, Alejandro; Peces-Barba, Germán; González-Parra, Emilio; Muñoz-Siscart, Raquel; González-Casaus, María Luisa; Lorenzo, Antonio; Huelmos, Ana; Goicolea, Javier; Ibáñez, Borja; Hernández, Gonzalo; Alonso-Pulpón, Luis M; Farré, Jerónimo; Lorenzo, Óscar; Mahíllo-Fernández, Ignacio; Egido, Jesús

    2016-01-01

    Introduction Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI. Methods and analysis The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144 patients with anterior STEMI will be assigned to receive calcifediol 0.266 mg capsules (Hidroferol SGC)/15 days or placebo on a 2:1 basis during 12 months. Primary objective: to evaluate the effect of calcifediol on LV remodelling defined as an increase in LV end-diastolic volume ≥10% (MRI). Secondary objectives: change in LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, diastolic function, sphericity index and size of fibrotic area; endothelial function; plasma levels of aminoterminal fragment of B-type natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone and phosphate). Differences in the effect of VD will be investigated according to the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be assessed. This is the first study to evaluate the effect of VD on cardiac remodelling in patients with STEMI. Ethics and dissemination This trial has been approved by the corresponding Institutional Review Board (IRB) and National Competent Authority (Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)). It will be conducted in accordance with good clinical practice (International Council for Harmonisation of

  3. [The role of multispiral computed tomography in assessment of viability of the myocardium and prognostication of left ventricular remodeling in patients with ST-elevation myocardial infarction].

    PubMed

    Veselova, T N; Merkulova, I N; Iarovaia, E B; Ternovoĭ, S K; Ruda, M Ia

    2013-01-01

    Aim of the study was to assess perfusion defect and viability of the myocardium by the method of multispiral computed tomography (MSCT) in patients with ST-elevation acute myocardial infarction (AMI) and to assess their prognostic role in development of remodeling of the left ventricle (LV). We included into the study 117 patients with AMI. MSCT with intravenous contrast enhancement was carried out on days 3-4 and at 12 months after AMI. In the arterial phase we estimated volume of myocardial perfusion defect, LV end diastolic and end systolic volumes (LVEDV and LVESV), and LV ejection fraction (EF). Three types of myocardial opacification were distinguished on tomograms in delayed phase of MSCT: type I - subendocardial residual defect (RD), type II - transmural RD, type III - transmural delayed hyper enhancement (DE). Patients were divided in 3 groups: (1) with subendocardial RD (n=63), (2) with transmural RD (n=28), (3) with transmural DE (n=26). Development of LV remodeling was registered if at repeat MSCT LVEDV increased more or equal 20% from baseline. In patients with signs of viable myocardium (group 1) volume of perfusion defect was substantially smaller than in patients with nonviable myocardium (groups 2 and 3): 1cm3 (0.4-2.4) vs. 7.3 cm3 (5.3-10.0) and 6.3 cm3 (5.0-15.0), respectively, p<0.001. Compared with groups 2 and 3 patients of group 1 more often were female (p=0.04), had inferior MI (p<0.001), and spontaneous reperfusion (p<0.001). After 12 months LV remodeling was registered in 19.3% of patients, all had signs of nonviable myocardium in more or equal 3 LV segments. In patients with perfusion defect more or equal 10 cm3 probability of development of LV remodeling exceeded 50%. Disturbances of perfusion abnormalities and number of nonviable LV segments were main predictors of LV remodeling.

  4. Bleeding and Infection With External Ventricular Drainage: A Systematic Review in Comparison to Adjudicated Adverse Events in the Ongoing CLEAR III Trial

    PubMed Central

    Dey, Mahua; Stadnik, Agnieszka; Riad, Fady; Zhang, Lingjiao; McBee, Nichol; Kase, Carlos; Carhuapoma, J. Ricardo; Ram, Malathi; Lane, Karen; Ostapkovich, Noeleen; Aldrich, Francois; Aldrich, Charlene; Jallo, Jack; Butcher, Ken; Snider, Ryan; Hanley, Daniel; Ziai, Wendy; Awad, Issam A.

    2014-01-01

    Background Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication. Objective We analyzed the rate of complications in the ongoing CLEAR III trial, providing a comparison with a systematic review of complications of EVD in the literature. Methods Cases were prospectively enrolled in the CLEAR III trial after placement of EVD for obstructive intraventricular hemorrhage (IVH) and randomized to receive recombinant tissue plasminogen activator (rt-PA) or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on CT scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled using STATA software. Results Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 cases enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced one or more new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis. Conclusion Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the current study, rates of new bleeds and bacterial meningitis/ventriculitis are very low, despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to > 60 trial sites. PMID:25635887

  5. Effects of a timely therapy with doxycycline on the left ventricular remodeling according to the pre-procedural TIMI flow grade in patients with ST-elevation acute myocardial infarction.

    PubMed

    Cerisano, Giampaolo; Buonamici, Piergiovanni; Valenti, Renato; Moschi, Guia; Taddeucci, Enrico; Giurlani, Letizia; Migliorini, Angela; Vergara, Ruben; Parodi, Guido; Sciagrà, Roberto; Romito, Roberta; Colonna, Paolo; Antoniucci, David

    2014-07-01

    Doxycycline has been demonstrated to reduced left ventricular (LV) remodeling, but its effect in patients with ST-elevation myocardial infarction (STEMI) and a baseline occluded [thrombolysis in myocardial infarction (TIMI) flow grade ≤1] infarct-related artery (IRA) is unknown. According to the baseline TIMI flow grade, 110 patients with a first STEMI were divided into 2 groups. Group 1: 77 patients with TIMI flow ≤1 (40 patients treated with doxycycline and 37 with standard therapy, respectively), and a Group 2: 33 patients with TIMI flow 2-3 (15 patients treated with doxycycline and 18 with standard therapy, respectively). The two randomized groups were well matched in baseline characteristics. A 2D-Echo was performed at baseline and at 6 months, together with a coronary angiography, for the remodeling and IRA patency assessment, respectively. The LV end-diastolic volume index (LVEDVi) decreased in Group 2 [-3 mL/m(2) (IQR: -12 to 4 mL/m(2))], and increased in Group 1 [6 mL/m(2) (IQR: -2 to 14 mL/m(2))], (p = 0.001). In Group 2, LVEDVi reduction was similar regardless of drug therapy, while in Group 1 the LVEDVi was smaller in patients treated with doxycycline as compared to control [3 mL/m(2) (IQR: -3 to 8 mL/m(2)) vs. 10 mL/m(2) (IQR: 1-27 mL/m(2)), p = 0.006]. A similar pattern was observed also for LV end-systolic volume and ejection fraction. In STEMI patients at higher risk, as those with a baseline TIMI flow grade ≤1, doxycycline reduces LV remodeling.

  6. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells.

    PubMed

    Zeng, Zhipeng; Yu, Kunwu; Chen, Long; Li, Weihua; Xiao, Hong; Huang, Zhengrong

    2016-01-01

    CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV) function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th) cells among the CD4+Foxp3- T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.

  7. [Enalapril reduces the degree of left ventricular remodeling after acute myocardial infarction and reduces the incidence of arrhythmia in ischemic disease].

    PubMed

    Altieri, P I; González, R; de Mello, W; Escobales, N

    1994-12-01

    The present study shows that enalapril prevents the excessive remodeling of the left ventricle after acute myocardial infarction. This randomized and double blind clinical study analysed 50 patients with an inferior myocardial infarction. The effect of enalapril was evaluated through cardiac volumes, ejection fraction, neurohormonal levels and incidence of the left ventricle disfunction after acute myocardial infarction. The patients treated with enalapril showed a significant reduction on the values of nor-epinefrine, angiotensine II, natriuretic hormone and vasopressine, four weeks after initiation of treatment. The ejection fraction and the level of the wall movement was more favourable, four weeks after infarction, in the group treated with enalapril. The incidence of congestive heart failure and arrhythmias was lower in the group treated with enalapril. So, we conclude that enalapril is a drug that prevents the excessive remodelling of the left ventricle after an acute myocardial infarction.

  8. Quantification of Coupled Stiffness and Fiber Orientation Remodeling in Hypertensive Rat Right-Ventricular Myocardium Using 3D Ultrasound Speckle Tracking with Biaxial Testing

    PubMed Central

    Park, Dae Woo; Sebastiani, Andrea; Yap, Choon Hwai; Simon, Marc A.; Kim, Kang

    2016-01-01

    Mechanical and structural changes of right ventricular (RV) in response to pulmonary hypertension (PH) are inadequately understood. While current standard biaxial testing provides information on the mechanical behavior of RV tissues using surface markers, it is unable to fully assess structural and mechanical properties across the full tissue thickness. In this study, the mechanical and structural properties of normotensive and pulmonary hypertension right ventricular (PHRV) myocardium through its full thickness were examined using mechanical testing combined with 3D ultrasound speckle tracking (3D-UST). RV pressure overload was induced in Sprague–Dawley rats by pulmonary artery (PA) banding. The second Piola–Kirchhoff stress tensors and Green-Lagrangian strain tensors were computed in the RV myocardium using the biaxial testing combined with 3D-UST. A previously established non-linear curve-fitting algorithm was applied to fit experimental data to a Strain Energy Function (SEF) for computation of myofiber orientation. The fiber orientations obtained by the biaxial testing with 3D-UST compared well with the fiber orientations computed from the histology. In addition, the re-orientation of myofiber in the right ventricular free wall (RVFW) along longitudinal direction (apex-to-outflow-tract direction) was noticeable in response to PH. For normotensive RVFW samples, the average fiber orientation angles obtained by 3D-UST with biaxial test spiraled from 20° at the endo-cardium to -42° at the epi-cardium (Δ = 62°). For PHRV samples, the average fiber orientation angles obtained by 3D-UST with biaxial test had much less spiral across tissue thickness: 3° at endo-cardium to -7° at epi-cardium (Δ = 10°, P<0.005 compared to normotensive). PMID:27780271

  9. Atlas-Based Ventricular Shape Analysis for Understanding Congenital Heart Disease.

    PubMed

    Farrar, Genevieve; Suinesiaputra, Avan; Gilbert, Kathleen; Perry, James C; Hegde, Sanjeet; Marsden, Alison; Young, Alistair A; Omens, Jeffrey H; McCulloch, Andrew D

    2016-12-01

    Congenital heart disease is associated with abnormal ventricular shape that can affect wall mechanics and may be predictive of long-term adverse outcomes. Atlas-based parametric shape analysis was used to analyze ventricular geometries of eight adolescent or adult single-ventricle CHD patients with tricuspid atresia and Fontans. These patients were compared with an "atlas" of non-congenital asymptomatic volunteers, resulting in a set of z-scores which quantify deviations from the control population distribution on a patient-by-patient basis. We examined the potential of these scores to: (1) quantify abnormalities of ventricular geometry in single ventricle physiologies relative to the normal population; (2) comprehensively quantify wall motion in CHD patients; and (3) identify possible relationships between ventricular shape and wall motion that may reflect underlying functional defects or remodeling in CHD patients. CHD ventricular geometries at end-diastole and end-systole were individually compared with statistical shape properties of an asymptomatic population from the Cardiac Atlas Project. Shape analysis-derived model properties, and myocardial wall motions between end-diastole and end-systole, were compared with physician observations of clinical functional parameters. Relationships between altered shape and altered function were evaluated via correlations between atlas-based shape and wall motion scores. Atlas-based shape analysis identified a diverse set of specific quantifiable abnormalities in ventricular geometry or myocardial wall motion in all subjects. Moreover, this initial cohort displayed significant relationships between specific shape abnormalities such as increased ventricular sphericity and functional defects in myocardial deformation, such as decreased long-axis wall motion. These findings suggest that atlas-based ventricular shape analysis may be a useful new tool in the management of patients with CHD who are at risk of impaired ventricular

  10. Association of left atrial reservoir function with left atrial structural remodeling related to left ventricular dysfunction in asymptomatic patients with hypertension: evaluation by two-dimensional speckle-tracking echocardiography.

    PubMed

    Miyoshi, Hirokazu; Oishi, Yoshifumi; Mizuguchi, Yukio; Iuchi, Arata; Nagase, Norio; Ara, Nusrat; Oki, Takashi

    2015-01-01

    Left atrial (LA) structural and functional abnormalities are vital steps on the pathway toward heart failure with preserved ejection fraction in asymptomatic patients. The purpose of this study was to assess the relationship of LA function, particularly reservoir function, with LA structural remodeling related to the left ventricular (LV) dysfunction in asymptomatic patients with hypertension (HT) using conventional, tissue Doppler, and 2-D speckle-tracking echocardiography. Fifty age-matched healthy individuals and 140 patients with HT, including 75 with LA volume index (LAVI)<29 ml/m2 (normal LA group) and 65 with LAVI≥29 ml/m2 (large LA group), were enrolled. We defined peak early diastolic transmitral flow velocity/peak early diastolic mitral annular motion velocity (E/e')/peak systolic LA strain (S-LAs) as LA diastolic stiffness. The LV mass index, relative LV wall thickness, peak atrial systolic transmitral flow velocity, LA total, active, and passive emptying volume indexes, and E/e'/S-LAs were greatest, and S-LAs, peak early diastolic LA strain, peak systolic LV longitudinal strain and circumferential strain rate, and peak early diastolic LV radial strain rate were lower in the large LA group compared with control and/or normal LA group. Multivariate linear regression analysis revealed that aging, LA remodeling, and LV systolic and diastolic dysfunction are defined as strong predictors related to increased LA diastolic stiffness in the large LA group. HT alters LA dynamics significantly, with resultant increased LA volume and diastolic stiffness related to LV diastolic and systolic dysfunction, even in asymptomatic patients. Earlier treatment with renin–angiotensin system inhibitors may improve abnormal LA-LV interaction in this patient population.

  11. Left ventricular remodelling and systolic function measurement with 64 multi-slice computed tomography versus second harmonic echocardiography in patients with coronary artery disease: a double blind study.

    PubMed

    Palazzuoli, Alberto; Cademartiri, Filippo; Geleijnse, Marcel L; Meijboom, Bob; Pugliese, Francesca; Soliman, Osama; Calabrò, Anna; Nuti, Ranuccio; de Feyter, Pim

    2010-01-01

    The present study evaluated LV volumes, ejection fraction (LVEF) and stroke volume (SV) obtained by 64-MDCT and to compare these data with those obtained by second harmonic 2D Echo, in patients referred for non-invasive coronary vessels evaluation. The most common technique in daily clinical practice used for determination of LV function is two-dimensional echocardiography (2D-TTE). Multi-detector computed tomography (MDCT) is an emerging new technique to detect coronary artery disease (CAD) and was recently proposed to assess LV function. 93 patients underwent to 64-MDCT for LV function and volumes assessment by segmental reconstruction algorithm (Argus) and compared with recent (2 months) 2D-TTE, all images were processed and interpreted by two observers blinded to the Echo and MDCT results. A close correlation between TTE and 64 MDCT was demonstrated for the ejection fraction LVEF (r=0.84), end-diastolic volume LVEDV (r=0.80) and end-systolic volume LVESV (r=0.85); acceptable correlation was recruited for stroke volume LVSV (r=0.58). Optimal results were recruited for inter-observer variability for 64-MDCT measured in 45 patients: LVESV (r=0.82, p<0.001), LVEDV (r=0.83, p<0.001), LVEF (r=0.69, p<0.002) and SV (r=0.66, p<0.001). Our results, showed that functional and temporal information contained in a coronary 64-MDCT study can be used to assess left ventricular (LV) systolic function and LV dimensions with good reproducibility and acceptable correlation respect to 2D-TTE. The combination of non-invasive coronary artery imaging and assessment of global LV function might became in the future a fast and conclusive cardiac work-up in patients with CAD.

  12. Combined baseline strain dyssynchrony index and its acute reduction predicts mid-term left ventricular reverse remodeling and long-term outcome after cardiac resynchronization therapy.

    PubMed

    Tatsumi, Kazuhiro; Tanaka, Hidekazu; Matsumoto, Kensuke; Miyoshi, Tatsuya; Hiraishi, Mana; Tsuji, Takayuki; Kaneko, Akihiro; Ryo, Keiko; Fukuda, Yuko; Norisada, Kazuko; Onishi, Tetsuari; Yoshida, Akihiro; Kawai, Hiroya; Hirata, Ken-ichi

    2014-04-01

    The objective of this study was to test the hypothesis that combining assessment of baseline radial strain dyssynchrony index (SDI), that expressed both left ventricular (LV) dyssynchrony and residual myocardial contractility, and of acute changes in this index can yield more accurate prediction of mid-term responders and long-term outcome after cardiac resynchronization therapy (CRT). Radial SDI for 75 CRT patients was calculated as the average difference between peak and end-systolic speckle tracking strain from 6 segments of the mid-LV short-axis view before and 8 ± 2 days after CRT. Mid-term responder was defined as ≥ 15% decrease in LV end-systolic volume 6 ± 2 months after CRT. Long-term outcome was tracked over 5 years. Baseline radial SDI ≥ 6.5% is considered predictive of responder and favorable outcome, as previously reported. Acute reduction in radial SDI ≥ 1.5% was found to be the best predictor of mid-term responders with CRT. Furthermore, patients with acute reductions in radial SDI ≥1.5% were associated with a significantly more favorable long-term outcome after CRT than those with radial SDI <1.5% (log rank P < 0.001). An important findings were that baseline radial SDI ≥6.5% and acute reductions in radial SDI ≥ 1.5% in 42 patients were associated with the highest event-free survival rate of 92%, whereas, 21 patients corresponding values of <6.5% and <1.5% were associated with low event-free survival rate of 46% (log rank P < 0.001). Combined assessment of baseline radial SDI and its acute reduction after CRT may have clinical implications for predicting responders and thus patients' care.

  13. Survival, Exercise Capacity, and Left Ventricular Remodeling in a Rat Model of Chronic Mitral Regurgitation: Serial Echocardiography and Pressure-Volume Analysis

    PubMed Central

    Kim, Kyung-Hee; Lee, Seung-Pyo; Kim, Hyung-Kwan; Seo, Jeong-Wook; Sohn, Dae-Won; Oh, Byung-Hee; Park, Young-Bae

    2011-01-01

    Background and Objectives The aims of this study were to establish a reliable model of chronic mitral regurgitation (MR) in rats and verify the pathophysiological features of this model by evaluating cardiac function using serial echocardiography and a pressure-volume analysis. Materials and Methods MR was created in 37 Sprague-Dawley rats by making a hole with a 23 gauge needle on the mitral leaflet through the left ventricular (LV) apex under the guidance of transesophageal echocardiography. Results Serial echocardiograms revealed that the LV began to dilate immediately after the MR operation and showed progressive dilation until the 14th week (LV end-systolic dimension at 14 weeks, 4.71±0.25 mm vs. 6.81±0.50 mm for sham vs. MR, p<0.01; LV end-diastolic dimension, 8.32±0.42 mm vs. 11.01±0.47 mm, p<0.01). The LV ejection fraction tended to increase immediately after the MR operation but started to decrease thereafter and showed a significant difference with the sham group from the 14th week (70.0±2.2% vs. 62.1±3.1% for sham vs. MR). In a pressure-volume analysis performed at the 14th week, the LV end-systolic pressure-volume relationship and +dp/dt decreased significantly in the MR group. A serial treadmill test revealed that exercise capacity remained in the normal range until the 14th week when it began to decrease (exercise duration, 406±45 seconds vs. 330±27 seconds, p<0.01). A pathological analysis showed no significance difference in interstitial fibrosis between the two groups. Conclusion We established a small animal model of chronic MR and verified its pathophysiological features. This model may provide a useful tool for future research on MR and volume overload heart failure. PMID:22125560

  14. Cardioprotective effects of lysyl oxidase inhibition against volume overload-induced extracellular matrix remodeling.

    PubMed

    El Hajj, Elia C; El Hajj, Milad C; Ninh, Van K; Gardner, Jason D

    2016-03-01

    A hallmark of heart failure (HF) is adverse extracellular matrix (ECM) remodeling, which is regulated by the collagen cross-linking enzyme, lysyl oxidase (LOX). In this study, we evaluate the efficacy of LOX inhibition to prevent adverse left ventricular (LV) remodeling and dysfunction using an experimental model of HF. Sprague-Dawley rats were subjected to surgically induced volume overload (VO) by creation of aortocaval fistula (ACF). A LOX inhibitor, beta-aminopropionitrile (BAPN; 100 mg/kg/day), was administered to rats with ACF or sham surgery at eight weeks postsurgery. Echocardiography was used to assess progressive alterations in cardiac ventricular structure and function. Left ventricular (LV) catheterization was used to assess alterations in contractility, stiffness, LV pressure and volume, and other indices of cardiac function. The LV ECM alterations were assessed by: (a) histological staining of collagen, (b) protein expression of collagen types I and III, (c) hydroxyproline assay, and (d) cross-linking assay. LOX inhibition attenuated VO-induced increases in cardiac stress, and attenuated increases in interstitial myocardial collagen, total collagen, and protein levels of collagens I and III. Both echocardiography and catheterization measurements indicated improved cardiac function post-VO in BAPN treated rats vs. untreated. Inhibition of LOX attenuated VO-induced decreases in LV stiffness and cardiac function. Overall, our data indicate that LOX inhibition was cardioprotective in the volume overloaded heart.

  15. Prenatal programming: adverse cardiac programming by gestational testosterone excess

    PubMed Central

    Vyas, Arpita K.; Hoang, Vanessa; Padmanabhan, Vasantha; Gilbreath, Ebony; Mietelka, Kristy A.

    2016-01-01

    Adverse events during the prenatal and early postnatal period of life are associated with development of cardiovascular disease in adulthood. Prenatal exposure to excess testosterone (T) in sheep induces adverse reproductive and metabolic programming leading to polycystic ovarian syndrome, insulin resistance and hypertension in the female offspring. We hypothesized that prenatal T excess disrupts insulin signaling in the cardiac left ventricle leading to adverse cardiac programming. Left ventricular tissues were obtained from 2-year-old female sheep treated prenatally with T or oil (control) from days 30–90 of gestation. Molecular markers of insulin signaling and cardiac hypertrophy were analyzed. Prenatal T excess increased the gene expression of molecular markers involved in insulin signaling and those associated with cardiac hypertrophy and stress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian target of rapamycin complex 1 (mTORC1), nuclear factor of activated T cells –c3 (NFATc3), and brain natriuretic peptide (BNP) compared to controls. Furthermore, prenatal T excess increased the phosphorylation of PI3K, AKT and mTOR. Myocardial disarray (multifocal) and increase in cardiomyocyte diameter was evident on histological investigation in T-treated females. These findings support adverse left ventricular remodeling by prenatal T excess. PMID:27328820

  16. Left ventricular apical diseases.

    PubMed

    Cisneros, Silvia; Duarte, Ricardo; Fernandez-Perez, Gabriel C; Castellon, Daniel; Calatayud, Julia; Lecumberri, Iñigo; Larrazabal, Eneritz; Ruiz, Berta Irene

    2011-08-01

    There are many disorders that may involve the left ventricular (LV) apex; however, they are sometimes difficult to differentiate. In this setting cardiac imaging methods can provide the clue to obtaining the diagnosis. The purpose of this review is to illustrate the spectrum of diseases that most frequently affect the apex of the LV including Tako-Tsubo cardiomyopathy, LV aneurysms and pseudoaneurysms, apical diverticula, apical ventricular remodelling, apical hypertrophic cardiomyopathy, LV non-compaction, arrhythmogenic right ventricular dysplasia with LV involvement and LV false tendons, with an emphasis on the diagnostic criteria and imaging features. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13244-011-0091-6) contains supplementary material, which is available to authorized users.

  17. The impact of 6 weeks of atrial fibrillation on left atrial and ventricular structure and function

    PubMed Central

    Kazui, Toshinobu; Henn, Mathew C.; Watanabe, Yoshiyuki; Kovács, Sándor J.; Lawrance, Christopher P.; Greenberg, Jason W.; Moon, Marc; Schuessler, Richard B.; Damiano, Ralph J.

    2015-01-01

    Objective The impact of prolonged episodes of atrial fibrillation on atrial and ventricular function has been incompletely characterized. The purpose of this study was to investigate the influence of atrial fibrillation on left atrial and ventricular function in a rapid paced porcine model of atrial fibrillation. Methods A control group of pigs (group 1, n = 8) underwent left atrial and left ventricular conductance catheter studies and fibrosis analysis. A second group (group 2, n = 8) received a baseline cardiac magnetic resonance imaging to characterize left atrial and left ventricular function. The atria were rapidly paced into atrial fibrillation for 6 weeks followed by cardioversion and cardiac magnetic resonance imaging. Results After 6 weeks of atrial fibrillation, left atrial contractility defined by atrial end-systolic pressure-volume relationship slope was significantly lower in group 2 than in group 1 (1.1 ± 0.5 vs 1.7 ± 1.0; P = .041), whereas compliance from the end-diastolic pressure-volume relationship was unchanged (1.5 ± 0.9 vs 1.6 ± 1.3; P = .733). Compared with baseline, atrial fibrillation resulted in a significantly higher contribution of left atrial reservoir volume to stroke volume (32% vs 17%; P = .005) and lower left atrial booster pump volume contribution to stroke volume (19% vs 28%; P = .029). Atrial fibrillation also significantly increased maximum left atrial volume (206 ± 41 mL vs 90 ± 21 mL; P < .001). Left atrial fibrosis in group 2 was significantly higher than in group 1. Atrial fibrillation decreased left ventricular ejection fraction (29% ± 9% vs 58 ± 8%; P < .001), but left ventricular stroke volume was unchanged. Conclusions In a chronic model of atrial fibrillation, the left atrium demonstrated significant structural remodeling and decreased contractility. These data suggest that early intervention in patients with persistent atrial fibrillation might mitigate against adverse atrial and ventricular structural

  18. Association Between Myocardial Mechanics and Ischemic LV Remodeling.

    PubMed

    D'Elia, Nicholas; D'hooge, Jan; Marwick, Thomas H

    2015-12-01

    The outcomes associated with heart failure after myocardial infarction are still poor. Both global and regional left ventricular (LV) remodeling are associated with the progression of the post-infarct patient to heart failure, but although global remodeling can be accurately measured, regional LV remodeling has been more difficult to investigate. Preliminary evidence suggests that post-MI assessment of LV mechanics using stress and strain may predict global (and possibly regional) LV remodeling. A method of predicting both global and regional LV remodeling might facilitate earlier, targeted, and more extensive clinical intervention in those most likely to benefit from novel interventions such as cell therapy.

  19. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation

    PubMed Central

    Bernardo, Bianca C.; Sapra, Geeta; Patterson, Natalie L.; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A.; McMullen, Julie R.

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions. PMID:26660322

  20. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

    PubMed

    Bernardo, Bianca C; Sapra, Geeta; Patterson, Natalie L; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A; McMullen, Julie R

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.

  1. Retinal remodeling.

    PubMed

    Jones, B W; Kondo, M; Terasaki, H; Lin, Y; McCall, M; Marc, R E

    2012-07-01

    Retinal photoreceptor degeneration takes many forms. Mutations in rhodopsin genes or disorders of the retinal pigment epithelium, defects in the adenosine triphosphate binding cassette transporter, ABCR gene defects, receptor tyrosine kinase defects, ciliopathies and transport defects, defects in both transducin and arrestin, defects in rod cyclic guanosine 3',5'-monophosphate phosphodiesterase, peripherin defects, defects in metabotropic glutamate receptors, synthetic enzymatic defects, defects in genes associated with signaling, and many more can all result in retinal degenerative disease like retinitis pigmentosa (RP) or RP-like disorders. Age-related macular degeneration (AMD) and AMD-like disorders are possibly due to a constellation of potential gene targets and gene/gene interactions, while other defects result in diabetic retinopathy or glaucoma. However, all of these insults as well as traumatic insults to the retina result in retinal remodeling. Retinal remodeling is a universal finding subsequent to retinal degenerative disease that results in deafferentation of the neural retina from photoreceptor input as downstream neuronal elements respond to loss of input with negative plasticity. This negative plasticity is not passive in the face of photoreceptor degeneration, with a phased revision of retinal structure and function found at the molecular, synaptic, cell, and tissue levels involving all cell classes in the retina, including neurons and glia. Retinal remodeling has direct implications for the rescue of vision loss through bionic or biological approaches, as circuit revision in the retina corrupts any potential surrogate photoreceptor input to a remnant neural retina. However, there are a number of potential opportunities for intervention that are revealed through the study of retinal remodeling, including therapies that are designed to slow down photoreceptor loss, interventions that are designed to limit or arrest remodeling events, and

  2. Role of reactive oxygen species in myocardial remodeling.

    PubMed

    Zhang, Min; Shah, Ajay M

    2007-03-01

    Adverse cardiac remodeling is a fundamental process in the progression to chronic heart failure. Although the mechanisms underlying cardiac remodeling are multi-factorial, a significant body of evidence points to the crucial roles of increased reactive oxygen species. This article reviews recent advances in delineating the different sources of production for reactive oxygen species (namely mitochondria, xanthine oxidase, uncoupled nitric oxide synthases, and NADPH oxidases) that may be involved in cardiac remodeling and the aspects of the remodeling process that they affect. These data could suggest new ways of targeting redox pathways for the prevention and treatment of adverse cardiac remodeling.

  3. Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension.

    PubMed

    Golob, Mark J; Tabima, Diana M; Wolf, Gregory D; Johnston, James L; Forouzan, Omid; Mulchrone, Ashley M; Kellihan, Heidi B; Bates, Melissa L; Chesler, Naomi C

    2017-04-11

    Pulmonary hypertension (PH) is a debilitating vascular disease that leads to pulmonary artery (PA) stiffening, which is a predictor of patient mortality. During PH development, PA stiffening adversely affects right ventricular function. PA stiffening has been investigated through the arterial nonlinear elastic response during mechanical testing using a canine PH model. However, only circumferential properties were reported and in the absence of chronic PH-induced PA remodeling. Remodeling can alter arterial nonlinear elastic properties via chronic changes in extracellular matrix (ECM) content and geometry. Here, we used an established constitutive model to demonstrate and differentiate between strain-stiffening, which is due to nonlinear elasticity, and remodeling-induced stiffening, which is due to ECM and geometric changes, in a canine model of chronic thromboembolic PH (CTEPH). To do this, circumferential and axial tissue strips of large extralobar PAs from control and CTEPH tissues were tested in uniaxial tension, and data were fit to a phenomenological constitutive model. Strain-induced stiffening was evident from mechanical testing as nonlinear elasticity in both directions and computationally by a high correlation coefficient between the mechanical data and model (R(2)=0.89). Remodeling-induced stiffening was evident from a significant increase in the constitutive model stress parameter, which correlated with increased PA collagen content and decreased PA elastin content as measured histologically. The ability to differentiate between strain- and remodeling-induced stiffening in vivo may lead to tailored clinical treatments for PA stiffening in PH patients.

  4. Right ventricular centripetal plication: an aggressive right ventricular exclusion technique.

    PubMed

    Sugiura, Junya; Murayama, Hiroomi; Okada, Noritaka

    2017-01-01

    In patients with a functional single ventricle such as neonatal Ebstein's anomaly or pulmonary atresia with intact ventricular septum, the right ventricle can compress the left ventricle and decrease its performance due to the volume or pressure overload of the right ventricle. We have performed right ventricular centripetal plication from the inside to exclude the right ventricle and to minimize the adverse effect on the left ventricle and the results have been satisfactory.

  5. Ventricular tachycardia

    MedlinePlus

    ... prevented by treating heart problems and avoiding certain medicines. Alternative Names Wide-complex tachycardia; V tach; Tachycardia - ventricular Images Implantable cardioverter-defibrillator ... Ventricular arrhythmias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  6. Tissue Inhibitor of Metalloproteinase-2 Gene Delivery Ameliorates Post-Infarction Cardiac Remodeling

    PubMed Central

    Ramani, Ravi; Nilles, Kathleen; Gibson, Gregory; Burkhead, Benjamin; Mathier, Michael; McNamara, Dennis; McTiernan, Charles F.

    2011-01-01

    Hypothesis Adenoviral-mediated (AdV-T2) overexpression of TIMP-2 would blunt ventricular remodeling and improve survival in a murine model of chronic ischemic injury. Methods Male mice (n=124) aged 10–14 weeks underwent either 1) left coronary artery ligation to induce myocardial infarction (MI group, n=36), 2) myocardial injection of 6×1010 viral particles of AdV-T2 immediately post-MI (MI+T2 group, n=30), 3) myocardial injection of 6×1010 viral particles of a control adenovirus (MI+Ct, n=38), or 4) received no intervention (controls, n=20). On post-MI day 7, surviving mice (n=79) underwent echocardiographic, immunohistochemical and biochemical analysis. Results In infarcted animals, the MI+T2 group demonstrated improved survival (p< 0.02), better preservation of developed pressure and ventricular diameter (p<0.04), and the lowest expression and activity of MMP-2 and MMP-9 (P<0.04) compared with MI and MI+Ct groups.. All infarcted hearts displayed significantly increased inflammatory cell infiltration (p<0.04 versus control, MI, or MI+T2), with infiltration highest in the MI+Ct group and lowest in the MI+T2 group (p<0.04). Conclusions Adenoviral mediated myocardial delivery of the TIMP-2 gene improves post-MI survival and limits adverse remodeling in a murine model of myocardial infarction. PMID:21348952

  7. Delayed recovery of right ventricular systolic function after repair of long-standing tricuspid regurgitation associated with severe right ventricular failure.

    PubMed

    Kim, Jong Hun; Kim, Kyung Hwa; Choi, Jong Bum; Kuh, Ja Hong

    2016-03-01

    After tricuspid valve surgery for long-standing tricuspid regurgitation associated with right ventricular failure, reverse remodelling of the enlarged right ventricle, including recovery of right ventricular systolic function, is unpredictable. We present the case of a 31-year old man with early reduction of dilated right ventricular dimensions and delayed recovery of impaired right ventricular systolic function after valve repair for traumatic tricuspid regurgitation lasting 16 years.

  8. A 2:1 AV rhythm: an adverse effect of a long AV delay during DDI pacing and its prevention by the ventricular intrinsic preference algorithm in DDD mode.

    PubMed

    Minamiguchi, Hitoshi; Oginosawa, Yasushi; Kohno, Ritsuko; Tamura, Masahito; Takeuchi, Masaaki; Otsuji, Yutaka; Abe, Haruhiko

    2012-07-01

    A 91-year-old woman received a dual-chamber pacemaker for sick sinus syndrome and intermittently abnormal atrioventricular (AV) conduction. The pacemaker was set in DDI mode with a 350-ms AV delay to preserve intrinsic ventricular activity. She complained of palpitation during AV sequential pacing. The electrocardiogram showed a 2:1 AV rhythm from 1:1 ventriculoatrial (VA) conduction during ventricular pacing in DDI mode with a long AV interval. After reprogramming of the pacemaker in DDD mode with a 250-ms AV interval and additional 100-ms prolongation of the AV interval by the ventricular intrinsic preference function, VA conduction disappeared and the patient's symptom were alleviated without increasing unnecessary right ventricular pacing.

  9. Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice

    PubMed Central

    Chen, Jinmiao; Hong, Tao; Ding, Suling; Deng, Long; Abudupataer, Mieradilijiang; Zhang, Weiwei; Tong, Minghong; Jia, Jianguo; Gong, Hui; Zou, Yunzeng; Wang, Timothy C.; Ge, Junbo; Yang, Xiangdong

    2017-01-01

    Histamine has pleiotropic pathophysiological effects, but its role in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Histidine decarboxylase (HDC) is the main enzyme involved in histamine production. Here, we clarified the roles of HDC-expressing cells and histamine in heart failure post-MI using HDC-EGFP transgenic mice and HDC-knockout (HDC−/−) mice. HDC+CD11b+ myeloid cell numbers markedly increased in the injured hearts, and histamine levels were up-regulated in the circulation post-MI. HDC−/− mice exhibited more adverse cardiac remodeling, poorer left ventricular function and higher mortality by increasing cardiac fibrogenesis post-MI. In vitro assays further confirmed that histamine inhibited heart fibroblast proliferation. Furthermore, histamine enhanced the signal transducer and activator of transcription (STAT)-6 phosphorylation level in murine heart fibroblasts, and the inhibitive effects of histamine on fibroblast proliferation could be blocked by JAK3/STAT6 signaling selective antagonist. STAT6-knockout (STAT6−/−) mice had a phenotype similar to that of HDC−/− mice post-MI; however, in contrast to HDC−/− mice, the beneficial effects of exogenous histamine injections were abrogated in STAT6−/− mice. These data suggest that histamine exerts protective effects by modulating cardiac fibrosis and remodeling post-MI, in part through the STAT6-dependent signaling pathway. PMID:28272448

  10. Remodeling of cell-cell junctions in arrhythmogenic cardiomyopathy.

    PubMed

    Asimaki, Angeliki; Saffitz, Jeffrey E

    2014-02-01

    Arrhythmogenic cardiomyopathy (AC) is a primary myocardial disorder characterized by a high incidence of ventricular arrhythmias often preceding the onset of ventricular remodeling and dysfunction. Approximately 50% of patients diagnosed with AC have one or more mutations in genes encoding desmosomal proteins, although non-desmosomal genes have also been associated with the disease. Increasing evidence implicates remodeling of intercalated disk proteins reflecting abnormal responses to mechanical load and aberrant cell signaling pathways in the pathogenesis of AC. This review summarizes recent advances in understanding disease mechanisms in AC that have come from studies of human myocardium and experimental models.

  11. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    PubMed

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  12. The multiple electrocardiographic manifestations of ventricular repolarization memory.

    PubMed

    Chiale, Pablo A; Etcheverry, Daniel; Pastori, Julio D; Fernandez, Pablo A; Garro, Hugo A; González, Mario D; Elizari, Marcelo V

    2014-08-01

    T wave "memory" is a peculiar variety of cardiac remodeling caused by a transient change in the course of ventricular depolarization (due to ventricular pacing, rate-dependent intraventricular block, ventricular preexcitation or tachyarrhythmias with wide QRS complexes). It is usually manifested by inverted T waves that appears when normal ventricular activation is restored. This phenomenon is cumulative and occurs earlier if the ventricular myocardium has previously been exposed to the same conditioning stimuli. In this article the different conditions giving rise to "classical" T wave memory development are reviewed and also "another" type of T wave memory is described. It is also shown that cardiac memory may induce not only negative (pseudo-primary) T waves but also a reversal of primary and pseudoprimary T waves leading to "normalization" of ventricular repolarization. The knowledge of these dissimilar consequences of T wave memory is essential to assess the characteristics of ventricular repolarization.

  13. Premature ventricular contractions associated with isotretinoin use*

    PubMed Central

    Alan, Sevil; Ünal, Betül; Yildirim, Aytül

    2016-01-01

    Isotretinoin has been considered a unique drug for acne treatment. However, it is associated with numerous adverse effects. Isotretinoin can trigger premature ventricular contractions. This report describes a 33-year-old-woman who presented with palpitations for 1 week while undergoing 1-month isotretinoin treatment for mild-moderate facial acne. An electrocardiogram and Holter monitoring showed premature ventricular contractions during isotretinoin (Roaccutane, Roche) treatment. Isotretinoin-related premature ventricular contractions were strongly suggested in this case due to the existence of documented premature ventricular contractions on electrocardiograms and the disappearance of these premature ventricular contractions two weeks after termination of the treatment To the authors' knowledge, there has been 1 reported case of premature ventricular contractions linked to isotretinoin use; this report describes a second such case. PMID:28099609

  14. Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment

    PubMed Central

    Azevedo, Paula S.; Polegato, Bertha F.; Minicucci, Marcos F.; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.

    2016-01-01

    Cardiac remodeling is defined as a group of molecular, cellular and interstitial changes that manifest clinically as changes in size, mass, geometry and function of the heart after injury. The process results in poor prognosis because of its association with ventricular dysfunction and malignant arrhythmias. Here, we discuss the concepts and clinical implications of cardiac remodeling, and the pathophysiological role of different factors, including cell death, energy metabolism, oxidative stress, inflammation, collagen, contractile proteins, calcium transport, geometry and neurohormonal activation. Finally, the article describes the pharmacological treatment of cardiac remodeling, which can be divided into three different stages of strategies: consolidated, promising and potential strategies. PMID:26647721

  15. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  16. Sertraline-induced ventricular tachycardia.

    PubMed

    Patel, Nishit H; Golwala, Harsh; Stavrakis, Stavros; Schechter, Eliot

    2013-01-01

    Sertraline is a selective serotonin reuptake inhibitor, which is a commonly used drug for major depressive disorder. Most frequently reported adverse effects of sertraline in patients receiving 50-150 mg/d are dry mouth, headache, diarrhea, nausea, vomiting, sweating, and dizziness. We hereby report one of the few cases of sertraline-induced ventricular tachycardia, which has been for the first time objectively assessed by the Naranjo scale. We therefore urge the primary care physicians and the cardiologists to keep sertraline as a possible precipitating factor for evaluation of ventricular tachycardia.

  17. Teaching resources. Chromatin remodeling.

    PubMed

    Lue, Neal F

    2005-07-26

    This Teaching Resource provides lecture notes and slides for a class covering chromatin remodeling mechanisms and is part of the course "Cell Signaling Systems: a Course for Graduate Students." The lecture begins with a discussion of chromatin organization and then proceeds to describe the process of chromatin remodeling through a review of chromatin remodeling complexes and methods used to study their function.

  18. Temperature-induced cardiac remodelling in fish

    PubMed Central

    Keen, Adam N.; Klaiman, Jordan M.; Shiels, Holly A.

    2017-01-01

    ABSTRACT Thermal acclimation causes the heart of some fish species to undergo significant remodelling. This includes changes in electrical activity, energy utilization and structural properties at the gross and molecular level of organization. The purpose of this Review is to summarize the current state of knowledge of temperature-induced structural remodelling in the fish ventricle across different levels of biological organization, and to examine how such changes result in the modification of the functional properties of the heart. The structural remodelling response is thought to be responsible for changes in cardiac stiffness, the Ca2+ sensitivity of force generation and the rate of force generation by the heart. Such changes to both active and passive properties help to compensate for the loss of cardiac function caused by a decrease in physiological temperature. Hence, temperature-induced cardiac remodelling is common in fish that remain active following seasonal decreases in temperature. This Review is organized around the ventricular phases of the cardiac cycle – specifically diastolic filling, isovolumic pressure generation and ejection – so that the consequences of remodelling can be fully described. We also compare the thermal acclimation-associated modifications of the fish ventricle with those seen in the mammalian ventricle in response to cardiac pathologies and exercise. Finally, we consider how the plasticity of the fish heart may be relevant to survival in a climate change context, where seasonal temperature changes could become more extreme and variable. PMID:27852752

  19. Exercise-induced cardiac remodeling.

    PubMed

    Weiner, Rory B; Baggish, Aaron L

    2012-01-01

    Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes.

  20. Surgical considerations for the explantation of the Parachute left ventricular partitioning device and the implantation of the HeartMate II left ventricular assist device

    PubMed Central

    Bansal, Shelley; Rosas, Paola C.; Mazzaferri, Ernest L.; Sai-Sudhakar, Chittoor B.

    2016-01-01

    Chronic heart failure is the leading cause of death in the world. With newer therapies, the burden of this disease has decreased; however, a significant number of patients remain refractive to existing therapies. Myocardial infarction often leads to ventricular remodeling and eventually contributes to heart failure. The Parachute™ (Cardiokinetix, Menlo Park, CA) is the first device designed for percutaneous ventricular restoration therapy, which reduces left ventricular volume and minimizes the risk of open surgical procedures. For the first time, we report a case of explantation of the Parachute ventricular partitioning device and transition to a HeartMate II™ left ventricular assist device and the surgical considerations for a successful outcome. PMID:27034560

  1. Widespread Myocardial Delivery of Heart-Derived Stem Cells by Nonocclusive Triple-Vessel Intracoronary Infusion in Porcine Ischemic Cardiomyopathy: Superior Attenuation of Adverse Remodeling Documented by Magnetic Resonance Imaging and Histology

    PubMed Central

    Tseliou, Eleni; Kanazawa, Hideaki; Dawkins, James; Gallet, Romain; Kreke, Michelle; Smith, Rachel; Middleton, Ryan; Valle, Jackelyn; Marbán, Linda; Kar, Saibal; Makkar, Rajendra; Marbán, Eduardo

    2016-01-01

    Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients. PMID:26784932

  2. Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig.

    PubMed

    Beaumont, Eric; Wright, Gary L; Southerland, Elizabeth M; Li, Ying; Chui, Ray; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

    2016-05-15

    Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15-20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling.

  3. Effects of Obstructive Sleep Apnea and Obesity on Cardiac Remodeling: The Wisconsin Sleep Cohort Study

    PubMed Central

    Korcarz, Claudia E.; Peppard, Paul E.; Young, Terry B.; Chapman, Carrie B.; Hla, K. Mae; Barnet, Jodi H.; Hagen, Erika; Stein, James H.

    2016-01-01

    Study Objectives: To characterize the prospective associations of obstructive sleep apnea (OSA) with future echocardiographic measures of adverse cardiac remodeling Methods: This was a prospective long-term observational study. Participants had overnight polysomnography followed by transthoracic echocardiography a mean (standard deviation) of 18.0 (3.7) y later. OSA was characterized by the apnea-hypopnea index (AHI, events/hour). Echocardiography was used to assess left ventricular (LV) systolic and diastolic function and mass, left atrial volume and pressure, cardiac output, systemic vascular resistance, and right ventricular (RV) systolic function, size, and hemodynamics. Multivariate regression models estimated associations between log10(AHI+1) and future echocardiographic findings. A secondary analysis looked at oxygen desaturation indices and future echocardiographic findings. Results: At entry, the 601 participants were mean (standard deviation) 47 (8) y old (47% female). After adjustment for age, sex, and body mass index, baseline log10(AHI+1) was associated significantly with future reduced LV ejection fraction and tricuspid annular plane systolic excursion (TAPSE) ≤ 15 mm. After further adjustment for cardiovascular risk factors, participants with higher baseline log10(AHI+1) had lower future LV ejection fraction (β = −1.35 [standard error = 0.6]/log10(AHI+1), P = 0.03) and higher odds of TAPSE ≤ 15 mm (odds ratio = 6.3/log10(AHI+1), 95% confidence interval = 1.3–30.5, P = 0.02). SaO2 desaturation indices were associated independently with LV mass, LV wall thickness, and RV area (all P < 0.03) Conclusions: OSA is associated independently with decreasing LV systolic function and with reduced RV function. Echocardiographic measures of adverse cardiac remodeling are strongly associated with OSA but are confounded by obesity. Hypoxia may be a stimulus for hypertrophy in individuals with OSA. Citation: Korcarz CE, Peppard PE, Young TB, Chapman CB, Hla

  4. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

    PubMed Central

    Dewald, Daniela; Schmitz, Eva J.; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT−/−)-mice (n = 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT−/−-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2−/−-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT−/−-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2−/−-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  5. Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling.

    PubMed

    Hoshikawa, Y; Voelkel, N F; Gesell, T L; Moore, M D; Morris, K G; Alger, L A; Narumiya, S; Geraci, M W

    2001-07-15

    Prostacyclin (PGI(2)) reduces pulmonary vascular resistance and attenuates vascular smooth muscle cell proliferation through signal transduction following ligand binding to its receptor. Because patients with severe pulmonary hypertension have a reduced PGI(2) receptor (PGI-R) expression in the remodeled pulmonary arterial smooth muscle, we hypothesized that pulmonary vascular remodeling may be modified PGI-R dependently. To test this hypothesis, PGI-R knockout (KO) and wild-type (WT) mice were subjected to a simulated altitude of 17,000 ft or Denver altitude for 3 wk, and right ventricular pressure and lung histology were assessed. The PGI-R KO mice developed more severe pulmonary hypertension and vascular remodeling after chronic hypoxic exposure when compared to the WT mice. Our results indicate that PGI(2) and its receptor play an important role in the regulation of hypoxia-induced pulmonary vascular remodeling, and that the absence of a functional receptor worsens pulmonary hypertension.

  6. Therapy with conventional antiarrhythmic drugs for ventricular arrhythmias.

    PubMed

    Nestico, P F; DePace, N L; Morganroth, J

    1984-09-01

    Conventional antiarrhythmic drugs are an important tool for the clinical cardiologist for the treatment of ventricular arrhythmias. Knowledge of the different properties of these drugs will help decrease the incidence of adverse effects and increase the frequency of successful therapy.

  7. Rat Heterotopic Heart Transplantation Model to Investigate Unloading-Induced Myocardial Remodeling

    PubMed Central

    Fu, Xuebin; Segiser, Adrian; Carrel, Thierry P.; Tevaearai Stahel, Hendrik T.; Most, Henriette

    2016-01-01

    Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation (hHTX) in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery. We herein review the current knowledge on the effects of volume unloading the left ventricle via different methods of hHTX in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under “reloaded” conditions. While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients. PMID:27807535

  8. Osteoprotegerin levels in ST-elevation myocardial infarction: Temporal profile and association with myocardial injury and left ventricular function

    PubMed Central

    Shetelig, Christian; Limalanathan, Shanmuganathan; Eritsland, Jan; Hoffmann, Pavel; Seljeflot, Ingebjørg; Gran, Jon Michael; Aukrust, Pål; Ueland, Thor; Andersen, Geir Øystein

    2017-01-01

    Background Elevated levels of osteoprotegerin (OPG) have been associated with adverse outcomes in ST-elevation myocardial infarction (STEMI). However, the role of OPG in myocardial injury and adverse remodeling in STEMI patients remains unclear. The aims of this observational cohort study were to evaluate: 1) the temporal profile of OPG during STEMI, 2) possible associations between OPG measured acutely and after 4 months, with infarct size, adverse left ventricular (LV) remodeling, microvascular obstruction (MVO) and myocardial salvage and 3) the effect of heparin administration on OPG levels. Methods Blood samples were drawn repeatedly from 272 STEMI patients treated with primary percutaneous coronary intervention (PCI). Cardiac magnetic resonance imaging (CMR) was performed in the acute phase and after 4 months. The effect of heparin administration on OPG levels was studied in 20 patients referred to elective coronary angiography. Results OPG levels measured acutely were significantly higher than Day 1 and during follow-up. OPG levels were correlated with age. No association was found between early OPG levels and CMR measurements at 4 months. Patients with >median OPG levels measured at Day 1 had larger final infarct size, lower LV ejection fraction (LVEF) at 4 months and higher frequency of MVO. There were no associations between OPG and change in end-diastolic volume or myocardial salvage. OPG remained associated with infarct size and LVEF after adjustment for relevant covariates, except peak troponin T and CRP. A 77% increase in OPG levels following heparin administration was found in patients undergoing elective coronary angiography. Conclusions OPG was found to be associated with myocardial injury, but not with LV remodeling or myocardial salvage. The use of OPG as a biomarker in STEMI patients seems to be limited by a strong association with age, confounding effect of heparin administration, and little additive value to established biomarkers. PMID

  9. Cardiac remodelling and RAS inhibition

    PubMed Central

    Ferrario, Carlos M.

    2016-01-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin–angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  10. Novel approaches to the post-myocardial infarction/heart failure neural remodeling.

    PubMed

    D'Elia, Emilia; Pascale, Alessia; Marchesi, Nicoletta; Ferrero, Paolo; Senni, Michele; Govoni, Stefano; Gronda, Edoardo; Vanoli, Emilio

    2014-09-01

    The review aims to discuss the role of nerve growth factor (NGF) as a potential novel biomarker in post-myocardial infarction (MI) and in heart failure (HF), with a specific focus on neural remodeling and sprouting processes occurring after tissue damage. Many experimental data show that MI induces nerve sprouting, leading to increased sympathetic outflow and higher risk of ventricular arrhythmias and sudden cardiac death. In this framework, cardiac and circulating NGF might be an indicator of the innervation process and neural remodeling: it dramatically increases after MI, while it declines along with advanced HF and ventricular dysfunction. The bimodal behavior of NGF in acute and chronic settings leads to the speculation that NGF modulation may be a pharmacological target for intervention in different stages of the ischemic heart disease. Specifically, a fascinating possibility is to support or to inhibit NGF receptors, in order to prevent negative cardiac remodeling after MI and consequent ventricular dysfunction.

  11. Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity

    PubMed Central

    Zavadzkas, Juozas A.; Rivers, William T.; McLean, Julie E.; Chang, Eileen I.; Bouges, Shenikqua; Matthews, Robert G.; Koval, Christine N.; Stroud, Robert E.; Spinale, Francis G.

    2010-01-01

    Increased matrix metalloproteinase (MMP) abundance occurs with adverse left ventricular (LV) remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained aberrant electrical activation of the LV, with consequent dyskinesia, alters interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n = 10, 30–35 kg) was achieved by pacing (150 beats/min) at left atrial and LV sites such that normal atrioventricular activation (60 min) was followed by regional early LV activation for 60 min within 1.5 cm of the paced site and restoration of normal atrioventricular pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the LV pacing site and a remote LV site were monitored at 30-min intervals. During aberrant electrical stimulation, interstitial MMP activity at the paced site was increased (122 ± 4%) compared with the remote region (100%, P < 0.05). Restoration of atrioventricular pacing after the 60-min period of aberrant electrical activation normalized segmental shortening (8.5 ± 0.4%), but MMP activity remained elevated (121 ± 6%, P < 0.05). This study demonstrates that despite the restoration of mechanical function, disturbances in electrical conduction, in and of itself, can cause acute increases in regional in vivo MMP activation and, therefore, contribute to myocardial remodeling. PMID:20472759

  12. Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity.

    PubMed

    Mukherjee, Rupak; Zavadzkas, Juozas A; Rivers, William T; McLean, Julie E; Chang, Eileen I; Bouges, Shenikqua; Matthews, Robert G; Koval, Christine N; Stroud, Robert E; Spinale, Francis G

    2010-07-01

    Increased matrix metalloproteinase (MMP) abundance occurs with adverse left ventricular (LV) remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained aberrant electrical activation of the LV, with consequent dyskinesia, alters interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n = 10, 30-35 kg) was achieved by pacing (150 beats/min) at left atrial and LV sites such that normal atrioventricular activation (60 min) was followed by regional early LV activation for 60 min within 1.5 cm of the paced site and restoration of normal atrioventricular pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the LV pacing site and a remote LV site were monitored at 30-min intervals. During aberrant electrical stimulation, interstitial MMP activity at the paced site was increased (122 +/- 4%) compared with the remote region (100%, P < 0.05). Restoration of atrioventricular pacing after the 60-min period of aberrant electrical activation normalized segmental shortening (8.5 +/- 0.4%), but MMP activity remained elevated (121 +/- 6%, P < 0.05). This study demonstrates that despite the restoration of mechanical function, disturbances in electrical conduction, in and of itself, can cause acute increases in regional in vivo MMP activation and, therefore, contribute to myocardial remodeling.

  13. Remodeling A School Shop?

    ERIC Educational Resources Information Center

    Baker, G. E.

    1970-01-01

    Presents guidelines for remodeling a school shop combining major considerations of funds, program changes, class management, and flexibility, with the needs of wiring, painting, and placement of equipment. (Author)

  14. Reduced scar maturation and contractility lead to exaggerated left ventricular dilation after myocardial infarction in mice lacking AMPKα1.

    PubMed

    Noppe, Gauthier; Dufeys, Cécile; Buchlin, Patricia; Marquet, Nicolas; Castanares-Zapatero, Diego; Balteau, Magali; Hermida, Nerea; Bouzin, Caroline; Esfahani, Hrag; Viollet, Benoit; Bertrand, Luc; Balligand, Jean-Luc; Vanoverschelde, Jean-Louis; Beauloye, Christophe; Horman, Sandrine

    2014-09-01

    Cardiac fibroblasts (CF) are crucial in left ventricular (LV) healing and remodeling after myocardial infarction (MI). They are typically activated into myofibroblasts that express alpha-smooth muscle actin (α-SMA) microfilaments and contribute to the formation of contractile and mature collagen scars that minimize the adverse dilatation of infarcted areas. CF predominantly express the α1 catalytic subunit of AMP-activated protein kinase (AMPKα1), while AMPKα2 is the major catalytic isoform in cardiomyocytes. AMPKα2 is known to protect the heart by preserving the energy charge of cardiac myocytes during injury, but whether AMPKα1 interferes with maladaptative heart responses remains unexplored. In this study, we investigated the role of AMPKα1 in modulating LV dilatation and CF fibrosis during post-MI remodeling. AMPKα1 knockout (KO) and wild type (WT) mice were subjected to permanent ligation of the left anterior descending coronary artery. The absence of AMPKα1 was associated with increased CF proliferation in infarcted areas, while expression of the myodifferentiation marker α-SMA was decreased. Faulty maturation of myofibroblasts might derive from severe down-regulation of the non-canonical transforming growth factor-beta1/p38 mitogen-activated protein kinase (TGF-β1/p38 MAPK) pathway in KO infarcts. In addition, lysyl oxidase (LOX) protein expression was dramatically reduced in the scar of KO hearts. Although infarct size was similar in AMPK-KO and WT hearts subjected to MI, these changes resulted in compromised scar contractility, defective scar collagen maturation, and exacerbated adverse remodeling, as indicated by increased LV diastolic dimension 30days after MI. Our data genetically demonstrate the centrality of AMPKα1 in post-MI scar formation and highlight the specificity of this catalytic isoform in cardiac fibroblast/myofibroblast biology.

  15. Isolated ventricular noncompaction.

    PubMed

    Okçün Baniş; Tekin, Abdullah; Oz, Büge; Küçükoğlu, M Serdar

    2004-04-01

    Isolated ventricular noncompaction of myocardium is a rare congenital disease due to an arrest of myocardial morphogenesis during foetal development. It is characterized by a thin compacted epicardial and an extremely thickened endocardial layer with prominent trabeculations and deep intertrabecular recesses. The persistence of myocardial noncompaction is usually an associated anomaly in patients with congenital left or right ventricular outflow tract obstruction. However, isolated noncompaction of myocardium is not associated with any factors that would explain it apart from the foetal arrest of compaction of the ventricular myocardium. The disease results in systolic and diastolic ventricular dysfunction, systemic embolism and ventricular arrhythmias. We describe a case of isolated noncompaction of the ventricular myocardium in a 20-year-old man who presented initially with ventricular tachycardia.

  16. Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 1D Simulation Study

    PubMed Central

    Gomez, Juan F.; Cardona, Karen; Romero, Lucia; Ferrero, Jose M.; Trenor, Beatriz

    2014-01-01

    Background Heart failure is a final common pathway or descriptor for various cardiac pathologies. It is associated with sudden cardiac death, which is frequently caused by ventricular arrhythmias. Electrophysiological remodeling, intercellular uncoupling, fibrosis and autonomic imbalance have been identified as major arrhythmogenic factors in heart failure etiology and progression. Objective In this study we investigate in silico the role of electrophysiological and structural heart failure remodeling on the modulation of key elements of the arrhythmogenic substrate, i.e., electrophysiological gradients and abnormal impulse propagation. Methods Two different mathematical models of the human ventricular action potential were used to formulate models of the failing ventricular myocyte. This provided the basis for simulations of the electrical activity within a transmural ventricular strand. Our main goal was to elucidate the roles of electrophysiological and structural remodeling in setting the stage for malignant life-threatening arrhythmias. Results Simulation results illustrate how the presence of M cells and heterogeneous electrophysiological remodeling in the human failing ventricle modulate the dispersion of action potential duration and repolarization time. Specifically, selective heterogeneous remodeling of expression levels for the Na+/Ca2+ exchanger and SERCA pump decrease these heterogeneities. In contrast, fibroblast proliferation and cellular uncoupling both strongly increase repolarization heterogeneities. Conduction velocity and the safety factor for conduction are also reduced by the progressive structural remodeling during heart failure. Conclusion An extensive literature now establishes that in human ventricle, as heart failure progresses, gradients for repolarization are changed significantly by protein specific electrophysiological remodeling (either homogeneous or heterogeneous). Our simulations illustrate and provide new insights into this

  17. Role of echocardiography in diagnosis and risk stratification in heart failure with left ventricular systolic dysfunction

    PubMed Central

    Ciampi, Quirino; Villari, Bruno

    2007-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Echocardiography represents the "gold standard" in the assessment of LV systolic dysfunction and in the recognition of systolic heart failure, since dilatation of the LV results in alteration of intracardiac geometry and hemodynamics leading to increased morbidity and mortality. The functional mitral regurgitation is a consequence of adverse LV remodelling that occurs with a structurally normal valve and it is a marker of adverse prognosis. Diastolic dysfunction plays a major role in signs and symptoms of HF and in the risk stratification, and provides prognostic information independently in HF patients and impaired systolic function. Ultrasound lung comets are a simple echographic sign of extravascular lung water, more frequently associated with left ventricular diastolic and/or systolic dysfunction, which can integrate the clinical and pathophysiological information provided by conventional echocardiography and provide a useful information for prognostic stratification of HF patients. Contractile reserve is defined as the difference between values of an index of left ventricular contractility during peak stress and its baseline values and the presence of myocardial viability predicts a favorable outcome. A non-invasive echocardiographic method for the evaluation of force-frequency relationship has been proposed to assess the changes in contractility during stress echo. In conclusion, in HF patients, the evaluation of systolic, diastolic function and myocardial contractile reserve plays a fundamental role in the risk stratification. The highest risk is present in HF patients with a heart that is weak, big, noisy, stiff and wet. PMID:17910744

  18. Role of echocardiography in diagnosis and risk stratification in heart failure with left ventricular systolic dysfunction.

    PubMed

    Ciampi, Quirino; Villari, Bruno

    2007-10-02

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Echocardiography represents the "gold standard" in the assessment of LV systolic dysfunction and in the recognition of systolic heart failure, since dilatation of the LV results in alteration of intracardiac geometry and hemodynamics leading to increased morbidity and mortality. The functional mitral regurgitation is a consequence of adverse LV remodelling that occurs with a structurally normal valve and it is a marker of adverse prognosis. Diastolic dysfunction plays a major role in signs and symptoms of HF and in the risk stratification, and provides prognostic information independently in HF patients and impaired systolic function. Ultrasound lung comets are a simple echographic sign of extravascular lung water, more frequently associated with left ventricular diastolic and/or systolic dysfunction, which can integrate the clinical and pathophysiological information provided by conventional echocardiography and provide a useful information for prognostic stratification of HF patients. Contractile reserve is defined as the difference between values of an index of left ventricular contractility during peak stress and its baseline values and the presence of myocardial viability predicts a favorable outcome. A non-invasive echocardiographic method for the evaluation of force-frequency relationship has been proposed to assess the changes in contractility during stress echo. In conclusion, in HF patients, the evaluation of systolic, diastolic function and myocardial contractile reserve plays a fundamental role in the risk stratification. The highest risk is present in HF patients with a heart that is weak, big, noisy, stiff and wet.

  19. The Multiple Electrocardiographic Manifestations of Ventricular Repolarization Memory

    PubMed Central

    Chiale, Pablo A; Etcheverry, Daniel; Pastori, Julio D; Fernández, Pablo A; Garro, Hugo A; González, Mario D; Elizari, Marcelo V

    2014-01-01

    T wave “memory” is a peculiar variety of cardiac remodeling caused by a transient change in the course of ventricular depolarization (due to ventricular pacing, rate-dependent intraventricular block, ventricular preexcitation or tachyarrhythmias with wide QRS complexes). It is usually manifested by inverted T waves that appears when normal ventricular activation is restored. This phenomenon is cumulative and occurs earlier if the ventricular myocardium has previously been exposed to the same conditioning stimuli. In this article the different conditions giving rise to “classical” T wave memory development are reviewed and also “another” type of T wave memory is described. It is also shown that cardiac memory may induce not only negative (pseudo-primary) T waves but also a reversal of primary and pseudo-primary T waves leading to “normalization” of ventricular repolarization. The knowledge of these dissimilar consequences of T wave memory is essential to assess the characteristics of ventricular repolarization. PMID:24827802

  20. Remodeling the Media Center.

    ERIC Educational Resources Information Center

    Baule, Steven M.

    1998-01-01

    Discusses items that need to be considered when remodeling a school media center. Highlights include space and location for various functions, including projections of print versus electronic media; electrical and data wiring needs; lighting; security and supervision; and reuse of existing furniture and equipment. (LRW)

  1. Androgenic anabolic steroids also impair right ventricular function.

    PubMed

    Kasikcioglu, Erdem; Oflaz, Huseyin; Umman, Berrin; Bugra, Zehra

    2009-05-01

    Chronic anabolic steroid use suppresses left ventricular functions. However, there is no information regarding the chronic effects of anabolic steroids on right ventricular function which also plays a key role in global cardiac function. The main objective of the present study was to investigate the effects of androgenic anabolic steroids usage among athletes on remodeling the right part of the heart. Androgenic-anabolic steroids-using bodybuilders had smaller diastolic velocities of both ventricles than drug-free bodybuilders and sedentary counterparts. This study shows that androgenic anabolic steroids-using bodybuilders exhibited depressed diastolic functions of both ventricles.

  2. Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice

    PubMed Central

    Diwan, Abhinav; Krenz, Maike; Syed, Faisal M.; Wansapura, Janaka; Ren, Xiaoping; Koesters, Andrew G.; Li, Hairong; Kirshenbaum, Lorrie A.; Hahn, Harvey S.; Robbins, Jeffrey; Jones, W. Keith; Dorn, Gerald W.

    2007-01-01

    Following myocardial infarction, nonischemic myocyte death results in infarct expansion, myocardial loss, and ventricular dysfunction. Here, we demonstrate that a specific proapoptotic gene, Bnip3, minimizes ventricular remodeling in the mouse, despite having no effect on early or late infarct size. We evaluated the effects of ablating Bnip3 on cardiomyocyte death, infarct size, and ventricular remodeling after surgical ischemia/reperfusion (IR) injury in mice. Immediately following IR, no significant differences were observed between Bnip3–/– and WT mice. However, at 2 days after IR, apoptosis was diminished in Bnip3–/– periinfarct and remote myocardium, and at 3 weeks after IR, Bnip3–/– mice exhibited preserved LV systolic performance, diminished LV dilation, and decreased ventricular sphericalization. These results suggest myocardial salvage by inhibition of apoptosis. Forced cardiac expression of Bnip3 increased cardiomyocyte apoptosis in unstressed mice, causing progressive LV dilation and diminished systolic function. Conditional Bnip3 overexpression prior to coronary ligation increased apoptosis and infarct size. These studies identify postischemic apoptosis by myocardial Bnip3 as a major determinant of ventricular remodeling in the infarcted heart, suggesting that Bnip3 may be an attractive therapeutic target. PMID:17909626

  3. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects

    PubMed Central

    Rajagopalan, Viswanathan; Zhang, Youhua; Ojamaa, Kaie; Chen, Yue-feng; Pingitore, Alessandro; Pol, Christine J.; Saunders, Debra; Balasubramanian, Krithika; Towner, Rheal A.; Gerdes, A. Martin

    2016-01-01

    Background A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI. Methods and Results Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy. Conclusions Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans. PMID:26981865

  4. Nucleosome Remodeling and Epigenetics

    PubMed Central

    Becker, Peter B.; Workman, Jerry L.

    2013-01-01

    Eukaryotic chromatin is kept flexible and dynamic to respond to environmental, metabolic, and developmental cues through the action of a family of so-called “nucleosome remodeling” ATPases. Consistent with their helicase ancestry, these enzymes experience conformation changes as they bind and hydrolyze ATP. At the same time they interact with DNA and histones, which alters histone–DNA interactions in target nucleosomes. Their action may lead to complete or partial disassembly of nucleosomes, the exchange of histones for variants, the assembly of nucleosomes, or the movement of histone octamers on DNA. “Remodeling” may render DNA sequences accessible to interacting proteins or, conversely, promote packing into tightly folded structures. Remodeling processes participate in every aspect of genome function. Remodeling activities are commonly integrated with other mechanisms such as histone modifications or RNA metabolism to assemble stable, epigenetic states. PMID:24003213

  5. Role of Arginase in Vessel Wall Remodeling

    PubMed Central

    Durante, William

    2013-01-01

    Arginase metabolizes the semi-essential amino acid l-arginine to l-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and l-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages toward an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide (NO) synthesis by competing with NO synthase for substrate, l-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease. PMID:23717309

  6. Pediatric ventricular assist devices

    PubMed Central

    Burki, Sarah; Zafar, Farhan; Morales, David Luis Simon

    2015-01-01

    The domain of pediatric ventricular assist device (VAD) has recently gained considerable attention. Despite the fact that, historically, the practice of pediatric mechanical circulatory support (MCS) has lagged behind that of adult patients, this gap between the two groups is narrowing. Currently, the Berlin EXCOR VAD is the only pediatric-specific durable VAD approved by the U.S Food and Drug Administration (FDA). The prospective Berlin Heart trial demonstrated a successful outcome, either bridge to transplantation (BTT), or in rare instances, bridge to recovery, in approximately 90% of children. Also noted during the trial was, however, a high incidence of adverse events such as embolic stroke, bleeding and infection. This has incentivized some pediatric centers to utilize adult implantable continuous-flow devices, for instance the HeartMate II and HeartWare HVAD, in children. As a result of this paradigm shift, the outlook of pediatric VAD support has dramatically changed: Treatment options previously unavailable to children, including outpatient management and even destination therapy, have now been becoming a reality. The sustained demand for continued device miniaturization and technological refinements is anticipated to extend the range of options available to children—HeartMate 3 and HeartWare MVAD are two examples of next generation VADs with potential pediatric application, both of which are presently undergoing clinical trials. A pediatric-specific continuous-flow device is also on the horizon: the redesigned Infant Jarvik VAD (Jarvik 2015) is undergoing pre-clinical testing, with a randomized clinical trial anticipated to follow thereafter. The era of pediatric VADs has begun. In this article, we discuss several important aspects of contemporary VAD therapy, with a particular focus on challenges unique to the pediatric population. PMID:26793341

  7. Chromatin Remodeling and Plant Immunity.

    PubMed

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    2017-01-01

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance?

  8. Revascularization in severe left ventricular dysfunction.

    PubMed

    Velazquez, Eric J; Bonow, Robert O

    2015-02-17

    The highest-risk patients with heart failure with reduced ejection fraction are those with ischemic cardiomyopathy and severe left ventricular systolic dysfunction (ejection fraction≤35%). The cornerstone of treatment is guideline-driven medical therapy for all patients and implantable device therapy for appropriately selected patients. Surgical revascularization offers the potential for improved survival and quality of life, particularly in patients with more extensive multivessel disease and the greatest degree of left ventricular systolic dysfunction and remodeling. These are also the patients at greatest short-term risk of mortality with coronary artery bypass graft surgery. The short-term risks of surgery need to be balanced against the potential for long-term benefit. This review discusses the evolving data on the role of surgical revascularization, surgical ventricular reconstruction, and mitral valve surgery in this high-risk patient population.

  9. Arrhythmogenic right ventricular cardiomyopathy: new insights into mechanisms of disease.

    PubMed

    Saffitz, Jeffrey E; Asimaki, Angeliki; Huang, Hayden

    2010-01-01

    Arrhythmogenic right ventricular cardiomyopathy is a primary heart muscle disorder characterized by the early occurrence of arrhythmias often out of proportion to the extent of structural remodeling and contractile derangement. Approximately 40% of patients with arrhythmogenic right ventricular cardiomyopathy have one or more mutations in genes encoding proteins in desmosomes, intercellular adhesion junctions which, in cardiac myocytes, reside within intercalated disks. Some desmosomal proteins fulfill roles both as structural proteins in cell-cell adhesion junctions and as signaling molecules in pathways mediated by Wnt ligands. Evidence is increasing that mutations in desmosomal proteins can perturb the normal balance of critical proteins in junctions and the cytosol which, in turn, could alter gene expression by circumventing normal Wnt signaling pathways. This review highlights recent advances in understanding the pathogenesis of arrhythmogenic right ventricular cardiomyopathy and presents evidence suggesting that the disease is caused by a combination of altered cellular biomechanical behavior and altered signaling.

  10. Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity.

    PubMed

    Martínez-Martínez, Ernesto; López-Ándres, Natalia; Jurado-López, Raquel; Rousseau, Elodie; Bartolomé, Mará Visitación; Fernández-Celis, Amaya; Rossignol, Patrick; Islas, Fabian; Antequera, Alfonso; Prieto, Santiago; Luaces, María; Cachofeiro, Victoria

    2015-11-01

    Remodeling, diastolic dysfunction, and arterial stiffness are some of the alterations through which obesity affects the cardiovascular system. Fibrosis and inflammation are important mechanisms underlying cardiovascular remodeling, although the precise promoters involved in these processes are still unclear. Galectin-3 (Gal-3) induces inflammation and fibrosis in the cardiovascular system. We have investigated the potential role of Gal-3 in cardiac damage in morbidly obese patients, and we have evaluated the protective effect of the Gal-3 inhibition in the occurrence of cardiovascular fibrosis and inflammation in an experimental model of obesity. Morbid obesity is associated with alterations in cardiac remodeling, mainly left ventricular hypertrophy and diastolic dysfunction. Obesity and hypertension are the main determinants of left ventricular hypertrophy. Insulin resistance, left ventricular hypertrophy, and circulating levels of C-reactive protein and Gal-3 are associated with a worsening of diastolic function in morbidly obese patients. Obesity upregulates Gal-3 production in the cardiovascular system in a normotensive animal model of diet-induced obesity by feeding for 6 weeks a high-fat diet (33.5% fat). Gal-3 inhibition with modified citrus pectin (100 mg/kg per day) reduced cardiovascular levels of Gal-3, total collagen, collagen I, transforming and connective growth factors, osteopontin, and monocyte chemoattractant protein-1 in the heart and aorta of obese animals without changes in body weight or blood pressure. In morbidly obese patients, Gal-3 levels are associated with diastolic dysfunction. In obese animals, Gal-3 blockade decreases cardiovascular fibrosis and inflammation. These data suggest that Gal-3 could be a novel therapeutic target in cardiac fibrosis and inflammation associated with obesity.

  11. Compensatory Effect between Aortic Stiffening and Remodelling during Ageing

    PubMed Central

    Guala, Andrea; Camporeale, Carlo; Ridolfi, Luca

    2015-01-01

    The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy behaviour depends on a subtle balance between mechanical and geometrical properties. Several clinical studies demonstrated that such a balance progressively breaks down during ageing, when the aorta stiffens and remodels by increasing its diameter. These two degenerative processes however, have different impacts on the arterial wave pattern. They both tend to compensate for each other, thus reducing the detrimental effect they would have had if they had arisen individually. This remarkable compensatory mechanism is investigated by a validated multi-scale model, with the aim to elucidate how aortic stiffening and remodelling quantitatively impact the complex interplay between forward and reflected backward waves in the arterial network. We focus on the aorta and on the pressure at the ventricular-aortic interface, which epidemiological studies demonstrate to play a key role in cardiovascular diseases. PMID:26426360

  12. Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity, cumulative dose and remodeling

    PubMed Central

    2013-01-01

    Background The late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors. Methods Thirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO2). CMR measured ventricular function, mass, T1 and T2 values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T1 values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography. Results Patients had normal LVEF (59 ± 7%) but peak VO2 was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = −0.49). Increased ECV correlated with decreased mass/volume ratio (r = −0.64), decreased LV wall thickness/height ratio (r = −0.72), lower peak VO2(r = −0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO2 or cumulative dose. Conclusions Myocardial T1 and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning. PMID:23758789

  13. Remodeling with the sun

    SciTech Connect

    Bodzin, S.

    1997-05-01

    Remodeling is the perfect time to improve daylighting, direct gain heating and shading with passive solar techniques. It can also provide the best opportunity to add solar water heating or even photoboltaics to a home. This article describes addition of such energy efficient plans to a home in terms of what is needed and what the benefits are: adding windows, North glass, east and west glass, south glass, daylighting, the roof, shingles and roofing tiles, walls and floors, solar hot water, photovoltaics. Two side bars discuss the sunplace: a passive solar room and angles and overhangs.

  14. Extracellular Matrix Remodeling During the Progression of Volume Overload-Induced Heart Failure

    PubMed Central

    Hutchinson, Kirk R.; Stewart, James A.; Lucchesi, Pamela A.

    2009-01-01

    Volume overload-induced heart failure results in progressive left ventricular remodeling characterized by chamber dilation, eccentric cardiac myocyte hypertrophy and changes in extracellular matrix (ECM) remodeling changes. The ECM matrix scaffold is an important determinant of the structural integrity of the myocardium and actively participates in force transmission across the LV wall. In response to this hemodynamic overload, the ECM undergoes a distinct pattern of remodeling that differs from pressure overload. Once thought to be a static entity, the ECM is now regarded to be a highly adaptive structure that is dynamically regulated by mechanical stress, neurohormonal activation, inflammation and oxidative stress, that result in alterations in collagen and other matrix components and a net change in matrix metalloproteinase (MMP) expression and activation. These changes dictate overall ECM turnover during volume overload hear failure progression. This review will discuss the cellular and molecular mechanisms that dictate the temporal patterns of ECM remodeling during heart disease progression. PMID:19524591

  15. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    PubMed Central

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  16. Exposure to diesel exhaust particulates induces cardiac dysfunction and remodeling

    PubMed Central

    Bradley, Jessica M.; Cryar, Kipp A.; El Hajj, Milad C.; El Hajj, Elia C.

    2013-01-01

    Chronic exposure to diesel exhaust particulates (DEP) increases the risk of cardiovascular disease in urban residents, predisposing them to the development of several cardiovascular stresses, including myocardial infarctions, arrhythmias, thrombosis, and heart failure. DEP contain a high level of polycyclic aromatic hydrocarbons, which activate the aryl hydrocarbon receptor (AHR). We hypothesize that exposure to DEP elicits ventricular remodeling through the activation of the AHR pathway, leading to ventricular dilation and dysfunction. Male Sprague-Dawley rats were exposed by nose-only nebulization to DEP (SRM 2975, 0.2 mg/ml) or vehicle for 20 min/day × 5 wk. DEP exposure resulted in eccentric left ventricular dilation (8% increased left ventricular internal diameter at diastole and 23% decreased left ventricular posterior wall thickness at diastole vs. vehicle), as shown by echocardiograph assessment. Histological analysis using Picrosirius red staining revealed that DEP reduced cardiac interstitial collagen (23% decrease vs. vehicle). Further assessment of cardiac function using a pressure-volume catheter indicated impaired diastolic function (85% increased end-diastolic pressure and 19% decreased Tau vs. vehicle) and contractility (57 and 48% decreased end-systolic pressure-volume relationship and maximum change in pressure over time vs. end-diastolic volume compared with vehicle, respectively) in the DEP-exposed animals. Exposure to DEP significantly increased cardiac expression of AHR (19% increase vs. vehicle). In addition, DEP significantly decreased the cardiac expression of hypoxia inducible factor-1α, the competitive pathway to the AHR, and vascular endothelial growth factor, a downstream mediator of hypoxia inducible factor-1α (26 and 47% decrease vs. vehicle, respectively). These findings indicate that exposure to DEP induced left ventricular dilation by loss of collagen through an AHR-dependent mechanism. PMID:23887904

  17. Electroacupuncture improves cardiac function and remodeling by inhibition of sympathoexcitation in chronic heart failure rats.

    PubMed

    Ma, Luyao; Cui, Baiping; Shao, Yongfeng; Ni, Buqing; Zhang, Weiran; Luo, Yonggang; Zhang, Shijiang

    2014-05-15

    Chronic heart failure (CHF) is responsible for significant morbidity and mortality worldwide, mainly as a result of neurohumoral activation. Acupuncture has been used to treat a wide range of diseases and conditions. In this study, we investigated the effects of electroacupuncture (EA) on the sympathetic nerve activity, heart function, and remodeling in CHF rats after ligation of the left anterior descending coronary artery. CHF rats were randomly selected to EA and control groups for acute and chronic experiments. In the acute experiment, both the renal sympathetic nerve activity and cardiac sympathetic afferent reflex elicited by epicardial application of capsaicin were recorded. In the chronic experiment, we performed EA for 30 min once a day for 1 wk to test the long-term EA effects on heart function, remodeling, as well as infarct size in CHF rats. The results show EA significantly decreased the renal sympathetic nerve activity effectively, inhibited cardiac sympathetic afferent reflex, and lowered the blood pressure of CHF rats. Treating CHF rats with EA for 1 wk dramatically increased left ventricular ejection fraction and left ventricular fraction shortening, reversed the enlargement of left ventricular end-systolic dimension and left ventricular end-diastolic dimension, and shrunk the infarct size. In this experiment, we demonstrated EA attenuates sympathetic overactivity. Additionally, long-term EA improves cardiac function and remodeling and reduces infarct size in CHF rats. EA is a novel and potentially useful therapy for treating CHF.

  18. Is cardiac resynchronization therapy for right ventricular failure in pulmonary arterial hypertension of benefit?

    PubMed

    Rasmussen, Jason T; Thenappan, Thenappan; Benditt, David G; Weir, E Kenneth; Pritzker, Marc R

    2014-12-01

    Pulmonary arterial hypertension is a manifestation of a group of disorders leading to pulmonary vascular remodeling and increased pulmonary pressures. The right ventricular (RV) response to chronic pressure overload consists of myocardial remodeling, which is in many ways similar to that seen in left ventricular (LV) failure. Maladaptive myocardial remodeling often leads to intraventricular and interventricular dyssychrony, an observation that has led to cardiac resynchronization therapy (CRT) for LV failure. CRT has proven to be an effective treatment strategy in subsets of patients with LV failure resulting in improvement in LV function, heart failure symptoms, and survival. Current therapy for pulmonary arterial hypertension is based on decreasing pulmonary vascular resistance, and there is currently no effective therapy targeting the right ventricle or maladaptive ventricular remodeling in these patients. This review focuses on the RV response to chronic pressure overload, its effect on electromechanical coupling and synchrony, and how lessons learned from left ventricular cardiac resynchronization might be applied as therapy for RV dysfunction in the context of pulmonary arterial hypertension.

  19. Soluble ST2 Levels and Left Ventricular Structure and Function in Patients With Metabolic Syndrome

    PubMed Central

    Celic, Vera; Majstorovic, Anka; Pencic-Popovic, Biljana; Sljivic, Aleksandra; Lopez-Andres, Natalia; Roy, Ignacio; Escribano, Elena; Beunza, Maite; Melero, Amaia; Floridi, Federico; Magrini, Laura; Marino, Rossella; Salerno, Gerardo; Cardelli, Patrizia

    2016-01-01

    Background A biomarker that is of great interest in relation to adverse cardiovascular events is soluble ST2 (sST2), a member of the interleukin family. Considering that metabolic syndrome (MetS) is accompanied by a proinflammatory state, we aimed to assess the relationship between sST2 and left ventricular (LV) structure and function in patients with MetS. Methods A multicentric, cross-sectional study was conducted on180 MetS subjects with normal LV ejection fraction as determined by echocardiography. LV hypertrophy (LVH) was defined as an LV mass index greater than the gender-specific upper limit of normal as determined by echocardiography. LV diastolic dysfunction (DD) was assessed by pulse-wave and tissue Doppler imaging. sST2 was measured by using a quantitative monoclonal ELISA assay. Results LV mass index (β=0.337, P<0.001, linear regression) was independently associated with sST2 concentrations. Increased sST2 was associated with an increased likelihood of LVH [Exp (B)=2.20, P=0.048, logistic regression] and increased systolic blood pressure [Exp (B)=1.02, P=0.05, logistic regression]. Comparing mean sST2 concentrations (adjusted for age, body mass index, gender) between different LV remodeling patterns, we found the greatest sST2 level in the group with concentric hypertrophy. There were no differences in sST2 concentration between groups with and without LV DD. Conclusions Increased sST2 concentration in patients with MetS was associated with a greater likelihood of exhibiting LVH. Our results suggest that inflammation could be one of the principal triggering mechanisms for LV remodeling in MetS. PMID:27578507

  20. Antagonism of Stem Cell Factor/c-kit Signaling Attenuates Neonatal Chronic Hypoxia-Induced Pulmonary Vascular Remodeling

    PubMed Central

    Young, Karen C; Torres, Eneida; Hehre, Dorothy; Wu, Shu; Suguihara, Cleide; Hare, Joshua M.

    2015-01-01

    Background Accumulating evidence suggests that c-kit positive cells are present in the remodeled pulmonary vasculature bed of patients with pulmonary hypertension (PH). Whether stem cell factor (SCF)/ c-kit regulated pathways potentiate pulmonary vascular remodeling is unknown. Here, we tested the hypothesis that attenuated c-kit signaling would decrease chronic hypoxia-induced pulmonary vascular remodeling by decreasing pulmonary vascular cell mitogenesis. Methods Neonatal FVB/NJ mice treated with non-immune IgG (PL), or c-kit neutralizing antibody (ACK2) as well as c-kit mutant mice (WBB6F1- Kit W− v/ +) and their congenic controls, were exposed to normoxia (FiO2=0.21) or hypoxia (FiO2=0.12) for two weeks. Following this exposure, right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), pulmonary vascular cell proliferation and remodeling were evaluated. Results As compared to chronically hypoxic controls, c-kit mutant mice had decreased RVSP, RVH, pulmonary vascular remodeling and proliferation. Consistent with these findings, administration of ACK2 to neonatal mice with chronic hypoxia-induced PH decreased RVSP, RVH, pulmonary vascular cell proliferation and remodeling. This attenuation in PH was accompanied by decreased extracellular signal-regulated protein kinase (ERK) 1/2 activation. Conclusion SCF/c-kit signaling may potentiate chronic hypoxia-induced vascular remodeling by modulating ERK activation. Inhibition of c-kit activity may be a potential strategy to alleviate PH. PMID:26705118

  1. To Remodel or To Build?

    ERIC Educational Resources Information Center

    Rosenblum, Todd

    2009-01-01

    The question of remodeling an existing house to make it wheelchair accessible or building a new barrier-free house is a difficult decision. This article presents some initial questions and considerations followed by a list of pros and cons for remodeling an existing house vs. building a new house.

  2. Ventricular Septal Defect (VSD)

    MedlinePlus

    ... specially sized mesh device to close the hole. Hybrid procedure. A hybrid procedure uses surgical and catheter-based techniques. Access ... clinicalkey.com. Accessed Sept. 15, 2014. Konetti NR. Hybrid muscular ventricular defect closure: Surgeon or physician. Indian ...

  3. Premature Ventricular Contractions (PVCs)

    MedlinePlus

    ... in the body that may be caused by caffeine, tobacco, exercise or anxiety Injury to the heart ... may increase your risk of premature ventricular contractions: Caffeine, tobacco and alcohol Exercise High blood pressure (hypertension) ...

  4. Left Ventricular Hypertrophy

    MedlinePlus

    ... at the time of their diagnosis with hypertension. Aortic valve stenosis. This disease is a narrowing of the tissue ... muscle and disease. In addition to hypertension and aortic valve stenosis, factors that increase your risk for left ventricular ...

  5. No-Regrets Remodeling, 2nd Edition

    SciTech Connect

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  6. Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure

    PubMed Central

    Reis, José Rosino de Araújo Rocha; Cardoso, Juliano Novaes; Cardoso, Cristina Martins dos Reis; Pereira-Barretto, Antonio Carlos

    2015-01-01

    In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis. PMID:26131706

  7. Galectin-3 and post-myocardial infarction cardiac remodeling.

    PubMed

    Meijers, Wouter C; van der Velde, A Rogier; Pascual-Figal, Domingo A; de Boer, Rudolf A

    2015-09-15

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in order to preserve cardiac function. A hallmark herein is fibrosis formation, both in the early and late phase following acute myocardial infarction. Galectin-3, a β-galactoside-binding lectin, which is a shared factor in fibrosis formation in multiple organs, has an established role in cardiac fibrosis in the setting of pressure overload, neuro-endocrine activation and hypertension, but its role in post- myocardial infarction remodeling has received less attention. However, accumulative experimental studies have shown that myocardial galectin-3 expression is upregulated after myocardial infarction, both on mRNA and protein level. This already occurs shortly after myocardial infarction in the infarcted and border zone area, and also at a later stage in the spared myocardium, contributing to tissue repair and fibrosis. This is associated with typical aspects of fibrosis formation, such as apposition of matricellular proteins and increased factors of collagen turnover. Interestingly, myocardial fibrosis in experimental post-myocardial infarction cardiac remodeling could be attenuated by galectin-3 inhibition. In clinical studies, circulating galectin-3 levels have been shown to identify patients at risk for new-onset heart failure and atrial fibrillation. Circulating galectin-3 levels also predict progressive left ventricular dilatation after myocardial infarction. From literature we conclude that galectin-3 is an active player in cardiac remodeling after myocardial infarction. Future studies should focus on the dynamics of galectin-3 activation after myocardial infarction, and study the possibilities to target galectin-3.

  8. OSM mitigates post-infarction cardiac remodeling and dysfunction by up-regulating autophagy through Mst1 suppression.

    PubMed

    Hu, Jianqiang; Zhang, Lei; Zhao, Zhijing; Zhang, Mingming; Lin, Jie; Wang, Jiaxing; Yu, Wenjun; Man, Wanrong; Li, Congye; Zhang, Rongqing; Gao, Erhe; Wang, Haichang; Sun, Dongdong

    2016-11-04

    The incidence and prevalence of heart failure (HF) in the world are rapidly rising possibly attributed to the worsened HF following myocardial infarction (MI) in recent years. Here we examined the effects of oncostatin M (OSM) on postinfarction cardiac remodeling and the underlying mechanisms involved. MI model was induced using left anterior descending coronary artery (LAD) ligation. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulated MI. Our results revealed that OSM alleviated left ventricular remodeling, promoted cardiac function, restored mitochondrial cristae density and architecture disorders after 4weeks of MI. Enhanced autophagic flux was indicated in cardiomyocytes transduced with Ad-GFP -LC3 in the OSM treated group as compared with the MI group. OSM receptor Oβ knockout blocked the beneficial effects of OSM in postinfarction cardiac remodeling and cardiomyocytes autophagy. OSM pretreatment significantly alleviated left ventricular remodeling and dysfunction in Mst1 transgenic mice, while it failed to reverse further the postinfarction left ventricular dilatation and cardiac function in the Mst1 knockout mice. Our data revealed that OSM alleviated postinfarction cardiac remodeling and dysfunction by enhancing cardiomyocyte autophagy. OSM holds promise as a therapeutic target in treating HF after MI through Oβ receptor by inhibiting Mst1 phosphorylation.

  9. Vulnerability to ventricular fibrillation

    NASA Astrophysics Data System (ADS)

    Janse, Michiel J.

    1998-03-01

    One of the factors that favors the development of ventricular fibrillation is an increase in the dispersion of refractoriness. Experiments will be described in which an increase in dispersion in the recovery of excitability was determined during brief episodes of enhanced sympathetic nerve activity, known to increase the risk of fibrillation. Whereas in the normal heart ventricular fibrillation can be induced by a strong electrical shock, a premature stimulus of moderate intensity only induces fibrillation in the presence of regional ischemia, which greatly increases the dispersion of refractoriness. One factor that is of importance for the transition of reentrant ventricular tachycardia to ventricular fibrillation during acute regional ischemia is the subendocardial Purkinje system. After selective destruction of the Purkinje network by lugol, reentrant tachycardias still develop in the ischemic region, but they do not degenerate into fibrillation. Finally, attempts were made to determine the minimal mass of thin ventricular myocardium required to sustain fibrillation induced by burst pacing. This was done by freezing of subendocardial and midmural layers. The rim of surviving epicardial muscle had to be larger than 20 g. Extracellular electrograms during fibrillation in both the intact and the "frozen" left ventricle were indistinguishable, but activation patterns were markedly different. In the intact ventricle epicardial activation was compatible with multiple wavelet reentry, in the "frozen" heart a single, or at most two wandering reentrant waves were seen.

  10. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  11. Correlation of Left Ventricular Diastolic Function and Left Ventricular Geometry in Patients with Obstructive Sleep Apnoea Syndrome

    PubMed Central

    Wang, J; Zhang, H; Wu, C; Han, J; Guo, Z; Jia, C; Yang, L; Hao, Y; Xu, K; Liu, X; Si, J

    2015-01-01

    ABSTRACT Background: The aim of this study is to evaluate the correlation of the left ventricular diastolic function and the left ventricular geometry in patients with obstructive sleep apnoea syndrome (OSAS) by echocardiography. Methods: The 181 patients diagnosed with OSAS were divided into the normal geometry group (NG), the concentric remodelling group (CR), the eccentric hypertrophy group (EH) and the concentric hypertrophy group (CH). Pearson correlation analysis and multiple linear regression analysis were performed toward the correlation of the left ventricular diastolic function and the left ventricular geometry. Results: The E peak in the EH and CH group was significantly reduced, with significant difference; the E/A, Em, Am and Em/Am was reduced in the order of the CR, EH and CH groups, while E/Em was increased, and the difference was significant. Pearson correlation analysis revealed that the Em/Am showed significant negative correlations with the left ventricular mass index (LVMI) [r = −0.419] and relative wall thickness (RWT) [r = −0.289], while the E/Em was significantly positively correlated with the LVMI (r = 0.638) and RWT [r = 0.328] (p < 0.001). Multiple linear regression analysis revealed that LVMI and RWT had influence on the Em/Am and E/Em (r2 = 0.402, r2 = 0.107, p < 0.001). The left ventricular diastolic dysfunction was the worst in the CH group. Conclusions: There was correlation between the left ventricular diastolic dysfunction and the changes in cardiac geometry. PMID:26360680

  12. Ventricular Septal Defect (For Parents)

    MedlinePlus

    ... Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System ECG (Electrocardiogram) Anesthesia - What to Expect Tetralogy of ... Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System Contact Us Print Resources Send to a friend ...

  13. Ventricular Septal Defect (For Parents)

    MedlinePlus

    ... Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System ECG (Electrocardiogram) Anesthesia - What to Expect Tetralogy of ... Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System Contact Us Print Resources Send to a Friend ...

  14. Building and Remodeling Synapses

    PubMed Central

    Benson, Deanna L.; Huntley, George W.

    2011-01-01

    Synaptic junctions are generated by adhesion proteins that bridge the synaptic cleft to firmly anchor pre- and postsynaptic membranes. Several cell adhesion molecule (CAM) families localize to synapses, but it is not yet completely understood how each synaptic CAM family contributes to synapse formation and/or structure, and whether or how smaller groups of CAMs serve as minimal, functionally cooperative adhesive units upon which structure is based. Synapse structure and function evolve over the course of development, and in mature animals, synapses are composed of a greater number of proteins, surrounded by a stabilizing extracellular matrix, and often contacted by astrocytic processes. Thus, in mature networks undergoing plasticity, persistent changes in synapse strength, morphology or number must be accompanied by selective and regulated remodeling of the neuropil. Recent work indicates that regulated, extracellular proteolysis may be essential for this, and rather than simply acting permissively to enable synapse plasticity, is more likely playing a proactive role in driving coordinated synaptic structural and functional modifications that underlie persistent changes in network activity. PMID:20882551

  15. Large right ventricular thrombus.

    PubMed

    Sousa, Carla; Almeida, Pedro; Gonçalves, Alexandra; Rodrigues, João; Rangel, Inês; Macedo, Filipe; Maciel, M Júlia

    2014-01-01

    Right ventricular thrombosis is a rare yet potentially fatal condition. It has been described in association with hypercoagulability states, autoimmune diseases and dilated cardiomyopathy. Echocardiography constitutes the election tool for diagnosis and characterization of these entities, allowing for the differentiation between the various types of thrombi. We present a case of a patient with alcoholic dilated cardiomyopathy admitted for congestive heart failure and lower respiratory infection. In the diagnostic approach, a routine echocardiography revealed a large mural right ventricular thrombus in association with severe biventricular dysfunction. The patient was proposed for anticoagulation strategy, which he refused.

  16. Right ventricular failure in congenital heart disease.

    PubMed

    Cho, Young Kuk; Ma, Jae Sook

    2013-03-01

    Despite developments in surgical techniques and other interventions, right ventricular (RV) failure remains an important clinical problem in several congenital heart diseases (CHD). RV function is one of the most important predictors of mortality and morbidity in patients with CHD. RV failure is a progressive disorder that begins with myocardial injury or stress, neurohormonal activation, cytokine activation, altered gene expression, and ventricular remodeling. Pressure-overload RV failure caused by RV outflow tract obstruction after total correction of tetralogy of Fallot, pulmonary stenosis, atrial switch operation for transposition of the great arteries, congenitally corrected transposition of the great arteries, and systemic RV failure after the Fontan operation. Volume-overload RV failure may be caused by atrial septal defect, pulmonary regurgitation, or tricuspid regurgitation. Although the measurement of RV function is difficult because of many reasons, the right ventricle can be evaluated using both imaging and functional modalities. In clinical practice, echocardiography is the primary mode for the evaluation of RV structure and function. Cardiac magnetic resonance imaging is increasingly used for evaluating RV structure and function. A comprehensive evaluation of RV function may lead to early and optimal management of RV failure in patients with CHD.

  17. Atrial Electrophysiological Remodeling and Fibrillation in Heart Failure

    PubMed Central

    Pandit, Sandeep V.; Workman, Antony J.

    2016-01-01

    Heart failure (HF) causes complex, chronic changes in atrial structure and function, which can cause substantial electrophysiological remodeling and predispose the individual to atrial fibrillation (AF). Pharmacological treatments for preventing AF in patients with HF are limited. Improved understanding of the atrial electrical and ionic/molecular mechanisms that promote AF in these patients could lead to the identification of novel therapeutic targets. Animal models of HF have identified numerous changes in atrial ion currents, intracellular calcium handling, action potential waveform and conduction, as well as expression and signaling of associated proteins. These studies have shown that the pattern of electrophysiological remodeling likely depends on the duration of HF, the underlying cardiac pathology, and the species studied. In atrial myocytes and tissues obtained from patients with HF or left ventricular systolic dysfunction, the data on changes in ion currents and action potentials are largely equivocal, probably owing mainly to difficulties in controlling for the confounding influences of multiple variables, such as patient’s age, sex, disease history, and drug treatments, as well as the technical challenges in obtaining such data. In this review, we provide a summary and comparison of the main animal and human electrophysiological studies to date, with the aim of highlighting the consistencies in some of the remodeling patterns, as well as identifying areas of contention and gaps in the knowledge, which warrant further investigation. PMID:27812293

  18. Relationship between self-reported residential indoor remodeling and semen quality: a case-control study.

    PubMed

    Miao, Mao-Hua; Li, Zheng; Li, De-Kun; Yan, Bei; Liang, Hong; Zhi, Er-Lei; Du, Hong-Wei; Yuan, Wei

    2015-01-01

    The present study examined the association between residential indoor remodeling and poor semen quality. Sperm donors aged 18-45 years old were recruited in Shanghai, China. Semen specimens were collected and analyzed. An in-person interview was conducted to obtain information on the history of indoor remodeling and potential confounders. A total of 70 participants with abnormal semen quality (case group) and 68 controls were examined. A total of 20 subjects reported indoor remodeling in the recent 24 months, and among them 17 subjects reported indoor remodeling in the recent 12 months. Compared with participants with no history of indoor remodeling, participants with a history of indoor remodeling in the recent 24 months were more than three times as likely to have poor sperm quality (adjusted odds ratio = 3.8, 95% confidence interval: 1.3-12.0) after controlling for potential confounders. The association was strengthened when the analysis was restricted to those who had indoor remodeling in the recent 12 months. Our findings provide preliminary evidence that indoor remodeling has an adverse effect on semen quality.

  19. Remodeling of the myocardium in early trabeculation and cardiac valve formation; a role for TGFβ2.

    PubMed

    Kruithof, Boudewijn P T; Kruithof-De-Julio, Marianna; Poelmann, Robert E; Gittenberger-De-Groot, Adriana C; Gaussin, Vinciane; Goumans, Marie-José

    2013-01-01

    Trabeculation and the formation of the leaflets of the mitral and tricuspid valves both involve remodeling of the embryonic myocardium. The nature and possible connection of these myocardial remodeling processes, however, are unclear. Therefore, we examined the morphogenesis of the early ventricular and atrioventricular (AV) myocardium and report for the first time that the formation of the early trabeculae and the positioning of the valve primordia (endocardial cushions) into the ventricular lumen are part of one continuous myocardial remodeling process, which involves the dissociation of the myocardial layers. For the endocardial cushions, this process results in delamination from the AV myocardium. The AV myocardium that will harbor the right lateral cushion is the exception and becomes positioned in the ventricular lumen by folding of the right ventricle. As a consequence, remodeling of the left and right AV myocardium occurs differently with implications for the formation of the mural leaflets and annulus fibrosis. At both the right and left side, the valvular myocardium harbors a distinct molecular phenotype and its removal from the cardiac leaflets involves a second wave of delamination. Interestingly, in the TGFβ2-KO mouse, which is a known model for cushion and valve defects, remodeling of the early myocardium is disturbed as indicated by defective trabeculae formation, persistence of valvular myocardium, disturbed myocardial phenotypes and differential defects at left and right side of the AV canal. Based on these results we propose a new model clarifying early trabeculae formation and AV valve formation and provide new inroads for an enhanced understanding of congenital heart defects.

  20. Biomarkers to Predict Reverse Remodeling and Myocardial Recovery in Heart Failure.

    PubMed

    Motiwala, Shweta R; Gaggin, Hanna K

    2016-10-01

    Left ventricular remodeling appears to be a critical link between cardiac injury and the development and progression of heart failure with reduced ejection fraction (HFrEF). Several drug and device therapies that modify and reverse the remodeling process in patients with HFrEF are closely associated with improvement in clinical outcomes. Reverse remodeling, including partial or complete recovery of systolic function and structure, is possible but its determinants are incompletely understood. Methods to predict reverse remodeling in response to therapy are not well defined. Though non-invasive imaging techniques remain the most widely used methods of assessing reverse remodeling, serum biomarkers are now being investigated as more specific, mechanistically driven, and clinically useful predictors of reverse remodeling. Biomarkers that reflect myocyte stretch and stress, myocyte injury and necrosis, inflammation and fibrosis, and extracellular matrix turnover may be particularly valuable for predicting pathophysiologic changes and prognosis in individual patients. Their use may ultimately allow improved application of precision medicine in chronic HF.

  1. Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

    NASA Astrophysics Data System (ADS)

    Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

    2004-04-01

    To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

  2. Long-term cardiac remodeling and arrhythmias in nonelite marathon runners.

    PubMed

    Wilhelm, Matthias; Roten, Laurent; Tanner, Hildegard; Schmid, Jean-Paul; Wilhelm, Ilca; Saner, Hugo

    2012-07-01

    Long-term endurance sports are associated with atrial remodeling and atrial arrhythmias. More importantly, high-level endurance training may promote right ventricular (RV) dysfunction and complex ventricular arrhythmias. We investigated the long-term consequences of marathon running on cardiac remodeling as a potential substrate for arrhythmias with a focus on the right heart. We invited runners of the 2010 Grand Prix of Bern, a 10-mile race. Of 873 marathon and nonmarathon runners who applied, 122 (61 women) entered the final analysis. Subjects were stratified according to former marathon participations: control group (nonmarathon runners, n = 34), group 1 (1 marathon to 5 marathons, mean 2.7, n = 46), and group 2 (≥6 marathons, mean 12.8, n = 42). Mean age was 42 ± 7 years. Results were adjusted for gender, age, and lifetime training hours. Right and left atrial sizes increased with marathon participations. In group 2, right and left atrial enlargements were present in 60% and 74% of athletes, respectively. RV and left ventricular (LV) dimensions showed no differences among groups, and RV or LV dilatation was present in only 2.4% or 4.3% of marathon runners, respectively. In multiple linear regression analysis, marathon participation was an independent predictor of right and left atrial sizes but had no effect on RV and LV dimensions and function. Atrial and ventricular ectopic complexes during 24-hour Holter monitoring were low and equally distributed among groups. In conclusion, in nonelite athletes, marathon running was not associated with RV enlargement, dysfunction, or ventricular ectopy. Marathon running promoted biatrial remodeling.

  3. Attenuation of post-infarction remodeling in rats by sustained myocardial growth hormone administration.

    PubMed

    Daskalopoulos, Evangelos P; Vilaeti, Agapi D; Barka, Eleonora; Mantzouratou, Polixeni; Kouroupis, Dimitrios; Kontonika, Marianthi; Tourmousoglou, Christos; Papalois, Apostolos; Pantos, Constantinos; Blankesteijn, W Matthijs; Agathopoulos, Simeon; Kolettis, Theofilos M

    2015-01-01

    Prevention of left ventricular remodeling is an important therapeutic target post-myocardial infarction. Experimentally, treatment with growth hormone (GH) is beneficial, but sustained local administration has not been thoroughly investigated. We studied 58 rats (322 ± 4 g). GH was administered via a biomaterial-scaffold, following in vitro and in vivo evaluation of degradation and drug-release curves. Treatment consisted of intra-myocardial injection of saline or alginate-hydrogel, with or without GH, 10 min after permanent coronary artery ligation. Echocardiographic and histologic remodeling-indices were examined 3 weeks post-ligation, followed by immunohistochemical evaluation of angiogenesis, collagen, macrophages and myofibroblasts. GH-release completed at 3 days and alginate-degradation at ∼7 days. Alginate + GH consistently improved left ventricular end-diastolic and end-systolic diameters, ventricular sphericity, wall tension index and infarct-thickness. Microvascular-density and myofibroblast-count in the infarct and peri-infarct areas were higher after alginate + GH. Macrophage-count and collagen-content did not differ between groups. Early, sustained GH-administration enhances angiogenesis and myofibroblast-activation and ameliorates post-infarction remodeling.

  4. Evaluation of ventricular wall stress and cardiac function in patients with dilated cardiomyopathy.

    PubMed

    Scardulla, Francesco; Rinaudo, Antonino; Pasta, Salvatore; Scardulla, Cesare

    2016-01-01

    Dilated cardiomyopathy is a heart disease characterized by both left ventricular dilatation and left ventricular systolic dysfunction, leading to cardiac remodeling and ultimately heart failure. We aimed to investigate the effect of dilated cardiomyopathy on the pump performance and myocardial wall mechanics using patient-specific finite element analysis. Results evinced pronounced end-systolic wall stress on left ventricular wall of patients with dilated cardiomyopathy as compared to that of normal hearts. In dilated cardiomyopathy, both end-diastolic and end-systolic pressure-volume relationships of left ventricle and right ventricle were shifted to the right compared to controls, suggesting reduced myocardial contractility. We hereby propose that finite element analysis represents a useful tool to assess the myocardial wall stress and cardiac work, which are responsible for progressive left ventricular deterioration and poor clinical course.

  5. Zinc Levels in Left Ventricular Hypertrophy.

    PubMed

    Huang, Lei; Teng, Tianming; Bian, Bo; Yao, Wei; Yu, Xuefang; Wang, Zhuoqun; Xu, Zhelong; Sun, Yuemin

    2017-03-01

    Zinc is one of the most important trace elements in the body and zinc homeostasis plays a critical role in maintaining cellular structure and function. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. Our aim was to investigate whether there is a relationship between zinc and left ventricular hypertrophy (LVH). A total of 519 patients was enrolled and their serum zinc levels were measured in this study. We performed analyses on the relationship between zinc levels and LVH and the four LV geometry pattern patients: normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH. We performed further linear and multiple regression analyses to confirm the relationship between zinc and left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT). Our data showed that zinc levels were 710.2 ± 243.0 μg/L in the control group and were 641.9 ± 215.2 μg/L in LVH patients. We observed that zinc levels were 715 ± 243.5 μg/L, 694.2 ± 242.7 μg/L, 643.7 ± 225.0 μg/L, and 638.7 ± 197.0 μg/L in normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH patients, respectively. We further found that there was a significant inverse linear relationship between zinc and LVM (p = 0.001) and LVMI (p = 0.000) but did not show a significant relationship with RWT (p = 0.561). Multiple regression analyses confirmed that the linear relationship between zinc and LVM and LVMI remained inversely significant. The present study revealed that serum zinc levels were significantly decreased in the LVH patients, especially in the eccentric LVH and concentric LVH patients. Furthermore, zinc levels were significantly inversely correlated with LVM and LVMI.

  6. Left ventricular bronchogenic cyst.

    PubMed

    Wei, Xiang; Omo, Alfred; Pan, Tiecheng; Li, Jun; Liu, Ligang; Hu, Min

    2006-04-01

    Bronchogenic cysts occurring in the left ventricle are a medical rarity. One successfully operated case is reported herein. The location of the cyst was just between the epicardium and myocardium of the inferior left ventricular wall, adjacent to the apex of the heart. Complete excision was achieved through a left anterolateral thoracotomy without extracorporeal circulation.

  7. Bidirectional ventricular tachycardia?

    PubMed

    Serra, José L; Caresani, Julian A; Bono, Julio O

    2014-01-01

    A 65-year-old woman was admitted to the hospital because of a syncopal episode with documented transient complete atrioventricular block. A DDD pacemaker was implanted. Post implantation, the patient was diagnosed with bidirectional ventricular tachycardia. Analysis of the arrhythmia and differential diagnosis is performed.

  8. Aorto-ventricular tunnel

    PubMed Central

    McKay, Roxane

    2007-01-01

    Aorto-ventricular tunnel is a congenital, extracardiac channel which connects the ascending aorta above the sinutubular junction to the cavity of the left, or (less commonly) right ventricle. The exact incidence is unknown, estimates ranging from 0.5% of fetal cardiac malformations to less than 0.1% of congenitally malformed hearts in clinico-pathological series. Approximately 130 cases have been reported in the literature, about twice as many cases in males as in females. Associated defects, usually involving the proximal coronary arteries, or the aortic or pulmonary valves, are present in nearly half the cases. Occasional patients present with an asymptomatic heart murmur and cardiac enlargement, but most suffer heart failure in the first year of life. The etiology of aorto-ventricular tunnel is uncertain. It appears to result from a combination of maldevelopment of the cushions which give rise to the pulmonary and aortic roots, and abnormal separation of these structures. Echocardiography is the diagnostic investigation of choice. Antenatal diagnosis by fetal echocardiography is reliable after 18 weeks gestation. Aorto-ventricular tunnel must be distinguished from other lesions which cause rapid run-off of blood from the aorta and produce cardiac failure. Optimal management of symptomatic aorto-ventricular tunnel consists of diagnosis by echocardiography, complimented with cardiac catheterization as needed to elucidate coronary arterial origins or associated defects, and prompt surgical repair. Observation of the exceedingly rare, asymptomatic patient with a small tunnel may be justified by occasional spontaneous closure. All patients require life-long follow-up for recurrence of the tunnel, aortic valve incompetence, left ventricular function, and aneurysmal enlargement of the ascending aorta. PMID:17922908

  9. Pure right ventricular infarction.

    PubMed

    Inoue, Katsuji; Matsuoka, Hiroshi; Kawakami, Hideo; Koyama, Yasushi; Nishimura, Kazuhisa; Ito, Taketoshi

    2002-02-01

    A 76-year-old man with chest pain was admitted to hospital where electrocardiography (ECG) showed ST-segment elevation in leads V1-4, indicative of acute anterior myocardial infarction. ST-segment elevation was also present in the right precordial leads V4R-6R. Emergency coronary angiography revealed that the left coronary artery was dominant and did not have significant stenosis. Aortography showed ostial occlusion of the right coronary artery (RCA). Left ventriculography showed normal function and right ventriculography showed a dilated right ventricle and severe hypokinesis of the right ventricular free wall. Conservative treatment was selected because the patient's symptoms soon ameliorated and his hemodynamics was stable. 99mTc-pyrophosphate and 201Tl dual single-photon emission computed tomography showed uptake of 99mTc-pyrophosphate in only the right ventricular free wall, but no uptake of 99mTc-pyrophosphate and no perfusion defect of 201Tl in the left ventricle. The peak creatine kinase (CK) and CK-MB were 1,381 IU/L and 127 IU/L, respectively. His natural course was favorable and the chest pain disappeared under medication. Two months after the onset, the ECG showed poor R progression in leads V1-4 indicating an old anterior infarction. Coronary angiography confirmed the ostial stenosis of the hypoplastic RCA. This was a case of pure right ventricular free wall infarction because of the occlusion of the ostium of the hypoplastic RCA, but not of the right ventricular branch. Because the electrocardiographic findings resemble those of an acute anterior infarction, it is important to consider pure right ventricular infarction in the differential diagnosis.

  10. Aorto-ventricular tunnel.

    PubMed

    McKay, Roxane

    2007-10-08

    Aorto-ventricular tunnel is a congenital, extracardiac channel which connects the ascending aorta above the sinutubular junction to the cavity of the left, or (less commonly) right ventricle. The exact incidence is unknown, estimates ranging from 0.5% of fetal cardiac malformations to less than 0.1% of congenitally malformed hearts in clinico-pathological series. Approximately 130 cases have been reported in the literature, about twice as many cases in males as in females. Associated defects, usually involving the proximal coronary arteries, or the aortic or pulmonary valves, are present in nearly half the cases. Occasional patients present with an asymptomatic heart murmur and cardiac enlargement, but most suffer heart failure in the first year of life. The etiology of aorto-ventricular tunnel is uncertain. It appears to result from a combination of maldevelopment of the cushions which give rise to the pulmonary and aortic roots, and abnormal separation of these structures. Echocardiography is the diagnostic investigation of choice. Antenatal diagnosis by fetal echocardiography is reliable after 18 weeks gestation. Aorto-ventricular tunnel must be distinguished from other lesions which cause rapid run-off of blood from the aorta and produce cardiac failure. Optimal management of symptomatic aorto-ventricular tunnel consists of diagnosis by echocardiography, complimented with cardiac catheterization as needed to elucidate coronary arterial origins or associated defects, and prompt surgical repair. Observation of the exceedingly rare, asymptomatic patient with a small tunnel may be justified by occasional spontaneous closure. All patients require life-long follow-up for recurrence of the tunnel, aortic valve incompetence, left ventricular function, and aneurysmal enlargement of the ascending aorta.

  11. [Dilated cardiomyopathy: a dynamic disease - clinical course, reverse remodeling and prognostic stratification].

    PubMed

    Merlo, Marco; Gigli, Marta; Poli, Stefano; Stolfo, Davide; Brun, Francesca; Lardieri, Gerardina; Pinamonti, Bruno; Zecchin, Massimo; Pivetta, Alberto; Vitrella, Giancarlo; Di Lenarda, Andrea; Sinagra, Gianfranco

    2016-01-01

    Dilated cardiomyopathy (DCM) is a relatively rare primary heart muscle disease with genetic or post-inflammatory etiology. In the last decade, the incidence and prevalence of the disease have significantly increased as a consequence of an earlier diagnosis supported by extensive familial screening programs and by the improvement in diagnostic techniques. Moreover, current therapeutic strategies have deeply modified the prognosis of DCM with a dramatic reduction in mortality. A significant number of patients with DCM present an impressive response to pharmacological and non-pharmacological therapy in terms of left ventricular reverse remodeling (reduction in ventricular size with improvement of systolic function), which confers a more favorable prognosis in the long term. However, the identification of patients with an increased likelihood of improvement after therapeutic optimization remains a challenging issue; in particular the assessment of arrhythmic risk carries important implications. Finally, the long-term follow-up of patients showing a significant left ventricular functional recovery under optimal treatment is still poorly known. Hence, the aim of the present review is to provide an insight into the clinical evolution/long-term follow-up of DCM, which should be actually considered a dynamic process rather than a static and chronic disease. Left ventricular reverse remodeling should be considered a key therapeutic goal, mostly associated with a long-standing recovery, but cannot be considered the expression of permanent "healing", confirming the need for a systematic and careful follow-up over time in this setting.

  12. Size, shape, and stamina: the impact of left ventricular geometry on exercise capacity.

    PubMed

    Lam, Carolyn S P; Grewal, Jasmine; Borlaug, Barry A; Ommen, Steve R; Kane, Garvan C; McCully, Robert B; Pellikka, Patricia A

    2010-05-01

    Although several studies have examined the cardiac functional determinants of exercise capacity, few have investigated the effects of structural remodeling. The current study evaluated the association between cardiac geometry and exercise capacity. Subjects with ejection fraction > or = 50% and no valvular disease, myocardial ischemia, or arrhythmias were identified from a large prospective exercise echocardiography database. Left ventricular mass index and relative wall thickness were used to classify geometry into normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. All of the subjects underwent symptom-limited treadmill exercise according to standard Bruce protocol. Maximal exercise tolerance was measured in metabolic equivalents. Of 366 (60+/-14 years; 57% male) subjects, 166 (45%) had normal geometry, 106 (29%) had concentric remodeling, 40 (11%) had eccentric hypertrophy, and 54 (15%) had concentric hypertrophy. Geometry was related to exercise capacity: in descending order, the maximum achieved metabolic equivalents were 9.9+/-2.8 in normal, 8.9+/-2.6 in concentric remodeling, 8.6+/-3.1 in eccentric hypertrophy, and 8.0+/-2.7 in concentric hypertrophy (all P<0.02 versus normal). Left ventricular mass index and relative wall thickness were negatively correlated with exercise tolerance in metabolic equivalents (r=-0.14; P=0.009 and r=-0.21; P<0.001, respectively). Augmentation of heart rate and ejection fraction with exercise were blunted in concentric hypertrophy compared with normal, even after adjusting for medications. In conclusion, the pattern of ventricular remodeling is related to exercise capacity among low-risk adults. Subjects with concentric hypertrophy display the greatest limitation, and this is related to reduced systolic and chronotropic reserve. Reverse remodeling strategies may prevent or treat functional decline in patients with structural heart disease.

  13. Left ventricular hypertrophy: an initial response to myocardial injury.

    PubMed

    Francis, G S; McDonald, K M

    1992-06-04

    The prevailing wisdom generally has been that the failing heart hypertrophies in response to increased wall stress. The increase in myocardial mass observed in heart failure is therefore a relatively late compensatory event geared to normalize wall stress. Although this is undoubtedly true, especially for heart failure resulting from a large anterior myocardial infarction accompanied by rapid left ventricular expansion, it is possible that an important form of hypertrophy occurs much earlier as an initial response to myocardial injury. One can hypothesize that the initial response to injury is a nonspecific phenotypic alteration of the cardiac myocyte to one of growth and development. Such changes may be driven by both trophic and mechanical forces and may be important in altering the architecture of the myocardial cell and surrounding cardiac interstitium. Preliminary data from a variety of models support the concept that neuroendocrine activity is an important component in the ventricular remodeling process, and that pharmacologic interventions designed to block systemic and tissue neuroendocrine activity may prevent excessive cardiac enlargement and its ultimate consequences. Because this concept has important implications for preventive cardiology, the results of several prevention trials, including the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), Studies of Left Ventricular Dysfunction (SOLVD), and Survival and Ventricular Enlargement (SAVE) are awaited eagerly.

  14. Activity-adjusted 24-hour ambulatory blood pressure and cardiac remodeling in children with sleep disordered breathing.

    PubMed

    Amin, Raouf; Somers, Virend K; McConnell, Keith; Willging, Paul; Myer, Charles; Sherman, Marc; McPhail, Gary; Morgenthal, Ashley; Fenchel, Matthew; Bean, Judy; Kimball, Thomas; Daniels, Stephen

    2008-01-01

    Questions remain as to whether pediatric sleep disordered breathing increases the risk for elevated blood pressure and blood pressure-dependent cardiac remodeling. We tested the hypothesis that activity-adjusted morning blood pressure surge, blood pressure load, and diurnal and nocturnal blood pressure are significantly higher in children with sleep disordered breathing than in healthy controls and that these blood pressure parameters relate to left ventricular remodeling. 24-hour ambulatory blood pressure parameters were compared between groups. The associations between blood pressure and left ventricular relative wall thickness and mass were measured. 140 children met the inclusion criteria. In children with apnea hypopnea index <5 per hour, a significant difference from controls was the morning blood surge. Significant increases in blood pressure surge, blood pressure load, and in 24-hour ambulatory blood pressure were evident in those whom the apnea hypopnea index exceeded 5 per hour. Sleep disordered breathing and body mass index had similar effect on blood pressure parameters except for nocturnal diastolic blood pressure, where sleep disordered breathing had a significantly greater effect than body mass index. Diurnal and nocturnal systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure predicted the changes in left ventricular relative wall thickness. Therefore, sleep disordered breathing in children who are otherwise healthy is independently associated with an increase in morning blood pressure surge, blood pressure load, and 24-hour ambulatory blood pressure. The association between left ventricular remodeling and 24-hour blood pressure highlights the role of sleep disordered breathing in increasing cardiovascular morbidity.

  15. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema.

    PubMed

    Desai, Ketaki V; Laine, Glen A; Stewart, Randolph H; Cox, Charles S; Quick, Christopher M; Allen, Steven J; Fischer, Uwe M

    2008-06-01

    Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures.

  16. Cardiac Body Surface Potentials in Rats with Experimental Pulmonary Hypertension during Ventricular Depolarization.

    PubMed

    Suslonova, O V; Smirnova, S L; Roshchevskaya, I M

    2016-11-01

    The spatial and the amplitude-temporal parameters of cardiac body surface potentials were examined in female Wistar rats with experimental pulmonary hypertension during ventricular depolarization. The cardiac body surface potentials have been led from 64 subcutaneous electrodes evenly distributed across the chest surface prior to and 4 weeks after subcutaneous injection of a single dose of monocrotaline (60 mg/kg). Right ventricular hypertrophy and electrophysiological remodeling of the heart developed in rats with experimental pulmonary hypertension in 4 weeks after monocrotaline injection; these changes led to a significant increase in amplitude and temporal characteristics of the cardioelectric field on the body surface in comparison with the initial state.

  17. Rotating Frame Spin Lattice Relaxation in a Swine Model of Chronic, Left Ventricular Myocardial Infarction

    PubMed Central

    Witschey, Walter RT; Pilla, James J; Ferrari, Giovanni; Koomalsingh, Kevin; Haris, Mohammed; Hinmon, Robin; Zsido, Gerald; Gorman, Joseph H; Gorman, Robert C; Reddy, Ravinder

    2010-01-01

    T1ρ relaxation times were quantified in a swine model of chronic, left ventricular myocardial infarction. It was found that there were low frequency relaxation mechanisms that suppress endogenous contrast at low spin lock amplitudes and in T2-weighted images. A moderate amplitude spin locking pulse could overcome these relaxation mechanisms. Relaxation dispersion data was measured over a range of RF field amplitudes and a model was formulated to include dipole-dipole relaxation modulated by molecular rotation and an apparent exchange mechanism. These techniques may find some use in the clinic for the observation of chronic, left ventricular cardiac remodeling. PMID:20677236

  18. Surgical Repair of Huge Left Ventricular Pseudoaneurysm After Sutureless Repair of Free Wall Rupture.

    PubMed

    Díez-Villanueva, Pablo; Sarraj, Anas; Navarrete, Gonzalo; Salamanca, Jorge; Pozo, Eduardo; Reyes, Guillermo; Alfonso, Fernando

    2017-02-01

    Left ventricular pseudoaneurysm (LVPsA) is a rare complication after sutureless patch repair of left ventricular free wall rupture (LVFWR), with few cases reported in the literature so far. We present the case of a young patient who early developed a huge LVPsA and moderate mitral regurgitation after sutureless patch repair for LVFWR after undergoing a successful Dor procedure using the "triple empanada patch technique" to exclude the LVPsA, remodel the left ventricle, and address the moderate mitral regurgitation. Serial echocardiograms during follow-up are strongly recommended, even in patients with successful patch repair, to facilitate timely diagnosis and management.

  19. Idiopathic fascicular ventricular tachycardia.

    PubMed

    Francis, Johnson; Venugopal, K; Khadar, S A; Sudhayakumar, N; Gupta, Anoop K

    2004-07-01

    Idiopathic fascicular ventricular tachycardia is an important cardiac arrhythmia with specific electrocardiographic features and therapeutic options. It is characterized by relatively narrow QRS complex and right bundle branch block pattern. The QRS axis depends on which fascicle is involved in the re-entry. Left axis deviation is noted with left posterior fascicular tachycardia and right axis deviation with left anterior fascicular tachycardia. A left septal fascicular tachycardia with normal axis has also been described. Fascicular tachycardia is usually seen in individuals without structural heart disease. Response to verapamil is an important feature of fascicular tachycardia. Rare instances of termination with intravenous adenosine have also been noted. A presystolic or diastolic potential preceding the QRS, presumed to originate from the Purkinje fibers can be recorded during sinus rhythm and ventricular tachycardia in many patients with fascicular tachycardia. This potential (P potential) has been used as a guide to catheter ablation. Prompt recognition of fascicular tachycardia especially in the emergency department is very important. It is one of the eminently ablatable ventricular tachycardias. Primary ablation has been reported to have a higher success, lesser procedure time and fluoroscopy time.

  20. Ventricular hypertrophy in cardiomyopathy.

    PubMed

    Oakley, C

    1971-01-01

    Semantic difficulties arise when hypertrophic obstructive cardiomyopathy is seen without obstruction and with congestive failure, and also when congestive cardiomyopathy is seen with gross hypertrophy but without heart failure. Retention of a small left ventricular cavity and a normal ejection fraction characterizes hypertrophic cardiomyopathy at all stages of the disorder. Congestive cardiomyopathy is recognized by the presence of a dilated left ventricular cavity and reduced ejection fraction regardless of the amount of hypertrophy and the presence or not of heart failure. Longevity in congestive cardiomyopathy seems to be promoted when hypertrophy is great relative to the amount of pump failure as measured by increase in cavity size. Conversely, death in hypertrophic cardiomyopathy is most likely when hypertrophy is greatest at a time when outflow tract obstruction has been replaced by inflow restriction caused by diminishing ventricular distensibility. Hypertrophy is thus beneficial and compensatory in congestive cardiomyopathy, whereas it may be the primary disorder and eventual cause of death in hypertrophic cardiomyopathy. Reasons are given for believing that hypertension may have been the original cause of left ventricular dilatation in some case of congestive cardiomyopathy in which loss of stroke output thenceforward is followed by normotension. Development of severe hypertension in these patients after recovery from a prolonged period of left ventricular failure with normotension lends weight to this hypothesis. No fault has been found in the large or small coronary arteries in either hypertrophic cardiomyopathy or congestive cardiomyopathy when they have been examined in life by selective coronary angiography, or by histological methods in biopsy or post-mortem material. Coronary blood supply may be a limiting factor in the compensatory hypertrophy of congestive cardiomyopathy, and the ability to hypertrophy may explain the better prognosis of some

  1. Apocynin improving cardiac remodeling in chronic renal failure disease is associated with up-regulation of epoxyeicosatrienoic acids.

    PubMed

    Zhang, Kun; Liu, Yu; Liu, Xiaoqiang; Chen, Jie; Cai, Qingqing; Wang, Jingfeng; Huang, Hui

    2015-09-22

    Cardiac remodeling is one of the most common cardiac abnormalities and associated with a high mortality in chronic renal failure (CRF) patients. Apocynin, a nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been showed cardio-protective effects. However, whether apocynin can improve cardiac remodeling in CRF and what is the underlying mechanism are unclear. In the present study, we enrolled 94 participants. In addition, we used 5/6 nephrectomized rats to mimic cardiac remodeling in CRF. Serum levels of epoxyeicosatrienoic acids (EETs) and its mainly metabolic enzyme-soluble epoxide hydrolase (sEH) were measured. The results showed that the serum levels of EETs were significantly decreased in renocardiac syndrome participants (P < 0.05). In 5/6 nephrectomized CRF model, the ratio of left ventricular weight / body weight, left ventricular posterior wall thickness, and cardiac interstitial fibrosis were significantly increased while ejection fraction significantly decreased (P < 0.05). All these effects could partly be reversed by apocynin. Meanwhile, we found during the process of cardiac remodeling in CRF, apocynin significantly increased the reduced serum levels of EETs and decreased the mRNA and protein expressions of sEH in the heart (P < 0.05). Our findings indicated that the protective effect of apocynin on cardiac remodeling in CRF was associated with the up-regulation of EETs. EETs may be a new mediator for the injury of kidney-heart interactions.

  2. Ablation of idiopathic ventricular tachycardia.

    PubMed

    Schreiber, Doreen; Kottkamp, Hans

    2010-09-01

    Idiopathic ventricular arrhythmias occur in patients without structural heart disease. They can arise from a variety of specific areas within both ventricles and in the supravalvular regions of the great arteries. Two main groups need to be differentiated: arrhythmias from the outflow tract (OT) region and idiopathic left ventricular, so-called fascicular, tachycardias (ILVTs). OT tachycardia typically originates in the right ventricular OT, but may also occur in the left ventricular OT, particularly in the sinuses of Valsalva or the anterior epicardium or the great cardiac vein. Activation mapping or pace mapping for the OT regions and mapping of diastolic potentials in ILVTs are the mapping techniques that are typically used. The ablation of idiopathic ventricular arrhythmias is highly successful, associated with only rare complications. Newly recognized entities of idiopathic ventricular tachycardias are those originating in the papillary muscles and in the atrioventricular annular regions.

  3. Capecitabine-induced ventricular fibrillation arrest: Possible Kounis syndrome.

    PubMed

    Kido, Kazuhiko; Adams, Val R; Morehead, Richard S; Flannery, Alexander H

    2016-04-01

    We report the case of capecitabine-induced ventricular fibrillation arrest, possibly secondary to type I Kounis syndrome. A 47-year-old man with a history of T3N1 moderately differentiated adenocarcinoma of the colon, status-post sigmoid resection, was started on adjuvant capecitabine approximately five months prior to presentation of cardiac arrest secondary to ventricular fibrillation. An electrocardiogram (EKG) revealed ST segment elevation on the lateral leads and the patient was taken emergently to the cardiac catheterization laboratory. The catheterization revealed no angiographically significant stenosis and coronary artery disease was ruled out. After ruling out other causes of cardiac arrest, the working diagnosis was capecitabine-induced ventricular fibrillation arrest. As such, an inflammatory work up was sent to evaluate for the possibility of a capecitabine hypersensitivity, or Kounis syndrome, and is the first documented report in the literature to do so when evaluating Kounis syndrome. Immunoglobulin E (IgE), tryptase, and C-reactive protein were normal but histamine, interleukin (IL)-6, and IL-10 were elevated. Histamine elevation supports the suspicion that our patient had type I Kounis syndrome. Naranjo adverse drug reaction probability scale indicates a probable adverse effect due to capecitabine with seven points. A case of capecitabine-induced ventricular fibrillation arrest is reported, with a potential for type 1 Kounis syndrome as an underlying pathology supported by immunologic work up.

  4. Experimental Myocardial Infarction Induces Altered Regulatory T Cell Hemostasis, and Adoptive Transfer Attenuates Subsequent Remodeling

    PubMed Central

    Sharir, Rinat; Semo, Jonathan; Shimoni, Sara; Ben-Mordechai, Tamar; Landa-Rouben, Natalie; Maysel-Auslender, Sofia; Shaish, Aviv; Entin–Meer, Michal; Keren, Gad; George, Jacob

    2014-01-01

    Background Ischemic cardiac damage is associated with upregulation of cardiac pro-inflammatory cytokines, as well as invasion of lymphocytes into the heart. Regulatory T cells (Tregs) are known to exert a suppressive effect on several immune cell types. We sought to determine whether the Treg pool is influenced by myocardial damage and whether Tregs transfer and deletion affect cardiac remodeling. Methods and Results The number and functional suppressive activity of Tregs were assayed in mice subjected to experimental myocardial infarction. The numbers of splenocyte-derived Tregs in the ischemic mice were significantly higher after the injury than in the controls, and their suppressive properties were significantly compromised. Compared with PBS, adoptive Treg transfer to mice with experimental infarction reduced infarct size and improved LV remodeling and functional performance by echocardiography. Treg deletion with blocking anti-CD25 antibodies did not influence infarct size or echocardiographic features of cardiac remodeling. Conclusion Treg numbers are increased whereas their function is compromised in mice with that underwent experimental infarction. Transfer of exogeneous Tregs results in attenuation of myocardial remodeling whereas their ablation has no effect. Thus, Tregs may serve as interesting potential interventional targets for attenuating left ventricular remodeling. PMID:25436994

  5. The role of echocardiography in the evaluation of cardiac re-modelling and differentiation between physiological and pathological hypertrophy in teenagers engaged in competitive amateur sports.

    PubMed

    Sulovic, Ljiljana S; Mahmutovic, Meho; Lazic, Snezana; Sulovic, Nenad

    2016-10-18

    Aims "Athlete's heart" is a cardiac adaptation to long-term intensive training. The aims of this study were to show the prevalence of left ventricular hypertrophy in teenagers who participate in sports, to define the different types of cardiac re-modelling, and to differentiate between physiological and pathological hypertrophy.

  6. Cardiac function and remodeling is attenuated in transgenic rats expressing the human kallikrein-1 gene after myocardial infarction.

    PubMed

    Koch, Matthias; Spillmann, Frank; Dendorfer, Andreas; Westermann, Dirk; Altmann, Christine; Sahabi, Merdad; Linthout, Sophie Van; Bader, Michael; Walther, Thomas; Schultheiss, Heinz-Peter; Tschöpe, Carsten

    2006-11-21

    Bradykinin coronary outflow, left ventricular performance and left ventricular dimensions of transgenic rats harboring the human tissue kallikrein-1 gene TGR(hKLK1) were investigated under basal and ischemic conditions. Bradykinin content in the coronary outflow of buffer-perfused, isolated hearts of controls and TGR(hKLK1) was measured by specific radioimmunoassay before and after global ischemia. Left ventricular function and left ventricular dimensions were determined in vivo using a tip catheter and echocardiography 6 days and 3 weeks after induction of myocardial infarction. Left ventricular type I collagen mRNA expression was analyzed by RNase protection assay. Compared to controls, basal bradykinin outflow was 3.5 fold increased in TGR(hKLK1). Ischemia induced an increase of bradykinin coronary outflow in controls but did not induce a further increase in TGR(hKLK1). However, despite similar unchanged infarction sizes, left ventricular function and remodeling improved in TGR(hKLK1) after myocardial infarction, indicated by an increase in left ventricular pressure (+34%; P<0.05), contractility (dp/dt max. +25%; P<0.05), and in ejection fraction (+20%; P<0.05) as well as by a reduction in left ventricular enddiastolic pressure (-49%, P<0.05), left ventricular enddiastolic diameter (-20%, P<0.05), and collagen mRNA expression (-15%, P<0.05) compared to controls. A chronically activated transgenic kallikrein kinin system with expression of human kallikrein-1 gene counteracts the progression of left ventricular contractile dysfunction after experimental myocardial infarction. Further studies have to show whether these results can be caused by other therapeutically options. Long acting bradykinin receptor agonists might be an alternative option to improve ischemic heart disease.

  7. Off-pump revascularization for significant left ventricular dysfunction.

    PubMed

    Woo, Y Joseph; Grand, Todd J; Liao, George P; Panlilio, Corinna M

    2006-08-01

    Left ventricular dysfunction is a predictor of perioperative morbidity and mortality in on-pump coronary artery bypass grafting. Obligatory global myocardial ischemia and injury induced during crossclamping as well as adverse systemic effects of cardiopulmonary bypass may induce a disproportionately greater overall physiologic insult in patients with poor ventricular function. All patients undergoing nonemergency off-pump coronary artery bypass by a single surgeon during an 18-month period were retrospectively analyzed. Two groups with preoperative ejection fraction classified as poor (10%-35%; n = 31) or normal (55%-80%; n = 60) were compared. The mean ejection fractions were 26% +/- 1% and 63% +/- 1% respectively, p < 0.000001. In those with significant left ventricular dysfunction, there were 2.8 +/- 0.1 grafts per patient, time to extubation was 8.4 +/- 1.2 hours, and discharge was after 4.9 +/- 0.6 days. These results were statistically equivalent to those in the group with normal left ventricular function. There was no intraaortic balloon pump insertion or mortality in either group. This technique provides an effective means of safely revascularizing patients with significant left ventricular dysfunction, and it may provide a valuable alternative approach in patients with ischemic cardiomyopathy.

  8. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    SciTech Connect

    Ostrup, Olga; Hyttel, Poul; Klaerke, Dan A.; Collas, Philippe

    2011-09-02

    Highlights: {yields} Xenopus egg extract remodels nuclei and alter cell growth characteristics. {yields} Ribosomal genes are reprogrammed within 6 h after extract exposure. {yields} rDNA reprogramming involves promoter targeting of SNF2H remodeling complex. {yields} Xenopus egg extract does not initiate stress-related response in somatic cells. {yields} Aza-cytidine elicits a stress-induced response in reprogrammed cells. -- Abstract: Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression. This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract and elicits a stress-type nuclear response. Thus, an early event of Xenopus egg extract-mediated nuclear reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling complex. Condition-specific and rapid silencing of ribosomal genes may serve as a sensitive marker for evaluation of various reprogramming methods.

  9. Mechanisms of ATP Dependent Chromatin Remodeling

    PubMed Central

    Gangaraju, Vamsi K.; Bartholomew, Blaine

    2007-01-01

    The inter-relationship between DNA repair and ATP dependent chromatin remodeling has begun to become very apparent with recent discoveries. ATP dependent remodeling complexes mobilize nucleosomes along DNA, promote the exchange of histones, or completely displace nucleosomes from DNA. These remodeling complexes are often categorized based on the domain organization of their catalytic subunit. The biochemical properties and structural information of several of these remodeling complexes are reviewed. The different models for how these complexes are able to mobilize nucleosomes and alter nucleosome structure are presented incorporating several recent findings. Finally the role of histone tails and their respective modifications in ATP-dependent remodeling are discussed. PMID:17306844

  10. Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

    PubMed Central

    Gomez, Juan F.; Cardona, Karen; Martinez, Laura; Saiz, Javier; Trenor, Beatriz

    2014-01-01

    Background Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure. Objective In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations. Methods The electrical activity of human transmural ventricular tissue (5 cm×5 cm) was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW) for reentry was evaluated following cross-field stimulation. Results No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components. Conclusion Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity. PMID:25054335

  11. Giant left ventricular pseudoaneurysm.

    PubMed

    Prakash, Sumi; Garg, Nadish; Xie, Gong-Yuan; Dellsperger, Kevin C

    2010-01-01

    Left ventricular (LV) pseudoaneurysm (PS) is an uncommon, often fatal complication associated with myocardial infarction, cardiothoracic surgery, trauma, and, rarely, infective endocarditis. A 28-year-old man with prior history of bioprosthetic mitral valve replacement presented with congestive heart failure and bacteremia with Abiotrophia granulitica. Transesophageal echocardiogram showed bioprosthesis dysfunction, large vegetations, mitral regurgitation, and probable PS. Cardiac and chest CT confirmed a PS communicating with the left ventricle Patient had pulseless electrical activity and died. Autopsy showed a giant PS with layered thrombus and pseudo-endothelialized cavity. Our case highlights the importance of multimodality imaging as an important tool in management of PS.

  12. Ventricular fibrillation and defibrillation

    PubMed Central

    Jones, P; Lodé, N

    2007-01-01

    Cardiac arrest in children is not often due to a disturbance in rhythm that is amenable to electrical defibrillation, contrary to the situation in adults. When a shockable rhythm is present, defibrillation using an external electric shock applied at an early stage after pre‐oxygenation and chest compressions is of proven efficacy. Success at conversion of ventricular fibrillation is dependent on the delay before delivering the shock and defibrillation efficiency, which is itself a function of thoracic impedance, energy dose and waveform. PMID:17895341

  13. Left ventricular dilatation and failure post-myocardial infarction: pathophysiology and possible pharmacologic interventions.

    PubMed

    Firth, B G; Dunnmon, P M

    1990-10-01

    An important antecedent to the development of late congestive heart failure is left ventricular dilatation and remodeling following myocardial infarction, which occurs in 30-40% of acute anterior transmural infarcts. Dilatation and remodeling commence within the first 24 hours following myocardial infarction and may be steadily progressive over months to years. Both the infarcted and uninfarcted regions of the myocardium are equally involved in the process. The remodeling process comprises left ventricular wall thinning (mainly due to cell slippage), chamber dilatation, and compensatory hypertrophy of the uninfarcted segment of the myocardium. The hypertrophy may initially be physiologic but may ultimately become a pathologic process, and thereby contribute to pump dysfunction. The possible reasons why the ventricular hypertrophy may ultimately be dysfunctional include alterations in local architecture and their sequelae alone or in concert with local changes in the beta-adrenergic, alpha-adrenergic, or renin angiotensin systems. At the present time, there are encouraging data to suggest that nitroglycerin, or the angiotensin converting enzyme inhibitor captopril, may ameliorate this process.

  14. Survival, haemodynamics and cardiac remodelling follow up in mice after myocardial infarction.

    PubMed

    Pons, S; Fornes, P; Hagege, A A; Heudes, D; Giudicelli, J-F; Richer, C

    2003-01-01

    1. In the present study, the time-course, over a 1 year period, of postischaemic dilated cardiomyopathy and/or development of congestive heart failure was investigated in mice in terms of survival and cardiac functional and structural characteristics. 2. C57BL/6 mice with myocardial infarction (MI mice; coronary ligation n = 78) or sham-operated animals (n = 45) were used and echocardiographic, haemodynamic and histomorphometric parameters were assessed at 3, 6 and 12 months post-MI. 3. At 12 months, the survival rate was 70% in MI mice. Left ventricular dysfunction was evidenced by a strong decrease in ejection fraction (EF; -48 and -53% at 6 and 12 months, respectively; both P < 0.05) and an increase in left ventricular end-diastolic pressure (+100% at both 6 and 12 months; both P < 0.05). There was no major worsening in cardiac function between 6 and 12 months, suggesting strong compensatory mechanisms. Cardiac remodelling was observed, characterized by strong left ventricular hypertrophy (+38 and +62% at 6 and 12 months, respectively; both P < 0.05) and dilatation (+53% at 6 months; P < 0.05), but collagen was not significantly increased. Significant correlations were found between EF (echocardiography) and dP/dtmax, between end-diastolic volume (echocardiography) and left ventricular internal perimeter (histomorphometry) and between left ventricular mass (echocardiography) and weight. 4. In conclusion, despite a high survival rate, the MI mouse model displays most of the hallmarks of postischaemic dilated cardiomyopathy and/or congestive heart failure, thus affording the necessary background for the subsequent evaluation of gene manipulation and/or drug effects. In addition, two-dimensional echocardiography appears to be a suitable tool for the long-term follow up of cardiac function and remodelling in this model.

  15. Structural remodeling and mechanical function in heart failure.

    PubMed

    Leonard, Bridget Louise; Smaill, Bruce Henry; LeGrice, Ian John

    2012-02-01

    The cardiac extracellular matrix (ECM) is the three-dimensional scaffold that defines the geometry and muscular architecture of the cardiac chambers and transmits forces produced during the cardiac cycle throughout the heart wall. The cardiac ECM is an active system that responds to the stresses to which it is exposed and in the normal heart is adapted to facilitate efficient mechanical function. There are marked differences in the short- and medium-term changes in ventricular geometry and cardiac ECM that occur as a result of volume overload, hypertension, and ischemic cardiomyopathy. Despite this, there is a widespread view that a common remodeling "phenotype" governs the final progression to end-stage heart failure in different forms of heart disease. In this review article, we make the case that this interpretation is not consistent with the clinical and experimental data on the topic. We argue that there is a need for new theoretical and experimental models that will enable stresses acting on the ECM and resultant deformations to be estimated more accurately and provide better spatial resolution of local signaling mechanisms that are activated as a result. These developments are necessary to link the effects of structural remodeling with altered cardiac mechanical function.

  16. Cerebral ventricular volume during hyponatraemia.

    PubMed Central

    Decaux, G; Szyper, M; Grivegnée, A

    1983-01-01

    In order to determine if the neurologic manifestations in chronic hyponatraemia result partly from brain oedema, we measured the cerebral ventricular volume before and after correction of hyponatraemia in eight patients with central nervous system manifestations. Only the three patients with seizures showed a clear change in the ventricular size and probably had brain oedema. PMID:6101182

  17. 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.

  18. Polycystic Ovary Syndrome Is Associated with Higher Left Ventricular Mass Index: The CARDIA Women's Study

    PubMed Central

    Ku, Ivy A.; Shah, Sanjiv J.; Daviglus, Martha L.; Schreiner, Pamela J.; Konety, Suma H.; Williams, O. Dale; Siscovick, David; Bibbins-Domingo, Kirsten

    2012-01-01

    Objective: The aim of the study was to determine whether young women with polycystic ovary syndrome (PCOS) have evidence of early structural changes in echocardiographic parameters as a measurement of cardiovascular risk. Methods: We investigated the association of PCOS and echocardiographic parameters in 984 black and white women in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort followed prospectively for 20 yr. Women ages 34–46 (Year 16) completed questionnaires recalling symptoms of oligomenorrhea and hirsutism in their 20s and 30s. Serum androgens were obtained at Year 2. Women in their 20s and 30s were classified into four mutually exclusive groups: 1) PCOS; 2) isolated oligomenorrhea (IO); 3) isolated hyperandrogenism (IH); and 4) reference group. Outcome measures were defined as echocardiography data from Year 5. We used multivariable linear regression models to evaluate the association of PCOS and its components with left ventricular (LV) mass index, left atrial (LA) diameter, LV ejection fraction (LVEF), and mitral inflow early wave to late wave ratio. Results: Among 984 participants, 42 women (4.3%) were classified as PCOS, 67 (6.8%) as IO, and 178 (18.0%) as IH. In multivariable linear regression analyses, women with PCOS had a 3.14 g/m2.7 (95% confidence interval, 0.48–5.81) higher LV mass index compared to the reference group (approximately 10% higher). PCOS women also had a 0.11 cm/m (95% confidence interval, 0.02–0.19) larger LA diameter, after adjustment for age and race. Conclusion: PCOS, but not IO or IH, is associated with a higher LV mass index and larger LA diameter in young women, suggestive of early adverse cardiac remodeling. Additional longitudinal studies are needed to evaluate whether this difference persists over time. PMID:23012389

  19. Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

    PubMed Central

    Muthuramu, Ilayaraja; Lox, Marleen; Jacobs, Frank; De Geest, Bart

    2014-01-01

    Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure. Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion. In contrast, the infarct area at 24 hr after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling. Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail. PMID:25489995

  20. Passive ventricular mechanics modelling using MRI of structure and function.

    PubMed

    Wang, V Y; Lam, H I; Ennis, D B; Young, A A; Nash, M P

    2008-01-01

    Patients suffering from dilated cardiomyopathy or myocardial infarction can develop left ventricular (LV) diastolic impairment. The LV remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions and this remodeling process can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element model was developed to incorporate physiological and mechanical information derived from in vivo magnetic resonance imaging (MRI) tissue tagging, in vivo LV cavity pressure recording and ex vivo diffusion tensor MRI (DTMRI) of a canine heart. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion (the primary eigenvector) in each voxel of a DTMRI directly correlates with the myocardial fibre orientation. This model was customized to the geometry of the canine LV during diastasis by fitting the segmented epicardial and endocardial surface data from tagged MRI using nonlinear finite element fitting techniques. Myofibre orientations, extracted from DTMRI of the same heart, were incorporated into this geometric model using a free form deformation methodology. Pressure recordings, temporally synchronized to the tissue tagging MRI data, were used to simulate the LV deformation during diastole. Simulation of the diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. This integrated physiological model will allow more insight into the regional passive diastolic mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction in pathological conditions.

  1. [Fascicular ventricular tachycardia].

    PubMed

    Chiarandà, G; Di Guardo, G; Gulizia, M; Lazzaro, A; Regolo, T

    2001-11-01

    Fascicular tachycardia is an uncommon idiopathic ventricular tachycardia, originating from the left ventricle; it usually occurs in young male patients, with a high prevalence in south-east Asiatic people. Electrocardiographic aspects of this unique ventricular tachycardia (right bundle branch block morphology and left or right-axis deviation, with a moderate QRS widening) and verapamil sensitivity make it often difficult the differential diagnosis with other forms of supraventricular tachycardia. Reentry is believed to be the operative mechanism of fascicular tachycardia, with the reentrant circuit located in the Purkinje network, in the region of the left posterior or anterior fascicle. The slow conduction zone participating in the reentry circuit, made up of partially depolarized Purkinje fibers, seems to be located in a relatively wide area, from the basal to the apical left interventricular septum. Intravenous verapamil is elective in acute treatment; however oral verapamil shows poor efficacy in preventing tachycardia relapses. Ablative approach is very effective; success is achieved in approximately 90% of patients, with rare complications. Recently diastolic potentials during fascicular tachycardia have been reported and these findings have given rise to new electrophysiological hypotheses and new indications about the successful ablation site.

  2. Neural remodeling in retinal degeneration.

    PubMed

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  3. Cellular FLICE-inhibitory protein protects against cardiac remodeling induced by angiotensin II in mice.

    PubMed

    Li, Hongliang; Tang, Qi-Zhu; Liu, Chen; Moon, Mark; Chen, Manyin; Yan, Ling; Bian, Zhou-Yan; Zhang, Yan; Wang, Ai-Bing; Nghiem, Mai P; Liu, Peter P

    2010-12-01

    The development of cardiac hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response that may eventually lead to ventricular dilatation and heart failure. Cellular FLICE-inhibitory protein (cFLIP) is a homologue of caspase 8 without caspase activity that inhibits apoptosis initiated by death receptor signaling. Previous studies showed that cFLIP expression was markedly decreased in the ventricular myocardium of patients with end-stage heart failure. However, the critical role of cFLIP on cardiac remodeling remains unclear. To specifically determine the role of cFLIP in pathological cardiac remodeling, we used heterozygote cFLIP(+/-) mice and transgenic mice with cardiac-specific overexpression of the human cFLIP(L) gene. Our results demonstrated that the cFLIP(+/-) mice were susceptible to cardiac hypertrophy and fibrosis through inhibition of mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2 signaling, whereas the transgenic mice displayed the opposite phenotype in response to angiotensin II stimulation. These studies indicate that cFLIP protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure.

  4. Exogenous midkine administration prevents cardiac remodeling in pacing-induced congestive heart failure of rabbits.

    PubMed

    Harada, Masahide; Hojo, Mayumi; Kamiya, Kaichiro; Kadomatsu, Kenji; Murohara, Toyoaki; Kodama, Itsuo; Horiba, Mitsuru

    2016-01-01

    Midkine (MK), a heparin-binding growth factor, has been shown to prevent cardiac remodeling after ischemic injury through its anti-apoptotic effect. Cell apoptosis is central to the pathophysiology of cardiac remodeling in congestive heart failure (CHF) of ischemic as well as non-ischemic origin. We hypothesized that MK exerts the anti-apoptotic cardioprotective effect in CHF of non-ischemic etiology. MK protein or vehicle (normal saline) was subcutaneously administered in tachycardia-induced CHF rabbits (right ventricular pacing, 350 beats/min, 4 weeks). The vehicle-treated rabbits (n = 19, control) demonstrated severe CHF and high mortality rate, whereas MK (n = 16) demonstrated a well-compensated state and a lower mortality rate. In echocardiography, left ventricular (LV) end-diastolic dimension decreased in MK versus control, whereas LV systolic function increased. In histological analysis (picrosirius red staining), MK decreased collagen deposition area compared with control. TUNEL staining showed that MK prevented cell apoptosis and minimized myocyte loss in the CHF rabbit ventricle, associated with activation of PI3-K/Akt signaling, producing a parallel decrease of Bax/Bcl-2 ratio. MK prevented progression of cardiac remodeling in the CHF rabbit, likely by activation of anti-apoptotic signaling. Exogenous MK application might be a novel therapeutic strategy for CHF due to non-ischemic origin.

  5. Ventricular longitudinal function is associated with microvascular obstruction and intramyocardial haemorrhage

    PubMed Central

    Foley, James R J; Musa, Tarique Al; Ripley, David P; Swoboda, Peter P; Erhayiem, Bara; Dobson, Laura E; McDiarmid, Adam K; Greenwood, John P; Plein, Sven

    2016-01-01

    Background Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are associated with adverse prognosis, independently of infarct size after reperfused ST-elevation myocardial infarction (STEMI). Mitral annular plane systolic excursion (MAPSE) is a well-established parameter of longitudinal function on echocardiography. Objective We aimed to investigate how acute MAPSE, assessed by a four-chamber cine-cardiovascular MR (CMR), is associated with MVO, IMH and convalescent left ventricular (LV) remodelling. Methods 54 consecutive patients underwent CMR at 3T (Intera CV, Philips Healthcare, Best, The Netherlands) within 3 days of reperfused STEMI. Cine, T2-weighted, T2* and late gadolinium enhancement (LGE) imaging were performed. Infarct and MVO extent were measured from LGE images. The presence of IMH was investigated by combined analysis of T2w and T2* images. Averaged-MAPSE (medial-MAPSE+lateral-MAPSE/2) was calculated from 4-chamber cine imaging. Results 44 patients completed the baseline scan and 38 patients completed 3-month scans. 26 (59%) patients had MVO and 25 (57%) patients had IMH. Presence of MVO and IMH were associated with lower averaged-MAPSE (11.7±0.4 mm vs 9.3±0.3 mm; p<0.001 and 11.8±0.4 mm vs 9.2±0.3 mm; p<0.001, respectively). IMH (β=−0.655, p<0.001) and MVO (β=−0.567, p<0.001) demonstrated a stronger correlation to MAPSE than other demographic and infarct characteristics. MAPSE ≤10.6 mm demonstrated 89% sensitivity and 72% specificity for the detection of MVO and 92% sensitivity and 74% specificity for IMH. LV remodelling in convalescence was not associated with MAPSE (AUC 0.62, 95% CI 0.44 to 0.77, p=0.22). Conclusions Postreperfused STEMI, LV longitudinal function assessed by MAPSE can independently predict the presence of MVO and IMH. PMID:27175286

  6. Beta-Adrenergic Blockade Therapy for Autonomic Dysfunction is Less Effective for Elderly Patients with Heart Failure and Reduced Left Ventricular Ejection Fraction

    PubMed Central

    Shimamoto, Ken; Kawana, Masatoshi

    2015-01-01

    OBJECTIVE Heart rate variability (HRV) has been reported to be an independent predictor of all-cause and sudden cardiac death in patients with heart failure. In the aging heart, however, both autonomic and cardiac functions appear to be altered. We assessed the relationship between aging and responsiveness of HRV and ventricular remodeling to beta-adrenergic blockade therapy in patients with heart failure and reduced ejection fraction (HFREF). METHODS Twenty-eight clinically stable patients with chronic heart failure, sinus rhythm, and left ventricular ejection fraction <50% as confirmed by echocardiography were included. At baseline and after carvedilol treatment, 24-hour ambulatory Holter monitor recording was used to analyze HRV indices by the maximum entropy method. Changes in these parameters were compared among three age groups. RESULTS HR decreased in all groups after carvedilol treatment, but was still highest in the youngest group despite the same treatment doses. Time and frequency domain variables improved. The response of time domain variables (the standard deviation of all normal sinus to normal sinus [NN] intervals and the standard deviation of the averages of NN intervals in all 5-minute or 30-minute segments) to carvedilol therapy significantly decreased with increasing age. Ventricular reverse remodeling induced by carvedilol therapy significantly decreased with increasing age. Increases in time domain variables and a low-frequency domain moderately correlated with left ventricular reverse remodeling. CONCLUSION Beta-adrenergic blockade therapy improved HRV variables and ventricular remodeling in HFREF patients; however, the response tended to be milder in the elderly. HRV improvement was associated with ventricular reverse remodeling. PMID:26483614

  7. Frontiers in growth and remodeling

    PubMed Central

    Menzel, Andreas; Kuhl, Ellen

    2012-01-01

    Unlike common engineering materials, living matter can autonomously respond to environmental changes. Living structures can grow stronger, weaker, larger, or smaller within months, weeks, or days as a result of a continuous microstructural turnover and renewal. Hard tissues can adapt by increasing their density and grow strong. Soft tissues can adapt by increasing their volume and grow large. For more than three decades, the mechanics community has actively contributed to understand the phenomena of growth and remodeling from a mechanistic point of view. However, to date, there is no single, unified characterization of growth, which is equally accepted by all scientists in the field. Here we shed light on the continuum modeling of growth and remodeling of living matter, and give a comprehensive overview of historical developments and trends. We provide a state-of-the-art review of current research highlights, and discuss challenges and potential future directions. Using the example of volumetric growth, we illustrate how we can establish and utilize growth theories to characterize the functional adaptation of soft living matter. We anticipate this review to be the starting point for critical discussions and future research in growth and remodeling, with a potential impact on life science and medicine. PMID:22919118

  8. Vascular Remodeling in Pulmonary Hypertension

    PubMed Central

    Shimoda, Larissa A; Laurie, Steven S.

    2013-01-01

    Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions and the appearance of cells expressing smooth muscle specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular trans-differentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting. PMID:23334338

  9. Electrical remodeling in a canine model of ischemic cardiomyopathy.

    PubMed

    Liu, Xian-Sheng; Jiang, Min; Zhang, Mei; Tang, Daniel; Clemo, Henry F; Higgins, Robert S D; Tseng, Gea-Ny

    2007-01-01

    The nature of electrical remodeling in a canine model of ischemic cardiomyopathy (ICM; induced by repetitive intracoronary microembolizations) that exhibits spontaneous ventricular tachycardia is not entirely clear. We used the patch-clamp technique to record action potentials and ionic currents of left ventricular myocytes isolated from the region affected by microembolizations. We also used the immunoblot technique to examine channel subunit expression in adjacent affected tissue. Ventricular myocytes and tissue isolated from the corresponding region of normal hearts served as control. ICM myocytes had prolonged action potential duration (APD) and more pronounced APD dispersion. Slow delayed rectifier current (I(Ks)) was reduced at voltages positive to 0 mV, along with a negative shift in its voltage dependence of activation. Immunoblots showed that there was no change in KCNQ1.1 (I(Ks) pore-forming or alpha-subunit), but KCNE1 (I(Ks) auxiliary or beta-subunit) was reduced, and KCNQ1.2 (a truncated KCNQ1 splice variant with a dominant-negative effect on I(Ks)) was increased. Transient outward current (I(to)) was reduced, along with an acceleration of the slow phase of recovery from inactivation. Immunoblots showed that there was no change in Kv4.3 (alpha-subunit of fast-recovering I(to) component), but KChIP2 (beta-subunit of fast-recovering component) and Kv1.4 (alpha-subunit of slow-recovering component) were reduced. Inward rectifier current was reduced. L-type Ca current was unaltered. The immunoblot data provide mechanistic insights into the observed changes in current amplitude and gating kinetics of I(Ks) and I(to). We suggest that these changes, along with the decrease in inward rectifier current, contribute to APD prolongation in ICM hearts.

  10. A long term follow up of 15 patients with arrhythmogenic right ventricular dysplasia.

    PubMed Central

    Blomström-Lundqvist, C; Sabel, K G; Olsson, S B

    1987-01-01

    The clinical course in 15 patients with features consistent with arrhythmogenic right ventricular dysplasia is described. At referral seven patients had abnormal physical findings, nine had abnormal electrocardiograms with non-specific right-sided abnormalities, and seven patients had increased heart size or prominent right ventricles on chest x ray. During long term follow up (mean 8.8 years, range 1.5 to 28 years) 11 patients had abnormal physical findings, 11 had electrocardiographic changes, and nine had increased heart size. Recurrent sustained right ventricular tachycardia was the most common arrhythmia (10 patients). Two patients experienced ventricular fibrillation. Seven patients suffered from over 10 episodes of ventricular tachycardia, nine required cardioversions, and 10 patients had associated serious symptoms such as syncope, severe hypotension, or cardiac arrest. Four patients required operation to correct the arrhythmia and three patients developed right heart failure. Two out of three deaths were sudden. These data suggest that in arrhythmogenic right ventricular dysplasia right ventricular abnormalities may be progressive and that the condition may affect the left ventricle. The course of the ventricular arrhythmias was highly variable and could not be predicted in individual patients. The potential for lethal ventricular arrhythmias is evident and warrants intensive diagnostic efforts to identify patients with adverse prognostic features. PMID:3676037

  11. Left ventricular hypertrophy or storage disease? the incremental value of speckle tracking strain bull's-eye.

    PubMed

    D'Andrea, Antonello; Radmilovic, Juri; Ballo, Piercarlo; Mele, Donato; Agricola, Eustachio; Cameli, Matteo; Rossi, Andrea; Esposito, Roberta; Novo, Giuseppina; Mondillo, Sergio; Montisci, Roberta; Gallina, Sabina; Bossone, Eduardo; Galderisi, Maurizio

    2017-03-19

    Left ventricular hypertrophy (LVH) develops in response to a variety of physical, genetic, and biochemical stimuli and represents the early stage of ventricular remodeling. In patients with LVH, subclinical left ventricular (LV) dysfunction despite normal ejection fraction (EF) may be present before the onset of symptoms, which portends a dismal prognosis. Strain measurement with two-dimensional speckle tracking echocardiography (STE) represents a highly reproducible and accurate alternative to LVEF determination. The present review focuses on current available evidence that supports the incremental value of STE in the diagnostic and prognostic workup of LVH. When assessing the components of LV contraction, STE has an incremental value in differentiating between primary and secondary LVH and in the differential diagnosis with storage diseases. In addition, STE provides unique information for the stratification of patients with LVH, enabling to detect intrinsic myocardial dysfunction before LVEF reduction.

  12. Traditional Chinese Medication Qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction in mice

    PubMed Central

    Tao, Lichan; Shen, Sutong; Fu, Siyi; Fang, Hongyi; Wang, Xiuzhi; Das, Saumya; Sluijter, Joost P. G.; Rosenzweig, Anthony; Zhou, Yonglan; Kong, Xiangqing; Xiao, Junjie; Li, Xinli

    2015-01-01

    In a multicenter randomized double-blind study we demonstrated that Qiliqiangxin (QLQX), a traditional Chinese medicine, had a protective effect in heart failure patients. However, whether and via which mechanism QLQX attenuates cardiac remodeling after acute myocardial infarction (AMI) is still unclear. AMI was created by ligating the left anterior descending coronary artery in mice. Treating the mice in the initial 3 days after AMI with QLQX did not change infarct size. However, QLQX treatment ameliorated adverse cardiac remodeling 3 weeks after AMI including better preservation of cardiac function, decreased apoptosis and reduced fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) was down-regulated in control animals after AMI and up-regulated by QLQX administration. Interestingly, expression of AKT, SAPK/JNK, and ERK was not altered by QLQX treatment. Inhibition of PPARγ reduced the beneficial effects of QLQX in AMI remodeling, whereas activation of PPARγ failed to provide additional improvement in the presence of QLQX, suggesting a key role for PPARγ in the effects of QLQX during cardiac remodeling after AMI. This study indicates that QLQX attenuates cardiac remodeling after AMI by increasing PPARγ levels. Taken together, QLQX warrants further investigation as as a therapeutic intervention to mitigate remodeling and heart failure after AMI. PMID:25669146

  13. Symbolic dynamics of ventricular tachycardia and ventricular fibrillation

    NASA Astrophysics Data System (ADS)

    Wang, Jun; Chen, Jie

    2010-05-01

    In this paper, the symbolic dynamics analysis was used to analyze the complexity of normal heartbeat signal (NSR), Ventricular tachycardia (VT) and ventricular fibrillation (VF) signals. By calculating the information entropy value of symbolic sequences, the complexities were quantified. Based on different information entropy values, NSR, VT and VF signals were distinguished with satisfactory results. The study showed that a sudden drop of symbolic sequence’s entropy value indicated that the patients most likely entered the episode of ventricular tachycardia and this was a crucial episode for the clinical treatment of patients. It had important clinical significance for the automatic diagnosis.

  14. Erythrocyte Stiffness during Morphological Remodeling Induced by Carbon Ion Radiation

    PubMed Central

    Zhang, Baoping; Liu, Bin; Zhang, Hong; Wang, Jizeng

    2014-01-01

    The adverse effect induced by carbon ion radiation (CIR) is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy) or X-rays (2, 4, 6, and 12 Gy) for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy). The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study provides a new

  15. Molecular Mechanisms of Right Ventricular Failure

    PubMed Central

    Reddy, Sushma; Bernstein, Daniel

    2015-01-01

    An abundance of data has provided insight into the mechanisms underlying the development of left ventricular (LV) hypertrophy and its progression to LV failure. In contrast, there is minimal data on the adaptation of the right ventricle (RV) to pressure and volume overload and the transition to RV failure. This is a critical clinical question, as the RV is uniquely at risk in many patients with repaired or palliated congenital heart disease and in those with pulmonary hypertension. Standard heart failure therapies have failed to improve function or survival in these patients, suggesting a divergence in the molecular mechanisms of RV vs. LV failure. Although, on the cellular level, the remodeling responses of the RV and LV to pressure overload are largely similar, there are several key differences: the stressed RV is more susceptible to oxidative stress, has a reduced angiogenic response, and is more likely to activate cell death pathways than the stressed LV. Together, these differences could explain the more rapid progression of the RV to failure vs. the LV. This review will highlight known molecular differences between the RV and LV responses to hemodynamic stress, the unique stressors on the RV associated with congenital heart disease, and the need to better understand these molecular mechanisms if we are to develop RV-specific heart failure therapeutics. PMID:26527692

  16. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  17. Arrhythmogenic right ventricular cardiomyopathy in a weimaraner

    PubMed Central

    Eason, Bryan D.; Leach, Stacey B.; Kuroki, Keiichi

    2015-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed postmortem in a weimaraner dog. Syncope, ventricular arrhythmias, and sudden death in this patient combined with the histopathological fatty tissue infiltration affecting the right ventricular myocardium are consistent with previous reports of ARVC in non-boxer dogs. Arrhythmogenic right ventricular cardiomyopathy has not been previously reported in weimaraners. PMID:26483577

  18. Pulsatile Fluid Shear in Bone Remodeling

    NASA Technical Reports Server (NTRS)

    Frangos, John A.

    1997-01-01

    The objective of this investigation was to elucidate the sensitivity to transients in fluid shear stress in bone remodeling. Bone remodeling is clearly a function of the local mechanical environment which includes interstitial fluid flow. Traditionally, load-induced remodeling has been associated with low frequency (1-2 Hz) signals attributed to normal locomotion. McLeod and Rubin, however, demonstrated in vivo remodeling events associated with high frequency (15-30 Hz) loading. Likewise, other in vivo studies demonstrated that slowly applied strains did not trigger remodeling events. We therefore hypothesized that the mechanosensitive pathways which control bone maintenance and remodeling are differentially sensitive to varying rates of applied fluid shear stress.

  19. Multiscale Characterization of Impact of Infarct Size on Myocardial Remodeling in an Ovine Infarct Model.

    PubMed

    Zhang, Pei; Li, Tielou; Griffith, Bartley P; Wu, Zhongjun J

    2015-01-01

    The surviving myocardium initially compensates the loss of injured myocardium after myocardial infarction (MI) and gradually becomes progressively dysfunctional. There have been limited studies on the effect of infarct size on temporal and spatial alterations in the myocardium during progressive myocardial remodeling. MI with three infarct sizes, i.e. 15, 25 and 35% of the left ventricular (LV) wall, was created in an ovine infarction model. The progressive LV remodeling over a 12-week period was studied. Echocardiography, sonomicrometry, and histological and molecular analyses were carried out to evaluate cardiac function, regional tissue contractile function, structural remodeling and cardiomyocyte hypertrophy, and calcium handling proteins. Twelve weeks after MI, the 15, 25 and 35% MI groups had normalized LV end diastole volumes of 1.4 ± 0.2, 1.7 ± 0.3 and 2.0 ± 0.4 ml/kg, normalized end systole volumes of 1.0 ± 0.1, 1.0 ± 0.2 and 1.3 ± 0.3 ml/kg and LV ejection fractions of 43 ± 3, 42 ± 6 and 34 ± 4%, respectively. They all differed from the sham group (p < 0.05). All the three MI groups exhibited larger wall areal expansion (remodeling strain), larger cardiomyocyte size and altered expression of calcium handing proteins in the adjacent myocardium compared to the remote counterpart from the infarct. A significant correlation was found between cardiomyocyte size and remodeling strain in the adjacent zone. A comparative analysis among the three MI groups showed that a larger infarct size (35 vs. 15% MI) was associated with larger remodeling strain, more serious impairment in the cellular structure and composition, and regional contractile function at regional tissue level and LV function at organ level.

  20. In Vivo Assessment of Pulmonary Arterial Wall Fibrosis by Intravascular Optical Coherence Tomography in Pulmonary Arterial Hypertension: A New Prognostic Marker of Adverse Clinical Follow-Up§

    PubMed Central

    Domingo, Enric; Grignola, Juan C; Aguilar, Rio; Montero, María Angeles; Arredondo, Christian; Vázquez, Manuel; López-Messeguer, Manuel; Bravo, Carlos; Bouteldja, Nadia; Hidalgo, Cristina; Roman, Antonio

    2013-01-01

    Background: The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hypertension (PAH) with clinical follow-up. Histology of PA specimens is also performed. Methods: 19 patients, aged 54±16 (4 men), functional class II-III were studied with right heart catheterization, PA Intravascular Ultrasound and optical coherence tomography (OCT) in inferior lobe segment. PA wall fibrosis was obtained by OCT ( area of fibrosis/PA cross sectional area × 100). Patients follow-up was blind to OCT. Events were defined as mortality, lung transplantation, need of intravenous prostaglandins or onset of right ventricular failure. Results: OCT measurements showed high intra- and interobserver agreement. There was a good correlation between OCT and histology in PA fibrosis from explanted lungs. Area of fibrosis was 1.4±0.8 mm2, % fibrosis was 22.3±8. Follow-up was 3.5 years (2.5-4.5). OCT %Fib was significantly correlated with PA capacitance (r=-0.536) and with pulmonary vascular rsistance (r=0.55). Patients were divided according to the median value of PA fibrosis. There were 10 patients with a high (≥ 22%) and 9 with a low fibrosis (<22%). Events occurred in 6 (1 death, 1 lung transplantation, 2 intravenous prostaglandins, 2 right heart failure) out of 10 patients with high and in 0 out of 9 patients with low fibrosis (p<0.01). Conclusions: In PAH, the severity of PA remodeling assessed by OCT wall fibrosis was significantly predictive of severely unfavorable clinical outcome. In vivo assessment of pulmonary arterial wall fibrosis by intravascular OCT in PAH is a promising new prognostic marker of adverse clinical outcome. PMID:23730366

  1. Weight reduction via life-style modifications results in reverse remodelling and cardiac functional improvement in a patient with obesity.

    PubMed

    Hou, Chang; Zheng, Bo; Yang, Ying; Wang, Xin-Gang; Zhang, Bin; Shi, Qiu-Ping; Chen, Ming

    2017-03-09

    The prevalence of obesity has increased strikingly in recent years. Obesity is associated with increased left ventricular end-diastolic dimension (LVEDD), ventricular wall thickness, left ventricular (LV) mass, left atrial diameter, subtle myocardial systolic as well as diastolic dysfunction and has been identified as an independent predictor of these changes. It's convinced that weight reduction results in cardiac reverse remodelling, while the functional changes after weight reduction are variable. Here, we present a recent case of man with moderate obesity who acquires favourable regression in chamber size, wall thickness and significant improvement in cardiac function. Briefly, after life-style modifications and comprehensive secondary prevention, great amounts of weight loss was achieved simultaneously with decreased LVEDD and increased LV ejection fraction. As dietary intervention and regular physical activity are pivotal for these benefits, this non-invasive approach for weight loss should be advocated in selected patients.

  2. Long-term Excessive Body Weight and Adult Left Ventricular Hypertrophy Are Linked Through Later Life Body Size and Blood Pressure: The Bogalusa Heart Study.

    PubMed

    Zhang, Huijie; Zhang, Tao; Li, Shengxu; Guo, Yajun; Shen, Wei; Fernandez, Camilo; Harville, Emily W; Bazzano, Lydia A; Urbina, Elaine M; He, Jiang; Chen, Wei

    2017-02-23

    Rationale: Childhood adiposity is associated with cardiac structure in later life, but little is known regarding to what extent childhood body weight affects adult left ventricular geometric patterns through adult body size and blood pressure (BP). Objective: Determine quantitatively the mediation effect of adult body weight and BP on the association of childhood BMI with adult left ventricular hypertrophy (LVH). Methods and Results: This longitudinal study consisted of 710 adults, age 26 to 48 years, who had been examined for BMI and BP measured 4 or more times during childhood and 2 or more times during adulthood, with a mean follow-up period of 28.0 years. After adjusting for age, race and sex, adult BMI had a significant mediation effect (76.4%, p<0.01) on the childhood BMI-adult LV mass index (LVMI) association. The mediation effects of adult systolic BP (SBP, 15.2%), long-term burden (12.1%) and increasing trends of SBP (7.9%) were all significant (p<0.01). Furthermore, these mediators also had significant mediation effects on the association of childhood BMI with adult LVH, eccentric and concentric hypertrophy. Importantly, the mediation effects of adult BMI were all significantly stronger than those of adult SBP on LVMI, LVH and LV remodeling patterns (p<0.01). Additionally, the mediation effect of SBP on concentric hypertrophy was significantly stronger than on eccentric hypertrophy (p<0.01). Conclusions: These findings suggest that increased childhood BMI has long-term adverse impact on subclinical changes in adult cardiac structure, and early life excessive body weight and adult LVH are linked through later life excessive body weight and elevated BP.

  3. Impact of family hypertension history on exercise-induced cardiac remodeling.

    PubMed

    Baggish, Aaron L; Weiner, Rory B; Yared, Kibar; Wang, Francis; Kupperman, Eli; Hutter, Adolph M; Picard, Michael H; Wood, Malissa J

    2009-07-01

    Left ventricular (LV) hypertrophy is a well-established, but highly variable, finding among exercise-trained persons. The causes for the variability in LV remodeling in response to exercise training remain incompletely understood. The present study sought to determine whether a family history of hypertension is a determinant of the cardiac response to exercise training. The cardiac parameters in 60 collegiate rowers (30 men/30 women; age 19.8 +/- 1.1 years) with (family history positive [FH+], n = 22) and without (family history negative [FH-], n = 38) a FH of hypertension were studied with echocardiography before and after 90 days of rowing training. The LV mass increased significantly in both groups. However, the LV mass increased significantly more in FH- persons (Delta 17 +/- 5 g/m(2)) than in FH+ persons (Delta 9 +/- 6 g/m(2), p <0.001) with distinctly differently patterns of LV hypertrophy between the 2 groups. FH- athletes experienced eccentric LV hypertrophy (relative wall thickness index 0.39 +/- 0.4) characterized by LV dilation. In contrast, FH+ athletes developed concentric LV hypertrophy (relative wall thickness index 0.44 +/- 0.3; p <0.001) characterized by LV wall thickening. Furthermore, the eccentric LV remodeling in FH- athletes was associated with a more robust enhancement of LV diastolic function than the concentric LV remodeling that occurred in FH+ athletes. In conclusion, these findings suggest that patterns of exercise-induced LV remodeling are strongly associated with FH history status.

  4. Catheter Ablation for Ventricular Arrhythmias

    PubMed Central

    Nof, Eyal; Stevenson, William G; John, Roy M

    2013-01-01

    Catheter ablation has emerged as an important and effective treatment option for many recurrent ventricular arrhythmias. The approach to ablation and the risks and outcomes are largely determined by the nature of the severity and type of underlying heart disease. In patients with structural heart disease, catheter ablation can effectively reduce ventricular tachycardia (VT) episodes and implantable cardioverter defibrillator (ICD) shocks. For VT and symptomatic premature ventricular beats that occur in the absence of structural heart disease, catheter ablation is often effective as the sole therapy. Advances in catheter technology, imaging and mapping techniques have improved success rates for ablation. This review discusses current approaches to mapping and ablation for ventricular arrhythmias. PMID:26835040

  5. Adverse drug reactions.

    PubMed

    O'Reilly-Foley, Georgina

    2017-04-05

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article defined the different types of adverse drug reactions (ADRs) and explored when they can occur. It emphasised the importance of being knowledgeable about medications, considering patient safety when patients are taking medications, being alert to the possibility of ADRs, and recognising and responding to suspected ADRs.

  6. Cardiac Resynchronization Therapy Restores Sympathovagal Balance in the Failing Heart by Differential Remodeling of Cholinergic Signaling

    PubMed Central

    DeMazumder, Deeptankar; Kass, David A.; O’Rourke, Brian; Tomaselli, Gordon F.

    2015-01-01

    Rationale Cardiac resynchronization therapy (CRT) is the only heart failure (HF) therapy documented to improve left ventricular (LV) function and reduce mortality. The underlying mechanisms are incompletely understood. While β-adrenergic signaling has been studied extensively, the effect of CRT on cholinergic signaling is unexplored. Objective We hypothesized that remodeling of cholinergic signaling plays an important role in the aberrant calcium signaling and depressed contractile and β-adrenergic responsiveness in dyssynchronous HF (DHF) that are restored by CRT. Methods and Results Canine tachypaced DHF and CRT models were generated to interrogate responses specific to dyssynchronous vs. resynchronized ventricular contraction during hemodynamic decompensation. Echocardiographic, electrocardiographic and invasive hemodynamic data were collected from normal controls, DHF and CRT models. LV tissue was used for biochemical analyses and functional measurements (calcium transient, sarcomere shortening) from isolated myocytes (N=42–104 myocytes/model; 6–9 hearts/model). Human LV myocardium was obtained for biochemical analyses from explanted failing (N=18) and non-failing (N=7) hearts. The M2 subtype of muscarinic acetylcholine receptors (M2-mAChR) was upregulated in human and canine HF compared to non-failing controls. CRT attenuated the increased M2-mAChR expression and Gαi-coupling, and enhanced M3-mAChR expression in association with enhanced calcium cycling, sarcomere shortening and β-adrenergic responsiveness. Despite model-dependent remodeling, cholinergic stimulation completely abolished isoproterenol-induced triggered activity in both DHF and CRT myocytes. Conclusions Remodeling of cholinergic signaling is a critical pathological component of human and canine HF. Differential remodeling of cholinergic signaling represents a novel mechanism for enhancing sympathovagal balance with CRT and may identify new targets for treatment of systolic HF. PMID

  7. Cardiac remodeling in the mouse model of Marfan syndrome develops into two distinctive phenotypes.

    PubMed

    Tae, Hyun-Jin; Petrashevskaya, Natalia; Marshall, Shannon; Krawczyk, Melissa; Talan, Mark

    2016-01-15

    Marfan syndrome (MFS) is a systemic disorder of connective tissue caused by mutations in fibrillin-1. Cardiac dysfunction in MFS has not been characterized halting the development of therapies of cardiac complication in MFS. We aimed to study the age-dependent cardiac remodeling in the mouse model of MFS FbnC1039G+/- mouse [Marfan heterozygous (HT) mouse] and its association with valvular regurgitation. Marfan HT mice of 2-4 mo demonstrated a mild hypertrophic cardiac remodeling with predominant decline of diastolic function and increased transforming growth factor-β canonical (p-SMAD2/3) and noncanonical (p-ERK1/2 and p-p38 MAPK) signaling and upregulation of hypertrophic markers natriuretic peptides atrium natriuretic peptide and brain natriuretic peptide. Among older HT mice (6-14 mo), cardiac remodeling was associated with two distinct phenotypes, manifesting either dilated or constricted left ventricular chamber. Dilatation of left ventricular chamber was accompanied by biochemical evidence of greater mechanical stress, including elevated ERK1/2 and p38 MAPK phosphorylation and higher brain natriuretic peptide expression. The aortic valve regurgitation was registered in 20% of the constricted group and 60% of the dilated group, whereas mitral insufficiency was observed in 40% of the constricted group and 100% of the dilated group. Cardiac dysfunction was not associated with the increase of interstitial fibrosis and nonmyocyte proliferation. In the mouse model fibrillin-1, haploinsufficiency results in the early onset of nonfibrotic hypertrophic cardiac remodeling and dysfunction, independently from valvular abnormalities. MFS heart is vulnerable to stress-induced cardiac dilatation in the face of valvular regurgitation, and stress-activated MAPK signals represent a potential target for cardiac management in MFS.

  8. Nox4 Is Expressed In Pulmonary Artery Adventitia And Contributes To Hypertensive Vascular Remodeling

    PubMed Central

    Barman, Scott A.; Chen, Feng; Su, Yunchao; Dimitropoulou, Christiana; Wang, Yusi; Catravas, John D.; Han, Weihong; Orfi, Laszlo; Szantai-Kis, Csaba; Keri, Gyorgy; Szabadkai, Istvan; Barabutis, Nektarios; Rafikova, Olga; Rafikov, Ruslan; Black, Stephen M.; Jonigk, Danny; Giannis, Athanassios; Asmis, Reto; Stepp, David W.; Ramesh, Ganesan; Fulton, David J.R.

    2014-01-01

    OBJECTIVE Pulmonary Hypertension (PH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PA) resulting in high pulmonary blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) is associated with increased pressure in PH. However, the cellular location of Nox4 and its contribution to aberrant vascular remodeling in PH remains poorly understood. Therefore, we sought to identify the vascular cells expressing Nox4 in PA and determine the functional relevance of Nox4 in PH. APPROACH AND RESULTS Elevated expression of Nox4 was detected in hypertensive PA from 3 rat PH models and human PH using qRT-PCR, Western blot, and immunofluorescence. In the vascular wall, Nox4 was detected in both endothelium and adventitia and perivascular staining was prominently increased in hypertensive lung sections, colocalizing with cells expressing fibroblast and monocyte markers and matching the adventitial location of ROS production. Small molecule inhibitors of Nox4 reduced adventitial ROS generation and vascular remodeling as well as ameliorating right ventricular hypertrophy and non-invasive indices of PA stiffness in monocrotaline (MCT)-treated rats as determined by morphometric analysis and high resolution digital ultrasound. Nox4 inhibitors improved PH in both prevention and reversal protocols and reduced the expression of fibroblast markers in isolated PA. In fibroblasts, Nox4 over-expression stimulated migration and proliferation and was necessary for matrix gene expression. CONCLUSIONS These findings indicate that Nox4 is prominently expressed in the adventitia and contributes to altered fibroblast behavior, hypertensive vascular remodeling and the development of PH. PMID:24947524

  9. Adverse cardiac events to monoclonal antibodies used for cancer therapy

    PubMed Central

    Kounis, Nicholas G; Soufras, George D; Tsigkas, Grigorios; Hahalis, George

    2014-01-01

    Monoclonal antibodies are currently used in the treatment of neoplastic, hematological, or inflammatory diseases, a practice that is occasionally associated with a variety of systemic and cutaneous adverse events. Cardiac adverse events include cardiomyopathy, ventricular dysfunction, arrhythmias, arrests, and acute coronary syndromes, such as acute myocardial infarction and vasospastic angina pectoris. These events generally follow hypersensitivity reactions including cutaneous erythema, pruritus chills, and precordial pain. Recently, IgE specific for therapeutic monoclonal antibodies have been detected, pointing to the existence of hypersensitivity and Kounis hypersensitivity-associated syndrome. Therefore, the careful monitoring of cardiovascular events is of paramount importance in the course of monoclonal antibody-based therapies. Moreover, further studies are needed to elucidate the pathophysiology of cardiovascular adverse events elicited by monoclonal antibodies and to identify preventive, protective, and therapeutic measures. PMID:25340003

  10. The Relationship of Myocardial Collagen Metabolism and Reverse Remodeling after Cardiac Resynchronization Therapy

    PubMed Central

    Stankovic, Ivan; Milasinovic, Goran; Nikcevic, Gabrijela; Kircanski, Bratislav; Jovanovic, Velibor; Raspopovic, Srdjan; Radovanovic, Nikola; Pavlovic, Sinisa U.

    2016-01-01

    Summary Background In the majority of patients with a wide QRS complex and heart failure resistant to optimal medical therapy, cardiac resynchronization therapy (CRT) leads to reverse ventricular remodeling and possibly to changes in cardiac collagen synthesis and degradation. We investigated the relationship of biomarkers of myocardial collagen metabolism and volumetric response to CRT. Methods We prospectively studied 46 heart failure patients (mean age 61±9 years, 87% male) who underwent CRT implantation. Plasma concentrations of amino-terminal propeptide type I (PINP), a marker of collagen synthesis, and carboxy-terminal collagen telopeptide (CITP), a marker of collagen degradation, were measured before and 6 months after CRT. Response to CRT was defined as 15% or greater reduction in left ventricular end-systolic volume at 6-month follow-up. Results Baseline PINP levels showed a negative correlation with both left ventricular end-diastolic volume (r=-0.51; p=0.032), and end-systolic diameter (r=-0.47; p=0.049). After 6 months of device implantation, 28 patients (61%) responded to CRT. No significant differences in the baseline levels of PINP and CITP between responders and nonresponders were observed (p>0.05 for both). During follow-up, responders demonstrated a significant increase in serum PINP level from 31.37±18.40 to 39.2±19.19 μg/L (p=0.049), whereas in non-responders serum PINP levels did not significantly change (from 28.12±21.55 to 34.47± 18.64 μg/L; p=0.125). There were no significant changes in CITP levels in both responders and non-responders (p>0.05). Conclusions Left ventricular reverse remodeling induced by CRT is associated with an increased collagen synthesis in the first 6 months of CRT implantation.

  11. Small artery remodelling in diabetes

    PubMed Central

    Rosei, Enrico Agabiti; Rizzoni, Damiano

    2010-01-01

    Abstract The aim of this article is to briefly review available data regarding changes in the structure of microvessels observed in patients with diabetes mellitus, and possible correction by effective treatment. The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small arteries of smooth muscle cells are restructured around a smaller lumen and there is no net growth of the vascular wall, although in some secondary forms of hypertension, a hypertrophic remodelling may be detected. Moreover, in non-insulin-dependent diabetes mellitus a hypertrophic remodelling of subcutaneous small arteries is present. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive and diabetic patients, over and above all other known cardiovascular risk factors. Therefore, regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure. In diabetic hypertensive patients, a significant regression of structural alterations of small resistance arteries with drugs blocking the renin–angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) was demonstrated. Alterations in the microcirculation represent a common pathological finding, and microangiopathy is one of the most important mechanisms involved in the development of organ damage as well as of clinical events in patients with diabetes mellitus. Renin–angiotensin system blockade seems to be effective in preventing/regressing alterations in microvascular structure. PMID:20646125

  12. Bone remodeling after renal transplantation.

    PubMed

    Bellorin-Font, Ezequiel; Rojas, Eudocia; Carlini, Raul G; Suniaga, Orlando; Weisinger, José R

    2003-06-01

    Several studies have indicated that bone alterations after transplantation are heterogeneous. Short-term studies after transplantation have shown that many patients exhibit a pattern consistent with adynamic bone disease. In contrast, patients with long-term renal transplantation show a more heterogeneous picture. Thus, while adynamic bone disease has also been described in these patients, most studies show decreased bone formation and prolonged mineralization lag-time faced with persisting bone resorption, and even clear evidence of generalized or focal osteomalacia in many patients. Thus, the main alterations in bone remodeling are a decrease in bone formation and mineralization up against persistent bone resorption, suggesting defective osteoblast function, decreased osteoblastogenesis, or increased osteoblast death rates. Indeed, recent studies from our laboratory have demonstrated that there is an early decrease in osteoblast number and surfaces, as well as in reduced bone formation rate and delayed mineralization after transplantation. These alterations are associated with an early increase in osteoblast apoptosis that correlates with low levels of serum phosphorus. These changes were more frequently observed in patients with low turnover bone disease. In contrast, PTH seemed to preserve osteoblast survival. The mechanisms of hypophosphatemia in these patients appear to be independent of PTH, suggesting that other phosphaturic factors may play a role. However, further studies are needed to determine the nature of a phosphaturic factor and its relationship to the alterations of bone remodeling after transplantation.

  13. Third ventricular meningiomas.

    PubMed

    Li, Puxian; Diao, Xingtao; Bi, Zhiyong; Hao, Shuyu; Ren, Xiaohui; Zhang, Junting; Xing, Jun

    2015-11-01

    We report 13 patients with third ventricular meningiomas (TVM) and discuss the clinical, radiological, pathological and surgical features, as well as follow-up of these tumors. TVM are rare intracranial tumors, and because of this, there are few reports in the literature. Of 11,600 intracranial meningiomas that were surgically treated and pathologically confirmed at Beijing Tian Tan Hospital over a period of 10 years (2003-2013), 13 TVM were selected for a retrospective review. We recorded the clinical, radiological, pathological, and surgical data and statistically analyzed the preoperative, postoperative and 6 month postoperative Karnofsky performance scale (KPS) scores. TVM represented 0.11% of intracranial meningiomas. Radiologically, TVM were divided into three groups: anterior (n=3), posterior (n=3), and entire third ventricle (n=7). Three patients (23.1%) were misdiagnosed preoperatively. Total removal was achieved in 61.5% (8/13) of patients, and subtotal resection was achieved in 38.5% (5/13). Pathologically, the tumors were World Health Organization (WHO) Grade I in 11 patients (84.6%) and WHO Grade II in two (15.6%). There were no statistically significant differences in the preoperative, postoperative, or 6 month postoperative KPS scores (F=0.814; p=0.401). TVM without dural attachments are rare neoplasms that should be differentiated from choroid plexus papilloma, craniopharyngioma, and pineocytoma. Surgery is the optimal treatment and may result in a favorable prognosis, and understanding of the radiological subtype can help with the choice of surgical approach.

  14. Conventional heart rate variability analysis of ambulatory electrocardiographic recordings fails to predict imminent ventricular fibrillation

    NASA Technical Reports Server (NTRS)

    Vybiral, T.; Glaeser, D. H.; Goldberger, A. L.; Rigney, D. R.; Hess, K. R.; Mietus, J.; Skinner, J. E.; Francis, M.; Pratt, C. M.

    1993-01-01

    OBJECTIVES. The purpose of this report was to study heart rate variability in Holter recordings of patients who experienced ventricular fibrillation during the recording. BACKGROUND. Decreased heart rate variability is recognized as a long-term predictor of overall and arrhythmic death after myocardial infarction. It was therefore postulated that heart rate variability would be lowest when measured immediately before ventricular fibrillation. METHODS. Conventional indexes of heart rate variability were calculated from Holter recordings of 24 patients with structural heart disease who had ventricular fibrillation during monitoring. The control group consisted of 19 patients with coronary artery disease, of comparable age and left ventricular ejection fraction, who had nonsustained ventricular tachycardia but no ventricular fibrillation. RESULTS. Heart rate variability did not differ between the two groups, and no consistent trends in heart rate variability were observed before ventricular fibrillation occurred. CONCLUSIONS. Although conventional heart rate variability is an independent long-term predictor of adverse outcome after myocardial infarction, its clinical utility as a short-term predictor of life-threatening arrhythmias remains to be elucidated.

  15. Rupture of Right Ventricular Free Wall Following Ventricular Septal Rupture in Takotsubo Cardiomyopathy with Right Ventricular Involvement

    PubMed Central

    Sung, June-Min; Chung, In-Hyun; Lee, Hye Young; Lee, Jae Hoon; Kim, Hyun-Jung; Byun, Young Sup; Kim, Byung Ok; Rhee, Kun Joo

    2017-01-01

    Most patients diagnosed with takotsubo cardiomyopathies are expected to almost completely recover, and their prognosis is excellent. However, complications can occur in the acute phase. We present a case of a woman with takotsubo cardiomyopathy with right ventricular involvement who developed a rupture of the right ventricular free wall following ventricular septal rupture, as a consequence of an acute increase in right ventricular afterload by left-to-right shunt. Our case report illustrates that takotsubo cardiomyopathy can be life threatening in the acute phase. Ventricular septal rupture in biventricular takotsubo cardiomyopathy may be a harbinger of cardiac tamponade by right ventricular rupture. PMID:27873520

  16. Rupture of Right Ventricular Free Wall Following Ventricular Septal Rupture in Takotsubo Cardiomyopathy with Right Ventricular Involvement.

    PubMed

    Sung, June Min; Hong, Sung Jin; Chung, In Hyun; Lee, Hye Young; Lee, Jae Hoon; Kim, Hyun Jung; Byun, Young Sup; Kim, Byung Ok; Rhee, Kun Joo

    2017-01-01

    Most patients diagnosed with takotsubo cardiomyopathies are expected to almost completely recover, and their prognosis is excellent. However, complications can occur in the acute phase. We present a case of a woman with takotsubo cardiomyopathy with right ventricular involvement who developed a rupture of the right ventricular free wall following ventricular septal rupture, as a consequence of an acute increase in right ventricular afterload by left-to-right shunt. Our case report illustrates that takotsubo cardiomyopathy can be life threatening in the acute phase. Ventricular septal rupture in biventricular takotsubo cardiomyopathy may be a harbinger of cardiac tamponade by right ventricular rupture.

  17. Remodeling, Renovation, & Conversion of Educational Facilities.

    ERIC Educational Resources Information Center

    Association of Physical Plant Administrators of Universities and Colleges, Washington, DC.

    Based on a series of workshops, this collection of papers provides a framework for thought--emphasizing planning within time, flexibility, and maintenance constraints--as well as a practical guide for actual engineering of remodeling/renovation/conversion projects. Is remodeling always less expensive than new construction? Should high initial…

  18. Chromatin remodeling: nucleosomes bulging at the seams.

    PubMed

    Peterson, Craig L

    2002-04-02

    ATP-dependent chromatin remodeling enzymes, such as SWI/SNF, hydrolyze thousands of ATPs to regulate gene expression on chromatin fibers. Recent mechanistic studies suggest that these enzymes generate localized changes in DNA topology that drive formation of multiple, remodeled nucleosomal states.

  19. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  20. Adverse reactions to vaccines.

    PubMed

    Martin, Bryan L; Nelson, Michael R; Hershey, Joyce N; Engler, Renata J M

    2003-06-01

    (The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.) Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prolonged disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rare reaction risk. There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced risk communication intervention. When they occur, vaccine related adverse events must be treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

  1. Nucleosome dynamics during chromatin remodeling in vivo.

    PubMed

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation.

  2. Calcium signalling remodelling and disease.

    PubMed

    Berridge, Michael J

    2012-04-01

    A wide range of Ca2+ signalling systems deliver the spatial and temporal Ca2+ signals necessary to control the specific functions of different cell types. Release of Ca2+ by InsP3 (inositol 1,4,5-trisphosphate) plays a central role in many of these signalling systems. Ongoing transcriptional processes maintain the integrity and stability of these cell-specific signalling systems. However, these homoeostatic systems are highly plastic and can undergo a process of phenotypic remodelling, resulting in the Ca2+ signals being set either too high or too low. Such subtle dysregulation of Ca2+ signals have been linked to some of the major diseases in humans such as cardiac disease, schizophrenia, bipolar disorder and Alzheimer's disease.

  3. Zika Virus Induced Cellular Remodeling.

    PubMed

    Rossignol, Evan D; Peters, Kristen N; Connor, John H; Bullitt, Esther

    2017-03-20

    Zika virus (ZIKV) has been associated with morbidities such as Guillain-Barré, infant microcephaly, and ocular disease. The spread of this positive-sense, single-stranded RNA virus and its growing public health threat underscore gaps in our understanding of basic ZIKV virology. To advance knowledge of the virus replication cycle within mammalian cells, we use serial section three-dimensional electron tomography to demonstrate the widespread remodeling of intracellular membranes upon infection with ZIKV. We report extensive structural rearrangements of the endoplasmic reticulum and reveal stages of the ZIKV viral replication cycle. Structures associated with RNA genome replication and virus assembly are observed integrated within the endoplasmic reticulum, and we show viruses in transit through the Golgi apparatus for viral maturation, and subsequent cellular egress. This study characterizes in detail the three-dimensional ultrastructural organization of the ZIKV replication cycle stages. Our results show close adherence of the ZIKV replication cycle to the existing flavivirus replication paradigm.

  4. Tissue remodelling in pulmonary fibrosis.

    PubMed

    Knudsen, Lars; Ruppert, Clemens; Ochs, Matthias

    2017-03-01

    Many lung diseases result in fibrotic remodelling. Fibrotic lung disorders can be divided into diseases with known and unknown aetiology. Among those with unknown aetiology, idiopathic pulmonary fibrosis (IPF) is a common diagnosis. Because of its progressive character leading to a rapid decline in lung function, it is a fatal disease with poor prognosis and limited therapeutic options. Thus, IPF has motivated many studies in the last few decades in order to increase our mechanistic understanding of the pathogenesis of the disease. The current concept suggests an ongoing injury of the alveolar epithelium, an impaired regeneration capacity, alveolar collapse and, finally, a fibroproliferative response. The origin of lung injury remains elusive but a diversity of factors, which will be discussed in this article, has been shown to be associated with IPF. Alveolar epithelial type II (AE2) cells play a key role in lung fibrosis and their crucial role for epithelial regeneration, stabilisation of alveoli and interaction with fibroblasts, all known to be responsible for collagen deposition, will be illustrated. Whereas mechanisms of collagen deposition and fibroproliferation are the focus of many studies in the field, the awareness of other mechanisms in this disease is currently limited to biochemical and imaging studies including quantitative assessments of lung structure in IPF and animal models assigning alveolar collapse and collapse induration crucial roles for the degradation of the lung resulting in de-aeration and loss of surface area. Dysfunctional AE2 cells, instable alveoli and mechanical stress trigger remodelling that consists of collapsed alveoli absorbed by fibrotic tissue (i.e., collapse induration).

  5. Left ventricular geometry and white matter lesions in ischemic stroke patients.

    PubMed

    Butenaerts, Demian; Chrzanowska-Wasko, Joanna; Slowik, Agnieszka; Dziedzic, Tomasz

    2016-06-01

    Abnormal left ventricular (LV) geometry is associated with extracardiac organ damage in patients with hypertension. The aim of this study was to determine the relationship between LV geometry and white matter lesions (WMLs) in ischemic stroke patients. We retrospectively analyzed data from 155 patients (median age 62; 49.8% male) with mild ischemic stroke (median National Institutes of Health Stroke Scale score 4) who underwent brain magnetic resonance imaging and echocardiography. Patients were categorized into four groups: normal LV geometry, concentric remodeling, eccentric left ventricular hypertrophy (LVH) and concentric LVH. WMLs were graded using the Fazekas scale on fluid-attenuated inversion recovery images. Extensive WMLs were defined as a Fazekas score > 2. Extensive WMLs were more prevalent in patients with concentric LVH, eccentric LVH and concentric remodeling than in those with normal LV geometry. After adjusting for hypertension, age, diabetes mellitus, hypercholesterolemia, glomerular filtration rate and ischemic heart disease, patients with concentric remodeling [odds ratio (OR) 3.94, 95% confidence interval (CI) 1.26-12.31, p = 0.02] and those with concentric LVH (OR 3.69, 95% CI 1.24-10.95, p = 0.02), but not patients with eccentric LVH (OR 2.44, 95% CI 0.72-8.29, p = 0.15), had higher risk of extensive WMLs than patients with normal LV geometry.

  6. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions.

  7. Airway remodeling in asthma: what really matters.

    PubMed

    Fehrenbach, Heinz; Wagner, Christina; Wegmann, Michael

    2017-03-01

    Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

  8. Fascicular ventricular tachycardia: experience with radiofrequency ablation.

    PubMed

    Magalhaes, Sónia; Gonçalves, Helena; Primo, João; Sá, Ana Paula; Silva, Paula; Rosas, Rui; Gama, Vasco

    2006-05-01

    at the tachycardia exit site failing, with no complications. If we include the success of a repeated case with three-dimensional mapping, the overall success rate was 80%. Ablation of fascicular tachycardia appears to be a good therapeutic option with a good success rate and without significant adverse events. The poor reproducibility as a consequence of contact inhibition during endocardial left ventricular mapping is the principal limiting factor. With the help of currently available mapping systems, we hope that this limitation will disappear, as it is now possible with some devices to acquire accurate information on suitable sites for subsequent radiofrequency application with little or no contact, facilitating the ablation procedure. Ablation at a site with simultaneous recording of DP and PP is considered by most authors to be more effective than that performed at the tachycardia exit site.

  9. Genetics Home Reference: arrhythmogenic right ventricular cardiomyopathy

    MedlinePlus

    ... Genetics Home Health Conditions ARVC arrhythmogenic right ventricular cardiomyopathy Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Arrhythmogenic right ventricular cardiomyopathy ( ARVC ) is a form of heart disease that ...

  10. An Unusual Etiology for Bidirectional Ventricular Tachycardia.

    PubMed

    Zhao, Yun-Tao; Wang, Lei; Yi, Zhong

    2016-03-01

    Bidirectional ventricular tachycardia is a rare variety of tachycardia with a morphologically distinct presentation. The QRS axis and/or morphology alternate in the frontal plane leads. We report a patient with bidirectional ventricular tachycardia in association with aconitine poisoning.

  11. Analysis of Ventricular Function by Computed Tomography

    PubMed Central

    Rizvi, Asim; Deaño, Roderick C.; Bachman, Daniel P.; Xiong, Guanglei; Min, James K.; Truong, Quynh A.

    2014-01-01

    The assessment of ventricular function, cardiac chamber dimensions and ventricular mass is fundamental for clinical diagnosis, risk assessment, therapeutic decisions, and prognosis in patients with cardiac disease. Although cardiac computed tomography (CT) is a noninvasive imaging technique often used for the assessment of coronary artery disease, it can also be utilized to obtain important data about left and right ventricular function and morphology. In this review, we will discuss the clinical indications for the use of cardiac CT for ventricular analysis, review the evidence on the assessment of ventricular function compared to existing imaging modalities such cardiac MRI and echocardiography, provide a typical cardiac CT protocol for image acquisition and post-processing for ventricular analysis, and provide step-by-step instructions to acquire multiplanar cardiac views for ventricular assessment from the standard axial, coronal, and sagittal planes. Furthermore, both qualitative and quantitative assessments of ventricular function as well as sample reporting are detailed. PMID:25576407

  12. Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure

    PubMed Central

    Piao, Lin; Marsboom, Glenn

    2011-01-01

    Right ventricular failure (RVF) is the leading cause of death in pulmonary arterial hypertension (PAH). Some patients with pulmonary hypertension are adaptive remodelers and develop RV hypertrophy (RVH) but retain RV function; others are maladaptive remodelers and rapidly develop RVF. The cause of RVF is unclear and understudied and most PAH therapies focus on regressing pulmonary vascular disease. Studies in animal models and human RVH suggest that there is reduced glucose oxidation and increased glycolysis in both adaptive and maladaptive RVH. The metabolic shift from oxidative mitochondrial metabolism to the less energy efficient glycolytic metabolism may reflect myocardial ischemia. We hypothesize that in maladaptive RVH a vicious cycle of RV ischemia and transcription factor activation causes a shift from oxidative to glycolytic metabolism thereby ultimately promoting RVF. Interrupting this cycle, by reducing ischemia or enhancing glucose oxidation, might be therapeutic. Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, has beneficial effects on RV function and metabolism in experimental RVH, notably improving glucose oxidation and enhancing RV function. This suggests the mitochondrial dysfunction in RVH may be amenable to therapy. In this mini review, we describe the role of impaired mitochondrial metabolism in RVH, using rats with adaptive (pulmonary artery banding) or maladaptive (monocrotaline-induced pulmonary hypertension) RVH as models of human disease. We will discuss the possible mechanisms, relevant transcriptional factors, and the potential of mitochondrial metabolic therapeutics in RVH and RVF. PMID:20820751

  13. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model

    PubMed Central

    Wang, Jessica Jen-Chu; Rau, Christoph; Avetisyan, Rozeta; Ren, Shuxun; Romay, Milagros C.; Gong, Ke Wei; Wang, Yibin; Lusis, Aldons J.

    2016-01-01

    We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls. PMID:27385019

  14. Cell-based therapy for prevention and reversal of myocardial remodeling.

    PubMed

    Karantalis, Vasileios; Balkan, Wayne; Schulman, Ivonne H; Hatzistergos, Konstantinos E; Hare, Joshua M

    2012-08-01

    Although pharmacological and interventional advances have reduced the morbidity and mortality of ischemic heart disease, there is an ongoing need for novel therapeutic strategies that prevent or reverse progressive ventricular remodeling following myocardial infarction, the process that forms the substrate for ventricular failure. The development of cell-based therapy as a strategy to repair or regenerate injured tissue offers extraordinary promise for a powerful anti-remodeling therapy. In this regard, the field of cell therapy has made major advancements in the past decade. Accumulating data from preclinical studies have provided novel insights into stem cell engraftment, differentiation, and interactions with host cellular elements, as well as the effectiveness of various methods of cell delivery and accuracy of diverse imaging modalities to assess therapeutic efficacy. These findings have in turn guided rationally designed translational clinical investigations. Collectively, there is a growing understanding of the parameters that underlie successful cell-based approaches for improving heart structure and function in ischemic and other cardiomyopathies.

  15. Maternal Uterine Vascular Remodeling During Pregnancy

    PubMed Central

    Osol, George; Mandala, Maurizio

    2009-01-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms. PMID:19196652

  16. Arterial–Ventricular Coupling with Aging and Disease

    PubMed Central

    Chantler, Paul D.; Lakatta, Edward G.

    2012-01-01

    Age is the dominant risk factor for cardiovascular diseases. Understanding the coupling between the left ventricle (LV) and arterial system, termed arterial–ventricular coupling (EA/ELV), provides important mechanistic insights into the complex cardiovascular system and its changes with aging in the absence and presence of disease. EA/ELV can be indexed by the ratio of effective arterial elastance (EA; a measure of the net arterial load exerted on the LV) to left ventricular end-systolic elastance (ELV; a load-independent measure of left ventricular chamber performance). Age-associated alterations in arterial structure and function, including diameter, wall thickness, wall stiffness, and endothelial dysfunction, contribute to a gradual increase in resting EA with age. Remarkably there is a corresponding increase in resting ELV with age, due to alterations to LV remodeling (loss in myocyte number, increased collagen) and function. These age-adaptations at rest likely occur, at least, in response to the age-associated increase in EA and ensure that EA/ELV is closely maintained within a narrow range, allowing for optimal energetic efficiency at the expense of mechanical efficacy. This optimal coupling at rest is also maintained when aging is accompanied by the presence of hypertension, and obesity, despite further increases in EA and ELV in these conditions. In contrast, in heart failure patients with either reduced or preserved ejection fraction, EA/ELV at rest is impaired. During dynamic exercise, EA/ELV decreases, due to an acute mismatch between the arterial and ventricular systems as ELV increases disproportionate compared to EA (≈200 vs. 40%), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. However, with advancing age the reduction in EA/ELV during acute maximal exercise is blunted, due to a blunted increase ELV. This impaired EA/ELV is further amplified in the presence of disease, and may

  17. [Right ventricular assessment with echocardiography].

    PubMed

    Fayssoil, Abdallah; Abasse, Soumeth; Nardi, Olivier

    2009-05-01

    Right ventricular (RV) function is essential in cardio--pulmonary physiology and physiopathology. RV dysfunction has prognostic impact in inferior myocardial infarction, significant valvulopathies, congenital cardiopathies, arterial pulmonary hypertension and in patients suffering from acute or chronic heart failure. RV analysis relies on non invasive (echocardiography-Doppler, isotopic technology, cardiac magnetic resonance imaging) and/or invasive approaches (right cardiac catheterization). Neglected a short time ago, RV assessment has regained interest with tissular Doppler imaging, strain imaging and 2D speckle tracking. We review echocardiography and Doppler -parameters used for right -ventricular assessment.

  18. Nonlinear dynamics in ventricular fibrillation.

    PubMed Central

    Hastings, H M; Evans, S J; Quan, W; Chong, M L; Nwasokwa, O

    1996-01-01

    Electrogram recordings of ventricular fibrillation appear complex and possibly chaotic. However, sequences of beat-to-beat intervals obtained from these recordings are generally short, making it difficult to explicitly demonstrate nonlinear dynamics. Motivated by the work of Sugihara on atmospheric dynamics and the Durbin-Watson test for nonlinearity, we introduce a new statistical test that recovers significant dynamical patterns from smoothed lag plots. This test is used to show highly significant nonlinear dynamics in a stable canine model of ventricular fibrillation. Images Fig. 3 PMID:8816831

  19. [Heart failure with preserved left ventricular ejection fraction].

    PubMed

    Maeder, Micha T; Rickli, Hans

    2013-10-16

    Heart failure with preserved left ventricular ejection fraction (LVEF; HFpEF) is a common type of heart failure in the elderly, and it typically represents advanced hypertensive heart disease. The left ventricle in patients with HFpEF is characterized by concentric remodeling, normal LVEF, but reduced left longitudinal shortening, and importantly diastolic dysfunction. Dyspnoe and fatigue in patients with HFpEF are due to impaired left ventricular filling with a rapid increase in filling pressures and the lack of an increase in stroke volume during exercise. The diagnosis of HFpEF requires the careful exclusion of non-cardiac causes of dyspnoe as well as cardiac causes of dyspnoe associated with preserved LVEF other than HFpEF, primarily coronary artery disease and valve disease. Then, the following findings are required to make a diagnosis of HFpEF: a non-dilated left ventricle with an LVEF >50% and the presence of a significant diastolic impairment, which can be assessed using invasive haemodynamics, echocardiography, natriuretic peptides, or a combination of these tools. In contrast to patients with heart failure and reduced LVEF there is still no established treatment for patients with HFpEF, which prolongs survival or reduces the rate of hospitalizations for heart failure. There is currently however intense research going on in this field, and results from large trials evaluating the effects of various interventions on clinical endpoints are expected within the next years.

  20. EVALUATION OF RIGHT AND LEFT VENTRICULAR DIASTOLIC FILLING

    PubMed Central

    Pasipoularides, Ares

    2013-01-01

    A conceptual fluid-dynamics framework for diastolic filling is developed. The convective deceleration load (CDL) is identified as an important determinant of ventricular inflow during the E-wave (A-wave) upstroke. Convective deceleration occurs as blood moves from the inflow anulus through larger-area cross-sections toward the expanding walls. Chamber dilatation underlies previously unrecognized alterations in intraventricular flow dynamics. The larger the chamber, the larger become the endocardial surface and the CDL. CDL magnitude affects strongly the attainable E-wave (A-wave) peak. This underlies the concept of diastolic ventriculoannular disproportion. Large vortices, whose strength decreases with chamber dilatation, ensue after the E-wave peak and impound inflow kinetic energy, averting an inflow-impeding, convective Bernoulli pressure-rise. This reduces the CDL by a variable extent depending on vortical intensity. Accordingly, the filling vortex facilitates filling to varying degrees, depending on chamber volume. The new framework provides stimulus for functional genomics research, aimed at new insights into ventricular remodeling. PMID:23585308

  1. Dealing with surgical left ventricular assist device complications

    PubMed Central

    Kilic, Arman; Acker, Michael A.

    2015-01-01

    Left ventricular assist devices (LVAD) will undoubtedly have an increasing role due to the aging population, anticipated concomitant increase in the prevalence of end-stage heart failure, and improvements in LVAD technology and outcomes. As with any surgical procedure, LVAD implantation is associated with an adverse event profile. Such complications of LVAD therapy include bleeding, infection, pump thrombosis, right heart failure, device malfunction, and stroke. Although each has a unique management, early recognition and diagnosis of these complications is uniformly paramount. In this review, we provide an overview of managing surgical complications of LVADs. PMID:26793336

  2. Right ventricular outflow obstruction with intact ventricular septum in adults.

    PubMed Central

    Werner, A M; Darrell, J C; Pallegrini, R V; Woelfel, G F; Grant, K; Marrangoni, A G

    1997-01-01

    Cardiothoracic surgeons whose practice is limited to adults rarely see patients with right ventricular outflow obstruction and an intact ventricular septum. Of more than 10,000 open-heart procedures performed at our institution from 1983 to 1993 (in patients 18 to 75 years old), only 5 procedures were for correction of this problem. Both the pulmonary valve and the subvalvular area were abnormal in these 5 patients, and 4 of the 5 had subvalvular stenosis. The gradient across the right ventricular outflow tract was measured by cardiac catheterization before repair in all patients and averaged 118 mmHg. Various surgical approaches were used for repair. In the 2 patients whose pressures were measured postoperatively, the gradients were 25 mmHg and 45 mmHg, respectively. There were no operative deaths. At follow-up (range, 2 months to 5 years after surgery), all patients were in New York Heart Association functional class I and all had murmurs. Those who underwent echocardiography were found to have minimal gradients across the right ventricular outflow tract. Images PMID:9205983

  3. Reverse remodeling and recovery from cachexia in rats with aldosteronism.

    PubMed

    Cheema, Yaser; Zhao, Wenyuan; Zhao, Tieqiang; Khan, M Usman; Green, Kelly D; Ahokas, Robert A; Gerling, Ivan C; Bhattacharya, Syamal K; Weber, Karl T

    2012-08-15

    The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca(2+), coupled to oxidative stress with increased H(2)O(2) production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal.

  4. Long-term efficacy of oral encainide in frequent and repetitive ventricular arrhythmias.

    PubMed

    Bongiorni, M G; Levorato, D; Arlotta, C; Paperini, L; Contini, C

    1988-07-01

    The short- and long-term efficacy of oral encainide was studied in 14 patients with chronic high-frequency ventricular arrhythmias and in 14 patients with chronic frequent episodes of non-sustained ventricular tachycardia (NSVT). Encainide efficacy was assessed during a dose-titration period and in a 36-month follow-up also studying the drug effects on routine haematologic data and left ventricular function (LVF). During dose-titration, encainide caused a 78.3% decrease in the average hourly frequency of isolated PVC and a 96.1% reduction in NSVT episodes in the two groups of patients. On follow-up (11 patients in each group) the mean percentage reductions were 95.1% in isolated PVC and 99.7% in NSVT episodes. Encainide did not impair LVF as showed by the comparison of echocardiographic fractional shortening before and after 12 months of treatment. Minor adverse effects of encainide were dose-related visual disturbances in two patients. A major adverse effect was the appearance of sustained VT in one NYHA class IV patient. Oral encainide effectively reduces the frequency of PVC and NSVT, it does not impair left ventricular function and it is associated with infrequent minor side effects. Uncommon, but severe, side effects may appear in patients with marked impairment of left ventricular function.

  5. Simulations of trabecular remodeling and fatigue: is remodeling helpful or harmful?

    PubMed

    van Oers, René F M; van Rietbergen, Bert; Ito, Keita; Huiskes, Rik; Hilbers, Peter A J

    2011-05-01

    Microdamage-targeted resorption is paradoxal, because it entails the removal of bone from a region that was already overloaded. Under continued intense loading, resorption spaces could potentially cause more damage than they remove. To investigate this problem, we incorporated damage algorithms in a computer-simulation model for trabecular remodeling. We simulated damage accumulation and bone remodeling in a trabecular architecture, for two fatigue regimens, a 'moderate' regimen, and an 'intense' regimen with a higher number of loading cycles per day. Both simulations were also performed without bone remodeling to investigate if remodeling removed or exacerbated the damage. We found that remodeling tends to remove damage under the 'moderate' fatigue regimen, but it exacerbates damage under the 'intense' regimen. This harmful effect of remodeling may play a role in the development of stress fractures.

  6. Diagnosis and prognosis of right ventricular infarction.

    PubMed Central

    Rodrigues, E A; Dewhurst, N G; Smart, L M; Hannan, W J; Muir, A L

    1986-01-01

    The values of several non-invasive methods for the diagnosis of right ventricular necrosis in inferior myocardial infarction were compared in 51 consecutive patients who underwent serial radionuclide ventriculography, pyrophosphate scintigraphy, and cross sectional echocardiography. In addition a unipolar electrocardiographic lead V4R was recorded on admission, daily, and during episodes of further pain. Profound right ventricular dysfunction was evident in 50% of patients studied by radionuclide methods after inferior myocardial infarction but recognition on clinical groups alone was poor. Functionally important right ventricular infarction was best detected and followed serially by radionuclide ventriculography. Echocardiographic methods for evaluating right ventricular ejection fraction correlated poorly with radionuclide methods. Increased uptake of radioactivity by the right ventricle on pyrophosphate scintigraphy usually indicated poor right ventricular function, but a scan that was negative in the right ventricular territory did not exclude dysfunction. ST segment elevation in V4R was not specific for right ventricular infarction and its routine use may lead to overdiagnosis of this condition. Serial measurements suggest that profound right ventricular dysfunction persists after acute inferior infarction and is associated with considerable morbidity and mortality. Of 25 patients with severe right ventricular dysfunction, six died in the late hospital period. In the remaining 19 patients mean right ventricular ejection fraction over a two month period did not improve; six patients had persistent right ventricular dyskinesia and features of chronic right ventricular failure developed in three survivors. Images Fig. 1 PMID:3015175

  7. Minireview: Nuclear Receptor Regulation of Osteoclast and Bone Remodeling

    PubMed Central

    Jin, Zixue; Li, Xiaoxiao

    2015-01-01

    Osteoclasts are bone-resorbing cells essential for skeletal remodeling and regeneration. However, excessive osteoclasts often contribute to prevalent bone degenerative diseases such as osteoporosis, arthritis, and cancer bone metastasis. Osteoclast dysregulation is also associated with rare disorders such as osteopetrosis, pycnodysostosis, Paget's disease, and Gorham-Stout syndrome. The nuclear receptor (NR) family of transcription factors functions as metabolic sensors that control a variety of physiological processes including skeletal homeostasis and serves as attractive therapeutic targets for many diseases. In this review, we highlight recent findings on the new players and the new mechanisms for how NRs regulate osteoclast differentiation and bone resorption. An enhanced understanding of NR functions in osteoclastogenesis will facilitate the development of not only novel osteoprotective medicine but also prudent strategies to minimize the adverse skeletal effects of certain NR-targeting drugs for a better treatment of cancer and metabolic diseases. PMID:25549044

  8. Adverse effects of thyroid hormone preparations and antithyroid drugs.

    PubMed

    Bartalena, L; Bogazzi, F; Martino, E

    1996-07-01

    Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.

  9. Raise the Floor When Remodeling Science Labs

    ERIC Educational Resources Information Center

    Nation's Schools, 1972

    1972-01-01

    A new remodeling idea adopts the concept of raised floor covering gas, water, electrical, and drain lines. The accessible floor has removable panels set into an adjustable support frame 24 inches above a concrete subfloor. (Author)

  10. Lead Poisoning in Remodeling of Old Homes

    ERIC Educational Resources Information Center

    Barnes, Bart

    1973-01-01

    An article based on Dr. Muriel D. Wolf's study of elevated blood lead levels in children and adults present during the remodeling of old homes. Lead poisoning examples, symptoms, and precautions are given. (ST)

  11. B.B. Contracting & Remodeling Information Sheet

    EPA Pesticide Factsheets

    B.B. Contracting & Remodeling (the Company) is located in St. Louis, Missouri. The settlement involves renovation activities conducted at property constructed prior to 1978, located in St. Louis, Missouri.

  12. Ventricular Tachycardia Precipitated by the Use of the Diet Supplement Hydroxycut Gummies

    PubMed Central

    Thano, Estela; Bohnenberger, Kristin A.; McAllister, Matthew W.; Wannenburg, Thomas; Hsu, Steve; Gurley, Bill J.; Kim, Robert

    2015-01-01

    Background: Dietary supplements have a long history of causing adverse effects. Ventricular arrhythmias have not been described with Hydroxycut Gummies. Objective: To report a case of ventricular arrhythmia after prolonged use of a popular dietary supplement, Hydroxycut Gummies. Case Report: An 18-year-old female with no significant past medical history presented with life-threatening ventricular arrhythmia following about 10 days of use of Hydroxycut Gummies, a legal dietary supplement previously unreported to cause this complication. The patient received external cardioversion due to progressive decline in mental status and persistent hypotension and was initiated on intravenous procainamide at an outside hospital. Left ventricular ejection fraction was 45% to 50%, and cardiac MRI showed no definite finding of infarct, myocarditis, or fibrosis. Beta-blocker therapy was initiated, and there was a progressive reduction in ventricular arrhythmia burden with an improvement of symptoms over the next few days. Two and a half months after the initial hospitalization, follow-up Holter monitor revealed occasional accelerated idioventricular rhythm events and a significant reduction in, but still occasional, long monomorphic ventricular tachycardia events. None of the ingredients listed in this product have been associated with cardiac dysrhythmias in the literature. One phytochemical potentially in the product is alpha-quinidine, which could be the cause of the adverse event. However, there was no other identifiable etiology for the ventricular tachycardia, which resolved after the discontinuation of supplement and the addition of beta-blocker therapy. Conclusion: Hydroxycut Gummies should be considered a probable cause of this patient’s arrhythmia given the lack of another etiology and a Naranjo Scale score of 6. PMID:26448674

  13. Predictors of Left Ventricle Remodeling: Combined Plasma B-type Natriuretic Peptide Decreasing Ratio and Peak Creatine Kinase-MB.

    PubMed

    Hsu, Jen-Te; Chung, Chang-Min; Chu, Chi-Ming; Lin, Yu-Shen; Pan, Kuo-Li; Chang, Jung-Jung; Wang, Po-Chang; Chang, Shih-Tai; Yang, Teng-Yao; Jang, Shih-Jung; Yang, Tsung-Han; Hsiao, Ju-Feng

    2017-01-01

    Background: Previous studies reported that patients who had an acute myocardial infarction (AMI) have found that measuring B-type natriuretic peptide (BNP) during the subacute phase of left ventricular (LV) remodeling can predict the possible course of LV remodeling. This study assessed the use of serial BNP serum levels combined with early creatine kinase-MB (CK-MB) to predict the development of significant LV remodeling in AMI patients. Methods: Nighty-seven patients with new onset AMI were assessed using serial echocardiographic studies and serial measurements of BNP levels, both performed on day-2 (BNP1), day-7 (BNP2), day-90 (BNP3), and day-180 (BNP4) after admission. LV remodeling was defined as >20% increase in biplane LV end-diastolic volume on day-180 compared to baseline (day-2). Results: Patients were divided into LV remodeling [LVR(+)] and non LV remodeling [LVR(-)] groups. No first-week BNP level was found to predict remodeling. However, the two groups had significantly different day-90 BNP level (208.1 ± 263.7 pg/ml vs. 82.4 ± 153.7 pg/ml, P = 0.039) and significantly different 3-month BNP decrease ratios ( R BNP13) (14.4 ± 92.2% vs. 69.4 ± 25.9%, P < 0.001). The appropriate cut-off value for R BNP13 was 53.2% (AUC = 0.764, P < 0.001). Early peak CK-MB (cut-off 48.2 ng/ml; AUC = 0.672; P = 0.014) was another independent predictor of remodeling. Additionally, combining peak CK-MB and R BNP13 offered an excellent discrimination for half-year remodeling when assessed by ROC curve (AUC = 0.818, P < 0.001). Conclusion: R BNP13 is a significant independent predictor of 6-month LV remodeling. The early peak CK-MB additionally offered an incremental power to the predictions derived from serial BNP examinations.

  14. Predictors of Left Ventricle Remodeling: Combined Plasma B-type Natriuretic Peptide Decreasing Ratio and Peak Creatine Kinase-MB

    PubMed Central

    Hsu, Jen-Te; Chung, Chang-Min; Chu, Chi-Ming; Lin, Yu-Shen; Pan, Kuo-Li; Chang, Jung-Jung; Wang, Po-Chang; Chang, Shih-Tai; Yang, Teng-Yao; Jang, Shih-Jung; Yang, Tsung-Han; Hsiao, Ju-Feng

    2017-01-01

    Background: Previous studies reported that patients who had an acute myocardial infarction (AMI) have found that measuring B-type natriuretic peptide (BNP) during the subacute phase of left ventricular (LV) remodeling can predict the possible course of LV remodeling. This study assessed the use of serial BNP serum levels combined with early creatine kinase-MB (CK-MB) to predict the development of significant LV remodeling in AMI patients. Methods: Nighty-seven patients with new onset AMI were assessed using serial echocardiographic studies and serial measurements of BNP levels, both performed on day-2 (BNP1), day-7 (BNP2), day-90 (BNP3), and day-180 (BNP4) after admission. LV remodeling was defined as >20% increase in biplane LV end-diastolic volume on day-180 compared to baseline (day-2). Results: Patients were divided into LV remodeling [LVR(+)] and non LV remodeling [LVR(-)] groups. No first-week BNP level was found to predict remodeling. However, the two groups had significantly different day-90 BNP level (208.1 ± 263.7 pg/ml vs. 82.4 ± 153.7 pg/ml, P = 0.039) and significantly different 3-month BNP decrease ratios (RBNP13) (14.4 ± 92.2% vs. 69.4 ± 25.9%, P < 0.001). The appropriate cut-off value for RBNP13 was 53.2% (AUC = 0.764, P < 0.001). Early peak CK-MB (cut-off 48.2 ng/ml; AUC = 0.672; P = 0.014) was another independent predictor of remodeling. Additionally, combining peak CK-MB and RBNP13 offered an excellent discrimination for half-year remodeling when assessed by ROC curve (AUC = 0.818, P < 0.001). Conclusion: RBNP13 is a significant independent predictor of 6-month LV remodeling. The early peak CK-MB additionally offered an incremental power to the predictions derived from serial BNP examinations. PMID:28138312

  15. Adverse cutaneous drug reaction.

    PubMed

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR.

  16. Facts about Ventricular Septal Defect

    MedlinePlus

    ... Living With Heart Defects Data & Statistics Tracking & Research Articles & Key Findings Free Materials Multimedia and Tools Links to Other Websites Information For... Media Policy Makers Facts about Ventricular Septal Defect Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir ...

  17. Periostin as a modulator of chronic cardiac remodeling after myocardial infarction

    PubMed Central

    Minicucci, Marcos F.; dos Santos, Priscila P.; Rafacho, Bruna P. M.; Gonçalves, Andréa F.; Ardisson, Lidiane P.; Batista, Diego F.; Azevedo, Paula S.; Polegato, Bertha F.; Okoshi, Katashi; Pereira, Elenize J.; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.

    2013-01-01

    OBJECTIVE: After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction. METHODS: Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles). RESULTS: Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012). CONCLUSIONS: Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats. PMID:24212842

  18. Simulated Microgravity and Recovery-Induced Remodeling of the Left and Right Ventricle.

    PubMed

    Zhong, Guohui; Li, Yuheng; Li, Hongxing; Sun, Weijia; Cao, Dengchao; Li, Jianwei; Zhao, Dingsheng; Song, Jinping; Jin, Xiaoyan; Song, Hailin; Yuan, Xinxin; Wu, Xiaorui; Li, Qi; Xu, Qing; Kan, Guanghan; Cao, Hongqing; Ling, Shukuan; Li, Yingxian

    2016-01-01

    Physiological adaptations to microgravity involve alterations in cardiovascular systems. These adaptations result in cardiac remodeling and orthostatic hypotension. However, the response of the left ventricle (LV) and right ventricle (RV) following hindlimb unloading (HU) and hindlimb reloading (HR) is not clear and the underlying mechanism remains to be understood. In this study, three groups of mice were subjected to HU by tail suspension for 28 days. Following this, two groups were allowed to recover for 7 or 14 days. The control group was treated equally, with the exception of tail suspension. Echocardiography was performed to detect the structure and function changes of heart. Compared with the control, the HU group of mice showed reduced LV-EF (ejection fraction), and LV-FS (fractional shortening). However, mice that were allowed to recover for 7 days after HU (HR-7d) showed increased LVIDs (systolic LV internal diameter) and LV Vols (systolic LV volume). Mice that recovered for 14 days (HR-14d) returned to the normal state. In comparison, RV-EF and RV-FS didn't recover to the normal conditions till being reloaded for 14 days. Compared with the control, RVIDd (diastolic RV internal diameter), and RV Vold (diastolic RV volume) were reduced in HU group and recovered to the normal conditions in HR-7d and HR-14d groups, in which groups RVIDs (systolic RV internal diameter) and RV Vols (systolic RV volume) were increased. Histological analysis and cardiac remodeling gene expression results indicated that HU induces left and right ventricular remodeling. Western blot demonstrated that the phosphorylation of HDAC4 and ERK1/2 and the ratio of LC3-II / LC3-I, were increased following HU and recovered following HR in both LV and RV, and the phosphorylation of AMPK was inhibited in both LV and RV following HU, but only restored in LV following HR for 14 days. These results indicate that simulated microgravity leads to cardiac remodeling, and the remodeling changes can

  19. Simulated Microgravity and Recovery-Induced Remodeling of the Left and Right Ventricle

    PubMed Central

    Zhong, Guohui; Li, Yuheng; Li, Hongxing; Sun, Weijia; Cao, Dengchao; Li, Jianwei; Zhao, Dingsheng; Song, Jinping; Jin, Xiaoyan; Song, Hailin; Yuan, Xinxin; Wu, Xiaorui; Li, Qi; Xu, Qing; Kan, Guanghan; Cao, Hongqing; Ling, Shukuan; Li, Yingxian

    2016-01-01

    Physiological adaptations to microgravity involve alterations in cardiovascular systems. These adaptations result in cardiac remodeling and orthostatic hypotension. However, the response of the left ventricle (LV) and right ventricle (RV) following hindlimb unloading (HU) and hindlimb reloading (HR) is not clear and the underlying mechanism remains to be understood. In this study, three groups of mice were subjected to HU by tail suspension for 28 days. Following this, two groups were allowed to recover for 7 or 14 days. The control group was treated equally, with the exception of tail suspension. Echocardiography was performed to detect the structure and function changes of heart. Compared with the control, the HU group of mice showed reduced LV-EF (ejection fraction), and LV-FS (fractional shortening). However, mice that were allowed to recover for 7 days after HU (HR-7d) showed increased LVIDs (systolic LV internal diameter) and LV Vols (systolic LV volume). Mice that recovered for 14 days (HR-14d) returned to the normal state. In comparison, RV-EF and RV-FS didn't recover to the normal conditions till being reloaded for 14 days. Compared with the control, RVIDd (diastolic RV internal diameter), and RV Vold (diastolic RV volume) were reduced in HU group and recovered to the normal conditions in HR-7d and HR-14d groups, in which groups RVIDs (systolic RV internal diameter) and RV Vols (systolic RV volume) were increased. Histological analysis and cardiac remodeling gene expression results indicated that HU induces left and right ventricular remodeling. Western blot demonstrated that the phosphorylation of HDAC4 and ERK1/2 and the ratio of LC3-II / LC3-I, were increased following HU and recovered following HR in both LV and RV, and the phosphorylation of AMPK was inhibited in both LV and RV following HU, but only restored in LV following HR for 14 days. These results indicate that simulated microgravity leads to cardiac remodeling, and the remodeling changes can

  20. Bone remodeling as a spatial evolutionary game.

    PubMed

    Ryser, Marc D; Murgas, Kevin A

    2017-04-07

    Bone remodeling is a complex process involving cell-cell interactions, biochemical signaling and mechanical stimuli. Early models of the biological aspects of remodeling were non-spatial and focused on the local dynamics at a fixed location in the bone. Several spatial extensions of these models have been proposed, but they generally suffer from two limitations: first, they are not amenable to analysis and are computationally expensive, and second, they neglect the role played by bone-embedded osteocytes. To address these issues, we developed a novel model of spatial remodeling based on the principles of evolutionary game theory. The analytically tractable framework describes the spatial interactions between zones of bone resorption, bone formation and quiescent bone, and explicitly accounts for regulation of remodeling by bone-embedded, mechanotransducing osteocytes. Using tools from the theory of interacting particle systems we systematically classified the different dynamic regimes of the spatial model and identified regions of parameter space that allow for global coexistence of resorption, formation and quiescence, as observed in physiological remodeling. In coexistence scenarios, three-dimensional simulations revealed the emergence of sponge-like bone clusters. Comparison between spatial and non-spatial dynamics revealed substantial differences and suggested a stabilizing role of space. Our findings emphasize the importance of accounting for spatial structure and bone-embedded osteocytes when modeling the process of bone remodeling. Thanks to the lattice-based framework, the proposed model can easily be coupled to a mechanical model of bone loading.

  1. Lycopene attenuates inflammation and apoptosis in post-myocardial infarction remodeling by inhibiting the nuclear factor-κB signaling pathway.

    PubMed

    He, Qin; Zhou, Wei; Xiong, Caijin; Tan, Gang; Chen, Manhua

    2015-01-01

    Inflammatory response and cardiomyocyte apoptosis are important processes in ventricular remodeling post-myocardial infarction (MI) and may form the basic mechanisms in the development of chronic heart failure. The nuclear factor κB (NF-κB) signaling pathway could promote inflammation and apoptosis and it has been demonstrated that lycopene inhibits cigarette smoke extract-mediated NF-κB activation. Therefore, it was hypothesized that the NF-κB signaling pathway may be a key target of lycopene in the reversal of ventricular remodeling post MI. An MI model was established by left anterior descending coronary artery ligation in mice. Following ligation, the mice were administered with lycopene (10 mg/kg/day) or saline. The mice underwent echocardiography and were sacrificed after 4 weeks. The mRNA expression of fibrosis markers transforming growth factor-β1 (TGF-β1), collagen I and III and inflammatory markers tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were examined by quantitative polymerase chain reaction. The protein expression of apoptotic markers, including caspase-3, -8, -9 and activation of the NF-κB signaling pathway were analyzed by western blotting. Lycopene reduced the expression of TGF-β1, collagen I, collagen III, TNF-α, IL-1β, caspase-3, -8 and -9 and inhibited the activation of the NF-κB signaling pathway. The level of ventricular remodeling post-MI was also attenuated following treatment with lycopene. Lycopene may inhibit the NF-κB signaling pathway thereby reducing the inflammatory response and cardiomyocyte apoptosis post-MI, which could be a key mechanism of lycopene in attenuating ventricular remodeling.

  2. Left Ventricular Aneurysm Presenting as a Late Complication of Childhood Chemotherapy.

    PubMed

    Thyagarajan, Braghadheeswar; Munshi, Lubna Bashir; Amor, Martin Miguel

    2015-01-01

    Cardiotoxicity is a well known adverse effect of chemotherapy. Multiple cardiac injuries have been reported including cardiomyopathy, pericarditis, myocarditis, angina, arrhythmias, and myocardial infarction. A left ventricular aneurysm due to chemotherapy is a rare and a dangerous complication which is particularly challenging in diagnosis requiring a high index of suspicion and periodic imaging. We present a case of a young Caucasian male with a past medical history of Acute Lymphocytic Leukemia status after chemotherapy during his childhood diagnosed with left ventricular aneurysm several years later.

  3. A 54-year-old woman with premature ventricular complexes and a rapidly changing ECG

    PubMed Central

    Bencharif, Sarah; Leung, Lawrence

    2015-01-01

    Premature ventricular complexes (PVCs) are common findings in asymptomatic participants during ECG recordings. While most PVCs are treated conservatively, some patients may develop adverse cardiac events needing further investigations and definitive ablation by radiofrequency. Spectral strain ultrasonography has demonstrated ventricular dysfunction as a sequel to high burden PVCs, but the exact underlying pathophysiology is still uncertain. Cohort studies have associated PVCs with increased risks for overall cardiovascular morbidity and mortality, and yet consensus is still lacking for threshold in treating PVCs. Our case is that of a 54-year-old woman with an unusual bradycardiac presentation of PVCs and an ECG that changed rapidly within minutes. PMID:25827918

  4. Pathophysiology and clinical relevance of pulmonary remodelling in pulmonary hypertension due to left heart diseases.

    PubMed

    Dupuis, Jocelyn; Guazzi, Marco

    2015-04-01

    Pulmonary hypertension (PH) in left heart disease, classified as group II, is the most common form of PH that occurs in approximately 60% of cases of reduced and preserved left ventricular ejection fraction. Although relatively much is known about hemodynamic stages (passive or reactive) and their consequences on the right ventricle (RV) there is no consensus on the best hemodynamic definition of group II PH. In addition, the main pathways that lead to lung capillary injury and impaired biology of small artery remodelling processes are largely unknown. Typical lung manifestations of an increased pulmonary pressure and progressive RV-pulmonary circulation uncoupling are an abnormal alveolar capillary gas diffusion, impaired lung mechanics (restriction), and exercise ventilation inefficiency. Of several classes of pulmonary vasodilators currently clinically available, oral phosphodiesterase 5 inhibition, because of its strong selectivity for targeting the cyclic guanosine monophosphate pathway in the pulmonary circulation, is increasingly emerging as an attractive opportunity to reach hemodynamic benefits, reverse capillary injury, and RV remodelling, and improve functional capacity. Guanylate cyclase stimulators offer an additional intriguing opportunity but the lack of selectivity and systemic effects might preclude some of the anticipated benefits on the pulmonary circulation. Future trials will determine whether new routes of pharmacologic strategy aimed at targeting lung structural and vascular remodelling might affect morbidity and mortality in left heart disease populations. We believe that this therapeutic goal rather than a pure hemodynamic effect might ultimately emerge as an important challenge for the clinician.

  5. Inhibition of heat shock protein 90 improves pulmonary arteriole remodeling in pulmonary arterial hypertension

    PubMed Central

    Zhao, Zhi-Min; Liu, Su-Xuan; Zhang, Guan-Xin; Yang, Fan; Wang, Yang; Wu, Feng; Zhao, Xian-Xian; Xu, Zhi-Yun

    2016-01-01

    While the molecular chaperone heat shock protein 90 (HSP90) is involved in a multitude of physiological and pathological processes, its role relating to pulmonary arterial hypertension (PAH) remains unclear. In the present study, we investigated the effect in which HSP90 improves pulmonary arteriole remodeling, and explored the therapeutic utility of targeting HSP90 as therapeutic drug for PAH. By Elisa and immunohistochemistry, HSP90 was found to be increased in both plasma and membrane walls of pulmonary arterioles from PAH patients. Moreover, plasma HSP90 levels positively correlated with mean pulmonary arterial pressure and C-reactive protein. In a monocrotaline-induced rat model of PH, we found that 17-AAG, a HSP90-inhibitor, alleviated the progress of PH, demonstrated by lower pulmonary arterial pressure and absence of right ventricular hypertrophy. Immunohistochemical staining demonstrated that 17-AAG improved pulmonary arteriole remodeling on the basis of reduced wall thickness and wall area. The inflammatory response attributed to PH could be attenuated by 17-AAG through reduction of NF-κB signaling. Moreover, 17-AAG was found to suppress PDGF-stimulated proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through induction of cell cycle arrest in the G1 phase. In conclusion, HSP90 inhibitor 17-AAG could improve pulmonary arteriole remodeling via inhibiting the excessive proliferation of PASMCs, and inhibition of HSP90 may represent a therapeutic avenue for the treatment of PAH. PMID:27472464

  6. The effect of high-intensity aerobic interval training on postinfarction left ventricular remodelling

    PubMed Central

    Godfrey, Richard; Theologou, Thomas; Dellegrottaglie, Santo; Binukrishnan, Sukumaran; Wright, Jay; Whyte, Gregory; Ellison, Georgina

    2013-01-01

    This is the third in a series of case studies on an individual with normal coronaries who sustained an idiopathic acute myocardial infarction . Bilateral pulmonary emboli almost 2 years post-myocardial infarction (MI) revealed coagulopathy as the cause. The original MI resulted in 16% myocardial scar tissue. An increasing number of patients are surviving MI, hence the burden for healthcare often shifts to heart failure. Accumulating evidence suggests high-intensity aerobic interval exercise (AHIT) is efficacious in improving cardiac function in health and disease. However, its impact on MI scar has never been assessed. Accordingly, the 50-year-old subject of this case study undertook 60 weeks of regular AHIT. Successive cardiac MRI results demonstrate, for the first time, a decrease in MI scar with exercise and, alongside mounting evidence of high efficacy and low risk, suggests AHIT may be increasingly important in future prevention and reversing of disease and or amelioration of symptoms. PMID:23413285

  7. Left ventricular assist device malposition interrogated by 4-D cine computed tomography.

    PubMed

    Bolen, Michael A; Popovic, Zoran B; Gonzalez-Stawinski, Gonzalo; Schoenhagen, Paul

    2011-01-01

    67-year-old female with left ventricular assist device (LVAD) presented with recurrent low-flow alarms. No clear etiology could be determined by history, or evaluation with radiograph and echocardiogram. Computed tomographic (CT) imaging with 3-D and 4-D assessment identified the abnormality as steep angulation of the inflow cannula and partial obstruction by the adjacent anterior wall, likely in part caused by recovered left ventricular function and reverse remodeling. Improved left ventricle size and function was correlated by semi-automated analysis of CT data, which also indicated mild right ventricle dilation and systolic dysfunction. LVAD explantation was performed, and has been well tolerated by the patient. Echocardiography remains the primary imaging modality to assess patients post LVAD placement, but in this instance CT provided valuable information to identify the abnormality and help direct patient management. CT assessment in patients with LVAD additionally provides valuable information prior to redo sternotomy for pump explantation, revision, or transplantation.

  8. Fibrinolysis inhibitors adversely affect remodeling of tissues sealed with fibrin glue.

    PubMed

    Krishnan, Lissy K; Vijayan Lal, Arthur; Uma Shankar, P R; Mohanty, Mira

    2003-01-01

    Experiments have been carried out to determine if aprotinin and epsilon -amino caproic acid increases the quality of Fibrin glue. A rat model was used for tissues such as liver and skin while rabbits were used for application of glue in dura mater. Apposition of all the tissues, glued with fibrin was found to be good and remnants of the polymerized fibrin were seen even on the seventh day of application, though inhibitors were not incorporated with the glue. In skin, excessive amounts of fibrin remained as a result of addition of aprotinin and epsilon -amino caproic acid, as compared to the glue applied without any inhibitor. After dural sealing, the wound repair and new bone formation at craniotomy site progressed well in the fibrin glue applied area as compared to the commercially available glue that contained aprotinin. The adhesive strength of the glue without or with fibrinolysis inhibitors was found to be similar, after 1h grafts on rat back. The observations from this study suggests that the use of aprotinin with fibrin glue may not be required because, even liver tissue that is known to have high fibrinolytic activity was sealed and repaired well in the absence of plasminogen inhibitors. On the other hand, it was found that if inhibitors were added, nondegraded matrix remained in the tissue even after 15 days and affected migration of repair cells. Thus, the inhibition of fibrinolysis after fibrin glue application is found detrimental to wound healing.

  9. Telithromycin: review of adverse effects.

    PubMed

    2014-11-01

    Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.

  10. Simulation of motor current waveforms in monitoring aortic valve state during ventricular assist device support.

    PubMed

    Alonazi, Khalid A; Lovell, Nigel H; Dokos, Socrates

    2016-08-01

    Monitoring of aortic valve (AV) opening and closure during left ventricular assist device (LVAD) heart pump support is crucial in preventing AV abnormalities and remodeling caused by anomalous resirculation. In this study, simulations of LVAD motor current waveforms were undertaken to investigate AV response to rotary blood pump assistance, as well as to detect AV open and close status under heart failure conditions. A two-dimensional fluid-structure interaction finite-element model is presented to predict AV state during LVAD outflow. The data will be useful in the development of a pump speed controller for optimal management of pump outflow.

  11. Utility of magnetic resonance imaging in the evaluation of left ventricular thickening.

    PubMed

    Fulton, Nicholas; Rajiah, Prabhakar

    2017-04-01

    Left ventricular (LV) thickening can be due to hypertrophy (concentric, asymmetric, eccentric) or remodelling (concentric or asymmetric). Pathological thickening may be caused by pressure overload, volume overload, infiltrative disorders, hypertrophic cardiomyopathy, athlete's heart or neoplastic infiltration. Magnetic resonance imaging (MRI) plays an important role in the comprehensive evaluation of LV thickening, including: establishing diagnosis, determining LV geometry, establishing aetiology, quantification, identifying prognostic factors, serial follow-up and treatment response. In this article, we review the aetiologies and pathophysiology of LV thickening, and demonstrate the comprehensive role of MRI in the evaluation of LV thickening.

  12. Form follows function: developmental and physiological view on ventricular myocardial architecture.

    PubMed

    Sedmera, David

    2005-10-01

    The arrangement of myocytes within the ventricle is critical for its contractile performance, as evidenced by significant functional impairment seen in cardiomyopathies associated with myofiber disarray or post-infarction remodeling. A review on this topic by Anderson and associates provides anatomical insight gained from a multitude of approaches, and concludes that the best concept is that of syncytial continuum with supporting collagenous matrix. The overall arrangement is in the form of several intertwined helices, and the authors find no support for a recently suggested ventricular myocardial band hypothesis. This commentary aims at providing a developmental and physiological perspective on this purely anatomical concept. Unlike some other organ systems, the developing heart has to function since very early stages to support the oxygen and nutrition demands of the growing embryo, thus putting some constraints on heart development. The ventricular myocardial architecture transforms from a single-layered tube through trabeculated stages into a mature form that relies on a multi-layered compact zone. The first evidence of helical patterns is found in trabeculated hearts during ventricular contraction, and layers with different helix pitch develop during later fetal stages as the compact zone thickens. The second major point determining ventricular contraction is the sequence of its electrical activation. The ventricular activation sequence changes concomitantly with its morphology, from slow peristaltoid through base-to-apex pattern found in looped trabeculated hearts, to mature apex-to-base direction. Thus, adult ventricular myocardial architecture is best understood when one also considers the way it developed together with its electrical activation sequence and contraction pattern.

  13. Electronegative LDL-mediated cardiac electrical remodeling in a rat model of chronic kidney disease

    PubMed Central

    Lee, An-Sheng; Chen, Wei-Yu; Chan, Hua-Chen; Chung, Ching-Hu; Peng, Hsien-Yu; Chang, Chia-Ming; Su, Ming-Jai; Chen, Chu-Huang; Chang, Kuan-Cheng

    2017-01-01

    The mechanisms underlying chronic kidney disease (CKD)–associated higher risks for life-threatening ventricular tachyarrhythmias remain poorly understood. In rats subjected to unilateral nephrectomy (UNx), we examined cardiac electrophysiological remodeling and relevant mechanisms predisposing to ventricular arrhythmias. Adult male Sprague-Dawley rats underwent UNx (n = 6) or sham (n = 6) operations. Eight weeks later, the UNx group had higher serum blood urea nitrogen and creatinine levels and a longer electrocardiographic QTc interval than did the sham group. Patch-clamp studies revealed epicardial (EPI)-predominant prolongation of the action potential duration (APD) at 50% and 90% repolarization in UNx EPI cardiomyocytes compared to sham EPI cardiomyocytes. A significant reduction of the transient outward potassium current (Ito) in EPI but not in endocardial (ENDO) cardiomyocytes of UNx rats led to a decreased transmural gradient of Ito. The reduction of Ito currents in UNx EPI cardiomyocytes was secondary to downregulation of KChIP2 but not Kv4.2, Kv4.3, and Kv1.4 protein expression. Incubation of plasma electronegative low-density lipoprotein (LDL) from UNx rats with normal EPI and ENDO cardiomyocytes recapitulated the electrophysiological phenotype of UNx rats. In conclusion, CKD disrupts the physiological transmural gradient of Ito via downregulation of KChIP2 proteins in the EPI region, which may promote susceptibility to ventricular tachyarrhythmias. Electronegative LDL may underlie downregulation of KChIP2 in CKD. PMID:28094801

  14. Left Ventricular Diastolic Function Assessment of a Heterogeneous Cohort of Pulmonary Arterial Hypertension Patients

    PubMed Central

    Hernandez-Suarez, Dagmar F.; Lopez Menendez, Francisco R.; Palm, Denada; Lopez-Candales, Angel

    2017-01-01

    Background Pulmonary arterial hypertension (PAH) is known to trigger right ventricular (RV) remodeling that might compromise left ventricular (LV) filling due to inter-ventricular interdependence. In this study, we aimed to examine standard echocardiographic measurements of LV diastolic function in PAH patients. Methods In this retrospective study, we identified clinical as well as complete echocardiographic data from 128 chronic PAH patients to fully assess LV diastolic dysfunction (LVDD) using standard recommended Doppler guidelines. Accordingly, patients were divided into three groups: LVDD 0, LVDD 1 and LVDD 2. Results The mean age of the studied population was 57 ± 14 years with a mean pulmonary artery systolic pressure (PASP) of 55 ± 21 mm Hg. A total of 36% of the study patients had normal LV diastolic function. However, 64% had LVDD with LVDD stage 1 being the most common (48%). In terms of echocardiographic data, significant differences were found among the three LVDD groups in regards to PASP, LV end systolic and diastolic volumes, tricuspid annular plane systolic excursion, right ventricular fractional area change as well as many other tissue Doppler imaging parameters. Finally, just age and PASP were predictors of abnormal LV diastolic function (P < 0.05). Conclusions Impaired relaxation is a common abnormality in PAH patients. Additional studies are warranted to determine whether LVDD alters prognosis or is related to changes in the symptomatic profile of this group of patients. PMID:28270896

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

    PubMed Central

    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.

    2016-01-01

    Aims 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 Ca2+ 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. Methods and results 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 Ca2+ 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. Conclusion Elevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca2+ release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression. PMID:27226008

  16. Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing

    NASA Technical Reports Server (NTRS)

    Taylor, J. A.; Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.

    1996-01-01

    OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9%