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Sample records for myocardial contractility depression

  1. Acute exposure to Catha edulis depresses contractility and induces myocardial infarction in spontaneously contracting, isolated rabbit’s heart

    PubMed Central

    Al-Hashem, Fahaid H.; Dallak, Mohammad A.; Nwoye, Luke O.; Bin-Jaliah, Ismaeel M.; Al-Amri, Hasan S.; Rezk, Mahmoud H.; Sakr, Hussein F.; Shatoor, Abdullah S.; Al-Khateeb, Mahmoud

    2011-01-01

    Khat chewing is a recreational habit known to pose major socio-economic and medical problems in countries of Southern Arabia and the Horn of Africa. Among other adverse health effects, khat chewing has been associated with an increased risk of myocardial infarction (MI) in heavy consumers. This study was carried out to examine the direct effects of Catha edulis extract on contractility of spontaneously contracting, isolated rabbit heart and to investigate its mechanism of action. Isolated six rabbit’s hearts attached to a Langendorff apparatus were perfused with extract at a constant flow rate and continuously bubbled with a 95% O2/5% CO2 gas mixture. Each heart served as its own control, as responses were recorded before and after administration of C. edulis extract. Varying concentrations of extract (50, 100 and 250 mg/ml) were loaded in the perfusate, their effects recorded and effluent fluid collected for assay of cardiac enzymes. Histological examination of the cardiac tissue was performed at the end of perfusion with 250 mg/ml extract. This study revealed that acute exposure to C. edulis extract exerted negative inotropic and chronotropic effects on isolated hearts. The extract also had a vasoconstrictor effect on coronary vessels, independent of α1 adrenergic receptor stimulation. Histological examination of hearts perfused with 250 mg/ml C. edulis extract revealed the presence of histological changes unique to myocardial infarction, a finding consistent with observed increased levels of cardiac enzymes in perfusates. Thus, we have demonstrated experimentally a direct cardiac depressant- and MI inducing effects of C. edulis extract. These results are consistent with the earlier reported deleterious effects of khat on cardiovascular function among khat chewers. PMID:23961167

  2. Acute exposure to Catha edulis depresses contractility and induces myocardial infarction in spontaneously contracting, isolated rabbit's heart.

    PubMed

    Al-Hashem, Fahaid H; Dallak, Mohammad A; Nwoye, Luke O; Bin-Jaliah, Ismaeel M; Al-Amri, Hasan S; Rezk, Mahmoud H; Sakr, Hussein F; Shatoor, Abdullah S; Al-Khateeb, Mahmoud

    2012-01-01

    Khat chewing is a recreational habit known to pose major socio-economic and medical problems in countries of Southern Arabia and the Horn of Africa. Among other adverse health effects, khat chewing has been associated with an increased risk of myocardial infarction (MI) in heavy consumers. This study was carried out to examine the direct effects of Catha edulis extract on contractility of spontaneously contracting, isolated rabbit heart and to investigate its mechanism of action. Isolated six rabbit's hearts attached to a Langendorff apparatus were perfused with extract at a constant flow rate and continuously bubbled with a 95% O2/5% CO2 gas mixture. Each heart served as its own control, as responses were recorded before and after administration of C. edulis extract. Varying concentrations of extract (50, 100 and 250 mg/ml) were loaded in the perfusate, their effects recorded and effluent fluid collected for assay of cardiac enzymes. Histological examination of the cardiac tissue was performed at the end of perfusion with 250 mg/ml extract. This study revealed that acute exposure to C. edulis extract exerted negative inotropic and chronotropic effects on isolated hearts. The extract also had a vasoconstrictor effect on coronary vessels, independent of α1 adrenergic receptor stimulation. Histological examination of hearts perfused with 250 mg/ml C. edulis extract revealed the presence of histological changes unique to myocardial infarction, a finding consistent with observed increased levels of cardiac enzymes in perfusates. Thus, we have demonstrated experimentally a direct cardiac depressant- and MI inducing effects of C. edulis extract. These results are consistent with the earlier reported deleterious effects of khat on cardiovascular function among khat chewers. PMID:23961167

  3. Differential depression of myocardial contractility by volatile anesthetics in vitro: comparison with uncouplers of excitation-contraction coupling.

    PubMed

    Lynch, C

    1990-04-01

    Depression of rested state contractions (RSCs) and 0.1-0.25 Hz contractions by equianesthetic concentrations of isoflurane (2.5%), halothane (1.5%), and enflurane (3.5%) was studied in guinea pig papillary muscles in which tension development was enhanced by 0.1 microM isoproterenol. In a second series of experiments, an RSC was elicited, followed by a second contraction elicited with stimulus intervals of 300-600 ms. In both types of experiments, the results were similar. Halothane and enflurane depressed rapid initial tension development more than isoflurane. This initial tension development was also selectively depressed by 0.1 microM ryanodine, which specifically decreases Ca2+ release from the sarcoplasmic reticulum (SR). Isoflurane and also enflurane depressed a delayed and late peaking component of tension development, which was very prominent after rest and was depressed by 200 microM procaine or 500 microM benzocaine. Although isoflurane and enflurane were similar to the local anesthetics in depressing late tension, unlike the local anesthetics they prolonged the late phase of tension development as well. The late tension of the RSC is associated with Ca2+, which enters the rested myocyte on depolarization and may be transiently sequestered in the SR before release. Both early initial and late tension development are depressed to a similar degree by application of 10-20 nM nifedipine. These results emphasize the multiple differing actions of the volatile anesthetics on myocardial contractions, with halothane and isoflurane possessing distinct depressant characteristics. PMID:1691397

  4. Regional left ventricular myocardial contractility and stress in a finite element model of posterobasal myocardial infarction.

    PubMed

    Wenk, Jonathan F; Sun, Kay; Zhang, Zhihong; Soleimani, Mehrdad; Ge, Liang; Saloner, David; Wallace, Arthur W; Ratcliffe, Mark B; Guccione, Julius M

    2011-04-01

    Recently, a noninvasive method for determining regional myocardial contractility, using an animal-specific finite element (FE) model-based optimization, was developed to study a sheep with anteroapical infarction (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001). Using the methodology developed in the previous study (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001), which incorporates tagged magnetic resonance images, three-dimensional myocardial strains, left ventricular (LV) volumes, and LV cardiac catheterization pressures, the regional myocardial contractility and stress distribution of a sheep with posterobasal infarction were investigated. Active material parameters in the noninfarcted border zone (BZ) myocardium adjacent to the infarct (T(max_B)), in the myocardium remote from the infarct (T(max_R)), and in the infarct (T(max_I)) were estimated by minimizing the errors between FE model-predicted and experimentally measured systolic strains and LV volumes using the previously developed optimization scheme. The optimized T(max_B) was found to be significantly depressed relative to T(max_R), while T(max_I) was found to be zero. The myofiber stress in the BZ was found to be elevated, relative to the remote region. This could cause further damage to the contracting myocytes, leading to heart failure. PMID:21428685

  5. [Myocardial depression in the burn patient].

    PubMed

    Carrillo-Esper, Raúl; Sánchez-Zúñiga, Martín de Jesús

    2006-01-01

    Myocardial depression and heart failure are frequent complications in critically ill burn patients. The physiopathology is complex and involves the activation of inflammatory pathways, ischemia-reperfusion, oxidative stress and endothelial lesion. Diagnosis should be made early by means of hemodynamic monitoring. Treatment is accomplished by inotropics that act on different pathways of the contractile function and immune response associated with antioxidants and allopurinol. PMID:16887086

  6. Depressed phosphatidic acid-induced contractile activity of failing cardiomyocytes.

    PubMed

    Tappia, Paramjit S; Maddaford, Thane G; Hurtado, Cecilia; Panagia, Vincenzo; Pierce, Grant N

    2003-01-10

    The effects of phosphatidic acid (PA), a known inotropic agent, on Ca(2+) transients and contractile activity of cardiomyocytes in congestive heart failure (CHF) due to myocardial infarction were examined. In control cells, PA induced a significant increase (25%) in active cell shortening and Ca(2+) transients. The phospholipase C (PLC) inhibitor, 2-nitro-4-carboxyphenyl N,N-diphenylcarbonate, blocked the positive inotropic action induced by PA, indicating that PA induces an increase in contractile activity and Ca(2+) transients through stimulation of PLC. Conversely, in failing cardiomyocytes there was a loss of PA-induced increase in active cell shortening and Ca(2+) transients. PA did not alter resting cell length. Both diastolic and systolic [Ca(2+)] were significantly elevated in the failing cardiomyocytes. In vitro assessment of the cardiac sarcolemmal (SL) PLC activity revealed that the impaired failing cardiomyocyte response to PA was associated with a diminished stimulation of SL PLC activity by PA. Our results identify an important defect in the PA-PLC signaling pathway in failing cardiomyocytes, which may have significant implications for the depressed contractile function during CHF. PMID:12504106

  7. Circadian rhythms in fatty acid-induced depression of myocardial contractile function: Potential mediation by the circadian clock within the cardiomyocyte

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in susceptibility to cardiovascular (CV) pathologic events (e.g., arrhythmias, myocardial infarction) are well established. These phenomena have been explained largely by diurnal variations in neurohumoral influences, such as sympathetic activity. Circadian clocks are intracellular...

  8. Green tea extract given before regional myocardial ischemia-reperfusion in rats improves myocardial contractility by attenuating calcium overload.

    PubMed

    Liou, Ying-Ming; Hsieh, Shih-Rong; Wu, Tsu-Juey; Chen, Jan-Yow

    2010-11-01

    There is evidence for a negative correlation between green tea consumption and cardiovascular diseases. The aim of the present study was to examine whether green tea extract (GTE) given before regional myocardial ischemia could improve depression of myocardial contractility by preventing cytosolic Ca(2+) overload. Regional ischemia-reperfusion (IR) was induced in rats by ligating the left anterior descending branch for 20 min, then releasing the ligature. Ligation induced ventricular arrhythmias in rats without GTE pretreatment, but decreased arrhythmogenesis was seen in rats pretreated 30 min earlier with GTE (400 mg/kg). During reperfusion, arrhythmias only occurred during the initial 5 min, and GTE pretreatment had no effect. After overnight recovery, serum cTnI levels were greatly increased in control post-IR rats but only slightly elevated in GTE-pretreated post-IR rats. Myocardial contractility measured by echocardiography was still depressed after 3 days in control post-IR rats, but not in GTE-pretreated post-IR rats. No myocardial ischemic injury was seen in post-IR rats with or without GTE pretreatment. Using freshly isolated single heart myocytes, GTE was found to attenuate the post-IR injury-associated cytosolic Ca(2+) overload and modulate changes in the levels and distribution of myofibril, adherens junction, and gap junction proteins. In summary, GTE pretreatment protects cardiomyocytes from IR injury by preventing cytosolic Ca(2+) overload, myofibril disruption, and alterations in adherens and gap junction protein expression and distribution. PMID:20922441

  9. Catecholamines and myocardial contractile function during hypodynamia and with an altered thyroid hormone balance

    NASA Technical Reports Server (NTRS)

    Pruss, G. M.; Kuznetsov, V. I.; Zhilinskaya, A. A.

    1980-01-01

    The dynamics of catecholamine content and myocardial contractile function during hypodynamia were studied in 109 white rats whose motor activity was severely restricted for up to 30 days. During the first five days myocardial catecholamine content, contractile function, and physical load tolerance decreased. Small doses of thyroidin counteracted this tendency. After 15 days, noradrenalin content and other indices approached normal levels and, after 30 days, were the same as control levels, although cardiac functional reserve was decreased. Thyroidin administration after 15 days had no noticeable effect. A detailed table shows changes in 17 indices of myocardial contractile function during hypodynamia.

  10. Magnetic Resonance Elastography as a Method to Estimate Myocardial Contractility

    PubMed Central

    Kolipaka, Arunark; Aggarwal, Shivani R.; McGee, Kiaran P.; Anavekar, Nandan; Manduca, Armando; Ehman, Richard L.; Araoz, Philip A.

    2012-01-01

    Purpose To determine whether increasing epinephrine infusion in an in-vivo pig model is associated with an increase in end-systolic magnetic resonance elastography (MRE)-derived effective stiffness. Methods Finite element modeling (FEM) was performed to determine range of myocardial wall thicknesses that could be used for analysis. Then MRE was performed on 5-pigs to measure the end-systolic effective stiffness with epinephrine infusion. Epinephrine was continuously infused intravenously in each pig to increase the heart-rate in increments of 20%. For each such increase end-systolic effective stiffness was measured using MRE. In each pig, Student’s t-test was used to compare effective end-systolic stiffness at baseline and at initial infusion of epinephrine. Least-square linear regression was performed to determine the correlation between normalized end-systolic effective stiffness and increase in heart-rate with epinephrine infusion. Results FEM showed that phase gradient inversion could be performed on wall thickness ~≥1.5cm. In pigs, effective end-systolic stiffness significantly increased from baseline to the first infusion in all pigs (p=0.047). A linear correlation was found between normalized effective end-systolic stiffness and percent increase in heart-rate by epinephrine infusion with R2 ranging from 0.86–0.99 in 4-pigs. In one of the pigs the R2 value was 0.1. A linear correlation with R2=0.58 was found between normalized effective end-systolic stiffness and percent increase in heart-rate when pooling data points from all pigs. Conclusion Noninvasive MRE-derived end-systolic effective myocardial stiffness may be a surrogate for myocardial contractility. PMID:22334349

  11. Lidocaine Enhances Contractile Function of Ischemic Myocardial Regions in Mouse Model of Sustained Myocardial Ischemia

    PubMed Central

    Kania, Gabriela; Osto, Elena; Jakob, Philipp; Krasniqi, Nazmi; Beck-Schimmer, Beatrice; Blyszczuk, Przemyslaw; Eriksson, Urs

    2016-01-01

    Rationale Perioperative myocardial ischemia is common in high-risk patients. The use of interventional revascularisation or even thrombolysis is limited in this patient subset due to exceedingly high bleeding risks. Blockade of voltage-gated sodium channels (VGSC) with lidocaine had been suggested to reduce infarct size and cardiomyocyte cell death in ischemia/reperfusion models. However, the impact of lidocaine on cardiac function during sustained ischemia still remains unclear. Methods Sustained myocardial ischemia was induced by ligation of the left anterior descending artery in 12–16 weeks old male BALB/c mice. Subcutaneous lidocaine (30 mg/kg) was used to block VGSC. Cardiac function was quantified at baseline and at 72h by conventional and speckle-tracking based echocardiography to allow high-sensitivity in vivo phenotyping. Infarct size and cardiomyocyte cell death were assessed post mortem histologically and indirectly using troponin measurements. Results Ischemia strongly impaired both, global systolic and diastolic function, which were partially rescued in lidocaine treated in mice. No differences regarding infarct size and cardiomyocyte cell death were observed. Mechanistically, and as shown with speckle-tracking analysis, lidocaine specifically improves residual contractility in the ischemic but not in the remote, non-ischemic myocardium. Conclusion VGSC blockade with lidocaine rescues function of ischemic myocardium as a potential bridging to revascularisation in the setting of perioperative myocardial ischemia. PMID:27140425

  12. Mesenteric lymph from rats with trauma-hemorrhagic shock causes abnormal cardiac myocyte function and induces myocardial contractile dysfunction

    PubMed Central

    Sambol, Justin T.; Lee, Marlon A.; Jiang, Mingshan; Dosi, Garima; Dong, Wei; Deitch, Edwin A.

    2011-01-01

    Myocardial contractile dysfunction develops following trauma-hemorrhagic shock (T/HS). We have previously shown that, in a rat fixed pressure model of T/HS (mean arterial pressure of 30–35 mmHg for 90 min), mesenteric lymph duct ligation before T/HS prevented T/HS-induced myocardial contractile depression. To determine whether T/HS lymph directly alters myocardial contractility, we examined the functional effects of physiologically relevant concentrations of mesenteric lymph collected from rats undergoing trauma-sham shock (T/SS) or T/HS on both isolated cardiac myocytes and Langendorff-perfused whole hearts. Acute application of T/HS lymph (0.1–2%), but not T/SS lymph, induced dual inotropic effects on myocytes with an immediate increase in the amplitude of cell shortening (1.4 ± 0.1-fold) followed by a complete block of contraction. Similarly, T/HS lymph caused dual, positive and negative effects on cellular Ca2+ transients. These effects were associated with changes in the electrophysiological properties of cardiac myocytes; T/HS lymph initially prolonged the action potential duration (action potential duration at 90% repolarization, 3.3 ± 0.4-fold), and this was followed by a decrease in the plateau potential and membrane depolarization. Furthermore, intravenous infusion of T/HS lymph, but not T/SS lymph, caused myocardial contractile dysfunction at 24 h after injection, which mimicked actual T/HS-induced changes; left ventricular developed pressure (LVDP) and the maximal rate of LVDP rise and fall (±dP/dtmax) were decreased and inotropic response to Ca2+ was blunted. However, the contractile responsiveness to β-adrenergic receptor stimulation in the T/HS lymph-infused hearts remained unchanged. These results suggest that T/HS lymph directly causes negative inotropic effects on the myocardium and that T/HS lymph-induced changes in myocyte function are likely to contribute to the development of T/HS-induced myocardial dysfunction. PMID:21700891

  13. Circadian rhythms in myocardial metabolism and contractile function; influence of workload and oleate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple extra-cardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its ...

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  15. [The cardioprotective action of the anticonvulsant preparation sodium valproate in disorders of cardiac contractile function caused by acute myocardial infarct in rats].

    PubMed

    Belkina, L M; Korchazhkina, N B; Kamskova, Iu G; Fomin, N A

    1997-01-01

    The preventive and therapeutical effects of sodium valproate (SV), 200 mg/kg, on cardiac contractile disorders (developed pressure, rate-pressure products, dp/dt) were studied in rats having 2-day myocardial infarction (MI). The postinfarction rather than preinfarction use of SV substantially restricted the depressed resting left ventricular function. Given by two regimens, SV increased cardiac resistance to the maximum isometric load induced by 60-sec ligation of the ascending aorta. The cardioprotective effect of the drug was shown due to its positive chronotropic action rather than its inotropic one. Thus, SV may be used as an effective drug for the prevention and treatment of postinfarct cardiac dysfunctions. PMID:9235532

  16. A single resistance exercise session improves myocardial contractility in spontaneously hypertensive rats.

    PubMed

    Fernandes, A A; Faria, T de O; Ribeiro Júnior, R F; Costa, G P; Marchezini, B; Silveira, E A; Angeli, J K; Stefanon, I; Vassallo, D V; Lizardo, J H

    2015-09-01

    Resistance training evokes myocardial adaptation; however, the effects of a single resistance exercise session on cardiac performance are poorly understood or investigated. This study aimed to investigate the effects of a single resistance exercise session on the myocardial contractility of spontaneously hypertensive rats (SHRs). Male 3-month-old SHRs were divided into two groups: control (Ct) and exercise (Ex). Control animals were submitted to sham exercise. Blood pressure was measured in conscious rats before the exercise session to confirm the presence of arterial hypertension. Ten minutes after the exercise session, the animals were anesthetized and killed, and the hearts were removed. Cardiac contractility was evaluated in the whole heart by the Langendorff technique and by isometric contractions of isolated left ventricular papillary muscles. SERCA2a, phospholamban (PLB), and phosphorylated PLB expression were investigated by Western blot. Exercise increased force development of isolated papillary muscles (Ex=1.0±0.1 g/mg vs Ct=0.63±0.2 g/mg, P<0.05). Post-rest contraction was greater in the exercised animals (Ex=4.1±0.4% vs Ct=1.7±0.2%, P<0.05). Papillary muscles of exercised animals developed greater force under increasing isoproterenol concentrations (P<0.05). In the isolated heart, exercise increased left ventricular isovolumetric systolic pressure (LVISP; Δ +39 mmHg; P<0.05) from baseline conditions. Hearts from the exercised rats presented a greater response to increasing diastolic pressure. Positive inotropic intervention to calcium and isoproterenol resulted in greater LVISP in exercised animals (P<0.05). The results demonstrated that a single resistance exercise session improved myocardial contractility in SHRs. PMID:26176315

  17. A single resistance exercise session improves myocardial contractility in spontaneously hypertensive rats

    PubMed Central

    Fernandes, A.A.; Faria, T. de O.; Ribeiro, R.F.; Costa, G.P.; Marchezini, B.; Silveira, E.A.; Angeli, J.K.; Stefanon, I.; Vassallo, D.V.; Lizardo, J.H.

    2015-01-01

    Resistance training evokes myocardial adaptation; however, the effects of a single resistance exercise session on cardiac performance are poorly understood or investigated. This study aimed to investigate the effects of a single resistance exercise session on the myocardial contractility of spontaneously hypertensive rats (SHRs). Male 3-month-old SHRs were divided into two groups: control (Ct) and exercise (Ex). Control animals were submitted to sham exercise. Blood pressure was measured in conscious rats before the exercise session to confirm the presence of arterial hypertension. Ten minutes after the exercise session, the animals were anesthetized and killed, and the hearts were removed. Cardiac contractility was evaluated in the whole heart by the Langendorff technique and by isometric contractions of isolated left ventricular papillary muscles. SERCA2a, phospholamban (PLB), and phosphorylated PLB expression were investigated by Western blot. Exercise increased force development of isolated papillary muscles (Ex=1.0±0.1 g/mg vs Ct=0.63±0.2 g/mg, P<0.05). Post-rest contraction was greater in the exercised animals (Ex=4.1±0.4% vs Ct=1.7±0.2%, P<0.05). Papillary muscles of exercised animals developed greater force under increasing isoproterenol concentrations (P<0.05). In the isolated heart, exercise increased left ventricular isovolumetric systolic pressure (LVISP; Δ +39 mmHg; P<0.05) from baseline conditions. Hearts from the exercised rats presented a greater response to increasing diastolic pressure. Positive inotropic intervention to calcium and isoproterenol resulted in greater LVISP in exercised animals (P<0.05). The results demonstrated that a single resistance exercise session improved myocardial contractility in SHRs. PMID:26176315

  18. Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload.

    PubMed Central

    Nakano, K; Swindle, M M; Spinale, F; Ishihara, K; Kanazawa, S; Smith, A; Biederman, R W; Clamp, L; Hamada, Y; Zile, M R

    1991-01-01

    It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload. PMID:1828252

  19. Myocardial contractility in the echo lab: molecular, cellular and pathophysiological basis

    PubMed Central

    Bombardini, Tonino

    2005-01-01

    In the standard accepted concept, contractility is the intrinsic ability of heart muscle to generate force and to shorten, independently of changes in the preload or afterload with fixed heart rates. At molecular level the crux of the contractile process lies in the changing concentrations of Ca2+ ions in the myocardial cytosol. Ca2+ ions enter through the calcium channel that opens in response to the wave of depolarization that travels along the sarcolemma. These Ca2+ ions "trigger" the release of more calcium from the sarcoplasmic reticulum (SR) and thereby initiate a contraction-relaxation cycle. In the past, several attempts were made to transfer the pure physiological concept of contractility, expressed in the isolated myocardial fiber by the maximal velocity of contraction of unloaded muscle fiber (Vmax), to the in vivo beating heart. Suga and Sagawa achieved this aim by measuring pressure/volume loops in the intact heart: during a positive inotropic intervention, the pressure volume loop reflects a smaller end-systolic volume and a higher end-systolic pressure, so that the slope of the pressure volume relationship moves upward and to the left. The pressure volume relationship is the most reliable index for assessing myocardial contractility in the intact circulation and is almost insensitive to changes in preload and after load. This is widely used in animal studies and occasionally clinically. The limit of the pressure volume relationship is that it fails to take into account the frequency-dependent regulation of contractility: the frequency-dependent control of transmembrane Ca2+ entry via voltage-gated Ca2+ channels provides cardiac cells with a highly sophisticated short-term system for the regulation of intracellular Ca2+ homeostasis. An increased stimulation rate increases the force of contraction: the explanation is repetitive Ca2+ entry with each depolarization and, hence, an accumulation of cytosolic calcium. As the heart fails, there is a change in

  20. Myocardial Mitochondrial and Contractile Function Are Preserved in Mice Lacking Adiponectin

    PubMed Central

    Braun, Martin; Hettinger, Niko; Koentges, Christoph; Pfeil, Katharina; Cimolai, Maria C.; Hoffmann, Michael M.; Osterholt, Moritz; Doenst, Torsten; Bode, Christoph; Bugger, Heiko

    2015-01-01

    Adiponectin deficiency leads to increased myocardial infarct size following ischemia reperfusion and to exaggerated cardiac hypertrophy following pressure overload, entities that are causally linked to mitochondrial dysfunction. In skeletal muscle, lack of adiponectin results in impaired mitochondrial function. Thus, it was our objective to investigate whether adiponectin deficiency impairs mitochondrial energetics in the heart. At 8 weeks of age, heart weight-to-body weight ratios were not different between adiponectin knockout (ADQ-/-) mice and wildtypes (WT). In isolated working hearts, cardiac output, aortic developed pressure and cardiac power were preserved in ADQ-/- mice. Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups. While myocardial oxygen consumption was slightly reduced (-24%) in ADQ-/- mice in isolated working hearts, rates of maximal ADP-stimulated mitochondrial oxygen consumption and ATP synthesis in saponin-permeabilized cardiac fibers were preserved in ADQ-/- mice with glutamate, pyruvate or palmitoyl-carnitine as a substrate. In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups. Phosphorylation of AMP-activated protein kinase and SIRT1 activity were not decreased, expression and acetylation of PGC-1α were unchanged, and mitochondrial content of OXPHOS subunits was not decreased in ADQ-/- mice. Finally, increasing energy demands due to prolonged subcutaneous infusion of isoproterenol did not differentially affect cardiac contractility or mitochondrial function in ADQ-/- mice compared to WT. Thus, mitochondrial and contractile function are preserved in hearts of mice lacking adiponectin, suggesting that adiponectin may be expendable in the regulation of mitochondrial energetics and contractile function in the heart under non-pathological conditions. PMID:25785965

  1. AMP-Activated Protein Kinase Deficiency Exacerbates Aging-Induced Myocardial Contractile Dysfunction

    PubMed Central

    Turdi, Subat; Fan, Xiujuan; Li, Ji; Zhao, Junxing; Huff, Anna F.; Du, Min; Ren, Jun

    2010-01-01

    Aging is associated with myocardial dysfunction although the underlying mechanism is unclear. AMPK, a key cellular fuel sensor for energy metabolism, is compromised with aging. This study examined the role of AMPK deficiency in aging-associated myocardial dysfunction. Young or old minwild-type (WT) and transgenic mice with overexpression of a mutant AMPK α2 subunit (kinase dead, KD) were used. AMPK α isoform activity, myocardial function and morphology were examined. DCF and JC-1 fluorescence probes were employed to quantify reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm), respectively. KD mice displayed significantly reduced α2 but not α1 AMPK isoform activity at both ages with a greater effect at old age. Aging itself decreased α1 isoform activity. Cardiomyocyte contractile function, intracellular Ca2+ handling and SERCA2a levels were compromised with aging, the effects of which were exacerbated by AMPK deficiency. H&E staining revealed cardiomyocyte hypertrophy with aging, which was more pronounced in KD mice. TEM micrographs displayed severe disruption of mitochondrial ultrastructure characterized by swollen, irregular shape and disrupted cristae in aged KD compared with WT mice. Aging enhanced ROS production and reduced ΔΨm, the effects of which were accentuated by AMPK deficiency. Immunoblotting data depicted unchanged Akt phosphorylation and a significant decrease in mitochondrial biogenesis cofactor PGC-1α in aged groups. AMPK deficiency but not aging decreased the phosphorylation of ACC and eNOS. Expression of membrane Glut4 and HSP90 was decreased in aged KD mice. Moreover, treatment of the AMPK activator metformin attenuated aging-induced cardiomyocyte contractile defects. Collectively, our data suggest a role for AMPK deficiency in aging-induced cardiac dysfunction possibly through disrupted mitochondrial function and ROS production. PMID:20477759

  2. Myocardial contractility in the stress echo lab: from pathophysiological toy to clinical tool.

    PubMed

    Bombardini, Tonino; Zoppè, Monica; Ciampi, Quirino; Cortigiani, Lauro; Agricola, Eustachio; Salvadori, Stefano; Loni, Tiziana; Pratali, Lorenza; Picano, Eugenio

    2013-01-01

    Up-regulation of Ca2+ entry through Ca2+ channels by high rates of beating is involved in the frequency-dependent regulation of contractility: this process is crucial in adaptation to exercise and stress and is universally known as force-frequency relation (FFR). Disturbances in calcium handling play a central role in the disturbed contractile function in myocardial failure. Measurements of twitch tension in isolated left-ventricular strips from explanted cardiomyopathic hearts compared with non-failing hearts show flat or biphasic FFR, while it is up-sloping in normal hearts. Starting in 2003 we introduced the FFR measurement in the stress echo lab using the end-systolic pressure (ESP)/End-systolic volume index (ESVi) ratio (the Suga index) at increasing heart rates. We studied a total of 2,031 patients reported in peer-reviewed journals: 483 during exercise, 34 with pacing, 850 with dobutamine and 664 during dipyridamole stress echo. We demonstrated the feasibility of FFR in the stress echo lab, the clinical usefulness of FFR for diagnosing latent contractile dysfunction in apparently normal hearts, and residual contractile reserve in dilated idiopathic and ischemic cardiomyopathy. In 400 patients with left ventricular dysfunction (ejection fraction 30 ± 9%) with negative stress echocardiography results, event-free survival was higher (p < 0.001) in patients with ΔESPVR (the difference between peak and rest end-systolic pressure-volume ratio, ESPVR) ≥ 0.4 mmHg/mL/m2. The prognostic stratification of patients was better with FFR, beyond the standard LV ejection fraction evaluation, also in the particular settings of severe mitral regurgitation or diabetics without stress-induced ischemia. In the particular setting of selection of heart transplant donors, the stress echo FFR was able to correctly select 34 marginal donor hearts efficiently transplanted in emergency recipients. Starting in 2007, we introduced an operator-independent cutaneous sensor

  3. Relation of coronary microvascular dysfunction in hypertrophic cardiomyopathy to contractile dysfunction independent from myocardial injury.

    PubMed

    Timmer, Stefan A J; Germans, Tjeerd; Götte, Marco J W; Rüssel, Iris K; Lubberink, Mark; Ten Berg, Jurrien M; Ten Cate, Folkert J; Lammertsma, Adriaan A; Knaapen, Paul; van Rossum, Albert C

    2011-05-15

    We studied the spatial relations among hyperemic myocardial blood flow (hMBF), contractile function, and morphologic tissue alterations in 19 patients with hypertrophic cardiomyopathy (HC). All patients were studied with oxygen-15 water positron emission tomography during rest and adenosine administration to assess myocardial perfusion. Cardiovascular magnetic resonance was performed to derive delayed contrast-enhanced images and to calculate contractile function (E(cc)) with tissue tagging. Eleven healthy subjects underwent similar positron emission tomographic and cardiovascular magnetic resonance scanning protocols and served as a control group. In the HC group, hMBF averaged 2.46 ± 0.91 ml/min/g and mean E(cc) was -14.7 ± 3.4%, which were decreased compared to the control group (3.97 ± 1.48 ml/min/g and -17.7 ± 3.2%, respectively, p <0.001 for the 2 comparisons). Delayed contrast enhancement (DCE) was present only in patients with HC, averaging 6.2 ± 10.3% of left ventricular mass. In the HC group, E(cc) and DCE in the septum (-13.7 ± 3.6% and 10.2 ± 13.6%) significantly differed from the lateral wall (-16.0 ± 2.8% and 2.4 ± 5.9%, p <0.001 for the 2 comparisons). In general, hMBF and E(cc) were decreased in segments displaying DCE compared to nonenhanced segments (p <0.001 for the comparisons). In the HC group, univariate analysis revealed relations of hMBF to E(cc) (r = -0.45, p <0.001) and DCE (r = -0.31, p <0.001). Multivariate analysis revealed that E(cc) was independently related to hMBF (beta -0.37, p <0.001) and DCE (beta 0.28, p <0.001). In conclusion, in HC hMBF is impaired and related to contractile function independent from presence of DCE. When present, DCE reflected a progressed disease state as characterized by an increased perfusion deficit and contractile dysfunction. PMID:21377644

  4. Depression by relaxin of neurally induced contractile responses in the mouse gastric fundus.

    PubMed

    Baccari, Maria Caterina; Nistri, Silvia; Quattrone, Silvia; Bigazzi, Mario; Bani Sacchi, Tatiana; Calamai, Franco; Bani, Daniele

    2004-01-01

    The peptide hormone relaxin, which attains high circulating levels during pregnancy, has been shown to depress small-bowel motility through a nitric oxide (NO)-mediated mechanism. In the present study we investigated whether relaxin also influences gastric contractile responses in mice. Female mice in proestrus or estrus were treated for 18 h with relaxin (1 microg s.c.) or vehicle (controls). Mechanical responses of gastric fundal strips were recorded via force-displacement transducers. Evaluation of the expression of nitric oxide synthase (NOS) isoforms was performed by immunohistochemistry and Western blot. In control mice, neurally induced contractile responses elicited by electrical field stimulation (EFS) were reduced in amplitude by addition of relaxin to the organ bath medium. In the presence of the NO synthesis inhibitor l-NNA, relaxin was ineffective. Direct smooth muscle contractile responses were not influenced by relaxin or l-NNA. In strips from relaxin-pretreated mice, the amplitude of neurally induced contractile responses was also reduced in respect to the controls, while that of direct smooth muscle contractions was not. Further addition of relaxin to the bath medium did not influence EFS-induced responses, whereas l-NNA did. An increased expression of NOS I and NOS III was observed in gastric tissues from relaxin-pretreated mice. In conclusion, the peptide hormone relaxin depresses cholinergic contractile responses in the mouse gastric fundus by up-regulating NO biosynthesis at the neural level. PMID:14522837

  5. Effect of exercise training and myocardial infarction on force development and contractile kinetics in isolated canine myocardium.

    PubMed

    Canan, Benjamin D; Haizlip, Kaylan M; Xu, Ying; Monasky, Michelle M; Hiranandani, Nitisha; Milani-Nejad, Nima; Varian, Kenneth D; Slabaugh, Jessica L; Schultz, Eric J; Fedorov, Vadim V; Billman, George E; Janssen, Paul M L

    2016-04-15

    It is well known that moderate exercise training elicits a small increase in ventricular mass (i.e., a physiological hypertrophy) that has many beneficial effects on overall cardiac health. It is also well known that, when a myocardial infarction damages part of the heart, the remaining myocardium remodels to compensate for the loss of viable functioning myocardium. The effects of exercise training, myocardial infarction (MI), and their interaction on the contractile performance of the myocardium itself remain largely to be determined. The present study investigated the contractile properties and kinetics of right ventricular myocardium isolated from sedentary and exercise trained (10-12 wk progressively increasing treadmill running, begun 4 wk after MI induction) dogs with and without a left ventricular myocardial infarction. Exercise training increased force development, whereas MI decreased force development that was not improved by exercise training. Contractile kinetics were significantly slower in the trained dogs, whereas this impact of training was less or no longer present after MI. Length-dependent activation, both evaluated on contractile force and kinetics, was similar in all four groups. The control exercise-trained group exhibited a more positive force-frequency relationship compared with the sedentary control group while both sedentary and trained post-MI dogs had a more negative relationship. Last, the impact of the β-adrenergic receptor agonist isoproterenol resulted in a similar increase in force and acceleration of contractile kinetics in all groups. Thus, exercise training increased developed force but slowed contractile kinetics in control (noninfarcted animals), actions that were attenuated or completely absent in post-MI dogs. PMID:26823341

  6. Chronic Lead Exposure Increases Blood Pressure and Myocardial Contractility in Rats

    PubMed Central

    Fioresi, Mirian; Simões, Maylla Ronacher; Furieri, Lorena Barros; Broseghini-Filho, Gilson Brás; Vescovi, Marcos Vinícius A.; Stefanon, Ivanita; Vassallo, Dalton Valentim

    2014-01-01

    We investigated the cardiovascular effects of lead exposure, emphasising its direct action on myocardial contractility. Male Wistar rats were sorted randomly into two groups: control (Ct) and treatment with 100 ppm of lead (Pb) in the drinking water. Blood pressure (BP) was measured weekly. At the end of the treatment period, the animals were anaesthetised and haemodynamic parameters and contractility of the left ventricular papillary muscles were recorded. Blood and tissue samples were properly stored for further biochemical investigations. Statistical analyses were considered to be significant at p<0.05. The lead concentrations in the blood reached approximately 13 µg/dL, while the bone was the site of the highest deposition of this metal. BP in the Pb-treated group was higher from the first week of lead exposure and remained at the same level over the next four weeks. Haemodynamic evaluations revealed increases in systolic (Ct: 96±3.79 vs. Pb: 116±1.37 mmHg) and diastolic blood pressure (Ct: 60±2.93 vs. Pb: 70±3.38 mmHg), left ventricular systolic pressure (Ct: 104±5.85 vs. Pb: 120±2.51 mmHg) and heart rate (Ct: 307±10 vs. Pb: 348±16 bpm). Lead treatment did not alter the force and time derivatives of the force of left ventricular papillary muscles that were contracting isometrically. However, our results are suggestive of changes in the kinetics of calcium (Ca++) in cardiomyocytes increased transarcolemmal Ca++ influx, low Ca++ uptake by the sarcoplasmic reticulum and high extrusion by the sarcolemma. Altogether, these results show that despite the increased Ca++ influx that was induced by lead exposure, the myocytes had regulatory mechanisms that prevented increases in force, as evidenced in vivo by the increased systolic ventricular pressure. PMID:24841481

  7. Depression Increases Sympathetic Activity and Exacerbates Myocardial Remodeling after Myocardial Infarction: Evidence from an Animal Experiment

    PubMed Central

    Liu, Tao; Yuan, Xiaoran; Ruan, Bing; Sun, Lifang; Tang, Yanhong; Yang, Bo; Hu, Dan; Huang, Congxin

    2014-01-01

    Depression is an independent risk factor for cardiovascular events and mortality in patients with myocardial infarction (MI). Excessive sympathetic activation and serious myocardial remodeling may contribute to this association. The aim of this study was to discuss the effect of depression on sympathetic activity and myocardial remodeling after MI. Wild-type (WT) rats were divided into a sham group (Sham), a myocardial infarction group (MI), a depression group (D), and a myocardial infarction plus depression group (MI+D). Compared with controls, the MI+D animals displayed depression-like behaviors and attenuated body weight gain. The evaluation of sympathetic activity showed an increased level in plasma concentrations of epinephrine and norepinephrine and higher expression of myocardial tyrosine hydroxylase in the MI+D group than the control groups (p<0.05 for all). Cardiac function and morphologic analyses revealed a decreased fractional shortening accompanied by increased left ventricular dimensions, thinning myocardium wall, and reduced collagen repair in the MI+D group compared with the MI group (p<0.05 for all). Frequent premature ventricular contractions, prolonged QT duration and ventricular repolarization duration, shorted effective refractory period, and increased susceptibility to ventricular arrhythmia were displayed in MI+D rats. These results indicate that sympathetic hyperactivation and exacerbated myocardial remodeling may be a plausible mechanism linking depression to an adverse prognosis after MI. PMID:25036781

  8. Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

    NASA Technical Reports Server (NTRS)

    Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.

    2000-01-01

    BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

  9. [Role of nitric oxide in the development of the myocardial contractile reactions in trained animals].

    PubMed

    Shymans'ka, T V; Hoshovs'ka, Iu V; Sahach, V F

    2010-01-01

    Intensive constitutive production of nitric oxide (NO) during physical training improves vasodilatation and heart function. However, it remains unclear how NO takes part in myocardial adaptation to workload, which is accompanied by an increased heart inflow and intracellular calcium content. Using isolated rat heart by Langendorf preparation, we studied myocardial response to gradually increased left ventricular volume (Frank-Starling low) and increasing concentration of Ca2+ in the perfusion solution (from 1.7 mM to 12.5 mM) in trained and untrained rats. It was shown that 4 weeks swimming course improved heart function: heart rate was decreased; contractile activity (dP/dt max) and coronary flow were increased by 20% and 33%, respectively. Equal volume stretching of balloon in left ventricle provoked greater contraction in trained comparing to untrained hearts, demonstrating extended functional reserves after swimming course. Mitochondrial membrane potential was significantly increased in hearts of trained rats. Furthermore, training prevented fast increase of the end diastolic pressure during calcium upload. Mitochondrial factor release due to opening of mitochondrial permeability transition pore (MPTP) in trained hearts was detected at higher concentrations of calcium that reveals extended calcium capacity of mitochondria and lesser sensitivity of MPTP to its inductor-calcium. Blockade of NO synthesis with L-NAME application of (10(-4) M for 15 min) abolished reaction of trained heart during Frank-Starling and calcium upload. Thus, heart adaptation to physical training and extension of functional reserves in heart are provided by endogenous NO production. Key words: nitric oxide, Frank-Starling low, physical training, calcium upload, mitochondrial permeability transition, membrane potential. PMID:21265074

  10. Cardioselective Dominant-negative Thyroid Hormone Receptor (Δ337T) Modulates Myocardial Metabolism and Contractile Dfficiency

    SciTech Connect

    Hyyti, Outi M.; Olson, Aaron; Ge, Ming; Ning, Xue-Han; Buroker, Norman E.; Chung, Youngran; Jue, Thomas; Portman, Michael A.

    2008-06-03

    Dominant- negative thyroid hormone receptors (TRs) show elevated expression relative to ligand-binding TRs during cardiac hypertrophy. We tested the hypothesis that overexpression of a dominant-negative TR alters cardiac metabolism and contractile efficiency (CE). We used mice expressing the cardioselective dominant-negative TRβ1 mutation Δ337T. Isolated working Δ337T hearts and nontransgenic control (Con) hearts were perfused with 13C-labeled free fatty acids (FFA), acetoacetate (ACAC), lactate, and glucose at physiological concentrations for 30 min. 13C NMR spectroscopy and isotopomer analyses were used to determine substrate flux and fractional contributions (Fc) of acetyl-CoA to the citric acid cycle (CAC). Δ337T hearts exhibited rate depression but higher developed pressure and CE, defined as work per oxygen consumption (MV˙ O2). Unlabeled substrate Fc from endogenous sources was higher in Δ337T, but ACAC Fc was lower. Fluxes through CAC, lactate, ACAC, and FFA were reduced in Δ337T. CE and Fc differences were reversed by pacing Δ337T to Con rates, accompanied by an increase in FFA Fc. Δ337T hearts lacked the ability to increase MV˙ O2. Decreases in protein expression for glucose transporter-4 and hexokinase-2 and increases in pyruvate dehydrogenase kinase-2 and -4 suggest that these hearts are unable to increase carbohydrate oxidation in response to stress. These data show that Δ337T alters the metabolic phenotype in murine heart by reducing substrate flux for multiple pathways. Some of these changes are heart rate dependent, indicating that the substrate shift may represent an accommodation to altered contractile protein kinetics, which can be disrupted by pacing stress.

  11. Depressive Symptoms Are Associated with Mental Stress-Induced Myocardial Ischemia after Acute Myocardial Infarction

    PubMed Central

    Wei, Jingkai; Pimple, Pratik; Shah, Amit J.; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon A.; Ibeanu, Ijeoma; Murrah, Nancy; Shallenberger, Lucy; Raggi, Paolo; Vaccarino, Viola

    2014-01-01

    Objectives Depression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI. Methods We studied 98 patients (49 women and 49 men) age 38–60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores. Results There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress. Conclusion Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress. PMID:25061993

  12. Myocardial depression by ketamine. Haemodynamic and metabolic observations in animals.

    PubMed

    Chamberlain, J H; Seed, R G; Undre, N

    1981-04-01

    This study investigated the effect of ketamine on myocardial function. In dogs the drug was infused directly into the left main coronary artery. The concentration chosen was similar to the peak concentration found following a bolus intravenous injection. A mild depression of inotropic state was found which recovered completely after stopping the infusion. Myocardial depression was confirmed in a guinea pig Langendorff preparation. No changes in high energy phosphates were found in these hearts after 45-60 minutes of perfusion with ketamine in the perfusion medium. This study confirms that myocardial depression occurs with ketamine but suggests that it is unlikely to be of clinical significance. Depletion of high energy phosphates did not seem to be the cause of the depression. PMID:7246986

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  14. Changes in myocardial cytoskeletal intermediate filaments and myocyte contractile dysfunction in dilated cardiomyopathy: an in vivo study in humans

    PubMed Central

    Di, S; Marotta, M; Salvatore, G; Cudemo, G; Cuda, G; De Vivo, F; Di, B; Ciaramella, F; Caputo, G; de Divitiis, O

    2000-01-01

    AIM—To investigate in vivo the intermediate cytoskeletal filaments desmin and vimentin in myocardial tissues from patients with dilated cardiomyopathy, and to determine whether alterations in these proteins are associated with impaired contractility.
METHODS—Endomyocardial biopsies were performed in 12 patients with dilated cardiomyopathy and in 12 controls (six women with breast cancer before anthracycline chemotherapy and six male donors for heart transplantation). Biopsy specimens were analysed by light microscopy and immunochemistry (desmin, vimentin). Myocyte contractile protein function was evaluated by the actin-myosin in vitro motility assay. Left ventricular ejection fraction was assessed by echocardiography and radionuclide ventriculography.
RESULTS—Patients with dilated cardiomyopathy had a greater cardiomyocyte diameter than controls (p < 0.01). The increase in cell size was associated with a reduction in contractile function, as assessed by actin-myosin motility (r = −0.643; p < 0.01). Quantitative immunochemistry showed increased desmin and vimentin contents (p < 0.01), and the desmin distribution was disturbed in cardiomyopathy. There was a linear relation between desmin distribution and actin-myosin sliding in vitro (r = 0.853; p < 0.01) and an inverse correlation between desmin content and ejection fraction (r = −0.773; p < 0.02). Negative correlations were also found between myocardial vimentin content and the actin-myosin sliding rate (r = −0.74; p < 0.02) and left ventricular ejection fraction (r = −0.68; p < 0.01).
CONCLUSIONS—Compared with normal individuals, the myocardial tissue of patients with dilated cardiomyopathy shows alterations of cytoskeletal intermediate filament distribution and content associated with reduced myocyte contraction.


Keywords: dilated cardiomyopathy; desmin; vimentin; cardiac biopsy; actin-myosin PMID:11083750

  15. Assessment and treatment of depression following myocardial infarction.

    PubMed

    Guck, T P; Kavan, M G; Elsasser, G N; Barone, E J

    2001-08-15

    Approximately 65 percent of patients with acute myocardial infarction report experiencing symptoms of depression. Major depression is present in 15 to 22 percent of these patients. Depression is an independent risk factor in the development of and mortality associated with cardiovascular disease in otherwise healthy persons. Persons who are depressed and who have pre-existing cardiovascular disease have a 3.5 times greater risk of death than patients who are not depressed and have cardiovascular disease. Physicians can assess patients for depression by using one of several easily administered and scored self-report inventories, including the SIG E CAPS + mood mnemonic. Cognitive-behavior therapy is the preferred psychologic treatment. Selective serotonin reuptake inhibitor antidepressants are the recommended pharmacologic treatment because of the relative absence of effects on the cardiovascular system. The combination of a selective serotonin reuptake inhibitor with cognitive-behavior therapy is often the most effective treatment for depression in patients with cardiovascular disease. PMID:11529263

  16. Taurine depresses cardiac contractility and enhances systemic heart glucose utilization in the cuttlefish, Sepia officinalis.

    PubMed

    MacCormack, Tyson J; Callaghan, N I; Sykes, A V; Driedzic, W R

    2016-02-01

    Taurine is the most abundant amino acid in the blood of the cuttlefish, Sepia officinalis, where levels can exceed 200 mmol L(-1). In mammals, intracellular taurine modulates cardiac Ca(2+) handling and carbohydrate metabolism at much lower concentrations but it is not clear if it exerts similar actions in cephalopods. Blood Ca(2+) levels are high in cephalopods and we hypothesized that taurine would depress cardiac Ca(2+) flux and modulate contractility in systemic and branchial hearts of cuttlefish. Heart performance was assessed with an in situ perfused systemic heart preparation and contractility was evaluated using isometrically contracting systemic and branchial heart muscle rings. Stroke volume, cardiac output, and Ca(2+) sensitivity were significantly lower in systemic hearts perfused with supplemental taurine (100 mmol L(-1)) than in controls. In muscle ring preparations, taurine impaired relaxation at high contraction frequencies, an effect abolished by supra-physiological Ca(2+) levels. Taurine did not affect oxygen consumption in non-contracting systemic heart muscle, but extracellular glucose utilization was twice that of control preparations. Collectively, our results suggest that extracellular taurine depresses cardiac Ca(2+) flux and potentiates glucose utilization in cuttlefish. Variations in taurine levels may represent an important mechanism for regulating cardiovascular function and metabolism in cephalopods. PMID:26644087

  17. Myocardial performance index is sensitive to changes in cardiac contractility, but is also affected by vascular load condition.

    PubMed

    Uemura, Kazunori; Kawada, Toru; Zheng, Can; Li, Meihua; Shishido, Toshiaki; Sugimachi, Masaru

    2013-01-01

    Myocardial performance index (MPI), or Tei index, is measured by Doppler echocardiography in clinical practice. MPI has been shown to be useful in evaluating left ventricular (LV) performance and predicting prognosis in cardiac patients. However, the effects of LV load and contractile states on MPI remain to be thoroughly investigated. In 14 anesthetized dogs, we obtained LV pressure-volume relationship with use of sonomicrometry and catheter-tip manometry. MPI was determined from the time derivative of LV volume and pressure. LV end-systolic pressure-volume ratio (Ees'), effective arterial elastance (Ea) and LV end-diastolic volume (Ved) were used as indices of LV contractility, afterload and preload, respectively. Hemodynamic conditions were varied over wide ranges [heart rate (HR), 66-192 bpm; mean arterial pressure, 71-177 mmHg] by infusing cardiovascular agents, by inducing ischemic heart failure and by electrical atrial pacing. Multiple linear regression analysis of pooled data (66 data sets) indicated that MPI (0.6-1.8) significantly correlated with Ees' [1.5-17.5 mmHg · ml(-1), p<0.0001, standard partial regression coefficient (β) =-0.66], Ea (3.6-21.9 mmHg · ml(-1), p<0.001, β = 0.4) and Ved (11-100 ml, p<0.0001, β = -0.69). MPI directly correlated with the time constant of isovolumic relaxation (19-66 ms, p<0.05), but not with HR or LV diastolic-stiffness (all p>0.1). Theoretical analysis also indicated that MPI decreases following the increases in LV contractility and in preload, while it increases in response to an increase in LV afterload. We conclude that MPI sensitively detects changes in LV contractility. However, MPI is also affected by changes in LV afterload and preload. PMID:24109782

  18. PDE3A Regulates Basal Myocardial Contractility through Interacting with SERCA2a-Signaling Complexes in Mouse Heart

    PubMed Central

    Beca, Sanja; Ahmad, Faiyaz; Shen, Weixing; Liu, Jie; Makary, Samy; Polidovitch, Nazari; Sun, Junhui; Hockman, Steven; Chung, Youn Wook; Movesian, Matthew; Murphy, Elizabeth; Manganiello, Vincent; Backx, Peter H.

    2013-01-01

    Rationale cAMP is an important regulator of myocardial function, and regulation of cAMP hydrolysis by cyclic nucleotide phosphodiesterases (PDEs) is a critical determinant of the amplitude, duration, and compartmentation of cAMP–mediated signaling. The role of different PDE isozymes, particularly PDE3A versus PDE3B, in the regulation of heart function remains unclear. Objective To determine the relative contribution of PDE3A versus PDE3B isozymes in the regulation of heart function and to dissect the molecular basis for this regulation. Methods and Results Compared to wild-type (WT) littermates, cardiac contractility and relaxation were enhanced in isolated hearts from PDE3A−/−, but not PDE3B−/−, mice. Furthermore, PDE3 inhibition had no effect on PDE3A−/− hearts but increased contractility in WT (as expected) and PDE3B−/− hearts to levels indistinguishable from PDE3A−/−. The enhanced contractility in PDE3A−/− hearts was associated with cAMP-dependent elevations in Ca2+ transient amplitudes and increased SR Ca2+ content, without changes in L-type Ca2+ currents (ICa,L) of cardiomyocytes, as well as with increased SR Ca2+-ATPase (SERCA2a) activity, SR Ca2+ uptake rates, and phospholamban (PLN) phosphorylation in SR fractions. Consistent with these observations, PDE3 activity was reduced ~8-fold in SR fractions from PDE3A−/− hearts. Co-immunoprecipitation experiments further revealed that PDE3A associates with both SERCA2a and PLN in a complex which also contains AKAP-18, PKA-RII and PP2A. Conclusion Our data support the conclusion that PDE3A is the primary PDE3 isozyme modulating basal contractility and SR Ca2+ content by regulating cAMP in microdomains containing macromolecular complexes of SERCA2a-PLN-PDE3A. PMID:23168336

  19. Ceramide-mediated depression in cardiomyocyte contractility through PKC activation and modulation of myofilament protein phosphorylation

    PubMed Central

    Simon, Jillian N.; Chowdhury, Shamim A.K.; Warren, Chad M.; Sadayappan, Sakthivel; Wieczorek, David F.; Solaro, R. John; Wolska, Beata M.

    2015-01-01

    Although ceramide accumulation in the heart is considered a major factor in promoting apoptosis and cardiac disorders, including heart failure, lipotoxicity and ischemia-reperfusion injury, little is known about ceramide’s role in mediating changes in contractility. In the present study, we measured the functional consequences of acute exposure of isolated field stimulated adult rat cardiomyocytes to C6-ceramide. Exogenous ceramide treatment depressed the peak amplitude and the maximal velocity of shortening without altering intracellular calcium levels or kinetics. The inactive ceramide analog C6-dihydroceramide had no effect on myocyte shortening or [Ca2+]i transients. Experiments testing a potential role for C6-ceramide-mediated effects on activation of protein kinase C (PKC) demonstrated evidence for signaling through the calcium-independent isoform, PKCε. We employed 2 dimensional electrophoresis and anti-phospho-peptide antibodies to test whether treatment of the cardiomyocytes with C6-ceramide altered myocyte shortening via PKC dependent phosphorylation of myofilament proteins. Compared to controls, myocytes treated with ceramide exhibited increased phosphorylation of myosin binding protein-C (cMyBP-C), specifically at Ser273 and Ser302, and troponin I (cTnI) at sites apart from Ser23/24, which could be attenuated with PKC inhibition. We conclude that the altered myofilament response to calcium resulting from multiple sites of PKC-dependent phosphorylation contributes to contractile dysfunction that is associated with cardiac diseases in which elevations in ceramides are present. PMID:25280528

  20. Variability in interbeat duration influences myocardial contractility in rat cardiac trabeculae.

    PubMed

    Torres, Carlos A A; Varian, Kenneth D; Janssen, Paul M L

    2008-01-01

    There is an intense search for positive inotropic strategies. It is well known that the interbeat duration is a critical determinant of cardiac contractility. Generally, when frequency increases, so does contractile strength. We hypothesize that the beat-to-beat variability at a given heart rate also modulates cardiac contractility. To test this hypothesis, thin, uniform rat cardiac trabeculae were isolated from the right ventricle and stimulated to isometrically contract, alternating between fixed steady state versus variable inter-beat intervals (same total number of beats in each period). Trabeculae were stimulated at 4 Hz with interbeat variation between 20 and 120% (n=17). In a second series of experiments trabeculae were stimulated at 3 different physiologic frequencies with a 40% interbeat variation. Fixed rate response was measured before and after each variable period and average force was calculated. In order to investigate the mechanism underlying the changes in contractility we used iontophoretically loaded bis-fura-2 salt to monitor intracellular calcium transients. We observed no significant change in force at 4 Hz (n=17), and 6 Hz (n=6) between fixed and variable pacing but observed a significant, 10% increase in contractile strength at 8 Hz (from 15.1 to 16.5 mN/mm(2), p<0.05, n=6). Our results show that under certain conditions, by simply introducing variation in the beat-to-beat duration without affecting the number of beats per minute, a positive inotropic effect with corresponding changes in the calcium transients can be generated. PMID:19440237

  1. A Novel Method for Quantifying Smooth Regional Variations in Myocardial Contractility Within an Infarcted Human Left Ventricle Based on Delay-Enhanced Magnetic Resonance Imaging.

    PubMed

    Genet, Martin; Chuan Lee, Lik; Ge, Liang; Acevedo-Bolton, Gabriel; Jeung, Nick; Martin, Alastair; Cambronero, Neil; Boyle, Andrew; Yeghiazarians, Yerem; Kozerke, Sebastian; Guccione, Julius M

    2015-08-01

    Heart failure is increasing at an alarming rate, making it a worldwide epidemic. As the population ages and life expectancy increases, this trend is not likely to change. Myocardial infarction (MI)-induced adverse left ventricular (LV) remodeling is responsible for nearly 70% of heart failure cases. The adverse remodeling process involves an extension of the border zone (BZ) adjacent to an MI, which is normally perfused but shows myofiber contractile dysfunction. To improve patient-specific modeling of cardiac mechanics, we sought to create a finite element model of the human LV with BZ and MI morphologies integrated directly from delayed-enhancement magnetic resonance (DE-MR) images. Instead of separating the LV into discrete regions (e.g., the MI, BZ, and remote regions) with each having a homogeneous myocardial material property, we assumed a functional relation between the DE-MR image pixel intensity and myocardial stiffness and contractility--we considered a linear variation of material properties as a function of DE-MR image pixel intensity, which is known to improve the accuracy of the model's response. The finite element model was then calibrated using measurements obtained from the same patient--namely, 3D strain measurements-using complementary spatial modulation of magnetization magnetic resonance (CSPAMM-MR) images. This led to an average circumferential strain error of 8.9% across all American Heart Association (AHA) segments. We demonstrate the utility of our method for quantifying smooth regional variations in myocardial contractility using cardiac DE-MR and CSPAMM-MR images acquired from a 78-yr-old woman who experienced an MI approximately 1 yr prior. We found a remote myocardial diastolic stiffness of C(0) = 0.102 kPa, and a remote myocardial contractility of T(max) = 146.9 kPa, which are both in the range of previously published normal human values. Moreover, we found a normalized pixel intensity range of 30% for the BZ, which is consistent with

  2. Superoxide dismutase attenuated post-ischaemic contractile dysfunction in a myocardial xanthine oxidase deficient species.

    PubMed

    Ooiwa, H; Miura, T; Iwamoto, T; Ogawa, T; Ishimoto, R; Adachi, T; Iimura, O

    1992-02-01

    1. We assessed the effect of polyethylene glycol conjugated superoxide dismutase (PEG-SOD) on myocardial stunning in the rabbit heart in which xanthine oxidase level is extremely low. 2. In open-chest anaesthetized rabbits, the left marginal branch of the coronary artery was occluded for 10 min and then reperfused for 30 min. A group of rabbits (PEG-SOD group) received 1000 units/kg of PED-SOD and another group (control group) was given saline 15 min before the coronary occlusion. 3. Regional systolic thickening fraction (TF) was similarly reduced to approximately -25% of baseline value during ischaemia in both groups. However recovery of TF after reperfusion was significantly better in the PEG-SOD group (n = 9) and TF at 30 min after reperfusion was 70.1 +/- 3.9% of baseline value compared with 44.9 +/- 3.4% in the control group (n = 9; P less than 0.05). Rate-pressure products, left ventricular pressure, and LV dP/dt max were not significantly different between the PEG-SOD treated and untreated control rabbits at any time during the experiment. PEG-SOD did not modify the regional myocardial blood flow (coloured microsphere method) during ischaemia/reperfusion, which was assessed by using separate groups of rabbits. 4. These findings indicate that oxygen free radicals are important in the pathogenesis of myocardial stunning in xanthine oxidase deficient hearts. PMID:1555325

  3. Exposure to low mercury concentration in vivo impairs myocardial contractile function

    SciTech Connect

    Furieri, Lorena Barros; Fioresi, Mirian; Junior, Rogerio Faustino Ribeiro; Bartolome, Maria Visitacion; Fernandes, Aurelia Araujo; Cachofeiro, Victoria; Lahera, Vicente; Salaices, Mercedes; Stefanon, Ivanita; Vassallo, Dalton Valentim

    2011-09-01

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

  4. Improved myocardial contractility with glucose-insulin-potassium infusion during pacing in coronary artery disease.

    PubMed

    McDaniel, H G; Rogers, W J; Russell, R O; Rackley, C E

    1985-04-01

    The metabolic and mechanical effects of a solution of glucose-insulin-potassium (G-I-K) were investigated in 18 patients who underwent diagnostic cardiac catheterization for coronary artery disease. All patients were paced at a rate of approximately 140 beats/min before and after infusion of G-I-K. Basal and paced left ventricular (LV) end-diastolic pressure, dP/dt, arterial substrate levels and osmolarity were measured in all 18 patients. In 13 patients cardiac index was also measured. In 5 patients arterial-coronary sinus measurements of oxygen, carbon dioxide, glucose, free fatty acids, lactate, alanine, glutamate, glutamine, ammonia and urea were made, in addition to coronary sinus blood flow. G-I-K increased the blood sugar level to approximately 200 mg/dl and raised the serum osmolarity 9 mosmol. Pacing alone raised the cardiac index 4% and pacing with G-I-K increased the cardiac index 6% (p less than 0.05). Pacing before G-I-K augmented dP/dt (21%) and pacing with G-I-K increased it (30%) (p less than 0.01). The metabolic changes noted included a shift in the respiratory quotient from 0.77 to 0.96 with G-I-K infusion (p less than 0.05). During G-I-K infusion the myocardial oxygen consumption at rest increased from 17.1 to 21.8 ml/min (23%, p less than 0.05). Myocardial oxygen consumption during pacing was similar before and after G-I-K infusion. Before G-I-K infusion nitrogen balance was slightly positive; after G-I-K infusion it was negative with regard to the nitrogen-containing compounds measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3885708

  5. AAV6-mediated Cardiac-specific Overexpression of Ribonucleotide Reductase Enhances Myocardial Contractility.

    PubMed

    Kolwicz, Stephen C; Odom, Guy L; Nowakowski, Sarah G; Moussavi-Harami, Farid; Chen, Xiaolan; Reinecke, Hans; Hauschka, Stephen D; Murry, Charles E; Mahairas, Gregory G; Regnier, Michael

    2016-02-01

    Impaired systolic function, resulting from acute injury or congenital defects, leads to cardiac complications and heart failure. Current therapies slow disease progression but do not rescue cardiac function. We previously reported that elevating the cellular 2 deoxy-ATP (dATP) pool in transgenic mice via increased expression of ribonucleotide reductase (RNR), the enzyme that catalyzes deoxy-nucleotide production, increases myosin-actin interaction and enhances cardiac muscle contractility. For the current studies, we initially injected wild-type mice retro-orbitally with a mixture of adeno-associated virus serotype-6 (rAAV6) containing a miniaturized cardiac-specific regulatory cassette (cTnT(455)) composed of enhancer and promotor portions of the human cardiac troponin T gene (TNNT2) ligated to rat cDNAs encoding either the Rrm1 or Rrm2 subunit. Subsequent studies optimized the system by creating a tandem human RRM1-RRM2 cDNA with a P2A self-cleaving peptide site between the subunits. Both rat and human Rrm1/Rrm2 cDNAs resulted in RNR enzyme overexpression exclusively in the heart and led to a significant elevation of left ventricular (LV) function in normal mice and infarcted rats, measured by echocardiography or isolated heart perfusions, without adverse cardiac remodeling. Our study suggests that increasing RNR levels via rAAV-mediated cardiac-specific expression provide a novel gene therapy approach to potentially enhance cardiac systolic function in animal models and patients with heart failure. PMID:26388461

  6. Simvastatin alleviates myocardial contractile dysfunction and lethal ischemic injury in rat heart independent of cholesterol-lowering effects.

    PubMed

    ADAMEOVA, A; HARCAROVA, A; MATEJIKOVA, J; PANCZA, D; KUZELOVA, M; CARNICKA, S; SVEC, P; BARTEKOVA, M; STYK, J; Ravingerová, T

    2009-01-01

    Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are most frequently used drugs in the prevention of coronary artery disease due to their cholesterol-lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection against myocardial ischemia-reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff-perfused hearts of healthy control (C) and diabetic-hypercholesterolemic (D-H; streptozotocin + high fat-cholesterol diet, 5 days) rats subjected to 30-min global ischemia followed by 40-min reperfusion for the examination of postischemic contractile dysfunction and reperfusion-induced ventricular arrhythmias or to 30-min (left anterior descending) coronary artery occlusion and 2-h reperfusion for the infarct size determination (IS; tetrazolium staining). Postischemic recovery of left ventricular developed pressure (LVDP) in animals with D-H was improved by simvastatin therapy (62.7+/-18.2 % of preischemic values vs. 30.3+/-5.7 % in the untreated D-H; P<0.05), similar to the values in the simvastatin-treated C group, which were 2.5-fold higher than those in the untreated C group. No ventricular fibrillation occurred in the simvastatin-treated C and D-H animals during reperfusion. Likewise, simvastatin shortened the duration of ventricular tachycardia (10.2+/-8.1 s and 57.8+/-29.3 s in C and D-H vs. 143.6+/-28.6 s and 159.3+/-44.3 s in untreated C and D-H, respectively, both P<0.05). The decreased arrhythmogenesis in the simvastatin-treated groups correlated with the limitation of IS (in % of risk area) by 66 % and 62 % in C and D-H groups, respectively. However, simvastatin treatment decreased plasma cholesterol levels neither in the D-H animals nor in C. The results indicate that other effects of statins (independent of cholesterol lowering) are involved in the

  7. Chlorine inhalation-induced myocardial depression and failure

    PubMed Central

    Zaky, Ahmed; Bradley, Wayne E; Lazrak, Ahmed; Zafar, Iram; Doran, Stephen; Ahmad, Aftab; White, Carl W; Dell'Italia, Louis J; Matalon, Sadis; Ahmad, Shama

    2015-01-01

    Victims of chlorine (Cl2) inhalation that die demonstrate significant cardiac pathology. However, a gap exists in the understanding of Cl2-induced cardiac dysfunction. This study was performed to characterize cardiac dysfunction occurring after Cl2 exposure in rats at concentrations mimicking accidental human exposures (in the range of 500 or 600 ppm for 30 min). Inhalation of 500 ppm Cl2 for 30 min resulted in increased lactate in the coronary sinus of the rats suggesting an increase in anaerobic metabolism by the heart. There was also an attenuation of myocardial contractile force in an ex vivo (Langendorff technique) retrograde perfused heart preparation. After 20 h of return to room air, Cl2 exposure at 500 ppm was associated with a reduction in systolic and diastolic blood pressure as well echocardiographic/Doppler evidence of significant left ventricular systolic and diastolic dysfunction. Cl2 exposure at 600 ppm (30 min) was associated with biventricular failure (observed at 2 h after exposure) and death. Cardiac mechanical dysfunction persisted despite increasing the inspired oxygen fraction concentration in Cl2-exposed rats (500 ppm) to ameliorate hypoxia that occurs after Cl2 inhalation. Similarly ex vivo cardiac mechanical dysfunction was reproduced by sole exposure to chloramine (a potential circulating Cl2 reactant product). These results suggest an independent and distinctive role of Cl2 (and its reactants) in inducing cardiac toxicity and potentially contributing to mortality. PMID:26109193

  8. Cardioplegia and myocardial preservation during cardiopulmonary bypass.

    PubMed

    Engelman, R M; Levitsky, S; O'Donoghue, M J; Auvil, J

    1978-09-01

    A standard experimental protocol was developed to explore the role of hypothermia and potassium cardioplegia in myocardial preservation during 120 minutes of ischemic arrest followed by 30 minutes of reperfusion. Seven different experimental groups of six animals each were evaluated using an in-vivo pig heart preparation. Hypothermic arrest without cardioplegia and cardioplegic arrest at normothermia were each compared to hypothermic cardioplegia. In addition, the use of an asanguineous hypothermic coronary perfusate without cardioplegia was compared to both multidose cardioplegia and single-dose cardioplegia followed by the same asanguineous perfusate. The parameters measured included: myocardial contractility and compliance, myocardial blood flow, endocardial/epicardial blood flow ratio, and electron microscopic studies. Myocardial preservation was inadequate with hypothermic arrest alone (without cardioplegia; and with cardioplegia at normothermia. In both experimental groups, myocardial contractility and compliance were so depressed that the) could not be accurately measured following ischemia and reperfusion while coronary blood flow remained significantly elevated. Preservation was improved but still inadequate following myocardial washout with a normokalemic or hypokalemic perfusate and following single dose cardioplegia plus myocardial washout. In the latter four groups, contractility ranged from 42 to 78% of control, and there was a decrease in compliance of 16 to 78%. Adequate preservation was found only after hypothermia and multidose potassium (35 mEq/L) cardioplegia. In this group, contractility was 129 +/- 13% of control and compliance increased by 21 +/- 24% compared to that of the control. PMID:14740689

  9. Intravenous Followed by X-ray Fused with MRI-Guided Transendocardial Mesenchymal Stem Cell Injection Improves Contractility Reserve in a Swine Model of Myocardial Infarction

    PubMed Central

    Schmuck, Eric G.; Koch, Jill M.; Hacker, Timothy A.; Hatt, Charles R.; Tomkowiak, Michael T.; Vigen, Karl K.; Hendren, Nicholas; Leitzke, Cathlyn; Zhao, Ying-qi; Li, Zhanhai; Centanni, John M.; Hei, Derek J.; Schwahn, Denise; Kim, Jaehyup; Hematti, Peiman

    2016-01-01

    The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed. IV MSC plus TE MSC treated group was superior to other groups for contractility reserve (p=0.02) and freedom from VT (p=0.03) but had more lymphocytic foci localized to the peri-infarct region (p= 0.002). No differences were observed in post-MI remodeling parameters. IV followed by XFM targeted TE MSC therapy improves contractility reserve and suppresses VT but does not affect post-MI remodeling and may cause an immune response. PMID:26374144

  10. Intravenous Followed by X-ray Fused with MRI-Guided Transendocardial Mesenchymal Stem Cell Injection Improves Contractility Reserve in a Swine Model of Myocardial Infarction.

    PubMed

    Schmuck, Eric G; Koch, Jill M; Hacker, Timothy A; Hatt, Charles R; Tomkowiak, Michael T; Vigen, Karl K; Hendren, Nicholas; Leitzke, Cathlyn; Zhao, Ying-Qi; Li, Zhanhai; Centanni, John M; Hei, Derek J; Schwahn, Denise; Kim, Jaehyup; Hematti, Peiman; Raval, Amish N

    2015-10-01

    The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed. IV MSC plus TE MSC treated group was superior to other groups for contractility reserve (p = 0.02) and freedom from VT (p = 0.03) but had more lymphocytic foci localized to the peri-infarct region (p = 0.002). No differences were observed in post-MI remodeling parameters. IV followed by XFM targeted TE MSC therapy improves contractility reserve and suppresses VT but does not affect post-MI remodeling and may cause an immune response. PMID:26374144

  11. Quantification and MRI Validation of Regional Contractile Dysfunction in Mice Post Myocardial Infarction Using High Resolution Ultrasound

    PubMed Central

    Li, Yinbo; Garson, Christopher D.; Xu, Yaqin; Beyers, Ronald J.; Epstein, Frederick H.; French, Brent A.; Hossack, John A.

    2007-01-01

    A versatile, computationally-efficient two-dimensional (2D) speckle-tracking method based on high resolution ultrasound imaging is proposed to quantify regional myocardial dysfunction in mice. Ultrasound scans were performed on the hearts of normal and post myocardial infarction (MI) mice with a Vevo770 scanner (VisualSonics, Toronto, Canada) operating at 30 MHz frequency. Regional myocardial motion was tracked using a 2D Minimum Sum of Absolute Differences (MSAD) block-matching algorithm. Motion analyses calculated from ultrasound images were compared to "gold-standard" analyses performed using small animal Magnetic Resonance Imaging (MRI). The radial and circumferential components of strain were compared between ultrasound and MRI short axis views and promising correlations were obtained (R = 0.90 and R = 0.85 for radial and circumferential strain, respectively). Therefore, ultrasound imaging, followed by 2D image tracking, provides an effective, low cost, mobile method to quantify murine cardiac function accurately and reliably. PMID:17434660

  12. Contractile Function During Angiotensin-II Activation

    PubMed Central

    Zhang, Min; Prosser, Benjamin L.; Bamboye, Moradeke A.; Gondim, Antonio N.S.; Santos, Celio X.; Martin, Daniel; Ghigo, Alessandra; Perino, Alessia; Brewer, Alison C.; Ward, Christopher W.; Hirsch, Emilio; Lederer, W. Jonathan; Shah, Ajay M.

    2015-01-01

    Background Renin-angiotensin system activation is a feature of many cardiovascular conditions. Activity of myocardial reduced nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2 or Nox2) is enhanced by angiotensin II (Ang II) and contributes to increased hypertrophy, fibrosis, and adverse remodeling. Recent studies found that Nox2-mediated reactive oxygen species production modulates physiological cardiomyocyte function. Objectives This study sought to investigate the effects of cardiomyocyte Nox2 on contractile function during increased Ang II activation. Methods We generated a cardiomyocyte-targeted Nox2-transgenic mouse model and studied the effects of in vivo and ex vivo Ang II stimulation, as well as chronic aortic banding. Results Chronic subpressor Ang II infusion induced greater cardiac hypertrophy in transgenic than wild-type mice but unexpectedly enhanced contractile function. Acute Ang II treatment also enhanced contractile function in transgenic hearts in vivo and transgenic cardiomyocytes ex vivo. Ang II–stimulated Nox2 activity increased sarcoplasmic reticulum (SR) Ca2+ uptake in transgenic mice, increased the Ca2+ transient and contractile amplitude, and accelerated cardiomyocyte contraction and relaxation. Elevated Nox2 activity increased phospholamban phosphorylation in both hearts and cardiomyocytes, related to inhibition of protein phosphatase 1 activity. In a model of aortic banding–induced chronic pressure overload, heart function was similarly depressed in transgenic and wild-type mice. Conclusions We identified a novel mechanism in which Nox2 modulates cardiomyocyte SR Ca2+ uptake and contractile function through redox-regulated changes in phospholamban phosphorylation. This mechanism can drive increased contractility in the short term in disease states characterized by enhanced renin-angiotensin system activation. PMID:26184620

  13. Aprotinin Exerts Differential and Dose Dependent Effects on Myocardial Contractility, Oxidative Stress and Cytokine Release Following Ischemia-Reperfusion

    PubMed Central

    McEvoy, Matthew D.; Taylor, Anna-Greta; Zavadzkas, Juozas A.; Mains, Ira M.; Ford, Rachael A.; Stroud, Robert E.; Jeffords, Laura B.; Beck, Christy U.; Reeves, Scott T.; Spinale, Francis G.

    2009-01-01

    Background Cardiac surgery can result in LV ischemia and reperfusion (I/R), the release of cytokines such as tumor necrosis factor, and oxidative-stress with release of myeloperoxidase. While aprotinin has been used in cardiac surgery, the likely multiple effects of this serine protease inhibitor limits clinical utility. This study tested the hypothesis that different APRO doses cause divergent effects on LV contractility, cytokine release and oxidative stress in the context of I/R. Methods/Results LV I/R (30 min I/60 min R) was induced in mice and LV contractility (maximal end-systolic elastance; Emax) determined. Mice were randomized to 2×104 KIU/kg aprotinin (n=11), 4 × 104 KIU/kg aprotinin (n=10), and Vehicle (saline, n=10). Based upon a fluorogenic assay, aprotinin doses of 2 and 4×104 KIU/kg resulted in plasma concentrations similar to those of the half and full Hammersmith doses, respectively. Following I/R, Emax fell by over 40% from baseline (p<0.05), and this effect was attenuated with 2 ×104 KIU/kg but not 4 ×104 KIU/kg aprotinin. Tumor necrosis factor increased by over 60% from control (p<0.05) with I/R, bit was reduced with 4 ×104 KIU/kg aprotinin. Myeloperoxidase increased with I/R, and was reduced to the greatest degree by 2 ×104 KIU/kg aprotinin. Conclusions Aprotinin influences LV contractility, cytokine release and oxidative stress which are dose dependent. These results provide mechanistic evidence that multiple pathways are differentially affected by aprotinin in a context relevant to cardiac surgery. PMID:18640335

  14. Contribution of diet and major depression to incidence of acute myocardial infarction (AMI)

    PubMed Central

    2010-01-01

    Background Despite significant improvements in the treatment of coronary heart disease (CHD), it is still a major cause of mortality and morbidity among the Iranian population. Epidemiological studies have documented that risk factors including smoking and the biochemical profile are responsible for the development of acute myocardial infarction (AMI). Psychological factors have been discussed as potential risk factors for coronary heart disease. Among emotional factors, depression correlates with coronary heart disease, particularly myocardial infarction. Methods This case-control study was conducted on 120 cases (69 males and 51 females) of acute myocardial infarction (AMI) and 120 controls, with a mean age of 62.48 ± 15.39 years. Cases and controls were matched by age, residence and sex. Results The results revealed that severe depression was independently associated with the risk of AMI (P = 0.025, OR = 2.6, 95% CI 1.1-5.8). The analysis of variables indicated that risk factors for developing depression were unmarried, low levels of polyunsaturated fatty acids (PUFAs), total dietary fiber (TDF) and carbohydrates. The levels of these dietary factors were lowest in severely depressed patients compared to those categorised as moderate or mild cases. Furthermore, severely depressed subjects were associated with higher levels of total cholesterol, high systolic blood pressure (SBP) and WHR. Age, income, a family history of coronary heart disease, education level, sex, employment and smoking were not associated with severe depression. Conclusion The present study demonstrated that severe depression symptoms are independent risk factors for AMI. Furthermore, severe depression was associated with an unhealthy diet and AMI risk factors. PMID:21087475

  15. Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model.

    PubMed

    Gautam, Milan; Fujita, Daiki; Kimura, Kazuhiro; Ichikawa, Hinako; Izawa, Atsushi; Hirose, Masamichi; Kashihara, Toshihide; Yamada, Mitsuhiko; Takahashi, Masafumi; Ikeda, Uichi; Shiba, Yuji

    2015-04-01

    The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (10×10(6)) resuspended in 100μL saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.7±10.6 vs. 22.4±3.4, p<0.05, n=5/group). Thereafter, all ADSC recipients were transplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.1±0.9 vs. 14.1±1.2, p<0.05, n≥12/group). Four weeks post-transplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, p<0.05, n≥12/group). To understand the electrical activity following transplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI. PMID

  16. Effects of a New Glutamic Acid Derivative on Myocardial Contractility of Stressed Animals under Conditions of Nitric Oxide Synthesis Blockade.

    PubMed

    Tyurenkov, I N; Perfilova, V N; Sadikova, N V; Berestovitskaya, V M; Vasil'eva, O S

    2015-07-01

    Glufimet (glutamic acid derivative) in a dose of 28.7 mg/kg limited the reduction of the cardiac functional reserve in animals subjected to 24-h stress under conditions of nonselective NO synthase blockade with L-NAME (10 mg/kg). Adrenoreactivity and increased afterload tests showed that the increment of myocardial contraction/relaxation rates, left-ventricular pressure, and HR were significantly higher in glufimet-treated stressed animals with NO synthesis blockade than in animals which received no glufimet. The efficiency of glufimet was higher than that of phenibut (the reference drug). PMID:26205724

  17. Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stimulation.

    PubMed

    Otsuki, Yuki; Nakamura, Yoshinobu; Harada, Shingo; Yamamoto, Yasutaka; Ogino, Kazuhide; Morikawa, Kumi; Ninomiya, Haruaki; Miyagawa, Shigeru; Sawa, Yoshiki; Hisatome, Ichiro; Nishimura, Motonobu

    2015-01-01

    Adipose stem cells (ASCs) are a source of regenerative cells available for autologous transplantation to hearts. We compared protective actions of ASC sheets on rat myocardial infarction (MI) in comparison with those of skeletal myoblast cell sheets. Their effects on infarcted hearts were evaluated by biological, histochemical as well as physiological analyses. ASC sheets secreted higher concentrations of angiogenic factors (HGF, VEGF, and bFGF; P < 0.05) under normoxic and hypoxic conditions than those of myoblast cell sheets, associated with reduction of cell apoptosis (P < 0.05). Like myoblast cell sheets, ASC sheets improved cardiac function (P < 0.05) and decreased the plasma level of ANP (P < 0.05) in MI hearts. ASC sheets restored cardiac remodeling characterized by fibrosis, cardiac hypertrophy and impaired angiogenesis (P < 0.05), which was associated with increases in angiogenic factors (P < 0.05). In isolated perfused rat hearts, ASC sheets improved both systolic and diastolic functions, which was comparable to cardiac functions of myoblast cell sheets, while both cell sheets failed to restore cardiac contractile response to either isoproterenol, pimobendan or dibutyryl cAMP. These results indicated that ASC sheets improved cardiac function and remodeling of MI hearts mediated by their paracrine action and this improvement was comparable to those by myoblast cell sheets. PMID:25749147

  18. Alcohol Dehydrogenase Protects against Endoplasmic Reticulum Stress-Induced Myocardial Contractile Dysfunction via Attenuation of Oxidative Stress and Autophagy: Role of PTEN-Akt-mTOR Signaling

    PubMed Central

    Pang, Jiaojiao; Fuller, Nathan D.; Hu, Nan; Barton, Linzi A.; Henion, Jeremy M.; Guo, Rui; Chen, Yuguo; Ren, Jun

    2016-01-01

    Background The endoplasmic reticulum (ER) plays an essential role in ensuring proper folding of the newly synthesized proteins. Aberrant ER homeostasis triggers ER stress and development of cardiovascular diseases. ADH is involved in catalyzing ethanol to acetaldehyde although its role in cardiovascular diseases other than ethanol metabolism still remains elusive. This study was designed to examine the impact of ADH on ER stress-induced cardiac anomalies and underlying mechanisms involved using cardiac-specific overexpression of alcohol dehydrogenase (ADH). Methods ADH and wild-type FVB mice were subjected to the ER stress inducer tunicamycin (1 mg/kg, i.p., for 48 hrs). Myocardial mechanical and intracellular Ca2+ properties, ER stress, autophagy and associated cell signaling molecules were evaluated. Results ER stress compromised cardiac contractile function (evidenced as reduced fractional shortening, peak shortening, maximal velocity of shortening/relengthening, prolonged relengthening duration and impaired intracellular Ca2+ homeostasis), oxidative stress and upregulated autophagy (increased LC3B, Atg5, Atg7 and p62), along with dephosphorylation of PTEN, Akt and mTOR, all of which were attenuated by ADH. In vitro study revealed that ER stress-induced cardiomyocyte anomaly was abrogated by ADH overexpression or autophagy inhibition using 3-MA. Interestingly, the beneficial effect of ADH was obliterated by autophagy induction, inhibition of Akt and mTOR. ER stress also promoted phosphorylation of the stress signaling ERK and JNK, the effect of which was unaffected by ADH transgene. Conclusions Taken together, these findings suggested that ADH protects against ER stress-induced cardiac anomalies possibly via attenuation of oxidative stress and PTEN/Akt/mTOR pathway-regulated autophagy. PMID:26807981

  19. Effect of Eye Movement Desensitization and Reprocessing (EMDR) on Depression in Patients With Myocardial Infarction (MI)

    PubMed Central

    Behnammoghadam, Mohammad; Alamdari, Ali Karam; Behnammoghadam, Aziz; Darban, Fatemeh

    2015-01-01

    Background: Coronary heart disease is the most important cause of death and inability in all communities. Depressive symptoms are frequent among post-myocardial infarction (MI) patients and may cause negative effects on cardiac prognosis. This study was conducted to identify efficacy of EMDR on depression of patients with MI. Methods: This study is a clinical trial. Sixty patients with MI were selected by simple sampling, and were separated randomly into experimental and control groups. To collect data, demographic questionnaire and Beck Depression Questionnaire were used. In experimental group, EMDR therapy were performed in three sessions alternate days for 45–90 minutes, during four months after their MI. Depression level of patients was measured before, and a week after EMDR therapy. Data were analyzed using paired –t- test, t–test, and Chi-square. Results: The mean depression level in experimental group 27.26± 6.41 before intervention, and it was 11.76 ± 3.71 after intervention. Hence, it showed a statistically significant difference (P<0.001). The mean depression level in control group was 24.53 ± 5.81 before intervention, and it was 31.66± 6.09 after intervention, so it showed statistically significant difference (P<0.001). The comparison of mean depression level at post treatment, in both groups showed statistically significant difference (P<0.001). Conclusion: EMDR is an effective, useful, efficient, and non-invasive method for treatment and reducing depression in patients with MI. PMID:26153191

  20. A neuroendocrine mechanism of co-morbidity of depression-like behavior and myocardial injury in rats.

    PubMed

    Xinxing, Wang; Wei, Liu; Lei, Wu; Rui, Zhan; Baoying, Jin; Lingjia, Qian

    2014-01-01

    Depression is generally a recurrent psychiatric disorder. Evidence shows that depression and cardiovascular diseases are common comorbid conditions, but the specific pathological mechanisms remain unclear. The purpose of this study is to determine the effects of depression induced by chronic unpredictable mild stress (CUMS) on myocardial injury and to further elucidate the biological mechanism of depression. Rats were used as a model. The CUMS procedure lasted for a total of 8 weeks. After 4 weeks of CUMS, treated rats exhibited a reduced sucrose preference and changes in scores on an open field test, body weight and content of 5-HT in the brain as compared with the values of these variables in controls. These changes indicated depression-like changes in CUMS rats and demonstrated the feasibility of the depression model. In addition, pathological changes in the myocardium and increased cardiomyocyte apoptosis demonstrated that myocardial injury had occurred after 6 weeks of CUMS and had increased significantly by the end of 8 weeks of CUMS. Plasma serotonin (5-HT), norepinephrine (NE) and epinephrine (E), all depression-related neuroendocrine factors, were measured by HPLC-ECD techniques, and the content of plasma corticosterone (GC) was evaluated by an I(125)-cortisol radioactivity immunoassay in control and CUMS rats. The results indicated that 5-HT had decreased, whereas NE, E and GC had increased in CUMS rats, and these factors might be associated with depression-induced myocardial injury. The effects of 5-HT, NE and GC on the survival rate of cultured cardiomyocytes were determined using an orthogonal design. The results showed that 5-HT was a more important factor affecting cell survival than GC or NE. The results suggested that normal blood levels of 5-HT had a cytoprotective effect. The neuroendocrine disorders characterized by decreased 5-HT combined with increased GC and NE mediated the occurrence of depression-induced myocardial injury. PMID:24551098

  1. A Neuroendocrine Mechanism of Co-Morbidity of Depression-Like Behavior and Myocardial Injury in Rats

    PubMed Central

    Lei, Wu; Rui, Zhan; Baoying, Jin; Lingjia, Qian

    2014-01-01

    Depression is generally a recurrent psychiatric disorder. Evidence shows that depression and cardiovascular diseases are common comorbid conditions, but the specific pathological mechanisms remain unclear. The purpose of this study is to determine the effects of depression induced by chronic unpredictable mild stress (CUMS) on myocardial injury and to further elucidate the biological mechanism of depression. Rats were used as a model. The CUMS procedure lasted for a total of 8 weeks. After 4 weeks of CUMS, treated rats exhibited a reduced sucrose preference and changes in scores on an open field test, body weight and content of 5-HT in the brain as compared with the values of these variables in controls. These changes indicated depression-like changes in CUMS rats and demonstrated the feasibility of the depression model. In addition, pathological changes in the myocardium and increased cardiomyocyte apoptosis demonstrated that myocardial injury had occurred after 6 weeks of CUMS and had increased significantly by the end of 8 weeks of CUMS. Plasma serotonin (5-HT), norepinephrine (NE) and epinephrine (E), all depression-related neuroendocrine factors, were measured by HPLC-ECD techniques, and the content of plasma corticosterone (GC) was evaluated by an I125–cortisol radioactivity immunoassay in control and CUMS rats. The results indicated that 5-HT had decreased, whereas NE, E and GC had increased in CUMS rats, and these factors might be associated with depression-induced myocardial injury. The effects of 5-HT, NE and GC on the survival rate of cultured cardiomyocytes were determined using an orthogonal design. The results showed that 5-HT was a more important factor affecting cell survival than GC or NE. The results suggested that normal blood levels of 5-HT had a cytoprotective effect. The neuroendocrine disorders characterized by decreased 5-HT combined with increased GC and NE mediated the occurrence of depression-induced myocardial injury. PMID:24551098

  2. Cardiac contractile dysfunction during mild coronary flow reductions is due to an altered calcium-pressure relationship in rat hearts.

    PubMed Central

    Figueredo, V M; Brandes, R; Weiner, M W; Massie, B M; Camacho, S A

    1992-01-01

    Coronary artery stenosis or occlusion results in reduced coronary flow and myocardial contractile depression. At severe flow reductions, increased inorganic phosphate (Pi) and intracellular acidosis clearly play a role in contractile depression. However, during milder flow reductions the mechanism(s) underlying contractile depression are less clear. Previous perfused heart studies demonstrated no change of Pi or pH during mild flow reductions, suggesting that changes of intravascular pressure (garden hose effect) may be the mediator of this contractile depression. Others have reported conflicting results regarding another possible mediator of contractility, the cytosolic free calcium (Cai). To examine the respective roles of Cai, Pi, pH, and vascular pressure in regulating contractility during mild flow reductions, Indo-1 calcium fluorescence and 31P magnetic resonance spectroscopy measurements were performed on Langendorff-perfused rat hearts. Cai and diastolic calcium levels did not change during flow reductions to 50% of control. Pi demonstrated a close relationship with developed pressure and significantly increased from 2.5 +/- 0.3 to 4.2 +/- 0.4 mumol/g dry weight during a 25% flow reduction. pH was unchanged until a 50% flow reduction. Increasing vascular pressure to superphysiological levels resulted in further increases of developed pressure, with no change in Cai. These findings are consistent with the hypothesis that during mild coronary flow reductions, contractile depression is mediated by an altered relationship between Cai and pressure, rather than by decreased Cai. Furthermore, increased Pi and decreased intravascular pressure may be responsible for this altered calcium-pressure relationship during mild coronary flow reductions. PMID:1430205

  3. Precordial ST segment depression during acute inferior myocardial infarction: early thallium-201 scintigraphic evidence of adjacent posterolateral or inferoseptal involvement

    SciTech Connect

    Lew, A.S.; Weiss, A.T.; Shah, P.K.; Maddahi, J.; Peter, T.; Ganz, W.; Swan, H.J.; Berman, D.S.

    1985-02-01

    To investigate the myocardial perfusion correlates of precordial ST segment depression during acute inferior myocardial infarction, a rest thallium-201 scintigram and a closely timed 12 lead electrocardiogram were obtained within 6 hours of the onset of infarction in 44 patients admitted with their first acute inferior myocardial infarction. Thirty-six patients demonstrated precordial ST segment depression (group 1) and eight did not (group 2). A perfusion defect involving the inferior wall was present in all 44 patients. Additional perfusion defects of the adjacent posterolateral wall (n . 20), the ventricular septum (n . 9) or both (n . 6) were present in 35 of 36 patients from group 1 compared with only 1 of 8 patients from group 2 (p less than 0.001). There was no significant difference in the frequency of multivessel coronary artery disease or disease of the left anterior descending artery between group 1 and group 2 or between patients with and those without a thallium-201 perfusion defect involving the ventricular septum. Thus, precordial ST segment depression during an acute inferior myocardial infarction is associated with thallium-201 scintigraphic evidence of more extensive involvement of the adjacent posterolateral or inferoseptal myocardial segments, which probably reflects the extent and pattern of distribution of the artery of infarction, rather than the presence of coexistent multivessel coronary artery disease or disease of the left anterior descending artery.

  4. Molecular and cellular mechanisms of myocardial stunning.

    PubMed

    Bolli, R; Marbán, E

    1999-04-01

    The past two decades have witnessed an explosive growth of knowledge regarding postischemic myocardial dysfunction or myocardial "stunning." The purpose of this review is to summarize current information regarding the pathophysiology and pathogenesis of this phenomenon. Myocardial stunning should not be regarded as a single entity but rather as a "syndrome" that has been observed in a wide variety of experimental settings, which include the following: 1) stunning after a single, completely reversible episode of regional ischemia in vivo; 2) stunning after multiple, completely reversible episodes of regional ischemia in vivo; 3) stunning after a partly reversible episode of regional ischemia in vivo (subendocardial infarction); 4) stunning after global ischemia in vitro; 5) stunning after global ischemia in vivo; and 6) stunning after exercise-induced ischemia (high-flow ischemia). Whether these settings share a common mechanism is unknown. Although the pathogenesis of myocardial stunning has not been definitively established, the two major hypotheses are that it is caused by the generation of oxygen-derived free radicals (oxyradical hypothesis) and by a transient calcium overload (calcium hypothesis) on reperfusion. The final lesion responsible for the contractile depression appears to be a decreased responsiveness of contractile filaments to calcium. Recent evidence suggests that calcium overload may activate calpains, resulting in selective proteolysis of myofibrils; the time required for resynthesis of damaged proteins would explain in part the delayed recovery of function in stunned myocardium. The oxyradical and calcium hypotheses are not mutually exclusive and are likely to represent different facets of the same pathophysiological cascade. For example, increased free radical formation could cause cellular calcium overload, which would damage the contractile apparatus of the myocytes. Free radical generation could also directly alter contractile filaments in a

  5. Cardiac-specific overexpression of metallothionein rescues nicotine-induced cardiac contractile dysfunction and interstitial fibrosis.

    PubMed

    Hu, Nan; Guo, Rui; Han, Xuefeng; Zhu, Baocheng; Ren, Jun

    2011-04-10

    Cigarette smoking is a devastating risk factor for cardiovascular diseases and nicotine is believed the main toxin component responsible for the toxic myocardial effects of smoking. Nonetheless, neither the precise mechanism of nicotine-induced cardiac dysfunction nor effective treatment is elucidated. The aim of this study was to evaluate the impact of cardiac-specific overexpression of heavy metal scavenger metallothionein on myocardial geometry and mechanical function following nicotine exposure. Adult male friend virus B (FVB) wild-type and metallothionein mice were injected with nicotine (2 mg/kg/d) intraperitoneally for 10 days. Mechanical and intracellular Ca²+ properties were examined. Myocardial histology (cross-sectional area and fibrosis) was evaluated by hematoxylin and eosin (H&E) and Masson trichrome staining, respectively. Oxidative stress and apoptosis were measured by fluoroprobe 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H₂DCFDA) fluorescence and caspase-3 activity, respectively. Nicotine exposure failed to affect the protein abundance of metallothionein. Our data revealed reduced echocardiographic contractile capacity (fractional shortening), altered cardiomyocyte contractile and intracellular Ca²+ properties including depressed peak shortening amplitude, maximal velocity of shortening/relengthening, resting and electrically-stimulated rise in intracellular Ca²+, as well as prolonged duration of relengthening and intracellular Ca²+ clearance in hearts from nicotine-treated FVB mice, the effect of which was ameliorated by metallothionein. Biochemical and histological findings depicted overt accumulation of reactive oxygen species (ROS), apoptosis and myocardial fibrosis without any change in myocardial cross-sectional area following nicotine treatment, which was mitigated by metallothionein. Taken together, our findings suggest the antioxidant metallothionein may reconcile short-term nicotine exposure

  6. Myocardial Protection in Beating Heart Cardiac Surgery: I: Pre- or Post-Conditioning with Inhibition of the es-ENT1 Nucleoside Transporter and Adenosine Deaminase Attenuates Post-MI Reperfusion-Mediated Ventricular Fibrillation and Regional Contractile Dysfunction

    PubMed Central

    Abd-Elfattah, Anwar S. A.; Aly, Hamdy; Hanan, Scott; Wechsler, Andrew S.

    2012-01-01

    Objectives To determine the role of the es-ENT1 nucleoside transporter in post-MI reperfusion injury-mediated ventricular fibrillation (VFib) and regional dysfunction. We used erythro-9 (2-hydroxy-3-nonyl)-adenine (EHNA) and p-nitrobenzylthioinosine (NBMPR) to inhibit both adenosine deamination and transport in a canine model of off pump acute MI. Methods Anesthetized adult dogs (n= 37), instrumented to monitor systolic segmental shortening (SS %) and wall thickening (WT %) using sonomicrometry, underwent 90 minutes of LAD coronary artery occlusion and 120 minutes reperfusion. Myocardial coronary blood flow, ATP pool, infarct size and the incidents of ventricular fibrillation and cardioversions were also measured. Animals received an intravenous infusion of the vehicle (Control) or 100μM of EHNA and 25 μM NBMPR before ischemia (preconditioning, PreC group) or just before reperfusion (postconditioning, PostC group). Results In the control group, ATP depletion was associated with accumulation of more inosine than adenosine during ischemia and washed out during reperfusion. Myocardial adenosine and inosine were the major nucleosides in the PreC- and Post-C groups during ischemia and remained detectable during reperfusion, respectively. In both groups, recovery of systolic SS% and WT%, and reduction in the incidence of VFib (p<0.05 vs. Control group) coincided with retention of myocardial nucleosides. Infarct sizes in the three groups were not significantly different, independent of myocardial blood flow during ischemia. Conclusion PreC-or PostC with EHNA/NBMPR significantly reduced the incidence of ventricular fibrillation and cardioversions and attenuated regional contractile dysfunction mediated by post-MI reperfusion injury and that es-ENT1 plays a major role in these events. PMID:22329983

  7. [Interesting PYP, 201Tl, MIBG, AM and BMIPP myocardial SPECT images in a patient under successful reperfusion therapy].

    PubMed

    Tanaka, T; Aizawa, T; Katou, K; Ogasawara, K; Kirigaya, H; Okamoto, K; Hosoi, H; Oota, A

    1992-06-01

    Various types of radiopharmacons such as 201Tl, 99mTc-pyrophosphate(PYP), 123I-metaiodobenzyl-guanidine(MIBG), 111In-antimyosin Fab (AM) and 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) were applied to a patient under successful reperfusion therapy. In the patient, elevated serum enzyme activity region in the subacute phase. Ten months after the ischemic event, AM uptake was noted at the region which maintained contractility. Two years after the ischemic event, depressed BMIPP uptake and delayed washout were noted at the apical region and the basal anteroseptal region. From these findings, the following conclusions were reached. Depressed 201Tl uptake was noted in the salvaged jeopardized myocardium. The lesions noted in the MIBG images showed depressed myocardial norepenephrine activity. This suggested that depressed sympathetic nervous function caused by severe ischemia persisted long after both myocardial perfusion and myocardial contractility had been restored. From abnormal AM uptake in the contractile myocardium myocardial cell damage, which permitted AM uptake, was persistent ten months after the ischemic event. Depressed BMIPP uptake and delayed washout suggested that abnormal fatty acid metabolism caused by severe ischemia was persistent. Severe ischemia caused various types of pathological states in the myocardium and radioisotope image was useful for studying these states. PMID:1535723

  8. The GSTM2 C-Terminal Domain Depresses Contractility and Ca2+ Transients in Neonatal Rat Ventricular Cardiomyocytes.

    PubMed

    Hewawasam, Ruwani P; Liu, Dan; Casarotto, Marco G; Board, Philip G; Dulhunty, Angela F

    2016-01-01

    The cardiac ryanodine receptor (RyR2) is an intracellular ion channel that regulates Ca2+ release from the sarcoplasmic reticulum (SR) during excitation-contraction coupling in the heart. The glutathione transferases (GSTs) are a family of phase II detoxification enzymes with additional functions including the selective inhibition of RyR2, with therapeutic implications. The C-terminal half of GSTM2 (GSTM2C) is essential for RyR2 inhibition, and mutations F157A and Y160A within GSTM2C prevent the inhibitory action. Our objective in this investigation was to determine whether GSTM2C can enter cultured rat neonatal ventricular cardiomyocytes and influence contractility. We show that oregon green-tagged GSTM2C (at 1 μM) is internalized into the myocytes and it reduces spontaneous contraction frequency and myocyte shortening. Field stimulation of myocytes evoked contraction in the same percentage of myocytes treated either with media alone or media plus 15 μM GSTM2C. Myocyte shortening during contraction was significantly reduced by exposure to 15 μM GSTM2C, but not 5 and 10 μM GSTM2C and was unaffected by exposure to 15 μM of the mutants Y160A or F157A. The amplitude of the Ca2+ transient in the 15 μM GSTM2C - treated myocytes was significantly decreased, the rise time was significantly longer and the decay time was significantly shorter than in control myocytes. The Ca2+ transient was not altered by exposure to Y160A or F157A. The results are consistent with GSTM2C entering the myocytes and inhibiting RyR2, in a manner that indicates a possible therapeutic potential for treatment of arrhythmia in the neonatal heart. PMID:27612301

  9. Impact of Depression on Risk of Myocardial Infarction, Stroke and Cardiovascular Death in Patients with Psoriasis: A Danish Nationwide Study.

    PubMed

    Egeberg, Alexander; Khalid, Usman; Gislason, Gunnar Hilmar; Mallbris, Lotus; Skov, Lone; Hansen, Peter Riis

    2016-02-01

    Psoriasis is associated with depression, myocardial infarction (MI) and stroke. Patients with depression have increased cardiovascular risk. However, the link between psoriasis, depression and cardiovascular disease is unclear. This link was investigated in a nationwide Danish cohort of patients with psoriasis (n = 29,406). Incidence rates were calculated, and incidence rate ratios (IRRs) adjusted for age, gender, socio-economic status, medication and comorbidity were estimated by Poisson regression models. Risk of MI (IRR 1.57, 95% confidence interval (95% CI) 1.07-2.29), stroke (IRR 1.95, 95% CI 1.43-2.66), and cardiovascular death (IRR 2.24, 95% CI 1.53-3.26) were increased significantly during acute depression, and risk of stroke (IRR 1.51, 95% CI 1.19-1.90) was increased significantly in chronic depression. During remission from depression, only the risk of stroke was increased. In conclusion, in patients with psoriasis, depression is associated with increased risk of MI, stroke and cardiovascular death, especially during acute depression. PMID:26280176

  10. Pancreatic Hypoperfusion and the Production of a Myocardial Depressant Factor in Hemorrhagic Shock

    PubMed Central

    Lefer, Allan M.; Spath, James A.

    1974-01-01

    Hemorrhagic shock was produced in dogs by bleeding to a systemic blood pressure of 45 mm Hg for 3 hours, followed by reinfusion of the shed blood. A rapid decrease in pancreatic blood flow occurred and pancreatic perfusion remained at 15-25% of control over the entire 3-hour oligemic period. As a consequence of this marked degree of pancreatic hypoperfusion, autolytic changes occurred in pancreatic acinar cell ultrastructure, particularly in the enlarging of lysosomes which developed many vacuoles. Plasma proteolytic indices (e.g., cathepsin D activity and amino nitrogen concentration) markedly increased during shock as well as the activity of a myocardial depressant factor (MDF). MDF was also produced in incubated pancreatic homogenates obtained from nonshocked dogs and in non-incubated homogenates from shocked dogs. MDF activity in the homogenates was closely correlated with amino nitrogen concentration. These data suggest that pancreatic hypoperfusion plays a key role in MDF formation and ultimately in the pathogenesis of circulatory shock. Moreover, MDF activity was found not to be associated either with pentobarbital concentration or the salt content of active fractions of plasma and pancreatic tissue. Ashing of active fractions was very effective in destroying MDF activity. These data are consistent with the earlier findings that indicate MDF to be a peptide having a molecular weight of 500-1,000. ImagesFig. 3. PMID:4835505

  11. Mitochondrial nitric oxide synthase participates in septic shock myocardial depression by nitric oxide overproduction and mitochondrial permeability transition pore opening.

    PubMed

    Xu, Ce; Yi, Chenju; Wang, Huiping; Bruce, Iain C; Xia, Qiang

    2012-01-01

    The aim of this study was to determine whether mitochondrial nitric oxide (NO) synthase (NOS) is involved in septic shock myocardial depression. The cecal ligation and puncture (CLP) method was used to induce septic shock. There was a significant depression of hemodynamic parameters recorded in the septic shock stage. After using nonselective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME), inducible NOS inhibitor aminoguanidine (AMG), and neuronal NOS inhibitor 7-nitroindazole (7-NI), depression of the parameters was partly attenuated. Nitric oxide production in isolated cardiac mitochondria increased obviously in the CLP-septic shock stage, L-NAME and 7-NI both decreased NO production significantly. Nitrite/nitrate (NOx) production in the septic shock stage was much greater than those in the corresponding sham groups, and NOx production in the cytosol by inducible NOS was greater. Treatment with AMG suppressed NOx production in the cytosol by iNOS, whereas treatment with 7-NI decreased NOx production in the mitochondria. Mitochondrial NOS expression increased significantly in the septic shock stage, and its overexpression was attenuated using 7-NI. There was no significant decrease in the mitochondrial permeability transition pore measurement in the CLP-septic shock group, whereas a significant decrease was observed in those treated with L-NAME or 7-NI. These results indicate that overexpression of mitochondrial NOS is involved in myocardial depression. PMID:21993446

  12. Changes in the profile of NO synthases affect coronary blood flow autoregulation and myocardial contractile activity during restraint stress in rats.

    PubMed

    Solodkov, A P; Lazuko, S S; Knyazev, E N; Nechaev, I N; Krainova, N A

    2014-12-01

    The efficiency of autoregulation of the coronary blood flow and contractile activity of the myocardium in the presence of inhibitors of constitutive and inducible NO synthases was studied in rats exposed to 6-h restraint stress. Intracoronary administration of S-methylisothiourea (10 μmol/liter), but not L-NAME (60 μmol/liter) fully prevented post-stress increase in the volume coronary blood flow rate, intensity of heart perfusion, and reduction of ventricular developed pressure at all levels of perfusion pressure. Real-time PCR showed 6-fold increased expression of inducible NO-synthase mRNA in the heart tissue against the background of unchanged expression of neuronal and endothelial NO synthases and 2-3-fold elevated content of transcripts of stress-inducible genes Hspa1a and Hspbp1. It was shown that the hypotension of coronary vessels and reduced contractile function of the myocardium are related to NO production by inducible NO synthase in endotheliocytes of coronary vessels and cardiomyocytes. PMID:25430647

  13. Overexpression of MMP-9 and Its Inhibitors in Blood Mononuclear Cells after Myocardial Infarction - Is It Associated with Depressive Symptomatology?

    PubMed Central

    Jönsson, Simon; Lundberg, Anna K.; Jonasson, Lena

    2014-01-01

    Background Matrix metalloproteinase (MMP)-9 may play a central role in the development and progression of atherosclerosis. Emerging evidence also indicates an association between MMP-9 and depressive symptomatology. Here, we investigated whether expression of MMP-9 and its inhibitors in blood mononuclear cells and plasma were related to depressive symptoms in patients with a recent myocardial infarction (MI). Methods and Results Blood sampling was performed between 6 and 18 months after MI in 57 patients. Forty-one clinically healthy subjects were included as controls. Gene expression of MMP-9 and its main tissue inhibitors TIMP-1 and -2 were analyzed in freshly isolated or cultured blood mononuclear cells. Corresponding protein levels were assessed in cell supernatants and plasma. In post-MI patients, mRNA levels of MMP-9 and TIMP-1 and -2 were significantly higher than in controls while protein levels in cell supernatants and plasma did not differ between groups. The Center for Epidemiological Studies - Depression (CES-D) scale was used to assess depressive symptomatology. Repeated assessments during the first 18 months after MI showed significantly higher CES-D scores in patients compared with controls. However, there were no relationships between depressive mood and any of the measurements of MMP-9 or TIMPs. Conclusion Our findings indicate that overexpression of MMP-9 and TIMPs in blood mononuclear cells and elevated depressive symptoms represent two unrelated phenomena after MI. PMID:25153995

  14. [Ventricular contractility: Physiology and clinical projection].

    PubMed

    Domenech, Raúl J; Parra, Víctor M

    2016-06-01

    The contractile state of the heart is the result of myocardial contractility, the intrinsic mechanism that regulates the force and the shortening of the ventricle and determines the ventricular ejection volume. However, the ejection volume is also modulated by ventricular preload (diastolic ventricular volume) and afterload (resistance to ejection). Accordingly, a decrease in contractility may be masked by changes in preload or afterload, maintaining a normal ejection volume and delaying the diagnosis of myocardial damage. Thus, it is necessary to develop a non-invasive method to measure contractility in the clinical practice. We review in this article the basic principles of cardiac contraction, the concept of contractility and its measurement with the ventricular pressure-volume loop, an experimental method that also measures most of the hemodynamic variables of the cardiac cycle including preload, afterload, ventricular work, ventricular lusitropy and arterial elastance. This method has been recently validated in cardiac patients and allows to evaluate the evolution of contractility in heart failure in a non invasive way. Although some modifications are still necessary, it will probably have an extensive use in practical cardiology in the near future. PMID:27598497

  15. Cardiac Overexpression of Metallothionein Rescues Cold Exposure-Induced Myocardial Contractile Dysfunction through Attenuation of Cardiac Fibrosis Despite Cardiomyocyte Mechanical Anomalies

    PubMed Central

    Zhang, Yingmei; Hu, Nan; Hua, Yinan; Richmond, Kacy L.; Dong, Feng; Ren, Jun

    2012-01-01

    Cold exposure is associated with an increased prevalence for cardiovascular disease although the mechanism is unknown. Metallothionein, a heavy metal scavenging antioxidant, protects against cardiac anomalies. This study was designed to examine the impact of metallothionein on cold exposure-induced myocardial dysfunction, intracellular Ca2+ derangement, fibrosis, ER stress and apoptosis. Echocardiographic, cardiomyocyte function and Masson trichrome staining were evaluated in friendly virus B (FVB) and cardiac-specific metallothionein transgenic mice following cold exposure (3 mo, 4°C). Cold exposure increased plasma levels of norepinephrine, endothelin-1 and TGF-β, reduced plasma NO levels and cardiac antioxidant capacity, enlarged ventricular end systolic diameter, compromised fractional shortening, promoted ROS production and apoptosis, and suppressed ER stress marker Bip, calregulin and phospho-eIF2α accompanied with cardiac fibrosis and elevated levels of matrix metalloproteinases and Smad-2/3 in FVB mice. Cold exposure-induced echocardiographic, histological, ER stress, ROS, apoptotic and fibrotic signaling changes (but not plasma markers) were greatly improved by metallothionein. In vitro metallothionein induction by zinc chloride ablated H2O2- but not TGF-β-induced cell proliferation in fibroblasts. In summary, our data suggested that metallothionein protects against cold exposure-induced cardiac anomalies possibly through attenuation of myocardial fibrosis. PMID:22565031

  16. Depressive Symptom Dimensions and Cardiovascular Prognosis among Women with Suspected Myocardial Ischemia: A Report from the NHLBI-Sponsored WISE Study

    PubMed Central

    Linke, Sarah E.; Rutledge, Thomas; Johnson, B. Delia; Vaccarino, Viola; Bittner, Vera; Cornell, Carol E.; Eteiba, Wafia; Sheps, David S.; Krantz, David S.; Parashar, Susmita; Merz, C. Noel Bairey

    2009-01-01

    Context: Symptoms of depression and cardiovascular disease overlap substantially. Differentiating between dimensions of depressive symptoms may improve our understanding of the relationship between depression and physical health. Objective: To compare symptom dimensions of depression as predictors of cardiovascular-related death and events among women with suspected myocardial ischemia. Design: Cohort study of women with suspected myocardial ischemia who were evaluated at baseline for history of cardiovascular-related problems, depressive symptoms using the Beck Depression Inventory (BDI), and coronary artery disease severity via coronary angiogram. Principal components analyses (PCA) of the BDI items were conducted to examine differential cardiovascular prognosis according to symptom dimensions of depression. Setting: The Women's Ischemia Syndrome Evaluation (WISE), a National Heart, Lung, and Blood Institute (NHLBI)–sponsored multi-center study assessing cardiovascular function using state-of-the-art techniques in women referred for coronary angiography to evaluate chest pain or suspected myocardial ischemia. Participants: 550 women (mean age = 58.4 [11.2] years) enrolled in WISE and followed for a median of 5.8 years. Main Outcome Measures: Cardiovascular-related mortality and events (stroke, myocardial infarction, and congestive heart failure). Results: Using a three-factor structure from PCA, somatic/affective (hazards ratio [HR]=1.35, 95% confidence interval [CI]=1.04-1.74) and appetitive (HR=1.42, 95%CI=1.21-1.68) but not cognitive/affective (HR=.89, 95%CI=.70-1.14) symptoms predicted cardiovascular prognosis in adjusted multivariate Cox regression analysis. Using a two-factor structure from PCA, adjusted results indicated that somatic (HR=1.63, 95% CI=1.28-2.08) but not cognitive/affective (HR=.87, 95% CI=.68-1.11) symptoms predicted worse prognosis. Conclusions: In a sample of women with suspected myocardial ischemia, somatic but not cognitive

  17. Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies

    PubMed Central

    Suffredini, Dante A.; Sampath-Kumar, Hanish; Li, Yan; Ohanjanian, Lernik; Remy, Kenneth E.; Cui, Xizhong; Eichacker, Peter Q.

    2015-01-01

    The US outbreak of B.anthracis infection in 2001 and subsequent cases in the US and Europe demonstrate that anthrax is a continuing risk for the developed world. While several bacterial components contribute to the pathogenesis of B. anthracis, production of lethal toxin (LT) is strongly associated with the development of hypotension and lethality. However, the mechanisms underlying the cardiovascular instability LT produces are unclear. Some evidence suggests that LT causes shock by impairing the peripheral vasculature, effects consistent with the substantial extravasation of fluid in patients dying with B. anthracis. Other data suggests that LT directly depresses myocardial function. However a clinical correlate for this latter possibility is less evident since functional studies and post-mortem examination in patients demonstrate absent or minimal cardiac changes. The purposes of this review were to first present clinical studies of cardiac functional and histologic pathology with B. anthracis infection and to then examine in vivo, in vitro, and ex vivo preclinical studies of LT’s myocardial effects. Together, these data suggest that it is unclear whether that LT directly depresses cardiac function. This question is important for the clinical management and development of new therapies for anthrax and efforts should continue to be made to answer it. PMID:26703730

  18. Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies.

    PubMed

    Suffredini, Dante A; Sampath-Kumar, Hanish; Li, Yan; Ohanjanian, Lernik; Remy, Kenneth E; Cui, Xizhong; Eichacker, Peter Q

    2015-12-01

    The US outbreak of B.anthracis infection in 2001 and subsequent cases in the US and Europe demonstrate that anthrax is a continuing risk for the developed world. While several bacterial components contribute to the pathogenesis of B. anthracis, production of lethal toxin (LT) is strongly associated with the development of hypotension and lethality. However, the mechanisms underlying the cardiovascular instability LT produces are unclear. Some evidence suggests that LT causes shock by impairing the peripheral vasculature, effects consistent with the substantial extravasation of fluid in patients dying with B. anthracis. Other data suggests that LT directly depresses myocardial function. However a clinical correlate for this latter possibility is less evident since functional studies and post-mortem examination in patients demonstrate absent or minimal cardiac changes. The purposes of this review were to first present clinical studies of cardiac functional and histologic pathology with B. anthracis infection and to then examine in vivo, in vitro, and ex vivo preclinical studies of LT's myocardial effects. Together, these data suggest that it is unclear whether that LT directly depresses cardiac function. This question is important for the clinical management and development of new therapies for anthrax and efforts should continue to be made to answer it. PMID:26703730

  19. Depression and the Risk of Myocardial Infarction and Coronary Death: A Meta-Analysis of Prospective Cohort Studies.

    PubMed

    Wu, Qing; Kling, Juliana M

    2016-02-01

    Findings regarding the association between depression and risk of coronary heart disease are inconsistent. We aimed to assess the association between depression and risk of myocardial infarction (MI) and coronary death through a meta-analysis.We performed an electronic literature search of MEDLINE, EMBASE, PsycINFO, ISI Web of Science, and Scopus databases through August 1, 2015, and manual search of the references of the eligible papers and related review articles. Two investigators independently conducted study selection and data abstraction. Disagreement was resolved by consensus. Confounder-adjusted hazard ratios (HRs) were pooled using a random-effects model. Heterogeneity was evaluated using the Cochran Q statistic and Higgins index. Publication bias was assessed by funnel plot and Egger test. Study quality was appraised with the Newcastle-Ottawa Scale.Among 19 eligible cohort studies including 323,709 participants, 8447 cases of MI and coronary death were reported during follow-up ranging from 4 to 37 years. The pooled adjusted HRs for patients with depression (vs those without) were 1.22 (95% CI, 1.13-1.32) for combined MI and coronary death, 1.31 (95% CI, 1.09-1.57) for MI alone (9 studies), and 1.36 (95% CI, 1.14-1.63) for coronary death alone (8 studies). The increased risk of MI and coronary death associated with depression was consistent using modified inclusion criteria, across most subgroups, and after adjusting for possible publication bias.Depression is associated with a significantly increased risk of MI and coronary death. Effective prevention and treatment of depression may decrease such risk. PMID:26871852

  20. Risk of anxiety and depressive disorders in patients with myocardial infarction: A nationwide population-based cohort study.

    PubMed

    Feng, Hsin-Pei; Chien, Wu-Chien; Cheng, Wei-Tung; Chung, Chi-Hsiang; Cheng, Shu-Meng; Tzeng, Wen-Chii

    2016-08-01

    Anxiety and depressive symptoms are associated with adverse cardiovascular events after an acute myocardial infarction (MI). However, most studies focusing on anxiety or depression have used rating scales or self-report methods rather than clinical diagnosis. This study aimed to investigate the association between psychiatrist-diagnosed psychiatric disorders and cardiovascular prognosis.We sampled data from the National Health Insurance Research Database; 1396 patients with MI were recruited as the study cohort and 13,960 patients without MI were recruited as the comparison cohort. Cox proportional hazard regression models were used to examine the effect of MI on the risk of anxiety and depressive disorders.During the first 2 years of follow-up, patients with MI exhibited a significantly higher risk of anxiety disorders (adjusted hazard ratio [HR] = 5.06, 95% confidence interval [CI]: 4.61-5.54) and depressive disorders (adjusted HR = 7.23, 95% CI: 4.88-10.88) than those without MI did. Greater risk for anxiety and depressive disorders was observed among women and patients aged 45 to 64 years following an acute MI. Patients with post-MI anxiety had a 9.37-fold (95% CI: 4.45-19.70) higher risk of recurrent MI than those without MI did after adjustment for age, sex, socioeconomic status, and comorbidities.This nationwide population-based cohort study provides evidence that MI increases the risk of anxiety and depressive disorders during the first 2 years post-MI, and post-MI anxiety disorders are associated with a higher risk of recurrent MI. PMID:27559951

  1. ST-segment depression on the initial electrocardiogram in acute myocardial infarction-prognostic significance and its effect on short-term mortality: A report from the National Registry of Myocardial Infarction (NRMI-2, 3, 4).

    PubMed

    Pitta, Sridevi R; Grzybowski, Mary; Welch, Robert D; Frederick, Paul D; Wahl, Robert; Zalenski, Robert J

    2005-04-01

    This study analyzed 255,256 patients who had acute myocardial infarction and were enrolled in the National Registry of Myocardial Infarction 2, 3, and 4 (1994 to 2002). The objective was to determine in-hospital mortality rate among patients who had ST-segment depression on the initial electrocardiogram. Patients who had ST-segment depression had an in-hospital mortality rate (15.8%) similar to that of patients who had ST-segment elevation or left bundle branch block (15.5%). After adjusting for observed differences, ST-segment depression was associated with only a slightly lower odds ratio (0.91) of mortality compared with ST-segment elevation or left bundle branch block. PMID:15781012

  2. The effect of written material and verbal method education on anxiety and depression in patients with myocardial infarction in selected hospitals in Iran

    PubMed Central

    AGHAKHANI, NADER; KHADEMVATAN, KAMAL; DEHGHANI, MOHAMMAD REZA

    2014-01-01

    Introduction: Myocardial infarction (MI) is the damage to the heart muscle, or myocardium, resulting from the lack of blood flow to the heart. MI patients experience mental and emotional problems such as depression and anxiety. These complications could cause delay in resuming work, decreased quality of life and increased risk of death. The role of education in facilitating adaptation is very important in these patients. The purpose of this study was to determine the effect of written material and verbal method education on anxiety and depression in patients with myocardial infarction in Urmia hospital in 2009. Methods: This study was a quasi-experimental study, comparing the effect of education on anxiety and depression in patients with myocardial infarction in hospitals affiliated to Urmia University of Medical Science. 124 patients were selected randomly and divided into two groups. The experimental group was educated through face to face training and an educational booklet (Written Material and Verbal Method). The control group did not receive any intervention. The level of anxiety and depression was evaluated, using HADS questionnaire at 3 intervals: after 48 hours of admission, the discharge day and 2 months after discharge. Results: The findings suggested that MI patients were worried about their social role, interpersonal relations and personal health. Such problems can aggravate symptoms and complicate the future care. There was no significant difference between the control and experimental groups before the intervention, but after the intervention, anxiety and depression in the experimental group was significantly less than that in the control group (p<0.05). Conclusion: Considering the beneficial results obtained from written materials and verbal method education on reducing anxiety and depression in cases with myocardial infarction, this may be one of the health care goals. More research on more patients is required to achieve more conclusive results

  3. Diurnal variations in myocardial metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The heart is challenged by a plethora of extracellular stimuli over the course of a normal day, each of which distinctly influences myocardial contractile function. It is therefore not surprising that myocardial metabolism also oscillates in a time-of-day dependent manner. What is becoming increasin...

  4. Myocardial failure with altered response to adrenaline in endotoxin shock

    PubMed Central

    Archer, L.T.; Black, M.R.; Hinshaw, L.B.

    1975-01-01

    regularly less in experimental hearts than the controls. Heart rate responses to adrenaline in both failing and non-failing hearts were identical. 5 In conclusion, it is suggested that myocardial contractile and relaxation characteristics and coronary vascular responses to adrenaline infusion are depressed in endotoxin shock during the period of demonstrated myocardial dysfunction. No distinct causal relationships were observed between the altered myocardial responsiveness and pathogenesis of heart dysfunction since myocardial dysfunction and altered responsiveness to adrenaline were generally observed together. Myocardial oedema formation after endotoxin as previously reported by this laboratory may bear a relationship to the depressed negative dP/dt response to adrenaline. PMID:1097013

  5. Comparative cardiac contractile actions of six narcotic analgesics: morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol (LAAM).

    PubMed

    Rendig, S V; Amsterdam, E A; Henderson, G L; Mason, D T

    1980-10-01

    Cardiac muscle contractile responses to six narcotic analgesics (morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol), at concentrations from 10(-8) to 10(-4) M, both in the presence and absence of the narcotic antagonist, naloxone, were studied in the isolated, isometric cat right ventricular papillary muscle preparation. Measurements of maximum developed tension (T), maximum rate of tension development (dT/dt) and time to peak tension indicated that no major changes in contractile function occurred with any narcotic at concentrations of 10(-8) to 10(-6) M except for small but significant (P < .05) increases in all three parameters at 10(-6) M fentanyl, and small but significant increases in dT/dt at 10(-8) to 10(-6) M meperidine. At 10(-5) M narcotic, dT/dt was significantly elevated in meperidine-treated muscles (+7%), but significantly reduced in muscles exposed to pentazocine (-8%) or l-alpha-acetylmethadol (-11%). For all six narcotics, the 10(-4) M drug concentration resulted in depression of contractile function that was often associated with nonresponsiveness to electrical stimulation. Pretreatment of muscles with naloxone (10(-4) M) did not prevent this reduction of contractile performance except at the highest concentration (10(-4) M) of meperidine. Following removal of drug, contractile performance improved to varying degrees (recovery to 72-97% of control T), except in l-alpha-acetylmethadol-treated muscles, in which there was no recovery of T. Isoproterenol (0.8 X 10(-7) M) elicited a positive inotropic response whether administered in the presence of 10(-4) M narcotic or following narcotic removal. We conclude that narcotic analgesics in high concentrations exert a direct myocardial depressant effect which is not prevented by naloxone and therefore is not mediated by interaction with opiate receptors. Rather, several effects, including myocardial depression, its reversibility by both drug removal and isoproterenol and

  6. Propofol Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-Alpha Expression and Myocardial Depression through Decreasing the Generation of Superoxide Anion in Cardiomyocytes

    PubMed Central

    Tang, Jing; Hu, Ji-Jie; Lu, Chun-Hua; Liang, Jia-Ni; Xiao, Jin-Fang; Liu, You-Tan; Lin, Chun-Shui; Qin, Zai-Sheng

    2014-01-01

    TNF-α has been shown to be a major factor responsible for myocardial depression in sepsis. The aim of this study was to investigate the effect of an anesthetic, propofol, on TNF-α expression in cardiomyocytes treated with LPS both in vivo and in vitro. In cultured cardiomyocytes, compared with control group, propofol significantly reduced protein expression of gp91phox and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and p38 MAPK, which associates with reduced TNF-α production. In in vivo mice studies, propofol significantly improved myocardial depression and increased survival rate of mice after LPS treatment or during endotoxemia, which associates with reduced myocardial TNF-α production, gp91phox, ERK1/2, and p38 MAPK. It is concluded that propofol abrogates LPS-induced TNF-α production and alleviates cardiac depression through gp91phox/ERK1/2 or p38 MAPK signal pathway. These findings have great clinical importance in the application of propofol for patients enduring sepsis. PMID:25180066

  7. [Interesting PYP, Tl-201, MIBG and AM myocardial SPECT images in a patient under successful reperfusion therapy].

    PubMed

    Tanaka, T; Aizawa, T; Kato, K; Ogasawara, K; Kirigaya, H; Okamoto, K

    1991-09-01

    Various types of radiopharmacons such as Tl-201, Tc-99m pyrophosphate (PYP), I-123 Metaiodobenzylguanidine (MIBG) and In-111 antimyosin Fab (AM), were applied to a patients under successful reperfusion therapy. In the patient QS waves in precordial leads and elevated serum enzyme activity was noted, however well anterior wall movement was maintained in chronic phase. At 4th hospital day PYP uptake was noted at apical region and basal anteroseptal region. Most portion of PYP uptake was overlapped by Tl-201 uptake. Depressed Tl-201 uptake in subacute phase improved. In chronic phase depressed MIBG uptake was noted at the region corresponding to the abnormal region in acute phase. Then months after the ischemic event AM uptake was noted at the region which maintained contractility. From these findings it was concluded as followings. Salvaged jeopardized myocardium remained ischemia in subacute phase. The lesions noted in the MIBG images showed depressed myocardial norepinephrine activity. This suggested that sympathetic nervous function was damaged by severe ischemia and the depressed sympathetic nervous function persisted long after myocardial perfusion had been restored. From abnormal AM uptake ten months after ischemic event it was suspected that myocardial cell membrane damage caused by severe ischemia might be persistent at the region which maintained contractility. Radioisotope image was useful to study pathological myocardium due to ischemic event. PMID:1837571

  8. Depression and Anxiety after Acute Myocardial Infarction Treated by Primary PCI

    PubMed Central

    Kala, Petr; Hudakova, Nela; Jurajda, Michal; Kasparek, Tomas; Ustohal, Libor; Parenica, Jiri; Sebo, Marek; Holicka, Maria

    2016-01-01

    Aims The main objective of the study was to find out prevalence of depression and anxiety symptoms in the population of patients with AMI with ST-segment elevation (STEMI), treated with primary PCI (pPCI). Secondary target indicators included the incidence of sleep disorders and loss of interest in sex. Methods and results The project enrolled 79 consecutive patients with the first AMI, aged <80 years (median 61 years, 21.5% of women) with a follow-up period of 12 months. Symptoms of depression or anxiety were measured using the Beck Depression Inventory II tests (BDI-II, cut-off value ≥14) and Self-Rating Anxiety Scale (SAS, cut-off ≥ 45) within 24 hours of pPCI, before the discharge, and in 3, 6 and 12 months). Results with the value p<0.05 were considered as statistically significant. The BDI-II positivity was highest within 24 hours after pPCI (21.5%) with a significant decline prior to the discharge (9.2%), but with a gradual increase in 3, 6 and 12 months (10.4%; 15.4%; 13.8% respectively). The incidence of anxiety showed a relatively similar trend: 8.9% after pPCI, and 4.5%, 10.8% and 6.2% in further follow-up. Conclusions Patients with STEMI treated by primary PCI have relatively low overall prevalence of symptoms of depression and anxiety. A significant decrease in mental stress was observed before discharge from the hospital, but in a period of one year after pPCI, prevalence of both symptoms was gradually increasing, which should be given medical attention. PMID:27074002

  9. Depression

    MedlinePlus

    ... make negative thinking worse. previous continue Depression Can Go Unrecognized People with depression may not realize they ... themselves or who have eating disorders or who go through extreme mood changes may have unrecognized depression. ...

  10. Depression

    MedlinePlus

    ... The depression generally lifts during spring and summer. Bipolar disorder is different from depression but is included in this list is because someone with bipolar disorder experiences episodes of extreme low moods (depression). But ...

  11. Depressed expression of MuRF1 and MAFbx in areas remote of recent myocardial infarction: a mechanism contributing to myocardial remodeling?

    PubMed

    Conraads, Viviane M; Vrints, Christiaan J; Rodrigus, Inez E; Hoymans, Vicky Y; Van Craenenbroeck, Emeline M; Bosmans, Johan; Claeys, Marc J; Van Herck, Paul; Linke, Axel; Schuler, Gerhard; Adams, Volker

    2010-03-01

    Ventricular remodeling following myocardial infarction (MI) includes myocardial hypertrophy, a process requiring increased protein synthesis and sarcomere assembly. The anti-hypertrophic effect of MuRF1/MafBx, both muscle-specific E3-ubiquitin ligases, has been demonstrated in animal experiments and in cultured cardiomyocytes. We assessed MuRF1/MAFbx expression in myocardium remote of recently (<2 weeks) infarcted regions (MI), compared with patients undergoing coronary artery bypass surgery, with normal systolic function and without previous infarction (control or Con). Left ventricular myocardial biopsies were obtained from the contralateral normal zone in MI (n = 14) patients and from the Con (n = 12) group. MuRF-1/MAFbx expression was assessed using RT-PCR and Western blot (WB). In addition, the myocardial expression of TNF-alpha was measured (RT-PCR) and troponin I, beta-myosin and phosphorylated Akt/Akt (pAkt/Akt) were quantified (WB). MuRF1 and MAFbx expression (mRNA and protein level) were significantly reduced in biopsies from MI patients. TNF-alpha was significantly higher in MI and exhibited a negative correlation with MuRF1 and MAFbx. The expression of troponin I and cardiomyocyte size were increased in MI in comparison to Con, whereas beta-myosin expression was not altered. When compared with Con, pAkt/Akt was elevated. The results of the present study suggest that the atrogenes MuRF1/MAFbx are involved in regulating the hypertrophic response, characteristic of the early post-infarction remodeling phase. Reduced expression of MuRF1 and MAFbx in the myocardium might permit hypertrophy, which is supported by the elevation of troponin I. A regulatory role of TNF-alpha needs to be confirmed in further experiments. PMID:19859778

  12. Role of microtubules in the contractile dysfunction of hypertrophied myocardium

    NASA Technical Reports Server (NTRS)

    Zile, M. R.; Koide, M.; Sato, H.; Ishiguro, Y.; Conrad, C. H.; Buckley, J. M.; Morgan, J. P.; Cooper, G. 4th

    1999-01-01

    OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.

  13. Fractal correlation properties of R-R interval dynamics and mortality in patients with depressed left ventricular function after an acute myocardial infarction

    NASA Technical Reports Server (NTRS)

    Huikuri, H. V.; Makikallio, T. H.; Peng, C. K.; Goldberger, A. L.; Hintze, U.; Moller, M.

    2000-01-01

    BACKGROUND: Preliminary data suggest that the analysis of R-R interval variability by fractal analysis methods may provide clinically useful information on patients with heart failure. The purpose of this study was to compare the prognostic power of new fractal and traditional measures of R-R interval variability as predictors of death after acute myocardial infarction. METHODS AND RESULTS: Time and frequency domain heart rate (HR) variability measures, along with short- and long-term correlation (fractal) properties of R-R intervals (exponents alpha(1) and alpha(2)) and power-law scaling of the power spectra (exponent beta), were assessed from 24-hour Holter recordings in 446 survivors of acute myocardial infarction with a depressed left ventricular function (ejection fraction depressed left ventricular function after an acute myocardial infarction.

  14. Depression

    MedlinePlus

    ... it might motivate the person to go for treatment. Treating Depression Your doctor or mental health expert can often treat your depression successfully. Different therapies seem to work for different people. For instance, ...

  15. Depressants

    MedlinePlus

    Drug Fact Sheet Depressants Overview Includes barbiturates (barbs), benzodiazepines (benzos) and sedative-hypnotics. Depressants will put you ... unsafe, increasing the likelihood of coma or death. Benzodiazepines were developed to replace barbiturates, though they still ...

  16. Role of cardiomyocyte circadian clock in myocardial metabolic adaptation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marked circadian rhythmicities in cardiovascular physiology and pathophysiology exist. The cardiomyocyte circadian clock has recently been linked to circadian rhythms in myocardial gene expression, metabolism, and contractile function. For instance, the cardiomyocyte circadian clock is essential f...

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

    NASA Technical Reports Server (NTRS)

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

    1973-01-01

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

  18. Depression.

    ERIC Educational Resources Information Center

    Strock, Margaret

    Approximately ten percent of the population suffers from a depressive illness each year. Although the economic cost is high, the cost in human suffering is immeasurable. To help educate the population about this disorder, this paper presents a definition of depression and its common manifestations. The symptoms that people often experience are…

  19. Attenuation of post-myocardial infarction depression in rats by n-3 fatty acids or probiotics starting after the onset of reperfusion.

    PubMed

    Gilbert, Kim; Arseneault-Bréard, Jessica; Flores Monaco, Fabio; Beaudoin, Alexanne; Bah, Thierno Madjou; Tompkins, Thomas A; Godbout, Roger; Rousseau, Guy

    2013-01-14

    Proinflammatory cytokines play a central role in depression-like behaviour and apoptosis in the limbic system after myocardial infarction (MI). A PUFA n-3 diet or the combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 probiotics, when given before the ischaemic period, reduce circulating proinflammatory cytokines as well as apoptosis in the limbic system. The present study was designed to determine if the same nutritional interventions maintain their beneficial effects when started after the onset of the reperfusion period and attenuate depression-like behaviour observed after MI. MI was induced by the occlusion of the left anterior descending coronary artery for 40 min in rats. After the onset of reperfusion, animals were fed with a high- or low-PUFA n-3 diet, combined or not with one billion live bacteria of L. helveticus and B. longum. At 3 d post-MI, caspase-3 enzymatic activities and terminal 2'-deoxyuridine, 5'-triphosphate (dUTP) nick-end labelling (TUNEL)-positive cells were decreased in the CA1, dentate gyrus (DG) and amygdala with the high-PUFA n-3 diet, as compared to the three other diets. Probiotics attenuated caspase-3 activity and TUNEL-positive cells in the DG and the medial amygdala. At 2 weeks post-MI, depression-like behaviour was observed in the low-PUFA n-3 diet without probiotics-group, and this behaviour was attenuated with the high-PUFA n-3 diet or/and probiotics. These results indicate that a high-PUFA n-3 diet or the administration of probiotics, starting after the onset of reperfusion, are beneficial to attenuate apoptosis in the limbic system and post-MI depression in the rat. PMID:23068715

  20. Depressants

    MedlinePlus

    ... marketed in the United States. Common places of origin Generally, legitimate pharmaceutical products are diverted to the illicit market. Teens can obtain depressants from the family medicine cabinet, friends, family members, the Internet, doctors, ...

  1. Depression

    MedlinePlus

    ... newborns, as well as jitteriness, difficulty feeding, and low blood sugar after delivery. However, moms who stop medications can ... a kind of antidepressant for treating depression and anxiety disorders. However, a number of research studies show ...

  2. Depressants

    MedlinePlus

    ... system. Doctors use them to treat things like insomnia or anxiety . But if depressant drugs (like sedatives, ... Other long-term effects include: impaired sexual function insomnia and other sleep problems breathing problems convulsions (similar ...

  3. Reduced sarcoplasmic reticulum Ca(2+) load mediates impaired contractile reserve in right ventricular pressure overload.

    PubMed

    Quaile, Michael P; Rossman, Eric I; Berretta, Remus M; Bratinov, George; Kubo, Hajime; Houser, Steven R; Margulies, Kenneth B

    2007-11-01

    Myocardial contractile reserve is significantly attenuated in patients with advanced heart failure. The aim of this study was to identify mechanisms of impaired contractile reserve in a large animal model that closely mimics human myocardial failure. Progressive right ventricular hypertrophy and failure were induced by banding the pulmonary artery in kittens. Isometric contractile force was measured in right ventricular trabeculae (n=115) from age-matched Control and Banded feline hearts. Rapid cooling contractures (RCC) were used to determine sarcoplasmic reticulum (SR) Ca(2+) load while assessing the ability of changes in rate, adrenergic stimulation and bath Ca(2+) to augment contractility. The positive force-frequency relationship and robust pre- and post-receptor adrenergic responses observed in Control trabeculae were closely paralleled by increases in RCC amplitude and the RCC2/RCC1 ratio. Conversely, the severely blunted force-frequency and adrenergic responses in Banded trabeculae were paralleled by an unchanged RCC amplitude and RCC2/RCC1 ratio. Likewise, supraphysiologic levels of bath Ca(2+) were associated with severely reduced contractility and RCC amplitude in Banded trabeculae compared to Controls. There were no differences in myofilament Ca(2+) sensitivity or length-dependent increases in contractility between Control and Banded trabeculae. There was a significant decrease in SR Ca(2+)-ATPase pump abundance and phosphorylation of phospholamban and ryanodine receptor in Banded trabeculae compared with Controls. A reduced ability to increase SR Ca(2+) load is the primary mechanism of reduced contractile reserve in failing feline myocardium. The similarity of impaired contractile reserve phenomenology in this feline model and transplanted hearts suggests mechanistic relevance to human myocardial failure. PMID:17931654

  4. [A case of stunned myocardium: dual SPECT findings similar to acute myocardial infarction (AMI)].

    PubMed

    Itho, K; Kohno, Y; Sudo, Y; Azuma, A; Sugihara, H; Asayama, J; Katsume, H; Nakagawa, M

    1993-02-01

    Emergent cardiac catheterization was performed on a 70-year-old female patient who was admitted for further evaluation of acute myocardial infarction. Coronary angiography didn't reveal any significant stenotic lesion, but levogram showed extensively abnormal contractility around the center of the apex region. On the second hospital day, 99mTc-PYP/201TlCl dual SPECT gave findings similar to those found in acute myocardial infarction, but myocardium--released enzyme stayed within the normal range. Two weeks after, 201TlCl myocardial scintigraphy showed disappearance of the perfusion defect, and normal contractility was observed on the levogram of the chronic phase. Since this case was clinically denied to be myocardial infarction, it was considered a typical case of stunned myocardium which showed prolonged left ventricular abnormal contractility with transient myocardial ischemia. This is a case suggestive for estimations of myocardial reversibility in patients with myocardial perfusion and metabolic disorder in dual SPECT. PMID:8434179

  5. [The action of strophanthin K and beta-acetyldigoxin in vitro on the energy transformation by the contractile protein system of the normal cardiomyocyte].

    PubMed

    Karsanov, N V; Macharashvili, T N; Magaldadze, V A

    1989-12-01

    It was shown in experiments on myocardial fiber bundles (MGFB) from normal heart that strophantin K and beta-acetildigoxin in vitro in concentration of 10(-6) M sharply increased the value of force generated by contractile protein system and its ability to perform work. In this case strophantin K significantly increased energy transformation efficiency. It was concluded that in myocardial contractile protein system a regulator of qualitative and quantitative energy transformation is functioning (a kind of economizer). PMID:2634440

  6. Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation

    NASA Technical Reports Server (NTRS)

    Makikallio, T. H.; Hoiber, S.; Kober, L.; Torp-Pedersen, C.; Peng, C. K.; Goldberger, A. L.; Huikuri, H. V.

    1999-01-01

    A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.

  7. Anabolic steroid- and exercise-induced cardio-depressant cytokines and myocardial β1 receptor expression in CD1 mice.

    PubMed

    Fineschi, Vittorio; Di Paolo, Marco; Neri, Margherita; Bello, Stefania; D'Errico, Stefano; Dinucci, Dinuccio; Parente, Ruggero; Pomara, Cristoforo; Rabozzi, Roberto; Riezzo, Irene; Turillazzi, Emanuela

    2011-02-01

    Few animal model studies have been conducted in order to evaluate the impact of androgenic anabolic steroids (AAS) supraphysiological doses on the cardiovascular system and myocardial injury. Twenty-five male CD1 mice (8-10 weeks old; 35g initial body weight) were randomized into three AAS treated groups and two control groups. The AAS mice received intramuscular Nandrolone Decanoate (DECA-DURABOLIN), vehicled in arachidis oil, for 42 days, twice per week, with different dosages, studying plasma lipid analysis, cardiac histopathological features, cardiac β (1) adrenergic receptor expression, and the effects of the myocardial expression of inflammatory mediators (IL-1β, TNF-α) on the induction of cardiomyocytes apoptosis (HSP 70, TUNEL), using proteomic and immunohistochemical analysis. The mice had free movements in their animal rooms (two groups) or exercised by running on a motor-driven treadmill the others three groups. Recurring high dose AAS administration and physical training in mice produce significant increase in body weight and for total cholesterol. A moderate increase of the heart weight, cardiac hypertrophy and wide colliquative myocytolysis, were observed in high dose AAS administration and physical training group. The expression of HSP70 and inflammatory cytokine IL-1β, increased in the three AAS-treated groups. TNF- α showed a more extensive expression in the AAS-high dose group. A significant apoptotic process randomly sparse in the myocardium was described. Our data support the hypothesis that the combined effects of vigorous training, anabolic steroid abuse and stimulation of the sympathetic nervous system, may predispose to myocardial injury. PMID:21050164

  8. Inhibition of AMPK accentuates prolonged caloric restriction-induced change in cardiac contractile function through disruption of compensatory autophagy.

    PubMed

    Zheng, Qijun; Zhao, Kun; Han, Xuefeng; Huff, Anna F; Cui, Qin; Babcock, Sara A; Yu, Shiqiang; Zhang, Yingmei

    2015-02-01

    Prolonged caloric restriction often results in alteration in heart geometry and function although the underlying mechanism remains poorly defined. Autophagy, a conserved pathway for bulk degradation of intracellular proteins and organelles, preserves energy and nutrient in the face of caloric insufficiency. This study was designed to examine the role of AMPK in prolonged caloric restriction-induced change in cardiac homeostasis and the underlying mechanism(s) involved with a focus on autophagy. Wild-type (WT) and AMPK kinase dead (KD) mice were caloric restricted (by 40%) for 30 weeks. Echocardiographic, cardiomyocyte contractile and intracellular Ca²⁺ properties, autophagy and autophagy regulatory proteins were evaluated. Caloric restriction compromised echocardiographic indices (decreased ventricular mass, left ventricular diameters, and cardiac output), cardiomyocyte contractile and intracellular Ca²⁺ properties associated with upregulated autophagy (Beclin-1, Atg5 and LC3BII-to-LC3BI ratio), increased autophagy adaptor protein p62, elevated phosphorylation of AMPK and TSC1/2, depressed phosphorylation of mTOR and ULK1. Although AMPK inhibition did not affect cardiac mechanical function, autophagy and autophagy signaling proteins, it significantly accentuated caloric restriction-induced changes in myocardial contractile function and intracellular Ca²⁺ handling. Interestingly, AMPK inhibition reversed caloric restriction-induced changes in autophagy and autophagy signaling. AMPK inhibition led to dampened levels of Beclin-1, Atg 5 and LC3B ratio along with suppressed phosphorylation of AMPK and TSC1/2 as well as elevated phosphorylation of mTOR and ULK1. Taken together, these data suggest an indispensible role for AMPK in the maintenance of cardiac homeostasis under prolonged caloric restriction-induced pathological changes possibly through autophagy regulation. This article is part of a Special Issue entitled: Autophagy and protein quality control in

  9. Role of Mitochondrial fission and fusion in cardiomyocyte contractility

    PubMed Central

    Givvimani, S; Pushpakumar, SB; Metreveli, N; Veeranki, S; Kundu, S; Tyagi, SC

    2015-01-01

    Background Mitochondria constitute 30% of cell volume and are engaged in two dynamic processes called fusion and fission, regulated by Drp-1(Dynamin related protein) and mitofusin 2 (Mfn2). Previously, we showed that Drp-1 inhibition ameliorates cardiovascular dysfunction following pressure overload in aortic banding model and myocardial infarction. As dynamic organelles, mitochondria are capable of changing their morphology in response to stress. However, whether such changes can alter their function and in turn cellular function is unknown. Further, a direct role of fission and fusion in cardiomyocyte contractility has not yet been studied. In this study, we hypothesize that disrupted fission and fusion balance by increased Drp-1 and decreased Mfn2 expression in cardiomyocytes affect their contractility through alterations in the calcium and potassium concentrations. Methods To verify this, we used freshly isolated ventricular myocytes from wild type mouse and transfected them with either siRNA to Drp-1 or Mfn2. Myocyte contractility studies were performed by IonOptix using a myopacer. Intracellular calcium and potassium measurements were done using flow cytometry. Immunocytochemistry (ICC) was done to evaluate live cell mitochondria and its membrane potential. Protein expression was done by Western blot and Immunocytochemistry. Results We found that silencing mitochondrial fission increased the myocyte contractility, while fusion inhibition decreased contractility with simultaneous changes in calcium and potassium. Also, we observed that increase in fission prompted decrease in Serca-2a and increase in cytochrome c leading to mitophagy. Conclusion Our results suggested that regulating mitochondrial fission and fusion have direct effects on overall cardiomyocyte contractility and thus function. PMID:25841124

  10. Depression

    MedlinePlus

    ... to eat at all Not being able to sleep, or sleeping too much Feeling very tired Feeling hopeless, irritable, anxious, or guilty Aches or pains, headaches, cramps, or digestive problems Thoughts of death or suicide Depression is a disorder of the brain. There are a variety of ...

  11. Prostaglandins attenuate cardiac contractile dysfunction produced by free radical generation but not by hydrogen peroxide.

    PubMed

    Zimmer, K M; Karmazyn, M

    1997-11-01

    The aim of this study was to examine and compare the potential influence of cyclooxygenase or lipoxygenase derived metabolites of arachidonic acid on myocardial injury produced either by a free radical generating system consisting of purine plus xanthine oxidase or that produced by hydrogen peroxide. A free radical generating system consisting of purine (2.3 mM) and xanthine oxidase (10 U/L) as well as hydrogen peroxide (75 microM) produced significant functional changes in the absence of either significant deficits in high energy phosphates or ultrastructural damage. Prostaglandin F2 alpha (30 nM) significantly attenuated both the negative inotropic effect of purine plus xanthine oxidase as well as the ability of the free radical generator to elevate diastolic pressure. An identical concentration of prostaglandin 12 (prostacyclin) significantly reduced diastolic pressure elevation only and had no effect on contractile depression. The salutary effects of the two PGs occurred in the absence of any inhibitory influence on superoxide anion generation produced by the purine and xanthine oxidase reaction. None of prostaglandins modulated the response to hydrogen peroxide. In addition, neither prostaglandin E2 nor leukotrienes exerted any effect on changes produced by either type of oxidative stress. A 5 fold elevation in the concentrations of free radical generators or hydrogen peroxide produced extensive injury as characterized by a virtual total loss in contractility, 400% elevation in diastolic pressure, ultrastructural damage and significant depletions in high energy phosphate content. None of these effects were modulated by eicosanoid treatment. Our results therefore demonstrate a selective ability of both prostaglandin F2 alpha and to a lesser extent prostacyclin, to attenuate dysfunction produced by purine plus xanthine oxidase but not hydrogen peroxide. It is possible that these eicosanoids may represent endogenous protective factors under conditions of enhanced

  12. Transient myocardial ischaemia after acute myocardial infarction.

    PubMed Central

    Currie, P; Saltissi, S

    1990-01-01

    The prevalence and characteristics of transient myocardial ischaemia were studied in 203 patients with recent acute myocardial infarction by both early (6.4 days) and late (38 days) ambulatory monitoring of the ST segment. Transient ST segment depression was much commoner during late (32% patients) than early (14%) monitoring. Most transient ischaemia (greater than 85% episodes) was silent and 80% of patients had only silent episodes. During late monitoring painful ST depression was accompanied by greater ST depression and tended to occur at a higher heart rate. Late transient ischaemia showed a diurnal distribution, occurred at a higher initial heart rate, and was more often accompanied by a further increase in heart rate than early ischaemia. Thus in the first 2 months after myocardial infarction transient ischaemia became increasingly common and more closely associated with increased myocardial oxygen demand. Because transient ischaemic episodes during early and late ambulatory monitoring have dissimilar characteristics they may also have different pathophysiologies and prognostic implications. PMID:2245108

  13. [Surgical revascularization in patients with acute myocardial infarction].

    PubMed

    Beyersdorf, F; Sarai, K; Mitrev, Z; Eckel, L; Maul, F D; Wendt, T; Satter, P

    1993-01-01

    This retrospective study was done to assess the results of emergency revascularization in patients with acute myocardial infarction. In addition, the influence of the mode of reperfusion was investigated in terms of morbidity and mortality. Between January 1987 and May 1992, 75 consecutive patients with acute coronary occlusion (in 87% PTCA-failure) received one of two different reperfusion protocols during emergency aortocoronary bypass operation. In 36 patients, the reperfusate was normal blood given at systemic pressure (uncontrolled reperfusion); in 39 patients, the ischemic area was initially reperfused for 20 minutes with a blood cardioplegic solution (substrate-enriched, hyperosmolar, hypocalcemic, alkalotic, diltiazem-enriched) given at 37 degrees C and at a perfusion pressure of 50 mmHg. Thereafter, the heart was kept in the beating empty state for 30 minutes before extra-corporeal circulation was discontinued (controlled reperfusion). Regional contractility (echocardiography, radionuclide ventriculography), electrocardiogram (ECG), release of creatine kinase and MB-isoenzyme of creatine kinase as well as hospital mortality were assessed. Quantification of regional contractility was done with a scoring system from 0 (normokinesis) to 4 (dyskinesis). Data are expressed as mean +/- standard error of the mean (SEM). Both groups were well matched for age, sex, and the distribution of the occluded artery. In the controlled reperfusion group, there was a higher incidence of additional significant stenosis (2.2 +/- 0.1 vs 1.7 +/- 0.1) and cardiogenic shock (36% vs 17%). Furthermore, the interval between coronary occlusion and reperfusion was longer in the controlled reperfusion group (4.1 +/- 0.3 vs 3.3 +/- 0.3 hrs; p > 0.05). Regional contractility returned to normal after controlled reperfusion (score 0.8 +/- 0.2; normokinesis = 0, slight hypokinesis = 1). In contrast, regional contractility remained depressed severely after uncontrolled reperfusion with normal

  14. Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction.

    PubMed

    Ngkelo, Anta; Richart, Adèle; Kirk, Jonathan A; Bonnin, Philippe; Vilar, Jose; Lemitre, Mathilde; Marck, Pauline; Branchereau, Maxime; Le Gall, Sylvain; Renault, Nisa; Guerin, Coralie; Ranek, Mark J; Kervadec, Anaïs; Danelli, Luca; Gautier, Gregory; Blank, Ulrich; Launay, Pierre; Camerer, Eric; Bruneval, Patrick; Menasche, Philippe; Heymes, Christophe; Luche, Elodie; Casteilla, Louis; Cousin, Béatrice; Rodewald, Hans-Reimer; Kass, David A; Silvestre, Jean-Sébastien

    2016-06-27

    Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca(2+) desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force-Ca(2+) interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. PMID:27353089

  15. [Subcellular basis of disorders of the contractile capacity of the heart in L-thyroxine-induced thyrotoxicosis].

    PubMed

    Karsanov, N V; Melashvili, N O; Khugashvili, Z G; Mamulashvili, L D; Azrumelashvili, M I; Khaindrava, G K; Kapanadze, R V

    1990-02-01

    In experiments on dogs, the authors examined the functional activity of three cardiomyocyte systems responsible for contraction-relaxation (the systems of contractile proteins, calcium transport and energy supply) in the dynamics of L-thyroxine-induced toxicosis. A fall in the capacity of the contractile protein system to generate energy and to perform was shown to play the leading role in decrease of myocardial reserve forces and reduction in cardiac contractility. There was a drop in the intensity of calcium transport through the membranes of the sarcoplasmic reticulum and mitochondria and a deficiency of the direct energy source for contraction only in the late period of the disease. PMID:2348627

  16. Myocardial Ischemia: Lack of Coronary Blood Flow or Myocardial Oxygen Supply/Demand Imbalance?

    PubMed

    Heusch, Gerd

    2016-07-01

    Regional myocardial blood flow and contractile function in ischemic myocardium are well matched, and there is no evidence for an oxygen supply/demand imbalance. Thus, myocardial ischemia is lack of coronary blood flow with electric, functional, metabolic, and structural consequences for the myocardium. All therapeutic interventions must aim to improve blood flow to ischemic myocardium as much and as quickly as possible. PMID:27390331

  17. Nitrendipine binding in congestive heart failure due to myocardial infarction

    SciTech Connect

    Dixon, I.M.; Lee, S.L.; Dhalla, N.S. )

    1990-03-01

    Depressed cardiac pump function is the hallmark of congestive heart failure, and it is suspected that decreased influx of Ca2+ into the cardiac cell is responsible for depressed contractile function. Since Ca2+ channels in the sarcolemmal membrane are considered to be an important route for the entry of Ca2+, we examined the status of Ca2+ receptors/channels in failing rat hearts after myocardial infarction of the left ventricular free wall. For this purpose, the left coronary artery was ligated and hearts were examined 4, 8, and 16 weeks later; sham-operated animals served as controls. Hemodynamic assessment revealed decreased total mechanical energy (left ventricular systolic pressure x heart rate), increased left ventricular diastolic pressure, and decreased positive and negative dP/dt in experimental animals at 4, 8, and 16 weeks. Although accumulation of ascites in the abdominal cavity was evident at 4 weeks, other clinical signs of congestive heart failure in experimental rats were evident from the presence of lung congestion and cardiac dilatation at 8 and 16 weeks after induction of myocardial infarction. The density of Ca2+ receptors/channels in crude membranes, as assessed by (3H)nitrendipine binding assay, was found to be decreased in the uninfarcted experimental left ventricle at 8 and 16 weeks; however, no change in the affinity of nitrendipine was evident. A similar depression in the specific binding of another dihydropyridine compound, (3H)PN200-110, was also evident in failing hearts. Brain and skeletal muscle crude membrane preparations, unlike those of the right ventricle and liver, revealed a decrease in Ca2+ receptors/channels density in experimental animals at 16 weeks.

  18. Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility

    PubMed Central

    Ennis, Irene L.; Li, Ronald A.; Murphy, Anne M.; Marbán, Eduardo; Nuss, H. Bradley

    2002-01-01

    Heart failure is characterized by depressed contractility and delayed repolarization. The latter feature predisposes the failing heart to ventricular arrhythmias and represents a logical target for gene therapy. Unfortunately, unopposed correction of the delay in repolarization will decrease the time available for calcium cycling during each heartbeat, potentially aggravating the depression of contractility. Here we describe the development and application of a novel gene therapy strategy designed to abbreviate excitation without depressing contraction. The calcium ATPase SERCA1 was coexpressed with the potassium channel Kir2.1 in guinea pig hearts. Myocytes from the hearts had bigger calcium transients and shorter action potentials. In vivo, repolarization was abbreviated, but contractile function remained unimpaired. Dual gene therapy of the sort described here can be generalized to exploit opposing or synergistic therapeutic principles to achieve a tailored phenotype. PMID:11827999

  19. Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness

    PubMed Central

    Ribeiro, Alexandre J. S.; Ang, Yen-Sin; Fu, Ji-Dong; Rivas, Renee N.; Mohamed, Tamer M. A.; Higgs, Gadryn C.; Srivastava, Deepak; Pruitt, Beth L.

    2015-01-01

    Single cardiomyocytes contain myofibrils that harbor the sarcomere-based contractile machinery of the myocardium. Cardiomyocytes differentiated from human pluripotent stem cells (hPSC-CMs) have potential as an in vitro model of heart activity. However, their fetal-like misalignment of myofibrils limits their usefulness for modeling contractile activity. We analyzed the effects of cell shape and substrate stiffness on the shortening and movement of labeled sarcomeres and the translation of sarcomere activity to mechanical output (contractility) in live engineered hPSC-CMs. Single hPSC-CMs were cultured on polyacrylamide substrates of physiological stiffness (10 kPa), and Matrigel micropatterns were used to generate physiological shapes (2,000-µm2 rectangles with length:width aspect ratios of 5:1–7:1) and a mature alignment of myofibrils. Translation of sarcomere shortening to mechanical output was highest in 7:1 hPSC-CMs. Increased substrate stiffness and applied overstretch induced myofibril defects in 7:1 hPSC-CMs and decreased mechanical output. Inhibitors of nonmuscle myosin activity repressed the assembly of myofibrils, showing that subcellular tension drives the improved contractile activity in these engineered hPSC-CMs. Other factors associated with improved contractility were axially directed calcium flow, systematic mitochondrial distribution, more mature electrophysiology, and evidence of transverse-tubule formation. These findings support the potential of these engineered hPSC-CMs as powerful models for studying myocardial contractility at the cellular level. PMID:26417073

  20. Chronic Contractile Dysfunction without Hypertrophy Does Not Provoke a Compensatory Transcriptional Response in Mouse Hearts.

    PubMed

    Matkovich, Scot J; Grubb, David R; McMullen, Julie R; Woodcock, Elizabeth A

    2016-01-01

    Diseased myocardium from humans and experimental animal models shows heightened expression and activity of a specific subtype of phospholipase C (PLC), the splice variant PLCβ1b. Previous studies from our group showed that increasing PLCβ1b expression in adult mouse hearts by viral transduction was sufficient to cause sustained contractile dysfunction of rapid onset, which was maintained indefinitely in the absence of other pathological changes in the myocardium. We hypothesized that impaired contractility alone would be sufficient to induce a compensatory transcriptional response. Unbiased, comprehensive mRNA-sequencing was performed on 6 biological replicates of rAAV6-treated blank, PLCβ1b and PLCβ1a (closely related but inactive splice variant) hearts 8 weeks after injection, when reduced contractility was manifest in PLCβ1b hearts without evidence of induced hypertrophy. Expression of PLCβ1b resulted in expression changes in only 9 genes at FDR<0.1 when compared with control and these genes appeared unrelated to contractility. Importantly, PLCβ1a caused similar mild expression changes to PLCβ1b, despite a complete lack of effect of this isoform on cardiac contractility. We conclude that contractile depression caused by PLCβ1b activation is largely independent of changes in the transcriptome, and thus that lowered contractility is not sufficient in itself to provoke measurable transcriptomic alterations. In addition, our data stress the importance of a stringent control group to filter out transcriptional changes unrelated to cardiac function. PMID:27359099

  1. Chronic Contractile Dysfunction without Hypertrophy Does Not Provoke a Compensatory Transcriptional Response in Mouse Hearts

    PubMed Central

    Grubb, David R.; McMullen, Julie R.; Woodcock, Elizabeth A.

    2016-01-01

    Diseased myocardium from humans and experimental animal models shows heightened expression and activity of a specific subtype of phospholipase C (PLC), the splice variant PLCβ1b. Previous studies from our group showed that increasing PLCβ1b expression in adult mouse hearts by viral transduction was sufficient to cause sustained contractile dysfunction of rapid onset, which was maintained indefinitely in the absence of other pathological changes in the myocardium. We hypothesized that impaired contractility alone would be sufficient to induce a compensatory transcriptional response. Unbiased, comprehensive mRNA-sequencing was performed on 6 biological replicates of rAAV6-treated blank, PLCβ1b and PLCβ1a (closely related but inactive splice variant) hearts 8 weeks after injection, when reduced contractility was manifest in PLCβ1b hearts without evidence of induced hypertrophy. Expression of PLCβ1b resulted in expression changes in only 9 genes at FDR<0.1 when compared with control and these genes appeared unrelated to contractility. Importantly, PLCβ1a caused similar mild expression changes to PLCβ1b, despite a complete lack of effect of this isoform on cardiac contractility. We conclude that contractile depression caused by PLCβ1b activation is largely independent of changes in the transcriptome, and thus that lowered contractility is not sufficient in itself to provoke measurable transcriptomic alterations. In addition, our data stress the importance of a stringent control group to filter out transcriptional changes unrelated to cardiac function. PMID:27359099

  2. The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha.

    PubMed Central

    Schulz, R; Panas, D L; Catena, R; Moncada, S; Olley, P M; Lopaschuk, G D

    1995-01-01

    1. Myocardial dysfunction during septic shock is associated with enhanced production of cytokines such as interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha). These cytokines depress cardiac mechanical function by a mechanism which is not well defined. 2. Bacterial endotoxin or cytokines cause the expression of Ca(2+)-independent nitric oxide (NO) synthase in cardiac myocytes, vascular endothelial cells and endocardial endothelial cells, causing enhanced production of NO. As NO has negative inotropic actions on cardiac muscle, we tested the sum effects of IL-1 beta plus TNF-alpha in the intact heart to determine whether enhanced expression of NO synthase activity in the cells that comprise the heart is involved in cardiac depression associated with cytokine stimulation. 3. Rat isolated working hearts perfused with IL-1 beta plus TNF-alpha showed a markedly greater depression in contractile function, measured as cardiac work, after 2 h of perfusion compared with time-matched control hearts. The depressant action of IL-1 beta plus TNF-alpha was first apparent after 1 h of perfusion; no early (15 min) cardiac depressant actions were seen. 4. The competitive inhibitor of Ca(2+)-dependent and Ca(2+)-independent NO synthases, NG-nitro-L-arginine methyl ester (L-NAME, 3 microM) when given concurrently with IL-1 beta plus TNF-alpha prevented the loss in contractile function such that these hearts after 2 h of perfusion had similar function to time-matched controls. L-NAME did not acutely reverse the loss of contractile function in hearts exposed for 2 h to IL-1 beta plus TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7536096

  3. MYOCARDIAL AKT: THE OMNIPRESENT NEXUS

    PubMed Central

    Sussman, Mark A.; Völkers, Mirko; Fischer, Kimberlee; Bailey, Brandi; Cottage, Christopher T.; Din, Shabana; Gude, Natalie; Avitabile, Daniele; Alvarez, Roberto; Sundararaman, Balaji; Quijada, Pearl; Mason, Matt; Konstandin, Mathias H.; Malhowski, Amy; Cheng, Zhaokang; Khan, Mohsin; McGregor, Michael

    2013-01-01

    One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses. PMID:21742795

  4. Contractile function of the myocardium with prolonged hypokinesia in patients with surgical tuberculosis

    NASA Technical Reports Server (NTRS)

    Zakutayeva, V. P.; Matiks, N. I.

    1978-01-01

    The changes in the myocardial contractile function with hypokinesia in surgical tuberculosis patients are discussed. The phase nature of the changes is noted, specifically the changes in the various systoles, diastole, and other parts of the cardiac cycle. The data compare these changes during confinement in bed with no motor activity to and with a return to motor activity after leaving the in-bed regimen.

  5. Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion

    PubMed Central

    Zou, Ning; Ao, Lihua; Cleveland, Joseph C.; Yang, Xiaoping; Su, Xin; Cai, Guang-Yun; Banerjee, Anirban; Fullerton, David A.; Meng, Xianzhong

    2010-01-01

    Previous studies showed that Toll-like receptor 4 (TLR4) modulates the myocardial inflammatory response to ischemia-reperfusion injury, and we recently found that cytokines link TLR4 to postischemic cardiac dysfunction. Although TLR4 can be activated in cultured cells by endogenous agents including heat shock protein 70, how it is activated during myocardial ischemia-reperfusion is unknown. In the present study, we examined 1) whether heat shock cognate protein 70 (HSC70), which is constitutively expressed in the myocardium, is released during ischemia-reperfusion; 2) whether extracellular HSC70 induces the myocardial inflammatory response and modulates cardiac function; and 3) whether HSC70 exerts these effects via TLR4. We subjected isolated mouse hearts to global ischemia-reperfusion via the Langendorff technique. Immunoblotting and immunostaining detected the release of HSC70 from the myocardium during reperfusion. Treatment with an antibody specific to HSC70 suppressed myocardial cytokine expression and improved cardiac functional recovery after ischemia-reperfusion. Recombinant HSC70 induced NF-κB activation and cytokine expression and depressed myocardial contractility in a TLR4-dependent manner. These effects required the substrate-binding domain of HSC70. Fluorescence resonance energy transfer analysis of isolated macrophages demonstrated that extracellular HSC70 interacts with TLR4. Therefore, this study demonstrates for the first time that 1) the myocardium releases HSC70 during ischemia-reperfusion, 2) extracellular HSC70 contributes to the postischemic myocardial inflammatory response and to cardiac dysfunction, 3) HSC70 exerts these effects through a TLR4-dependent mechanism, and 4) the substrate-binding domain of HSC70 is required to induce these effects. Thus extracellular HSC70 plays a critical role in regulating the myocardial innate immune response and cardiac function after ischemia-reperfusion. PMID:18441202

  6. Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose

    PubMed Central

    Bhatt, Niraj M.; Aon, Miguel A.; Tocchetti, Carlo G.; Shen, Xiaoxu; Dey, Swati; Ramirez-Correa, Genaro; O′Rourke, Brian; Gao, Wei Dong

    2014-01-01

    Hearts from type 2 diabetic (T2DM) subjects are chronically subjected to hyperglycemia and hyperlipidemia, both thought to contribute to oxidizing conditions and contractile dysfunction. How redox alterations and contractility interrelate, ultimately diminishing T2DM heart function, remains poorly understood. Herein we tested whether the fatty acid palmitate (Palm), in addition to its energetic contribution, rescues function by improving redox [glutathione (GSH), NAD(P)H, less oxidative stress] in T2DM rat heart trabeculae subjected to high glucose. Using cardiac trabeculae from Zucker Diabetic Fatty (ZDF) rats, we assessed the impact of low glucose (EG) and high glucose (HG), in absence or presence of Palm or insulin, on force development, energetics, and redox responses. We found that in EG ZDF and lean trabeculae displayed similar contractile work, yield of contractile work (Ycw), representing the ratio of force time integral over rate of O2 consumption. Conversely, HG had a negative impact on Ycw, whereas Palm, but not insulin, completely prevented contractile loss. This effect was associated with higher GSH, less oxidative stress, and augmented matrix GSH/thioredoxin (Trx) in ZDF mitochondria. Restoration of myocardial redox with GSH ethyl ester also rescued ZDF contractile function in HG, independently from Palm. These results support the idea that maintained redox balance, via increased GSH and Trx antioxidant activities to resist oxidative stress, is an essential protective response of the diabetic heart to keep contractile function. PMID:25485897

  7. Vascular Endothelial Growth Factor Prevents Apoptosis and Preserves Contractile Function in Hypertrophied Infant Heart

    PubMed Central

    Friehs, Ingeborg; Barillas, Rodrigo; Vasilyev, Nikolay V.; Roy, Nathalie; McGowan, Francis X.; del Nido, Pedro J.

    2012-01-01

    Background Cardiac hypertrophy is an adaptive response to increased workload that, if unrelieved, leads to heart failure. It has been reported that cardiomyocyte apoptosis contributes to failure, and that vascular endothelial growth factor (VEGF) treatment of hypertrophied myocardium increases capillary density and improves myocardial perfusion. In this study we hypothesized that VEGF treatment reduces cardiomyocyte apoptosis and thereby preserves myocardial contractile function. Methods and Results Newborn rabbits underwent aortic banding. At 4 and 6 weeks of age, hypertrophied animals were treated with intrapericardial administration of recombinant VEGF protein. Three groups of animals were investigated: age-matched controls (C), untreated hypertrophied (H), and VEGF-treated hypertrophied hearts (T). Cardiomyocyte apoptosis was determined by TUNEL staining and PARP cleavage (immunoblotting of nuclear extracts) and cardiac function by transthoracic echocardiography. Death attributable to severe heart failure occurred in 14 of 43 untreated and 2 of 29 VEGF-treated animals (P<0.01). TUNEL-positive cardiomyocyte nuclei (n/1000 nuclei) were significantly increased in untreated hearts at 5 weeks (H: 10±1.8 versus T: 3±0.7) and at 7 weeks (H: 13±3.6 versus T: 5±1.5; P<0.05). Increased apoptosis in untreated hypertrophy was also confirmed by the presence of PARP cleavage (H: 74±7 versus T: 41±4 arbitrary densitometry units; P<0.05). VEGF treatment preserved left ventricular mass, prevented dilation (T: 1.01±0.06 versus H: 0.77±0.07; P<0.05), and preserved contractility indices compared with untreated hearts. Conclusions Lack of adaptive capillary growth impairs myocardial perfusion and substrate delivery in hypertrophying myocardium. VEGF treatment reduces myocardial apoptosis and prolongs survival in a model of severe progressive left ventricular hypertrophy. Promoting capillary growth with VEGF reduces apoptosis, preserves myocardial contractile function, and

  8. Myocardial perfusion imaging for detection of silent myocardial ischemia

    SciTech Connect

    Beller, G.A.

    1988-04-21

    Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging. 11 references.

  9. Innate immune adaptor MyD88 mediates neutrophil recruitment and myocardial injury after ischemia-reperfusion in mice.

    PubMed

    Feng, Yan; Zhao, Huailong; Xu, Xinhua; Buys, Emmanuel S; Raher, Michael J; Bopassa, Jean C; Thibault, Helene; Scherrer-Crosbie, Marielle; Schmidt, Ulrich; Chao, Wei

    2008-09-01

    MyD88 is an adaptor protein critical for innate immune response against microbial infection and in certain noninfectious tissue injury. The present study examined the role of MyD88 in myocardial inflammation and injury after ischemia-reperfusion (I/R). I/R was produced by coronary artery ligation for 30 min followed by reperfusion. The ratios of area at risk to left ventricle (LV) were similar between wild-type (WT) and MyD88-deficient (MyD88-/-) mice. However, 24 h after I/R, the ratios of myocardial infarction to area at risk were 58% less in MyD88(-/-) than in WT mice (14 +/- 2% vs. 33 +/- 6%, P = 0.01). Serial echocardiographic studies demonstrated that there was no difference in baseline LV contractile function between the two groups. Twenty-four hours after I/R, LV ejection fraction (EF) and fractional shortening (FS) in WT mice were reduced by 44% and 62% (EF, 51 +/- 2%, and FS, 22 +/- 1%, P < 0.001), respectively, and remained depressed on the seventh day after I/R. In comparison, EF and FS in MyD88(-/-) mice were 67 +/- 3% and 33 +/- 2%, respectively, after I/R (P < 0.001 vs. WT). Similarly, LV function, as demonstrated by invasive hemodynamic measurements, was better preserved in MyD88(-/-) compared with WT mice after I/R. Furthermore, when compared with WT mice, MyD88(-/-) mice subjected to I/R had a marked decrease in myocardial inflammation as demonstrated by attenuated neutrophil recruitment and decreased expression of the proinflammatory mediators keratinocyte chemoattractant, monocyte chemoattractant protein-1, and ICAM-1. Taken together, these data suggest that MyD88 modulates myocardial inflammatory injury and contributes to myocardial infarction and LV dysfunction during I/R. PMID:18660455

  10. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    ERIC Educational Resources Information Center

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

    Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

  11. Heme-induced contractile dysfunction in human cardiomyocytes caused by oxidant damage to thick filament proteins.

    PubMed

    Alvarado, Gerardo; Jeney, Viktória; Tóth, Attila; Csősz, Éva; Kalló, Gergő; Huynh, An T; Hajnal, Csaba; Kalász, Judit; Pásztor, Enikő T; Édes, István; Gram, Magnus; Akerström, Bo; Smith, Ann; Eaton, John W; Balla, György; Papp, Zoltán; Balla, József

    2015-12-01

    Intracellular free heme predisposes to oxidant-mediated tissue damage. We hypothesized that free heme causes alterations in myocardial contractility via disturbed structure and/or regulation of the contractile proteins. Isometric force production and its Ca(2+)-sensitivity (pCa50) were monitored in permeabilized human ventricular cardiomyocytes. Heme exposure altered cardiomyocyte morphology and evoked robust decreases in Ca(2+)-activated maximal active force (Fo) while increasing Ca(2+)-independent passive force (F passive). Heme treatments, either alone or in combination with H2O2, did not affect pCa50. The increase in F passive started at 3 µM heme exposure and could be partially reversed by the antioxidant dithiothreitol. Protein sulfhydryl (SH) groups of thick myofilament content decreased and sulfenic acid formation increased after treatment with heme. Partial restoration in the SH group content was observed in a protein running at 140 kDa after treatment with dithiothreitol, but not in other proteins, such as filamin C, myosin heavy chain, cardiac myosin binding protein C, and α-actinin. Importantly, binding of heme to hemopexin or alpha-1-microglobulin prevented its effects on cardiomyocyte contractility, suggesting an allosteric effect. In line with this, free heme directly bound to myosin light chain 1 in human cardiomyocytes. Our observations suggest that free heme modifies cardiac contractile proteins via posttranslational protein modifications and via binding to myosin light chain 1, leading to severe contractile dysfunction. This may contribute to systolic and diastolic cardiac dysfunctions in hemolytic diseases, heart failure, and myocardial ischemia-reperfusion injury. PMID:26409224

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

    PubMed

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

    2016-07-01

    Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ETA) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ETA receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteins for biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, overt apoptosis and mitochondrial damage. ETA receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ETA receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ETA receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage. PMID:26089164

  13. Myocardial Bridge

    MedlinePlus

    ... artery. See also on this site: Ask a Texas Heart Institute Doctor: Search "myocardial bridge" Updated August ... comments. Terms of Use and Privacy Policy © Copyright Texas Heart Institute All rights reserved.

  14. Mechanochemical actuators of embryonic epithelial contractility.

    PubMed

    Kim, YongTae; Hazar, Melis; Vijayraghavan, Deepthi S; Song, Jiho; Jackson, Timothy R; Joshi, Sagar D; Messner, William C; Davidson, Lance A; LeDuc, Philip R

    2014-10-01

    Spatiotemporal regulation of cell contractility coordinates cell shape change to construct tissue architecture and ultimately directs the morphology and function of the organism. Here we show that contractility responses to spatially and temporally controlled chemical stimuli depend much more strongly on intercellular mechanical connections than on biochemical cues in both stimulated tissues and adjacent cells. We investigate how the cell contractility is triggered within an embryonic epithelial sheet by local ligand stimulation and coordinates a long-range contraction response. Our custom microfluidic control system allows spatiotemporally controlled stimulation with extracellular ATP, which results in locally distinct contractility followed by mechanical strain pattern formation. The stimulation-response circuit exposed here provides a better understanding of how morphogenetic processes integrate responses to stimulation and how intercellular responses are transmitted across multiple cells. These findings may enable one to create a biological actuator that actively drives morphogenesis. PMID:25246549

  15. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice

    PubMed Central

    Green, Eric M.; Wakimoto, Hiroko; Anderson, Robert L.; Evanchik, Marc J.; Gorham, Joshua M.; Harrison, Brooke C.; Henze, Marcus; Kawas, Raja; Oslob, Johan D.; Rodriguez, Hector M.; Song, Yonghong; Wan, William; Leinwand, Leslie A.; Spudich, James A.; McDowell, Robert S.; Seidman, J. G.; Seidman, Christine E.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is an inherited disease of heart muscle that can be caused by mutations in sarcomere proteins. Clinical diagnosis depends on an abnormal thickening of the heart, but the earliest signs of disease are hyperdynamic contraction and impaired relaxation. Whereas some in vitro studies of power generation by mutant and wild-type sarcomere proteins are consistent with mutant sarcomeres exhibiting enhanced contractile power, others are not. We identified a small molecule, MYK-461, that reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Here we demonstrate that early, chronic administration of MYK-461 suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain. These data indicate that hyperdynamic contraction is essential for HCM pathobiology and that inhibitors of sarcomere contraction may be a valuable therapeutic approach for HCM. PMID:26912705

  16. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice.

    PubMed

    Green, Eric M; Wakimoto, Hiroko; Anderson, Robert L; Evanchik, Marc J; Gorham, Joshua M; Harrison, Brooke C; Henze, Marcus; Kawas, Raja; Oslob, Johan D; Rodriguez, Hector M; Song, Yonghong; Wan, William; Leinwand, Leslie A; Spudich, James A; McDowell, Robert S; Seidman, J G; Seidman, Christine E

    2016-02-01

    Hypertrophic cardiomyopathy (HCM) is an inherited disease of heart muscle that can be caused by mutations in sarcomere proteins. Clinical diagnosis depends on an abnormal thickening of the heart, but the earliest signs of disease are hyperdynamic contraction and impaired relaxation. Whereas some in vitro studies of power generation by mutant and wild-type sarcomere proteins are consistent with mutant sarcomeres exhibiting enhanced contractile power, others are not. We identified a small molecule, MYK-461, that reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Here we demonstrate that early, chronic administration of MYK-461 suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain. These data indicate that hyperdynamic contraction is essential for HCM pathobiology and that inhibitors of sarcomere contraction may be a valuable therapeutic approach for HCM. PMID:26912705

  17. Calpain system and its involvement in myocardial ischemia and reperfusion injury

    PubMed Central

    Neuhof, Christiane; Neuhof, Heinz

    2014-01-01

    Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria. Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia, reperfusion and postischemic structural remodelling. The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains. Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria. Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria. Calpain inhibition can prevent or attenuate myocardial injury during ischemia, reperfusion, and in later stages of myocardial infarction. PMID:25068024

  18. Combretastatin A4 disodium phosphate-induced myocardial injury

    PubMed Central

    Tochinai, Ryota; Nagata, Yuriko; Ando, Minoru; Hata, Chie; Suzuki, Tomo; Asakawa, Naoyuki; Yoshizawa, Kazuhiko; Uchida, Kazumi; Kado, Shoichi; Kobayashi, Toshihide; Kaneko, Kimiyuki; Kuwahara, Masayoshi

    2016-01-01

    Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner.

  19. Combretastatin A4 disodium phosphate-induced myocardial injury.

    PubMed

    Tochinai, Ryota; Nagata, Yuriko; Ando, Minoru; Hata, Chie; Suzuki, Tomo; Asakawa, Naoyuki; Yoshizawa, Kazuhiko; Uchida, Kazumi; Kado, Shoichi; Kobayashi, Toshihide; Kaneko, Kimiyuki; Kuwahara, Masayoshi

    2016-07-01

    Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner. PMID:27559241

  20. Correlation between myocardial dysfunction and perfusion impairment in diabetic rats with velocity vector imaging and myocardial contrast echocardiography.

    PubMed

    Wei, Zhangrui; Zhang, Haibin; Su, Haili; Zhu, Ting; Zhu, Yongsheng; Zhang, Jun

    2012-11-01

    The purpose of this study was to investigate whether myocardial systolic dysfunction and perfusion impairment occur in diabetic rats, and to assess their relationship using velocity vector imaging (VVI) and myocardial contrast echocardiography (MCE). Forty-six rats were randomly divided into either control or the diabetes mellitus (DM) groups. DM was induced by intraperitoneal administration of streptozotocin. Twelve weeks later, 39 survival rats underwent VVI and MCE in short-axis view at the middle level of the left ventricle, both at rest and after dipyridamole stress. VVI-derived contractile parameters included peak systolic velocity (Vs ), circumferential strain (εc ), strain rate (SRc ), and their reserves. MCE-derived perfusion parameters consisted of myocardial blood flow (MBF) and myocardial flow reserve (MFR). At rest, SRc in the DM group was significantly lower than in the control group, Vs , εc , and MBF did not differ significantly between groups. After dipyridamole stress, all VVI parameters and their reserves in the DM group were significantly lower than those in the control group, MBF and MFR were substantially lower than those in the control group, too. Meanwhile, significant correlations between VVI parameter reserves and MFR were observed in the DM group. Both myocardial systolic function and perfusion were impaired in DM rats. Decreased MFR could be an important contributor to the reduction in myocardial contractile reserve. PMID:22931118

  1. Major depression

    MedlinePlus

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... Doctors do not know the exact causes of depression. It is believed that chemical changes in the ...

  2. Commonly used intravenous anesthetics decrease bladder contractility: An in vitro study of the effects of propofol, ketamine, and midazolam on the rat bladder

    PubMed Central

    Ceran, Canan; Pampal, Arzu; Goktas, Ozgur; Pampal, H. Kutluk; Olmez, Ercument

    2010-01-01

    Aim: This study was designed to test the hypothesis that propofol, ketamine, and midazolam could alter the contractile activity of detrusor smooth muscle. Materials and Methods: Four detrusor muscle strips isolated from each rat bladder (n = 12) were placed in 4 tissue baths containing Krebs-Henseleit solution. The carbachol (10 −8to 10−4mol/L)-induced contractile responses as well as 5, 10, 20, 30, 40, 50 Hz electrical field stimulation (EFS)-evoked contractile responses of the detrusor muscles were recorded using isometric contraction measurements. After obtaining basal responses, the in vitro effects of propofol, ketamine, midazolam (10−5 to 10−3 mol/L), and saline on the contractile responses of the detrusor muscle strips were recorded and evaluated. Results: All the 3 drugs reduced the carbachol-induced and/or EFS-evoked contractile responses of rat detrusor smooth muscles in different degrees. Midazolam (10−4 to 10−3 mol/L) caused a significant decrease in the contractile responses elicited by either EFS or carbachol (P=0.000−0.013). Propofol (10−3mol/L) caused a decrease only in EFS-evoked contractile responses (P=0.001−0.004) and ketamine (10−3mol/L) caused a decrease only in carbachol-induced contractile responses (P=0.001−0.034). Conclusion: We evaluated the effects of the 3 different intravenous anesthetics on detrusor contractile responses in vitro and found that there are possible interactions between anesthetic agents and detrusor contractile activity. The depressant effects of midazolam on the contractile activity were found to be more significant than ketamine and propofol. Despite the necessity of further studies, it could be a piece of wise advice to clinicians to keep the probable alterations due to intravenous anesthetics in mind, while evaluating the results of urodynamic studies in children under sedation. PMID:21116355

  3. Lipid emulsion rapidly restores contractility in stunned mouse cardiomyocytes: A comparison with therapeutic hypothermia

    PubMed Central

    Li, Jing; Fettiplace, Michael; Sy-Jou, Chen; Steinhorn, Benjamin; Shao, Zuohui; Zhu, Xiangdong; Li, Changqing; Harty, Shaun; Weinberg, Guy; Vanden Hoek, Terry L.

    2014-01-01

    Objective Cooling following cardiac arrest can improve survival significantly. However, delays in achieving target temperature may decrease the overall benefits of cooling. Here we test whether lipid emulsion, a clinically approved drug reported to exert cardioprotection, can rescue heart contractility in the setting of delayed cooling in stunned mouse cardiomyocytes. Design Cell culture study Setting Academic research laboratory Subjects Cardiomyocytes isolated from 1–2-day old C57BL6 mice Interventions Cardiomyocytes were exposed to 30 minutes of ischemia followed by 90 minutes reperfusion and 10 minutes isoproterenol with nine interventions: 1) no additional treatment; 2) intra-ischemic cooling at 32°C initiated 10 min prior to reperfusion; 3) delayed cooling started 20 minutes after reperfusion; 4) lipid emulsion + delayed cooling; 5) lipid emulsion (0.25%) administered at reperfusion; 6) lipid emulsion + intra-ischemic cooling; 7) delayed lipid emulsion; 8) lipid emulsion + delayed cooling + Akt inhibitor (API-2, 10 μM) and 9) lipid emulsion + delayed cooling + Erk inhibitor (U0126, 10 μM). Inhibitors were given to cells 1 h prior to ischemia. Measurements and Main Results Contractility was recorded by real-time phase-contrast imaging and analyzed with pulse image velocimetry in MATLAB. Ischemia diminished cell contraction. The cardioprotective effect of cooling was diminished when delayed but was rescued by lipid emulsion. Further, lipid emulsion on its own improved recovery of the contractility to an equal extent as intra-ischemic cooling. However, co-treatment of lipid emulsion and intra-ischemic cooling did not further improve the recovery compared to either treatment alone. Moreover, Akt and Erk inhibitors blocked lipid emulsion-induced protection. Conclusion Lipid emulsion improved contractility and rescued contractility in the context of delayed cooling. This protective effect required Akt and Erk signaling. Lipid emulsion might serve as a

  4. Metallothionein Abrogates GTP Cyclohydrolase I inhibition-Induced Cardiac Contractile and Morphological Defect: Role of Mitochondrial Biogenesis

    PubMed Central

    Ceylan-Isik, Asli F.; Guo, Kelly K.; Carlson, Edward C.; Privratsky, Jamie R.; Liao, Song-Jie; Cai, Lu; Chen, Alex F.; Ren, Jun

    2009-01-01

    One key mechanism for endothelial dysfunction is eNOS uncoupling, whereby eNOS generates O2•− rather than NO, due to deficient eNOS cofactor tetrahydrobiopterin (BH4). This study was designed to examine the effect of BH4 deficiency on cardiac morphology and function as well as the impact of metallothionein (MT) on BH4 deficiency-induced abnormalities, if any. FVB and cardiac-specific MT transgenic mice were exposed to 2,4-diamino-6-hydroxy-pyrimidine (DAHP, 10 mmol/l, 3 wks), an inhibitor of the BH4 synthetic enzyme GTP cyclohydrolase I. DAHP reduced plasma BH4 levels by 85% and elevated blood pressure in both FVB and MT mice. Echocardiography found decreased fractional shortening and increased end systolic diameter in DAHP-treated FVB mice. Cardiomyocytes from DAHP-treated FVB mice displayed enhanced O2•− production, contractile and intracellular Ca2+ defects including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, reduced intracellular Ca2+ rise and clearance. DAHP triggered mitochondrial swelling/myocardial filament aberrations and mitochondrial O2•− accumulation, assessed by TEM and MitoSOX Red fluorescence, respectively. DAHP also promoted the L-NAME inhibitable O2•− production and eNOS phosphorylation at Thr497. Although MT had little effect on cardiac mechanics and ultrastructure, it attenuated DAHP-induced defects in cardiac function, morphology, O2•− production and eNOS phosphorylation (Thr497). The DAHP-induced cardiomyocyte mechanical responses were alleviated by in vitro BH4 treatment. DAHP inhibited mitochondrial biogenesis, mitochondrial uncoupling protein 2 (UCP2) and chaperone HSP90, all but UCP2 was rescued by MT. Our data suggest a role of BH4 deficiency in cardiac dysfunction and therapeutic potential of antioxidants against eNOS uncoupling in the hearts. PMID:19398661

  5. Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction

    PubMed Central

    Sambol, Justin T.; Lee, Marlon A.; Caputo, Francis J.; Kawai, Kentaro; Badami, Chirag; Kawai, Tomoko; Deitch, Edwin A.; Yatani, Atsuko

    2009-01-01

    Clinical and experimental studies have shown that trauma combined with hemorrhage shock (T/HS) is associated with myocardial contractile dysfunction. However, the initial events triggering the cardiac dysfunction are not fully elucidated. Thus we tested the hypothesis that factors carried in intestinal (mesenteric) lymph contribute to negative inotropic effects in rats subjected to a laparotomy (T) plus hemorrhagic shock (HS; mean arterial blood pressure of 30–40 Torr for 90 min) using a Langendorff isolated heart preparation. Left ventricular (LV) function was assessed 24 h after trauma plus sham shock (T/SS) or T/HS by recording the LV developed pressure (LVDP) and the maximal rate of LVDP rise and fall ( ± dP/dtmax) in five groups of rats: 1) naive noninstrumented rats, 2) rats subjected to T/SS, 3) rats subjected to T/HS, 4) rats subjected to T/SS with mesenteric lymph duct ligation (T/SS+LDL), or 5) rats subjected to T/HS+LDL. Cardiac function was comparable in hearts from naive, T/SS, and T/SS+LDL rats. Both LVDP and ± dP/dtmax were significantly depressed after T/HS. The T/HS hearts also manifested a blunted responsiveness to increases in coronary flow rates and Ca2+, and this was prevented by LDL preceding T/HS. Although electrocardiograms were normal under physiological conditions, when the T/HS hearts were perfused with low Ca2+ levels (∼0.5 mM), prolonged P-R intervals and second-degree plus Wenckebach-type atrioventricular blocks were observed. No such changes occurred in the control or T/HS+LDL hearts. The effects of T/HS were similar to those of the Ca2+ channel antagonist diltiazem, indicating that an impairment of cellular Ca2+ handling contributes to T/HS-induced cardiac dysfunction. In conclusion, gut-derived factors carried in mesenteric lymph are responsible for acute T/HS-induced cardiac dysfunction. PMID:19008486

  6. Requirements for contractility in disordered cytoskeletal bundles

    NASA Astrophysics Data System (ADS)

    Lenz, Martin; Gardel, Margaret L.; Dinner, Aaron R.

    2012-03-01

    Actomyosin contractility is essential for biological force generation, and is well understood in highly organized structures such as striated muscle. Additionally, actomyosin bundles devoid of this organization are known to contract both in vivo and in vitro, which cannot be described by standard muscle models. To narrow down the search for possible contraction mechanisms in these systems, we investigate their microscopic symmetries. We show that contractile behavior requires non-identical motors that generate large-enough forces to probe the nonlinear elastic behavior of F-actin. This suggests a role for filament buckling in the contraction of these bundles, consistent with recent experimental results on reconstituted actomyosin bundles.

  7. Intravenous myocardial contrast echocardiography predicts regional and global left ventricular remodelling after acute myocardial infarction: comparison with low dose dobutamine stress echocardiography

    PubMed Central

    Abe, Y; Muro, T; Sakanoue, Y; Komatsu, R; Otsuka, M; Naruko, T; Itoh, A; Yoshiyama, M; Haze, K; Yoshikawa, J

    2005-01-01

    Objective: To assess the role of intravenous myocardial contrast echocardiography (MCE) in predicting functional recovery and regional or global left ventricular (LV) remodelling after acute myocardial infarction (AMI) compared with low dose dobutamine stress echocardiography (LDSE). Methods: 21 patients with anterior AMI and successful primary angioplasty underwent MCE and LDSE during the subacute stage (2–4 weeks after AMI). Myocardial perfusion and contractile reserve were assessed in each segment (12 segment model) with MCE and LDSE. The 118 dyssynergic segments in the subacute stage were classified as recovered, unchanged, or remodelled according to wall motion at six months’ follow up. Percentage increase in LV end diastolic volume (%ΔEDV) was also calculated. Results: The presence of perfusion was less accurate than the presence of contractile reserve in predicting regional recovery (55% v 81%, p < 0.0001). However, the absence of perfusion was more accurate than the absence of contractile reserve in predicting regional remodelling (83% v 48%, p < 0.0001). The number of segments without perfusion was an independent predictor of %ΔEDV, whereas the number of segments without contractile reserve was not. The area under the receiver operating characteristic curve showed that the number of segments without perfusion predicted substantial LV dilatation (%ΔEDV > 20%) more accurately than did the number of segments without contractile reserve (0.88 v 0.72). Conclusion: In successfully revascularised patients with AMI, myocardial perfusion assessed by MCE is predictive of regional and global LV remodelling rather than of functional recovery, whereas contractile reserve assessed by LDSE is predictive of functional recovery rather than of LV remodelling. PMID:15797931

  8. Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction†

    PubMed Central

    Huikuri, Heikki V.; Raatikainen, M.J. Pekka; Moerch-Joergensen, Rikke; Hartikainen, Juha; Virtanen, Vesa; Boland, Jean; Anttonen, Olli; Hoest, Nis; Boersma, Lucas V.A.; Platou, Eivind S.; Messier, Marc D.; Bloch-Thomsen, Poul-Erik

    2009-01-01

    Aims To determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF ≤ 0.40). Methods and results A total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 ± 11 years) with a mean LVEF of 31 ± 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component (<5.7 ln ms2) adjusted for clinical variables was 7.0 (95% CI: 2.4–20.3, P < 0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7–13.4, P = 0.003) also predicted the primary endpoint. Conclusion Fatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AMI. PMID:19155249

  9. Human myocardial Na,K-ATPase concentration in heart failure.

    PubMed

    Bundgaard, H; Kjeldsen, K

    1996-01-01

    The Na,K-ATPase is of major importance for active ion transport across the sarcolemma and thus for electrical as well as contractile function of the myocardium. Furthermore, it is receptor for digitalis glycosides. In human studies of the regulatory aspects of myocardial Na,K-ATPase concentration a major problem has been to obtain tissue samples. Methodological accomplishments in quantification of myocardial Na,K-ATPase using vanadate facilitated 3H-ouabain binding to intact samples have, however, made it possible to obtain reliable measurements on human myocardial necropsies obtained at autopsy as well as on biopsies of a wet weight of only 1-2 mg obtained during heart catheterisation. However, access to the ultimately, normal, vital myocardial tissue has come from the heart transplantation programs, through which myocardial samples from cardiovascular healthy organ donors have become available. In the present paper we evaluate the various values reported for normal human myocardial Na,K-ATPase concentration, its regulation in heart disease and the association with digitalization. Normal myocardial Na,K-ATPase concentration level is found to be 700 pmol/g wet weight. No major variations were found between or within the walls of the heart ventricles. During the first few years of life a marked decrease in myocardial Na,K-ATPase concentration is followed by a stable level obtained in early adulthood and normally maintained throughout life. In patients with enlarged cardiac x-ray silhouette a significant positive, linear correlation between left ventricular ejection fraction (EF) and Na,K-ATPase concentration was established. A maximum reduction in Na,K-ATPase concentration of 89% was obtained when EF was reduced to 20%. Generally, heart failure associated with heart dilatation, myocardial hypertrophy as well as ischaemic heart disease is associated with reductions in myocardial Na,K-ATPase concentration of around 25%. During digoxin treatment of heart failure

  10. Cardiac troponin T in the diagnosis of myocardial injury.

    PubMed

    Mair, J; Dienstl, F; Puschendorf, B

    1992-01-01

    In the last several decades serum levels of cardiac enzymes and isoenzymes have become the final arbiters by which myocardial damage is diagnosed or excluded. Because conventionally used enzymes are neither perfectly sensitive nor specific, there is need for a new sensitive and cardiospecific marker of myocardial damage. Cardiac troponin T (TnT) is a contractile protein unique to cardiac muscle and can be differentiated by immunologic methods from its skeletal-muscle isoform. An enzyme immunoassay specific for cardiac TnT is now available in a commercial kit for routine use. The biggest advantage of this assay is its cardiospecificity. TnT measurements, however, are also highly sensitive in diagnosis of myocardial injury and accurately discern even small amounts of myocardial necrosis. TnT measurements are, therefore, particularly useful in patients with borderline CK-MB and in clinical settings in which traditional enzymes fail to diagnose myocardial damage efficiently because of lack of specificity--for example, perioperative myocardial infarction or blunt heart trauma. TnT release kinetics reveal characteristics of both soluble, cytoplasmic, and structurally bound molecules. It starts to increase a few hours after the onset of myocardial damage and remains increased for several days. TnT allows late diagnosis of myocardial infarction. The diagnostic efficiency remains at 98% until 6 d after the onset of infarct-related symptoms. TnT is also useful in monitoring the effectiveness of thrombolytic therapy in myocardial infarction patients. The ratio of peak TnT concentration on day 1 to TnT concentration at day 4 discriminates between patients with successful (greater than 1) and failed (less than or equal to 1) reperfusion. TnT measurements are very sensitive and specific for the early and late diagnosis of myocardial damage and could, therefore, provide a new criterion in laboratory diagnosis of the occurrence of myocardial damage. PMID:1388708

  11. Architecture and Connectivity Govern Actin Network Contractility.

    PubMed

    Ennomani, Hajer; Letort, Gaëlle; Guérin, Christophe; Martiel, Jean-Louis; Cao, Wenxiang; Nédélec, François; De La Cruz, Enrique M; Théry, Manuel; Blanchoin, Laurent

    2016-03-01

    Actomyosin contractility plays a central role in a wide range of cellular processes, including the establishment of cell polarity, cell migration, tissue integrity, and morphogenesis during development. The contractile response is variable and depends on actomyosin network architecture and biochemical composition. To determine how this coupling regulates actomyosin-driven contraction, we used a micropatterning method that enables the spatial control of actin assembly. We generated a variety of actin templates and measured how defined actin structures respond to myosin-induced forces. We found that the same actin filament crosslinkers either enhance or inhibit the contractility of a network, depending on the organization of actin within the network. Numerical simulations unified the roles of actin filament branching and crosslinking during actomyosin contraction. Specifically, we introduce the concept of "network connectivity" and show that the contractions of distinct actin architectures are described by the same master curve when considering their degree of connectivity. This makes it possible to predict the dynamic response of defined actin structures to transient changes in connectivity. We propose that, depending on the connectivity and the architecture, network contraction is dominated by either sarcomeric-like or buckling mechanisms. More generally, this study reveals how actin network contractility depends on its architecture under a defined set of biochemical conditions. PMID:26898468

  12. Intestinal permeability and contractility in murine colitis.

    PubMed Central

    van Meeteren, M E; van Bergeijk, J D; van Dijk, A P; Tak, C J; Meijssen, M A; Zijlstra, F J

    1998-01-01

    We developed an in vitro organ bath method to measure permeability and contractility simultaneously in murine intestinal segments. To investigate whether permeability and contractility are correlated and influenced by mucosal damage owing to inflammation, BALB/c mice were exposed to a 10% dextran sulphate sodium (DSS) solution for 8 days to induce colitis. The effect of pharmacologically induced smooth muscle relaxation and contraction on permeability was tested in vitro. Regional permeability differences were observed in both control and 10% DSS-treated mice. Distal colon segments were less permeable to 3H-mannitol and 14C-PEG 400 molecules compared with proximal colon and ileum. Intestinal permeability in control vs. 10% DSS mice was not altered, although histologic inflammation score and IFN-gamma pro-inflammatory cytokine levels were significantly increased in proximal and distal colon. IL-1beta levels were enhanced in these proximal and distal segments, but not significantly different from controls. Any effect of pharmacologically induced contractility on intestinal permeability could not be observed. In conclusion, intestinal permeability and contractility are not correlated in this model of experimentally induced colitis in mice. Although simultaneous measurement in a physiological set-up is possible, this method has to be further validated. PMID:9705603

  13. Influence of the Thyroid State on the Intrinsic Contractile Properties and Energy Stores of the Myocardium*

    PubMed Central

    Buccino, Robert A.; Spann, James F.; Pool, Peter E.; Sonnenblick, Edmund H.; Braunwald, Eugene

    1967-01-01

    The intrinsic contractile properties of isolated cat papillary muscles and myocardial high energy phosphate stores were examined at three levels of thyroid activity and correlated with hemodynamic measurements in the intact animal. In addition, the relationship of thyroid state to endogenous norepinephrine stores and myocardial responsiveness to certain inotropic interventions were studied. In muscles from hyperthyroid cats, the velocity of shortening and the rate of tension development were markedly augmented, while duration of active state was decreased, compared to euthyroid muscles. These findings occurred in the presence and absence of intact norepinephrine stores and over a wide range of temperature and contraction frequency. The opposite changes occurred in muscles from hypothyroid cats. Isometric tension was slightly higher in muscles from hyperthyroid and lower in muscles from hypothyroid cats. The inotropic response to both norepinephrine and strophanthidin varied inversely with the level of thyroid state and allowed all three groups of muscles to reach a common ceiling of isometric tension regardless of thyroid state. Creatine phosphate and adenosine triphosphate stores were intact at all three levels of thyroid state. Thus, the level of thyroid activity profoundly affects the intrinsic contractile state of cardiac muscle, independent of both norepinephrine stores and alterations in high energy phosphate stores, and, in addition, modifies the responsiveness of cardiac muscle to inotropic agents. Images PMID:6061742

  14. Metallothionein Alleviates Oxidative Stress-Induced Endoplasmic Reticulum Stress and Myocardial Dysfunction

    PubMed Central

    Guo, Rui; Ma, Heng; Gao, Feng; Zhong, Li; Ren, Jun

    2009-01-01

    Oxidative stress and endoplasmic reticulum (ER) stress have been implicated in cardiovascular diseases although the interplay between the two is not clear. This study was designed to examine the influence of oxidative stress through glutathione depletion on myocardial ER stress and contractile function in the absence or presence of the heavy metal scavenger antioxidant metallothionein (MT). FVB and MT overexpression transgenic mice received the GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mM) in drinking water for 2 weeks. Oxidative stress, ER stress, apoptosis, cardiac function and ultrastructure were assessed using GSH/GSSG assay, reactive oxygen species (ROS), immunoblotting, caspase-3 activity, Langendorff perfused heart function (LVDP and ± dP/dt), and transmission electron microscopy. BSO led to a robust decrease in the GSH/GSSG ratio and increased ROS production, consolidating oxidative stress. Cardiac function and ultrastructure were compromised following BSO treatment, the effect of which was obliterated by MT. BSO promoted overt ER stress as evidenced by upregulated BiP, calregulin, phospho-IRE1α and phospho-eIF2α without affecting total IRE1α and eIF2α. BSO treatment led to apoptosis manifested as elevated expression of CHOP/GADD153, caspase-12 and Bax as well as caspase-3 activity, reduced Bcl-2 expression and JNK phosphorylation, all of which was ablated by MT. Moreover, both antioxidant N-acetylcysteine and the ER stress inhibitor tauroursodeoxycholic acid reversed the oxidative stress inducer menadione-elicited depression in cardiomyocyte contractile function. Taken together, these data suggested that ER stress occurs likely downstream of oxidative stress en route to cardiac dysfunction. PMID:19344729

  15. Novel inhibition of contractility by wortmannin in skeletal muscle

    PubMed Central

    Hong, S J; Chang, C C

    1998-01-01

    The effects of wortmannin and 2-(4-morpholinyl)-8-phenyl-1[4H]-benzopyran-4-one (LY294002), inhibitors of phosphatidylinositol 3-kinase, on the contractile responses of murine skeletal muscle were studied. Wortmannin (10–100 μM) suppressed twitch and tetanic contraction evoked by field stimulation of diaphragm without causing elevation of muscle tone. The inhibition was quasi-irreversible with IC50∼15 μM. In contrast, LY294002 increased twitch responses and elevated muscle tone.Wortmannin reversibly depressed the maximal slope of action potential upstroke by ∼40% and inhibited the membrane depolarization and spontaneous burst of action potential induced by crotamine, a polypeptide toxin that activates the Na+ channel of skeletal muscle.Wortmannin inhibited contractures evoked by high K+, ryanodine and caffeine, but potentiated the contracture induced by rapamycin, which binds to myoplasmic FK506 binding protein, an immunophilin closely associated with the ryanodine receptor. The contractures elicited by cardiotoxin, which disrupts the integrity of sarcolemma and thereby elevates `myoplasmic' Ca2+ level, were suppressed only slightly.In placed left atrium and ventricular strip, wortmannin and LY294002 produced a positive inotropic effect.The results suggest that, in addition to depressing the Ca2+ mobilization from sarcoplasmic reticulum, wortmannin exerts a novel inhibitory action on the excitation-contraction coupling in skeletal muscle but not in cardiac muscle. PMID:9692768

  16. Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3

    NASA Technical Reports Server (NTRS)

    Clancy, J. S.; Takeshima, H.; Hamilton, S. L.; Reid, M. B.

    1999-01-01

    Skeletal muscle expresses at least two isoforms of the calcium release channel in the sarcoplasmic reticulum (RyR1 and RyR3). Whereas the function of RyR1 is well defined, the physiological significance of RyR3 is unclear. Some authors have suggested that RyR3 participates in excitation-contraction coupling and that RyR3 may specifically confer resistance to fatigue. To test this hypothesis, we measured contractile function of diaphragm strips from adult RyR3-deficient mice (exon 2-targeted mutation) and their heterozygous and wild-type littermates. In unfatigued diaphragm, there were no differences in isometric contractile properties (twitch characteristics, force-frequency relationships, maximal force) among the three groups. Our fatigue protocol (30 Hz, 0.25 duty cycle, 37 degrees C) depressed force to 25% of the initial force; however, lack of RyR3 did not accelerate the decline in force production. The force-frequency relationship was shifted to higher frequencies and was depressed in fatigued diaphragm; lack of RyR3 did not exaggerate these changes. We therefore provide evidence that RyR3 deficiency does not alter contractile function of adult muscle before, during, or after fatigue.

  17. Feeding the fibrillating heart: Dichloroacetate improves cardiac contractile dysfunction following VF.

    PubMed

    Azam, Mohammed Ali; Wagg, Cory S; Massé, Stéphane; Farid, Talha; Lai, Patrick F H; Kusha, Marjan; Asta, John; Jaimes, Rafael; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Lopaschuk, Gary D; Nanthakumar, Kumaraswamy

    2015-11-01

    Ventricular fibrillation (VF) is an important cause of sudden cardiac arrest following myocardial infarction. Following resuscitation from VF, decreased cardiac contractile function is a common problem. During and following myocardial ischemia, decreased glucose oxidation, increased anaerobic glycolysis for cardiac energy production are harmful and energetically expensive. The objective of the present study is to determine the effects of dichloroacetate (DCA), a glucose oxidation stimulator, on cardiac contractile dysfunction following ischemia-induced VF. Male Sprague-Dawley rat hearts were Langendorff perfused in Tyrode's buffer. Once stabilized, hearts were subjected to 15 min of global ischemia and 5 min of aerobic reperfusion in the presence or absence of DCA. At the 6th min of reperfusion, VF was induced electrically, and terminated. Left ventricular (LV) pressure was measured using a balloon. Pretreatment with DCA significantly improved post-VF left ventricular developed pressure (LVDP) and dp/dtmax. In DCA-pretreated hearts, post-VF lactate production and pyruvate dehydrogenase (PDH) phosphorylation were significantly reduced, indicative of stimulated glucose oxidation, and inhibited anaerobic glycolysis by activation of PDH. Epicardial NADH fluorescence was increased during global ischemia above preischemic levels, but decreased below preischemia levels following VF, with no differences between nontreated controls and DCA-pretreated hearts, whereas DCA pretreatment increased NADH production in nonischemic hearts. With exogenous fatty acids (FA) added to the perfusion solution, DCA pretreatment also resulted in improvements in post-VF LVDP and dp/dtmax, indicating that the presence of exogenous FA did not affect the beneficial actions of DCA. In conclusion, enhancement of PDH activation by DCA mitigates cardiac contractile dysfunction following ischemia-induced VF. PMID:26342067

  18. Circumferential Strain Can Be Used to Detect Lipopolysaccharide-Induced Myocardial Dysfunction and Predict the Mortality of Severe Sepsis in Mice

    PubMed Central

    Chu, Ming; Gao, Yao; Zhou, Bin; Wu, Bingruo; Wang, Junhong; Xu, Di

    2016-01-01

    Background Sepsis-induced myocardial dysfunction is a common and severe complication of septic shock. However, conventional echocardiography often fails to reveal myocardial depression in severe sepsis. Recently, strain measurements based on speckle tracking echocardiography (STE) have been used to evaluate cardiac function. Aims To investigate the role of STE in detecting lipopolysaccharide (LPS)-induced cardiac dysfunction, M-mode and 2-D echocardiography were used in LPS-treated mice. Methods The mice were treated with a 10mg/kg (n = 10), 20mg/kg (n = 10) or 25mg/kg LPS (n = 30) to induce cardiac dysfunction. Subsequently, the ejection fraction (EF) and fractional shortening (FS) were measured with standard M-mode tracings, whereas the circumferential (Scirc) and radial strain (Srad) were measured with STE. Serum biochemical and cardiac histopathological examinations were performed to assess sepsis-induced myocardial injury. Results 20mg/kg LPS resulted in more deterioration, myocardial damage and cardiac contractile dysfunction based on serum biochemical and histological examinations. The mice that were subjected to 20mg/kg LPS exhibited reduced Scirc but no reduction in Srad, whereas on conventional echocardiography, the ejection fraction (EF) and fractional shortening (FS) were similar in the 10mg/kg and 20mg/kg groups. Moreover, Scirc was positively correlated with body temperature in the mice at 20 h after LPS injection (r = 0.746, p = 0.001), but no significant correlation was observed between Srad and body temperature (r = 0.356, p = 0.123). Moreover, the mice with high Scirc (-5.9% to -10.4%) exhibited reduced mortality following the administration of 25mg/kg LPS (p = 0.03) compared with the low-strain group (-2% to -5.9%). Conclusions Taken together, our findings indicate that circumferential strain is a specific and reliable indicator for evaluating LPS-induced cardiac dysfunction in mice. PMID:27177150

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  20. Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm.

    PubMed

    Wright, V P; Klawitter, P F; Iscru, D F; Merola, A J; Clanton, T L

    2005-05-01

    Acute exposure to severe hypoxia depresses contractile function and induces adaptations in skeletal muscle that are only partially understood. Previous studies have demonstrated that antioxidants (AOXs) given during hypoxia partially protect contractile function, but this has not been a universal finding. This study confirms that specific AOXs, known to act primarily as superoxide scavengers, protect contractile function in severe hypoxia. Furthermore, the hypothesis is tested that the mechanism of protection involves preservation of high-energy phosphates (ATP, creatine phosphate) and reductions of P(i). Rat diaphragm muscle strips were treated with AOXs and subjected to 30 min of hypoxia. Contractile function was examined by using twitch and tetanic stimulations and the degree of elevation in passive force occurring during hypoxia (contracture). High-energy phosphates were measured at the end of 30-min hypoxia exposure. Treatment with the superoxide scavengers 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron, 10 mM) or Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (50 microM) suppressed contracture during hypoxia and protected maximum tetanic force. N-acetylcysteine (10 or 18 mM) had no influence on tetanic force production. Contracture during hypoxia without AOXs was also shown to be dependent on the extracellular Ca(2+) concentration. Although hypoxia resulted in only small reductions in ATP concentration, creatine phosphate concentration was decreased to approximately 10% of control. There were no consistent influences of the AOX treatments on high-energy phosphates during hypoxia. The results demonstrate that superoxide scavengers can protect contractile function and reduce contracture in hypoxia through a mechanism that does not involve preservation of high-energy phosphates. PMID:15640388

  1. Myocardial protection with mild hypothermia.

    PubMed

    Tissier, Renaud; Ghaleh, Bijan; Cohen, Michael V; Downey, James M; Berdeaux, Alain

    2012-05-01

    Mild hypothermia, 32-35° C, is very potent at reducing myocardial infarct size in rabbits, dogs, sheep, pigs, and rats. The benefit is directly related to reduction in normothermic ischaemic time, supporting the relevance of early and rapid cooling. The cardioprotective effect of mild hypothermia is not limited to its recognized reduction of infarct size, but also results in conservation of post-ischaemic contractile function, prevention of no-reflow or microvascular obstruction, and ultimately attenuation of left ventricular remodelling. The mechanism of the anti-infarct effect does not appear to be related to diminished energy utilization and metabolic preservation, but rather to survival signalling that involves either the extracellular signal-regulated kinases and/or the Akt/phosphoinositide 3-kinase/mammalian target of rapamycin pathways. Initial clinical trials of hypothermia in patients with ST-segment elevation myocardial infarction were disappointing, probably because cooling was too slow to shorten normothermic ischaemic time appreciably. New approaches to more rapid cooling have recently been described and may soon be available for clinical use. Alternatively, it may be possible to pharmacologically mimic the protection provided by cooling soon after the onset of ischaemia with an activator of mild hypothermia signalling, e.g. extracellular signal-regulated kinase activator, that could be given by emergency medical personnel. Finally, the protection afforded by cooling can be added to that of pre- and post-conditioning because their mechanisms differ. Thus, myocardial salvage might be greatly increased by rapidly cooling patients as soon as possible and then giving a pharmacological post-conditioning agent immediately prior to reperfusion. PMID:22131353

  2. Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery.

    PubMed

    Py, G; Ramonatxo, C; Sirvent, P; Sanchez, A M J; Philippe, A G; Douillard, A; Galbès, O; Lionne, C; Bonnieu, A; Chopard, A; Cazorla, O; Lacampagne, A; Candau, R B

    2015-04-15

    Clenbuterol is a β2 -adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg(-1) day(-1) ) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po ) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P < 0.05). The fit of muscle contraction and relaxation force kinetics indicated that clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P < 0.05), and only the fast rate constant of relaxation in soleus muscle (P < 0.05). Myofibrillar ATPase activity increased in both relaxed and activated conditions in soleus (P < 0.001), suggesting that the depressed specific tension was not due to the myosin head alteration itself. Moreover, action potential-elicited Ca(2+) transients in flexor digitorum brevis fibres (fast twitch fibres) from clenbuterol-treated animals demonstrated decreased amplitude after 14 days (-19%, P < 0.01) and 21 days (-25%, P < 0.01). In conclusion, we showed that chronic clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca(2+) release during contraction could partially explain these deleterious effects. PMID:25656230

  3. Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery

    PubMed Central

    Py, G; Ramonatxo, C; Sirvent, P; Sanchez, A M J; Philippe, A G; Douillard, A; Galbès, O; Lionne, C; Bonnieu, A; Chopard, A; Cazorla, O; Lacampagne, A; Candau, R B

    2015-01-01

    Clenbuterol is a β2-adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg−1 day−1) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P < 0.05). The fit of muscle contraction and relaxation force kinetics indicated that clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P < 0.05), and only the fast rate constant of relaxation in soleus muscle (P < 0.05). Myofibrillar ATPase activity increased in both relaxed and activated conditions in soleus (P < 0.001), suggesting that the depressed specific tension was not due to the myosin head alteration itself. Moreover, action potential-elicited Ca2+ transients in flexor digitorum brevis fibres (fast twitch fibres) from clenbuterol-treated animals demonstrated decreased amplitude after 14 days (−19%, P < 0.01) and 21 days (−25%, P < 0.01). In conclusion, we showed that chronic clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca2+ release during contraction could partially explain these deleterious effects. PMID:25656230

  4. Stretch-induced increase in cardiac contractility is independent of myocyte Ca2+ while block of stretch channels by streptomycin improves contractility after ischemic stunning

    PubMed Central

    Rhodes, Samhita S; Camara, Amadou K S; Aldakkak, Mohammed; Heisner, James S; Stowe, David F

    2015-01-01

    Stretching the cardiac left ventricle (LV) enhances contractility but its effect on myoplasmic [Ca2+] is controversial. We measured LV pressure (LVP) and [Ca2+] as a function of intra-LV stretch in guinea pig intact hearts before and after 15 min global stunning ± perfusion with streptomycin (STM), a stretch-activated channel blocker. LV wall [Ca2+] was measured by indo-1 fluorescence and LVP by a saline-filled latex balloon inflated in 50 μL steps to stretch the LV. We implemented a mathematical model to interpret cross-bridge dynamics and myofilament Ca2+ responsiveness from the instantaneous relationship between [Ca2+] and LVP ± stretching. We found that: (1) stretch enhanced LVP but not [Ca2+] before and after stunning in either control (CON) and STM groups, (2) after stunning [Ca2+] increased in both groups although higher in STM versus CON (56% vs. 39%), (3) STM-enhanced LVP after stunning compared to CON (98% vs. 76% of prestunning values), and (4) stretch-induced effects on LVP were independent of [Ca2+] before or after stunning in both groups. Mathematical modeling suggested: (1) cooperativity in cross-bridge kinetics and myofilament Ca2+ handling is reduced after stunning in the unstretched heart, (2) stunning results in depressed myofilament Ca2+ sensitivity in the presence of attached cross-bridges regardless of stretch, and (3) the initial mechanism responsible for increased contractility during stretch may be enhanced formation of cross-bridges. Thus stretch-induced enhancement of contractility is not due to increased [Ca2+], whereas enhanced contractility after stunning in STM versus CON hearts results from improved Ca2+ handling and/or enhanced actinomyosin cross-bridge cycling. PMID:26290532

  5. Transient myocardial ischaemia after acute myocardial infarction does not induce ventricular arrhythmias.

    PubMed Central

    Currie, P; Saltissi, S

    1993-01-01

    OBJECTIVE--To see whether transient myocardial ischaemia on ambulatory monitoring after myocardial infarction is associated with ventricular arrhythmias. DESIGN--A prospective study. SETTING--The coronary care unit, general medical wards, and cardiorespiratory department of a major teaching hospital. PATIENTS--203 consecutive patients without specific exclusion criteria admitted with acute myocardial infarction. INTERVENTIONS--24 hour ambulatory electrocardiographic monitoring for ventricular arrhythmias and ST depression both early (mean 6.3 days after infarction, n = 201) and late (mean 38 days, n = 177). MAIN OUTCOME MEASURES--Episodes of myocardial ischaemia were identified during ambulatory monitoring by transient ST depression of > or = 1.0 mm lasting for > or = 30 s. Ventricular arrhythmias were single extrasystoles, couplets, or ventricular tachycardia. RESULTS--All ventricular arrhythmias were significantly more frequent in late than early monitoring. The arrhythmias included couplets (in 83/174 (48%) v 49/200 (25%) of patients, p = 0.0000028) and ventricular tachycardia (29/174 (17%) v 15/199 (8%), p = 0.0064). Patients with ST depression (29 early; 56 late), compared with those without ischaemia, did not experience a significant increase in single extrasystoles, couplets (31% v 23% early; 47% v 48% late), or ventricular tachycardia (3% v 8% early; 18% v 16% late). Even patients with frequent (> or = 3 episodes), and deep (> or = 1.5 mm) or prolonged (> or = 20 min) ST depression had no increase in arrhythmias. CONCLUSIONS--Ventricular arrhythmias after myocardial infarction are not associated with transient myocardial ischaemia during daily activities. This study does not support the belief that to abolish silent ischaemia would reduce the incidence of sudden death due to uncontrollable ventricular arrhythmias after myocardial infarction. PMID:8489860

  6. Spontaneous actin dynamics in contractile rings

    NASA Astrophysics Data System (ADS)

    Kruse, Karsten; Wollrab, Viktoria; Thiagarajan, Raghavan; Wald, Anne; Riveline, Daniel

    Networks of polymerizing actin filaments are known to be capable to self-organize into a variety of structures. For example, spontaneous actin polymerization waves have been observed in living cells in a number of circumstances, notably, in crawling neutrophils and slime molds. During later stages of cell division, they can also spontaneously form a contractile ring that will eventually cleave the cell into two daughter cells. We present a framework for describing networks of polymerizing actin filaments, where assembly is regulated by various proteins. It can also include the effects of molecular motors. We show that the molecular processes driven by these proteins can generate various structures that have been observed in contractile rings of fission yeast and mammalian cells. We discuss a possible functional role of each of these patterns. The work was supported by Agence Nationale de la Recherche, France, (ANR-10-LABX-0030-INRT) and by Deutsche Forschungsgemeinschaft through SFB1027.

  7. Actomyosin contractility rotates the cell nucleus

    PubMed Central

    Kumar, Abhishek; Maitra, Ananyo; Sumit, Madhuresh; Ramaswamy, Sriram; Shivashankar, G. V.

    2014-01-01

    The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells. PMID:24445418

  8. Oligophrenin1 protects mice against myocardial ischemia and reperfusion injury by modulating inflammation and myocardial apoptosis.

    PubMed

    Niermann, Christina; Gorressen, Simone; Klier, Meike; Gowert, Nina S; Billuart, Pierre; Kelm, Malte; Merx, Marc W; Elvers, Margitta

    2016-08-01

    The Rho family of small GTPases has been analyzed in cardiac physiology and pathophysiology including myocardial infarction (MI) in the last years. Contradictory results show either a protective or a declined effect of RhoA and the RhoA effector Rho-associated protein kinase (ROCK) in myocardial ischemia and reperfusion injury that is associated with cardiomyocyte survival and caspase-3 activation. Cardiac-specific deletion of Rac1 reduced ischemia reperfusion injury in diabetic hearts, whereas cardiomyocyte specific overexpression of active Rac1 predisposes the heart to increased myocardial injury with enhanced contractile dysfunction. GTPase-activating proteins (GAPs) control the activation of Rho proteins through stimulation of GTP hydrolysis. However, the impact of GAPs in myocardial ischemia and reperfusion injury remains elusive. Here we analyzed the role of oligophrenin1 (OPHN1), a RhoGAP with Bin/Amphiphysin/Rvs (BAR) domain known to regulate the activity of RhoA, Rac1 and Cdc42 in MI. The expression of Ophn1, RhoA and Rac1 is strongly upregulated 24h after myocardial ischemia. Loss of OPHN1 induced enhanced activity of Rho effector molecules leading to elevated cardiomyocyte apoptosis and increased migration of inflammatory cells into the infarct border zone of OPHN1 deficient mice. Consequently, echocardiography 24h after myocardial ischemia revealed declined left ventricle function in OPHN1 deficient mice. Our results indicate that OPHN1 mediated regulation of RhoA, Rac1 and Cdc42 is crucial for the preservation of cardiac function after myocardial injury. PMID:27117132

  9. Elastomeric contractile actuators for hand rehabilitation splints

    NASA Astrophysics Data System (ADS)

    Carpi, Federico; Mannini, Andrea; De Rossi, Danilo

    2008-03-01

    The significant electromechanical performances typically shown by dielectric elastomer actuators make this polymer technology particularly attractive for possible active orthoses for rehabilitation. Folded contractile actuators made of dielectric elastomers were recently described as a simple configuration, suitable to easily implement linear contractile devices. This paper describes an application of folded actuators for so-called hand splints: they consist of orthotic systems for hand rehabilitation. The dynamic versions of the state-of-the-art splints typically include elastic bands, which exert a passive elastic resistance to voluntary elongations of one or more fingers. In order to provide such splints with the possibility of electrically modulating the compliance of the resistive elements, the substitution of the passive elastic bands with the contractile actuators is here described. The electrical activation of the actuators is used to vary the compliance of the system; this enables modulations of the force that acts as an antagonist to voluntary finger movements, according to programmable rehabilitation exercises. The paper reports results obtained from the first prototype implementations of such a type of system.

  10. Contractile network models for adherent cells.

    PubMed

    Guthardt Torres, P; Bischofs, I B; Schwarz, U S

    2012-01-01

    Cells sense the geometry and stiffness of their adhesive environment by active contractility. For strong adhesion to flat substrates, two-dimensional contractile network models can be used to understand how force is distributed throughout the cell. Here we compare the shape and force distribution for different variants of such network models. In contrast to Hookean networks, cable networks reflect the asymmetric response of biopolymers to tension versus compression. For passive networks, contractility is modeled by a reduced resting length of the mechanical links. In actively contracting networks, a constant force couple is introduced into each link in order to model contraction by molecular motors. If combined with fixed adhesion sites, all network models lead to invaginated cell shapes, but only actively contracting cable networks lead to the circular arc morphology typical for strongly adhering cells. In this case, shape and force distribution are determined by local rather than global determinants and thus are suited to endow the cell with a robust sense of its environment. We also discuss nonlinear and adaptive linker mechanics as well as the relation to tissue shape. PMID:22400597

  11. Contractile network models for adherent cells

    NASA Astrophysics Data System (ADS)

    Guthardt Torres, P.; Bischofs, I. B.; Schwarz, U. S.

    2012-01-01

    Cells sense the geometry and stiffness of their adhesive environment by active contractility. For strong adhesion to flat substrates, two-dimensional contractile network models can be used to understand how force is distributed throughout the cell. Here we compare the shape and force distribution for different variants of such network models. In contrast to Hookean networks, cable networks reflect the asymmetric response of biopolymers to tension versus compression. For passive networks, contractility is modeled by a reduced resting length of the mechanical links. In actively contracting networks, a constant force couple is introduced into each link in order to model contraction by molecular motors. If combined with fixed adhesion sites, all network models lead to invaginated cell shapes, but only actively contracting cable networks lead to the circular arc morphology typical for strongly adhering cells. In this case, shape and force distribution are determined by local rather than global determinants and thus are suited to endow the cell with a robust sense of its environment. We also discuss nonlinear and adaptive linker mechanics as well as the relation to tissue shape.

  12. ATP-independent contractile proteins from plants

    NASA Astrophysics Data System (ADS)

    Knoblauch, Michael; Noll, Gundula A.; Müller, Torsten; Prüfer, Dirk; Schneider-Hüther, Ingrid; Scharner, Dörte; van Bel, Aart J. E.; Peters, Winfried S.

    2003-09-01

    Emerging technologies are creating increasing interest in smart materials that may serve as actuators in micro- and nanodevices. Mechanically active polymers currently studied include a variety of materials. ATP-driven motor proteins, the actuators of living cells, possess promising characteristics, but their dependence on strictly defined chemical environments can be disadvantagous. Natural proteins that deform reversibly by entropic mechanisms might serve as models for artificial contractile polypeptides with useful functionality, but they are rare. Protein bodies from sieve elements of higher plants provide a novel example. sieve elements form microfluidics systems for pressure-driven transport of photo-assimilates throughout the plant. Unique protein bodies in the sieve elements of legumes act as cellular stopcocks, by undergoing a Ca2+-dependent conformational switch in which they plug the sieve element. In living cells, this reaction is probably controlled by Ca2+-transporters in the cell membrane. Here we report the rapid, reversible, anisotropic and ATP-independent contractility in these protein bodies in vitro. Considering the unique biological function of the legume 'crystalloid' protein bodies and their contractile properties, we suggest to give them the distinctive name forisome ('gate-body'; from the Latin foris, the wing of a gate).

  13. SIRT3 deficiency impairs mitochondrial and contractile function in the heart.

    PubMed

    Koentges, Christoph; Pfeil, Katharina; Schnick, Tilman; Wiese, Sebastian; Dahlbock, Rabea; Cimolai, Maria C; Meyer-Steenbuck, Maximilian; Cenkerova, Katarina; Hoffmann, Michael M; Jaeger, Carsten; Odening, Katja E; Kammerer, Bernd; Hein, Lutz; Bode, Christoph; Bugger, Heiko

    2015-01-01

    Sirtuin 3 (SIRT3) is a mitochondrial NAD(+)-dependent deacetylase that regulates energy metabolic enzymes by reversible protein lysine acetylation in various extracardiac tissues. The role of SIRT3 in myocardial energetics and in the development of mitochondrial dysfunction in cardiac pathologies, such as the failing heart, remains to be elucidated. To investigate the role of SIRT3 in the regulation of myocardial energetics and function SIRT3(-/-) mice developed progressive age-related deterioration of cardiac function, as evidenced by a decrease in ejection fraction and an increase in enddiastolic volume at 24 but not 8 weeks of age using echocardiography. Four weeks following transverse aortic constriction, ejection fraction was further decreased in SIRT3(-/-) mice compared to WT mice, accompanied by a greater degree of cardiac hypertrophy and fibrosis. In isolated working hearts, a decrease in cardiac function in SIRT3(-/-) mice was accompanied by a decrease in palmitate oxidation, glucose oxidation, and oxygen consumption, whereas rates of glycolysis were increased. Respiratory capacity and ATP synthesis were decreased in cardiac mitochondria of SIRT3(-/-) mice. HPLC measurements revealed a decrease of the myocardial ATP/AMP ratio and of myocardial energy charge. Using LC-MS/MS, we identified increased acetylation of 84 mitochondrial proteins, including 6 enzymes of fatty acid import and oxidation, 50 subunits of the electron transport chain, and 3 enzymes of the tricarboxylic acid cycle. Lack of SIRT3 impairs mitochondrial and contractile function in the heart, likely due to increased acetylation of various energy metabolic proteins and subsequent myocardial energy depletion. PMID:25962702

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

    PubMed

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

    2016-03-01

    Diadenosine polyphosphates (Ap(n)As) are endogenously produced molecules which have been identified in various tissues of mammalian organism, including myocardium. Ap(n)As contribute to the blood clotting and are also widely accepted as regulators of blood vascular tone. Physiological role of Ap(n)As in cardiac muscle has not been completely elucidated. The present study aimed to investigate the effects of diadenosine tetra- (Ap4A) and penta- (Ap5A) polyphosphates on contractile function and action potential (AP) waveform in rat supraventricular and ventricular myocardium. We have also demonstrated the effects of A4pA and Ap5A in myocardial sleeves of pulmonary veins (PVs), which play a crucial role in genesis of atrial fibrillation. APs were recorded with glass microelectrodes in multicellular myocardial preparations. Contractile activity was measured in isolated Langendorff-perfused rat hearts. Both Ap4A and Ap5A significantly reduced contractility of isolated Langendorff-perfused heart and produced significant reduction of AP duration in left and right auricle, interatrial septum, and especially in right ventricular wall myocardium. Ap(n)As also shortened APs in rat pulmonary veins and therefore may be considered as potential proarrhythmic factors. Cardiotropic effects of Ap4A and Ap5A were strongly antagonized by selective blockers of P2 purine receptors suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), while P1 blocker DPCPX was not effective. We conclude that Ap(n)As may be considered as new class of endogenous cardioinhibitory compounds. P2 purine receptors play the central role in mediation of Ap4A and Ap5A inhibitory effects on electrical and contractile activity in different regions of the rat heart. PMID:26680209

  15. Innate immune adaptor MyD88 mediates neutrophil recruitment and myocardial injury after ischemia-reperfusion in mice

    PubMed Central

    Feng , Yan; Zhao, Huailong; Xu, Xinhua; Buys, Emmanuel S.; Raher, Michael J.; Bopassa, Jean C.; Thibault, Helene; Scherrer-Crosbie, Marielle; Schmidt, Ulrich; Chao, Wei

    2008-01-01

    MyD88 is an adaptor protein critical for innate immune response against microbial infection and in certain noninfectious tissue injury. The present study examined the role of MyD88 in myocardial inflammation and injury after ischemia-reperfusion (I/R). I/R was produced by coronary artery ligation for 30 min followed by reperfusion. The ratios of area at risk to left ventricle (LV) were similar between wild-type (WT) and MyD88-deficient (MyD88−/−) mice. However, 24 h after I/R, the ratios of myocardial infarction to area at risk were 58% less in MyD88−/− than in WT mice (14 ± 2% vs. 33 ± 6%, P = 0.01). Serial echocardiographic studies demonstrated that there was no difference in baseline LV contractile function between the two groups. Twenty-four hours after I/R, LV ejection fraction (EF) and fractional shortening (FS) in WT mice were reduced by 44% and 62% (EF, 51 ± 2%, and FS, 22 ± 1%, P < 0.001), respectively, and remained depressed on the seventh day after I/R. In comparison, EF and FS in MyD88−/− mice were 67 ± 3% and 33 ± 2%, respectively, after I/R (P < 0.001 vs. WT). Similarly, LV function, as demonstrated by invasive hemodynamic measurements, was better preserved in MyD88−/− compared with WT mice after I/R. Furthermore, when compared with WT mice, MyD88−/− mice subjected to I/R had a marked decrease in myocardial inflammation as demonstrated by attenuated neutrophil recruitment and decreased expression of the proinflammatory mediators keratinocyte chemoattractant, monocyte chemoattractant protein-1, and ICAM-1. Taken together, these data suggest that MyD88 modulates myocardial inflammatory injury and contributes to myocardial infarction and LV dysfunction during I/R. PMID:18660455

  16. R4496C RyR2 mutation impairs atrial and ventricular contractility

    PubMed Central

    Coppini, Raffaele; Scellini, Beatrice; Ferrara, Claudia; Pioner, Josè Manuel; Mazzoni, Luca; Priori, Silvia; Cerbai, Elisabetta; Tesi, Chiara; Poggesi, Corrado

    2016-01-01

    Ryanodine receptor (RyR2) is the major Ca2+ channel of the cardiac sarcoplasmic reticulum (SR) and plays a crucial role in the generation of myocardial force. Changes in RyR2 gating properties and resulting increases in its open probability (Po) are associated with Ca2+ leakage from the SR and arrhythmias; however, the effects of RyR2 dysfunction on myocardial contractility are unknown. Here, we investigated the possibility that a RyR2 mutation associated with catecholaminergic polymorphic ventricular tachycardia, R4496C, affects the contractile function of atrial and ventricular myocardium. We measured isometric twitch tension in left ventricular and atrial trabeculae from wild-type mice and heterozygous transgenic mice carrying the R4496C RyR2 mutation and found that twitch force was comparable under baseline conditions (30°C, 2 mM [Ca2+]o, 1 Hz). However, the positive inotropic responses to high stimulation frequency, 0.1 µM isoproterenol, and 5 mM [Ca2+]o were decreased in R4496C trabeculae, as was post-rest potentiation. We investigated the mechanisms underlying inotropic insufficiency in R4496C muscles in single ventricular myocytes. Under baseline conditions, the amplitude of the Ca2+ transient was normal, despite the reduced SR Ca2+ content. Under inotropic challenge, however, R4496C myocytes were unable to boost the amplitude of Ca2+ transients because they are incapable of properly increasing the amount of Ca2+ stored in the SR because of a larger SR Ca2+ leakage. Recovery of force in response to premature stimuli was faster in R4496C myocardium, despite the unchanged rates of recovery of L-type Ca2+ channel current (ICa-L) and SR Ca2+ content in single myocytes. A faster recovery from inactivation of the mutant R4496C channels could explain this behavior. In conclusion, changes in RyR2 channel gating associated with the R4496C mutation could be directly responsible for the alterations in both ventricular and atrial contractility. The increased RyR2 Po

  17. Depression in Coronary Artery Disease

    PubMed Central

    Safaie, Nasser; Jodati, Ahmad Reza; Raoofi, Mohammad; Khalili, Majid

    2012-01-01

    Introduction Depression is one of the Common psychological disorders. From the cognitive point of view, the unhealthy attitudes increase the severity of the depression. The aim of this study was to investigate depression and unhealthy attitudes in coronary patients hospitalized at Tabriz Shahid Madani Heart Center. Methods One hundred twenty eight hospitalized patients having myocardial Infarctions were studied regarding unhealthy attitudes, severity of depression and demographic data. Results The study showed a significant relation between unhealthy attitudes, BDI (Beck Depression Inventory) and severe depression. Moreover, a significant relation existed between gender and depression (P=0.0001). In addition, the level of education increased the intensity of unhealthy attitudes (P=0.0001). Several researches in both outside and inside Iran support the idea. Conclusion Based on present study and more other investigations, it can be suggested to provide the necessary elements and parameters such as antidepressant medication, psychologists, complementary treatment for coping with negative mood and its unwanted consequences. PMID:24250990

  18. Cell stiffness, contractile stress and the role of extracellular matrix

    SciTech Connect

    An, Steven S.; Kim, Jina; Ahn, Kwangmi; Trepat, Xavier; Drake, Kenneth J.; Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne; Fredberg, Jeffrey J.; Biswal, Shyam

    2009-05-15

    Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

  19. Cytoskeletal Role in the Contractile Dysfunction of Hypertrophied Myocardium

    NASA Astrophysics Data System (ADS)

    Tsutsui, Hiroyuki; Ishihara, Kazuaki; Cooper, George

    1993-04-01

    Cardiac hypertrophy in response to systolic pressure loading frequently results in contractile dysfunction of unknown cause. In the present study, pressure loading increased the microtubule component of the cardiac muscle cell cytoskeleton, which was responsible for the cellular contractile dysfunction observed. The linked microtubule and contractile abnormalities were persistent and thus may have significance for the deterioration of initially compensatory cardiac hypertrophy into congestive heart failure.

  20. Regulation of tissue morphodynamics: an important role for actomyosin contractility

    PubMed Central

    Siedlik, Michael J.; Nelson, Celeste M.

    2015-01-01

    Forces arising from contractile actomyosin filaments help shape tissue form during morphogenesis. Developmental events that result from actomyosin contractility include tissue elongation, bending, budding, and collective migration. Here, we highlight recent insights into these morphogenetic processes from the perspective of actomyosin contractility as a key regulator. Emphasis is placed on a range of results obtained through live imaging, culture, and computational methods. Combining these approaches in the future has the potential to generate a robust, quantitative understanding of tissue morphodynamics. PMID:25748251

  1. Canonical transient receptor potential 1 channel is involved in contractile function of glomerular mesangial cells.

    PubMed

    Du, Juan; Sours-Brothers, Sherry; Coleman, Rashadd; Ding, Min; Graham, Sarabeth; Kong, De-Hu; Ma, Rong

    2007-05-01

    Contractility of mesangial cells (MC) is tightly controlled by [Ca(2+)](i). Ca(2+) influx across the plasma membrane constitutes a major component of mesangial responses to vasoconstrictors. Canonical transient receptor potential 1 (TRPC1) is a Ca(2+)-permeable cation channel in a variety of cell types. This study was performed to investigate whether TRPC1 takes part in vasoconstrictor-induced mesangial contraction by mediating Ca(2+) entry. It was found that angiotensin II (AngII) evoked remarkable contraction of the cultured MC. Downregulation of TRPC1 using RNA interference significantly attenuated the contractile response. Infusion of AngII or endothelin-1 in rats caused a decrease in GFR. The GFR decline was significantly reduced by infusion of TRPC1 antibody that targets an extracellular domain in the pore region of TRPC1 channel. However, the treatment of TRPC1 antibody did not affect the AngII-induced vasopressing effect. Electrophysiologic experiments revealed that functional or biologic inhibition of TRPC1 significantly depressed AngII-induced channel activation. Fura-2 fluorescence-indicated that Ca(2+) entry in response to AngII stimulation was also dramatically inhibited by TRPC1 antibody and TRPC1-specific RNA interference. These results suggest that TRPC1 plays an important role in controlling contractile function of MC. Mediation of Ca(2+) entry might be the underlying mechanism for the TRPC1-associated MC contraction. PMID:17389736

  2. The mechanism of action of calcium antagonists on arrhythmias in early myocardial ischaemia: studies with nifedipine and DHM9.

    PubMed Central

    Curtis, M. J.; Walker, M. J.

    1988-01-01

    1. Nifedipine and DHM9 (carboxymethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate) were studied for their effects on arrhythmias resulting from regional myocardial ischaemia in conscious rats, and for their effects on left ventricular developed pressure in vitro. 2. Nifedipine possessed antiarrhythmic activity at a high dose of 10 mg kg-1 i.v., but not at 0.5 or 2 mg kg-1. Ventricular fibrillation (VF), tachycardia (VT), and ventricular premature beats (VPB) were all attenuated to a similar degree; nifedipine did not have a selectivity of action for high frequency arrhythmias. 3. Before coronary occlusion, the three doses of nifedipine reduced arterial blood pressure by a similar magnitude, indicating a similar (maximal) degree of systemic vasodilatation. The reductions in blood pressure were accompanied by reflex tachycardia. Heart rate and blood pressure did not correlate with the incidence or severity of arrhythmias. 4. DHM9 had no influence on arrhythmias, haemodynamic variables or the ECG, even at 20 mg kg-1 i.v. 5. Nifedipine concentration-dependently reduced contractility in perfused paced (5 Hz) rat ventricles in vitro. Raising the concentration of K+ in the perfusion fluid from 3 to 10 mequiv.l-1 increased the potency (-log10 EC50) of nifedipine up to four fold, and caused a significant depression in excitability. 6. DHM9 at up to 3 x 10(-5) M had no significant influence on ventricular contractility in vitro. 7. The results provided indirect evidence in support of the hypothesis that calcium antagonists inhibit ischaemia-induced arrhythmias by virtue of inhibition of the slow inward current (Isi) in the ischaemic ventricular myocardium. PMID:3207985

  3. PPAR-gamma activation fails to provide myocardial protection in ischemia and reperfusion in pigs.

    PubMed

    Xu, Ya; Gen, Michael; Lu, Li; Fox, Jennifer; Weiss, Sara O; Brown, R Dale; Perlov, Daniel; Ahmad, Hasan; Zhu, Peili; Greyson, Clifford; Long, Carlin S; Schwartz, Gregory G

    2005-03-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (I/R), thiazolidinedione PPAR-gamma activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-gamma activator that has been shown to be protective in I/R in large animals. However, because troglitazone contains both alpha-tocopherol and thiazolidinedione moieties, whether PPAR-gamma activation per se is protective in myocardial I/R in large animals remains uncertain. To address this question, 56 pigs were treated orally for 8 wk with troglitazone (75 mg x kg(-1) x day(-1)), rosiglitazone (3 mg x kg(-1) x day(-1)), or alpha-tocopherol (73 mg x kg(-1) x day(-1), equimolar to troglitazone dose) or received no treatment. Pigs were then anesthetized and subjected to 90 min of low-flow regional myocardial ischemia and 90 min of reperfusion. Myocardial expression of PPAR-gamma, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (Frank-Starling relations), substrate uptake, or expression of proinflammatory cytokines during I/R compared with untreated pigs. In contrast, preservation of myocardial contractile function and lactate uptake were greater and cytokine expression was attenuated in pigs treated with troglitazone or alpha-tocopherol compared with untreated pigs. Multivariate analysis indicated that presence of an alpha-tocopherol, but not a thiazolidinedione, moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-gamma activation is not protective in a porcine model of myocardial I/R. Protective effects of troglitazone are attributable to its alpha-tocopherol moiety. These findings, in

  4. Prognostic significance of transient myocardial ischaemia after first acute myocardial infarction: five year follow up study.

    PubMed Central

    Mickley, H.; Nielsen, J. R.; Berning, J.; Junker, A.; Møller, M.

    1995-01-01

    OBJECTIVE--To assess the five year prognostic significance of transient myocardial ischaemia on ambulatory monitoring after a first acute myocardial infarction, and to compare the diagnostic and long term prognostic value of ambulatory ST segment monitoring, maximal exercise testing, and echocardiography in patients with documented ischaemic heart disease. DESIGN--Prospective study. SETTING--Cardiology department of a teaching hospital. PATIENTS--123 consecutive men aged under 70 who were able to perform predischarge maximal exercise testing. INTERVENTIONS--Echocardiography two days before discharge (left ventricular ejection fraction), maximal bicycle ergometric testing one day before discharge (ST segment depression, angina, blood pressure, heart rate), and ambulatory ST segment monitoring (transient myocardial ischaemia) started at hospital discharge a mean of 11 (SD 5) days after infarction. MAIN OUTCOME MEASURES--Relation of ambulatory ST segment depression, exercise test variables, and left ventricular ejection fraction to subsequent objective (cardiac death or myocardial infarction) or subjective (need for coronary revascularisation) events. RESULTS--23 of the 123 patients had episodes of transient ST segment depression, of which 98% were silent. Over a mean of 5 (range 4 to 6) years of follow up, patients with ambulatory ischaemia were no more likely to have objective end points than patients without ischaemic episodes. If, however, subjective events were included an association between transient ST segment depression and an adverse long term outcome was found (Kaplan-Meier analysis; P = 0.004). The presence of exercise induced angina identified a similar proportion of patients with a poor prognosis (Kaplan-Meier analysis; P < 0.004). Both exertional angina and ambulatory ST segment depression had high specificity but poor sensitivity. The presence of exercise induced ST segment depression was of no value in predicting combined cardiac events. Indeed

  5. Depression - resources

    MedlinePlus

    Resources - depression ... Depression is a medical condition. If you think you may be depressed, see a health care provider. ... following organizations are good sources of information on depression : American Psychological Association -- www.apa.org/topics/depress/ ...

  6. Hibernating myocardium retains metabolic and contractile reserve despite regional reductions in flow, function, and oxygen consumption at rest.

    PubMed

    Fallavollita, James A; Malm, Brian J; Canty, John M

    2003-01-10

    Hibernating myocardium, characterized by reductions in flow and function at rest, has limited contractile reserve in response to increases in external workload. We hypothesized that this attenuation of function reflects an adaptive downregulation that prevents the development of metabolic evidence of ischemia during stress. To test this hypothesis, pigs were chronically instrumented with a proximal left anterior descending artery stenosis for 3 months, resulting in severe anteroapical hypokinesis with reduced resting perfusion (0.78+/-0.05 versus 0.94+/-0.07 mL x min(-1)x g(-1) in remote, P<0.01; and 0.99+/-0.08 in controls, P<0.05). Open-chest studies confirmed resting dysfunction compared with normal controls (segment shortening 9.2+/-2.2% versus 23.5+/-1.1%, P<0.05). Resting myocardial oxygen consumption was reduced (63+/-3 versus 77+/-6 microL x g(-1) x min(-1) in controls, P<0.05), yet lactate consumption was normal. Although subendocardial perfusion failed to increase during graded, intravenous epinephrine infusion (n=8), peak segment shortening (to 17.3+/-3.1%, P<0.05) and oxygen consumption (to 90+/-6 microL x g(-1) x min(-1), P<0.01) increased from the depressed resting levels. There was no lactate production in hibernating myocardium, and lactate uptake increased during stress (0.7+/-0.1 to 1.2+/-0.1 micromol x g(-1) x min(-1), P<0.05). The absence of metabolic evidence of ischemia was also confirmed during atrial pacing to a rate of 120 bpm (n=8). Thus, despite reductions in function and oxygen consumption at rest, hibernating myocardium retains the ability to increase metabolism without the development of acute ischemia. This supports the hypothesis that the downregulation of oxygen consumption and function in hibernating myocardium is an adaptive response that prevents a supply-demand imbalance during submaximal increases in cardiac workload when coronary flow reserve is limited. PMID:12522120

  7. Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes.

    PubMed

    Lee, Joon; Stagg, Mark A; Fukushima, Satsuki; Soppa, Gopal K R; Siedlecka, Urszula; Youssef, Samuel J; Suzuki, Ken; Yacoub, Magdi H; Terracciano, Cesare M N

    2009-04-01

    Adult progenitor cell transplantation has been proposed for the treatment of heart failure, but the mechanisms effecting functional improvements remain unknown. The aim of this study was to test the hypothesis that, in failing hearts treated with cell transplantation, the mechanical properties and excitation-contraction coupling of recipient cardiomyocytes are altered. Adult rats underwent coronary artery ligation, leading to myocardial infarction and chronic heart failure. After 3 wk, they received intramyocardial injections of either 10(7) green fluorescence protein (GFP)-positive bone marrow mononuclear cells or 5 x 10(6) GFP-positive skeletal myoblasts. Four weeks after injection, both cell types increased ejection fraction and reduced cardiomyocyte size. The contractility of isolated GFP-negative cardiomyocytes was monitored by sarcomere shortening assessment, Ca(2+) handling by indo-1 and fluo-4 fluorescence, and electrophysiology by patch-clamping techniques. Injection of either bone marrow cells or skeletal myoblasts normalized the impaired contractile performance and the prolonged time to peak of the Ca(2+) transient observed in failing cardiomyocytes. The smaller and slower L-type Ca(2+) current observed in heart failure normalized after skeletal myoblast, but not bone marrow cell, transplantation. Measurement of Ca(2+) sparks suggested a normalization of sarcoplasmic reticulum Ca(2+) leak after skeletal myoblast transplantation. The increased Ca(2+) wave frequency observed in failing myocytes was reduced by either bone marrow cells or skeletal myoblasts. In conclusion, the morphology, contractile performance, and excitation-contraction coupling of individual recipient cardiomyocytes are altered in failing hearts treated with adult progenitor cell transplantation. PMID:19181964

  8. Action of acetylstrophanthidin on experimental myocardial infarction.

    NASA Technical Reports Server (NTRS)

    Nola, G. T.; Pope, S. E.; Harrison, D. C.

    1972-01-01

    An experimental animal model with acute myocardial infarction of a size insufficient to produce profound heart failure or shock was used to study the effects of acute infarction on digitalis tolerance and the hemodynamic changes produced by moderate and large doses of acetylstrophanthidin. With acute myocardial infarction, digitalis toxic arrhythmias could be precipitated with significantly lower doses of digitalis than in animals without myocardial infarction. There was no precise correlation between the size of infarction and the toxic dose of glycoside. Coronary artery ligation produced a stable but relatively depressed circulatory state, as evidenced by lowered cardiac output and stroke volume and elevated systemic vascular resistance and left atrial mean pressure. When digitalis was infused, the following significant changes were observed at nontoxic doses: (1) elevation of aortic and left ventricular pressures; (2) further decline in cardiac output; and (3) decreased left atrial mean pressure.

  9. Acute inhibition of myoglobin impairs contractility and energy state of iNOS-overexpressing hearts.

    PubMed

    Wunderlich, Carsten; Flögel, Ulrich; Gödecke, Axel; Heger, Jacqueline; Schrader, Jürgen

    2003-06-27

    Elevated cardiac levels of nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) have been implicated in the development of heart failure. The surprisingly benign phenotype of recently generated mice with cardiac-specific iNOS overexpression (TGiNOS) provided the rationale to investigate whether NO scavenging by oxymyoglobin (MbO2) yielding nitrate and metmyoglobin (metMb) is involved in preservation of myocardial function in TGiNOS mice. 1H nuclear magnetic resonance (NMR) spectroscopy was used to monitor changes of cardiac myoglobin (Mb) metabolism in isolated hearts of wild-type (WT) and TGiNOS mice. NO formation by iNOS resulted in a significant decrease of the MbO2 signal and a concomitantly emerging metMb signal in spectra of TGiNOS hearts only (DeltaMbO2: -46.3+/-38.4 micromol/kg, DeltametMb: +41.4+/-17.6 micromol/kg, n=6; P<0.05) leaving contractility and energetics unaffected. Inhibition of the Mb-mediated NO degradation by carbon monoxide (20%) led to a deterioration of myocardial contractility in TGiNOS hearts (left ventricular developed pressure: 78.2+/-8.2% versus 96.7+/-4.6% of baseline, n=6; P<0.005), which was associated with a profound pertubation of cardiac energy state as assessed by 31P NMR spectroscopy (eg, phosphocreatine: 13.3+/-1.3 mmol/L (TGiNOS) versus 15.9+/-0.7 mmol/L (WT), n=6; P<0.005). These alterations could be fully antagonized by the NOS inhibitor S-ethylisothiourea. Our findings demonstrate that myoglobin serves as an important cytoplasmic buffer of iNOS-derived NO, which determines the functional consequences of iNOS overexpression. PMID:12775582

  10. A quantitative analysis of contractility in active cytoskeletal protein networks.

    PubMed

    Bendix, Poul M; Koenderink, Gijsje H; Cuvelier, Damien; Dogic, Zvonimir; Koeleman, Bernard N; Brieher, William M; Field, Christine M; Mahadevan, L; Weitz, David A

    2008-04-15

    Cells actively produce contractile forces for a variety of processes including cytokinesis and motility. Contractility is known to rely on myosin II motors which convert chemical energy from ATP hydrolysis into forces on actin filaments. However, the basic physical principles of cell contractility remain poorly understood. We reconstitute contractility in a simplified model system of purified F-actin, muscle myosin II motors, and alpha-actinin cross-linkers. We show that contractility occurs above a threshold motor concentration and within a window of cross-linker concentrations. We also quantify the pore size of the bundled networks and find contractility to occur at a critical distance between the bundles. We propose a simple mechanism of contraction based on myosin filaments pulling neighboring bundles together into an aggregated structure. Observations of this reconstituted system in both bulk and low-dimensional geometries show that the contracting gels pull on and deform their surface with a contractile force of approximately 1 microN, or approximately 100 pN per F-actin bundle. Cytoplasmic extracts contracting in identical environments show a similar behavior and dependence on myosin as the reconstituted system. Our results suggest that cellular contractility can be sensitively regulated by tuning the (local) activity of molecular motors and the cross-linker density and binding affinity. PMID:18192374

  11. Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide.

    PubMed

    Moro, Christian; Leeds, Charlotte; Chess-Williams, Russ

    2012-01-15

    In the bladder, nitric oxide (NO) is released from neuronal and non-neuronal sources, but its actions are unclear. Strips of urothelium plus lamina propria contract in response to agonists and develop spontaneous phasic contractions, and the aim of this study was to investigate the influence of NO on this activity. Isolated strips of urothelium/lamina propria from porcine bladder developed spontaneous contractions (3.5 ± 0.3 cycles/min) and contracted in response to carbachol and electrical field stimulation (EFS). The NO synthase inhibitor N(ω)-nitro-l-arginine (L-NNA, 100 μM) had no effects on the tissues, but the NO donors diethylamine NONOate (DEANO, 100 μM) and nitroprusside (10 μM) caused relaxation, slowed the spontaneous rate of contractions and inhibited responses to carbachol. Maximum tonic contractions to carbachol were reduced by 17 ± 4% (P<0.001) and 35 ± 5% (P<0.001) by DEANO and nitroprusside respectively and the potency of carbachol was also reduced. Carbachol also increased the spontaneous frequency of contraction and these rate responses were again inhibited by DEANO and nitroprusside, but unaffected by L-NNA. Similarly, responses to EFS were significantly depressed (52-70%) by DEANO (P<0.05), but were unaffected by L-NNA. These data demonstrate spontaneous contractile activity and also nerve and agonist-induced tonic contractile activity within the urothelium and lamina propria. This activity is sensitive to depression by NO, but NO does not appear to be spontaneously released to influence this activity, nor does it appear to be released by muscarinic receptor stimulation. However the results suggest that in situations where NO production is increased, NO can influence the contractile activity of this tissue. PMID:22119378

  12. Asymptomatic myocardial ischemia following cold provocation

    SciTech Connect

    Shea, M.J.; Deanfield, J.E.; deLandsheere, C.M.; Wilson, R.A.; Kensett, M.; Selwyn, A.P.

    1987-09-01

    Cold is thought to provoke angina in patients with coronary disease either by an increase in myocardial demand or an increase in coronary vascular resistance. We investigated and compared the effects of cold pressor stimulation and symptom-limited supine bicycle exercise on regional myocardial perfusion in 35 patients with stable angina and coronary disease and in 10 normal subjects. Regional myocardial perfusion was assessed with positron emission tomography and rubidium-82. Following cold pressor stimulation 24 of 35 patients demonstrated significant abnormalities of regional myocardial perfusion with reduced cation uptake in affected regions of myocardium: 52 +/- 9 to 43 +/- 9 (p less than 0.001 vs normal subjects). Among these 24 patients only nine developed ST depression and only seven had angina. In contrast, 29 of 35 patients underwent supine exercise, and abnormal regional myocardial perfusion occurred in all 29, with a reduction in cation intake from 48 +/- 10 to 43 +/- 14 (p less than 0.001 vs normal subjects). Angina was present in 27 of 29 and ST depression in 25 of 29. Although the absolute decrease in cation uptake was somewhat greater following cold as opposed to exercise, the peak heart rate after cold was significantly lower than that after exercise (82 +/- 12 vs 108 +/- 16 bpm, p less than 0.05). Peak systolic blood pressures after cold and exercise were similar (159 +/- 24 vs 158 +/- 28). Thus, cold produces much more frequent asymptomatic disturbances of regional myocardial perfusion in patients with stable angina and coronary disease than is suggested by pain or ECG changes.

  13. Prevalence and clinical significance of painless ST segment depression during early postinfarction exercise testing

    SciTech Connect

    Gibson, R.S.; Beller, G.A.; Kaiser, D.L.

    1987-03-01

    In a recent study of 190 survivors of acute myocardial infarction, the authors sought to determine whether exercise-induced painless ST segments depression indicates residual myocardial ischemia, as defined by /sup 201/Tl scintigraphic criteria. 2 weeks after uncomplicated myocardial infarction, and whether quantitative /sup 201/Tl imaging enhances the prognostic value of such an exercise electrocardiographic response.

  14. Emerging trends in the pathophysiology of lymphatic contractile function

    PubMed Central

    Chakraborty, Sanjukta; Davis, Michael J.; Muthuchamy, Mariappan

    2015-01-01

    Lymphatic contractile dysfunction is central to a number of pathologies that affect millions of people worldwide. Due to its critical role in the process of inflammation, a dysfunctional lymphatic system also compromises the immune response, further exacerbating a number of inflammation related diseases. Despite the critical physiological functions accomplished by the transport of lymph, a complete understanding of the contractile machinery of the lymphatic system lags far behind that of the blood vasculature. However, there has been a surge of recent research focusing on different mechanisms that underlie both physiological and pathophysiological aspects of lymphatic contractile function. This review summarizes those emerging paradigms that shed some novel insights into the contractile physiology of the lymphatics in normal as well as different disease states. In addition, this review emphasizes the recent progress made in our understanding of various contractile parameters and regulatory elements that contribute to the normal functioning of the lymphatics. PMID:25617600

  15. Effects of Acetaminophen on Left Atrial Contractility

    PubMed Central

    Chang, Jun-Hei; Cheng, Pao-Yun; Hsu, Chih-Hsueng; Chen, Yao-Chang; Hong, Po-Da

    2016-01-01

    Background It has been observed that acetaminophen shows cardioprotective efficacy in mammals. In this study, we investigated the electromechanical effects of acetaminophen on the left atrium (LA). Methods Conventional microelectrodes were used to record the action potentials (AP) in rabbit LA preparations. The action potential duration (APD) at repolarization levels of 90%, 50% and 20% of the AP amplitude (APD90, APD50, and APD20, respectively), resting membrane potential, and contractile force were measured during 2 Hz electrical stimulation before and after sequential acetaminophen administration to the LA. Results Acetaminophen (0.1, 0.3, 1, and 3 mM) reduced APD20 from 9.4 ± 1.2 to 8.0 ± 1.1 (p < 0.05), 7.1 ± 0.8 (p < 0.05), 7.8 ± 1.1, and 6.8 ± 1.2 ms (p < 0.05), respectively, and APD50 from 20.2 ± 1.9 to 17.4 ± 2.0, 15.6 ± 1.8 (p < 0.05), 15.8 ± 2.2 (p < 0.05), and 14.1 ± 2.4 ms (p < 0.05), respectively, in a concentration-dependent manner. APD90 was reduced from 72.0 ± 3.6 to 64.7 ± 4.2, 61.9 ± 4.3, 60.5 ± 3.7, and 53.4 ± 4.4 ms (p < 0.05), respectively. Acetaminophen increased LA contractility from 45 ± 9 to 52 ± 10 (p < 0.05), 55 ± 9 (p < 0.01), 58 ± 9 (p < 0.01), and 60 ± 9 mg (p < 0.01), respectively, in a concentration-dependent manner. In the presence of the NOS inhibitor L-NAME or PKG-I inhibitor DT-2, additional acetaminophen treatment did not significantly increase LA contractility. Conclusions Acetaminophen modulated the electromechanical characteristics of LA by inhibiting the NOS and PKG I pathway, and then contributed to the positive inotropic effect. PMID:27471362

  16. The Effect of Lipopolysaccharide on Ischemic-Reperfusion Injury of Heart: A Double Hit Model of Myocardial Ischemia and Endotoxemia

    PubMed Central

    Nader, Nader D.; Asgeri, Mehrdad; Davari-Farid, Sina; Pourafkari, Leili; Ahmadpour, Faraz; Porhomayon, Jahan; Javadzadeghan, Hassan; Negargar, Sohrab; Knight, Paul R.

    2015-01-01

    Introduction: Myocardial ischemia may coincide and interact with sepsis and inflammation. Our objective was to examine the effects of bacterial endotoxin on myocardial functions and cell injury during acute ischemia. Methods: Rabbits were pretreated with incremental doses of E. Coli lipopolysaccharide (LPS) or normal saline. Myocardial ischemia was induced by 50-minute occlusion of left anterior descending artery. S-TNFaR was additionally used to block the effects LPS. Results: Ventricular contractility as it was measured by dp/dt during systole decreased from 2445± 1298 to 1422 ± 944 mm Hg/s, P = .019. Isovolumetric relaxation time as an index of diastolic function was prolonged from 50±18 ms to 102± 64 ms following ischemia. Pretreatment with low concentrations of LPS (<1 μg) had no effect on dp/dt, while at higher concentrations it suppressed both contractility and prolonged IVRT. Cell injury as measured by cardiac troponin I level increased to 15.1± 3.2 ng/dL following ischemia and continued to rise with higher doses of LPS. While blocking TNFa did not improve the myocardial contractility after ischemia, it eliminated additional deleterious effects of LPS. Conclusion: Lower doses of LPS had no deleterious effect on myocardial function, whereas higher doses of this endotoxin cause cardiac dysfunction and increased extent of injury. PMID:26430494

  17. Myocardial imaging. Coxsackie myocarditis

    SciTech Connect

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  18. Intravenous levosimendan-norepinephrine combination during off-pump coronary artery bypass grafting in a hemodialysis patient with severe myocardial dysfunction

    PubMed Central

    2010-01-01

    This the case of a 63 year-old man with end-stage renal disease (on chronic hemodialysis), unstable angina and significantly impaired myocardial contractility with low left ventricular ejection fraction, who underwent off-pump one vessel coronary bypass surgery. Combined continuous levosimendan and norepinephrine infusion (at 0.07 μg/kg/min and 0.05 μg/kg/min respectively) started immediately after anesthesia induction and continued for 24 hours. The levosimendan/norepinephrine combination helped maintain an appropriate hemodynamic profile, thereby contributing to uneventful completion of surgery and postoperative hemodynamic stability. Although levosimendan is considered contraindicated in ESRD patients, this case report suggests that combined perioperative levosimendan/norepinephrine administration can be useful in carefully selected hemodialysis patients with impaired myocardial contractility and ongoing myocardial ischemia, who undergo off-pump myocardial revascularization surgery. PMID:20196861

  19. Effect of cardiac neural crest ablation on contractile force and calcium uptake and release in chick heart.

    PubMed

    Nosek, T M; Fogaça, R T; Hatcher, C J; Brotto, M A; Godt, R E

    1997-09-01

    Cardiac neural crest ablation (CNCA) in the chick embryo at stages 8-10 results in reduced contractility of the heart that can be observed as early as stage 14. We found that intact trabeculae from embryonic day (E) 15 experimental animals after CNCA display an approximately 50% decrease in twitch force relative to sham-operated E15 control animals. In control and CNCA trabeculae skinned in Triton X-100 and bathed in our standard solutions, neither maximum Ca(2+)-activated force nor Ca2+ sensitivity of the contractile apparatus was significantly different. CNCA resulted in a marked reduction in the magnitude of the Ca2+ transient in trabeculae, estimated using fura 2 acetoxymethyl ester. CNCA had no effect on the half-time of Ca2+ loading by the sarcoplasmic reticulum (SR) of saponin skinned trabeculae at fixed Ca2+. However, it slightly reduced the Ca2+ sensitivity of Ca2+ uptake by the SR. Its most dramatic effect was to essentially abolish Ca(2+)-induced Ca2+ release from the SR. These effects on Ca2+ metabolism explain, in part, the decrease in the intracellular Ca2+ transient and myocardial contractility observed with CNCA. PMID:9321838

  20. Glycolytic pathway (GP), kreb's cycle (KC), and hexose monophosphate shunt (HMS) activity in myocardial subcellular fractions exposed to cannabinoids

    SciTech Connect

    Watson, A.T.; Manno, B.R.; King, J.W.; Fowler, M.R.; Dempsey, C.A.; Manno, J.E.

    1986-03-05

    Delta-9-tetrahydrocannabinol (..delta../sup 9/-THC), the primary psychoactive component of marihuana, and its active metabolite 11-hydroxy-..delta../sup 9/-tetrahydrocannabinol (11-OH-..delta../sup 9/-THC) have been reported to produce a direct cardiac depressant effect. Studies in isolated perfused rat hearts have indicated a decreased force of contraction (inotropic response) when ..delta../sup 9/-THC or 11-OH-..delta../sup 9/-THC was administered in microgram amounts. The mechanism and site of action have not been explained or correlated with associated metabolic pathways. The purpose of this study was to investigate the effects of cannabinoids on major myocardial energy producing pathways, GP and KC, and a non-energy producing pathway, HMS. Cardiac ventricular tissue from male Sprague-Dawley rats (250-300 g) was excised and homogenized for subcellular fractionation. KC, GP and HMS activity was assayed in the appropriate fractions by measuring /sup 14/CO/sub 2/ generation from /sup 14/C-2-pyruvate, /sup 14/C-6-glucose and /sup 14/C-1-glucose respectively. Duplicate assays (n=8) were performed on tissue exposed to saline (control), empty liposomes (vehicle) and four doses each of ..delta../sup 9/-THC and 11-OH-..delta../sup 9/-THC. Changes in metabolic activity and decreases in cardiac contractile performance may be associated.

  1. Quantitation of myocardial fatty acid metabolism using PET

    SciTech Connect

    Bergmann, S.R.; Weinheimer, C.J.; Markham, J.; Herrero, P.

    1996-10-01

    Abnormalities of fatty acid metabolism in the heart presage contractile dysfunction and arrhythmias. This study was performed to determine whether myocardial fatty acid metabolism could be quantified noninvasively using PET and 1-{sup 11}C-palmitate. Anesthetized dogs were studied during control conditions; during administration of dobutamine; after oxfenicine; and during infusion of glucose. Dynamic PET data after administration of 1-{sup 11}C-palmitate were fitted to a four-compartment mathematical model. Modeled rates of palmitate utilization correlated closely with directly measured myocardial palmitate and total long-chain fatty acid utilization (r = 0.93 and 0.96, respectively, p < 0.001 for each) over a wide range of arterial fatty acid levels and altered patterns of myocardial substrate use (fatty acid extraction fraction ranging from 1% to 56%, glucose extraction fraction from 1% to 16% and myocardial fatty acid utilization from 1 to 484 nmole/g/min). The percent of fatty acid undergoing oxidation could also be measured. The results demonstrate the ability to quantify myocardial fatty acid utilization with PET. The approach is readily applicable for the determination of fatty acid metabolism noninvasively in patients. 37 refs., 5 figs., 4 tabs.

  2. Considerations For Contractile Electroactive Materials and Actuators

    SciTech Connect

    Lenore Rasmussen, Lewis D. Meixler and Charles A. Gentile

    2012-02-29

    Electroactive polymers (EAPs) that bend, swell, ripple (first generation materials), and now contract with low electric input (new development) have been produced. The mechanism of contraction is not well understood. Radionuclide-labeled experiments, molecular modeling, electrolyte experiments, pH experiments, and an ionic concentration experiment were used to determine the chain of events that occur during contraction and, reciprocally, expansion when the polarity is reversed, in these ionic EAPs. Plasma treatment of the electrodes, along with other strategies, allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface, analogous to nerves and tendons moving with muscles during movement. Challenges involved with prototyping actuation using contractile EAPs are also discussed.

  3. Considerations for Contractile Electroactive Materials and Actuators

    SciTech Connect

    Lenore Rasmussen, David Schramm, Paul Rasmussen, Kevin Mullaly, Ras Labs, LLC, Intelligent Materials for Prosthetics & Automation, Lewis D. Meixler, Daniel Pearlman and Alice Kirk

    2011-05-23

    Ras Labs produces contractile electroactive polymer (EAP) based materials and actuators that bend, swell, ripple, and contract (new development) with low electric input. In addition, Ras Labs produces EAP materials that quickly contract and expand, repeatedly, by reversing the polarity of the electric input, which can be cycled. This phenomenon was explored using molecular modeling, followed by experimentation. Applied voltage step functions were also investigated. High voltage steps followed by low voltage steps produced a larger contraction followed by a smaller contraction. Actuator control by simply adjusting the electric input is extremely useful for biomimetic applications. Muscles are able to partially contract. If muscles could only completely contract, nobody could hold an egg, for example, without breaking it. A combination of high and low voltage step functions could produce gross motor function and fine manipulation within the same actuator unit. Plasma treated electrodes with various geometries were investigated as a means of providing for more durable actuation.

  4. Considerations for contractile electroactive materials and actuators

    NASA Astrophysics Data System (ADS)

    Rasmussen, Lenore; Schramm, David; Rasmussen, Paul; Mullally, Kevin; Meixler, Lewis D.; Pearlman, Daniel; Kirk, Alice

    2011-04-01

    Ras Labs produces contractile electroactive polymer (EAP) based materials and actuators that bend, swell, ripple, and contract (new development) with low electric input. In addition, Ras Labs produces EAP materials that quickly contract and expand, repeatedly, by reversing the polarity of the electric input, which can be cycled. This phenomenon was explored using molecular modeling, followed by experimentation. Applied voltage step functions were also investigated. High voltage steps followed by low voltage steps produced a larger contraction followed by a smaller contraction. Actuator control by simply adjusting the electric input is extremely useful for biomimetic applications. Muscles are able to partially contract. If muscles could only completely contract, nobody could hold an egg, for example, without breaking it. A combination of high and low voltage step functions could produce gross motor function and fine manipulation within the same actuator unit. Plasma treated electrodes with various geometries were investigated as a means of providing for more durable actuation.

  5. Spiral waves on a contractile tissue

    NASA Astrophysics Data System (ADS)

    Mesin, L.; Ambrosi, D.

    2011-02-01

    In a healthy cardiac tissue, electric waves propagate in the form of a travelling pulse, from the apex to the base, and activate the contraction of the heart. Defects in the propagation can destabilize travelling fronts and originate possible new periodic solutions, as spiral waves. Spiral waves are quite stable, but the interplay between currents and strain can distort the periodic pattern, provided the coupling is strong enough. In this paper we investigate the stability of spiral waves on a contractile medium in a non-standard framework, in which the electrical potential dictates the active strain (not stress) of the muscle. The role of conducting and contracting fibers is included in the model and periodic boundary conditions are adopted. A correlation analysis allows to evaluate numerically the range of stability of the parameters for the spiral waves, depending on the strain of the contracted fibers and on the magnitude of the stretch activated current.

  6. Mechanisms of uterine contractility in laying hens.

    PubMed

    Kupittayanant, S; Kupittayanant, P; Suwannachat, C

    2009-10-01

    The physiological basis of uterine contractility in laying hens is not well understood, but a better understanding is important for understanding the mechanisms governing egg laying. The characteristics of uterine contractility arising spontaneously or by prostaglandin F(2alpha) (PGF(2alpha)) stimulation were therefore examined and the underlying mechanisms investigated. Uterine strips were isolated from laying hens 4h before oviposition and force measured. These strips remained healthy in vitro and produced regular spontaneous contractions. The contractions were phasic and could be recorded for several hours. Exposure to nifedipine, the specific L-type Ca channel blocker, led to the abolition of force. The contraction amplitude and frequency were significantly increased when Bay K8644, an agonist of L-type Ca channels, was applied or when the concentration of extracellular Ca was elevated. Spontaneous contractions were also significantly inhibited by wortmannin, the specific inhibitor of myosin light chain kinase (MLCK). When 1 microM PGF(2alpha) was applied to spontaneously contracting uterus, it significantly increased their amplitude and frequency of the contractions. As with spontaneous contractions, PGF(2alpha)-induced force production was abolished by nifedipine and wortmannin. In the absence of extracellular Ca, a small but tonic force was generated upon application of PGF(2alpha) which was not affected by wortmannin. Thus, extracellular Ca entry and MLCK phosphorylation are essential for uterine force production occurring spontaneously or by PGF(2alpha) stimulation. Our data supports the conclusion that the pathway dependent on extracellular Ca entry and MLCK phosphorylation predominates during PGF(2alpha) stimulation but suggests some involvement of an alternative force-producing pathway, presumably Ca-sensitization. PMID:19081211

  7. Endogenous nitric oxide and myocardial adaptation to ischemia.

    PubMed

    Heusch, G; Post, H; Michel, M C; Kelm, M; Schulz, R

    2000-07-21

    Ischemic myocardium does not inevitably undergo necrosis but rather can survive through downregulation of contractile function, ie, "hibernate." To study the role of endogenous NO in this adaptation, 41 enflurane-anesthetized swine were subjected to 90 minutes of moderate left anterior descending coronary artery hypoperfusion and assigned to placebo (P), to 30 mg/kg N(G)-nitro-L-arginine (L-NNA) IV to inhibit NO synthase, or to aortic constriction (AO) to match the increased left ventricular pressure observed with L-NNA. During normoperfusion, a regional myocardial external work index (WI, mm Hg. mm, sonomicrometry and micromanometry) was reduced with L-NNA (from 326+/-27 [SEM] to 250+/-19, P<0.05) but increased with AO (from 321+/-16 to 363+/-19, P<0.05 versus L-NNA). At 10 minutes of ischemia, WI was lower with L-NNA (109+/-10, P<0.05) than P (180+/-22) and AO (170+/-11) and did not change further at 85 minutes of ischemia. Relationships between WI and transmural myocardial blood flow and oxygen consumption were shifted rightward by L-NNA versus P and AO at both 10 and 85 minutes of ischemia. The maximal increment in calcium-activated external work was not different during normoperfusion among groups but was decreased during ischemia with L-NNA. L-NNA transiently increased myocardial contractile calcium sensitivity along with systemic pressure but reduced it during ongoing ischemia. The free-energy change of ATP hydrolysis after an early ischemic decrease recovered toward baseline values in all groups, and necrosis was absent after 2 (triphenyltetrazolium chloride staining) or 8 (histology) hours of reperfusion. Thus, endogenous NO contributes to hibernation by reducing oxygen consumption and preserving calcium sensitivity and contractile function without an energy cost during ischemia. PMID:10903999

  8. [The effect of transcardiac galvanization on the course of the physical rehabilitation of patients with an acute myocardial infarct based on the data from a measured loading test].

    PubMed

    Maslov, A G; Vidiakov, G E; Shishkin, M S; Metelkin, A V; Sidorova, T I; Kuz'min, M V; Anashkina, V G

    1993-01-01

    Transcardiac galvanization effect was assessed in 76 patients with primary noncomplicated macrofocal anterior myocardial infarction admitted to hospital within initial 6 hours of the disease. As shown by the evidence obtained at bicycle ergometry, tetrapolar rheography and clinical examination, transcardiac galvanization within 3 days of the infarction enhances hospital physical rehabilitation course, increases exercise tolerance by the disease month 6, promotes an increase in myocardial maximal oxygen consumption, increases coronary reserve and improves cardiac contractility. PMID:8266661

  9. Cardiac MRI: a Translational Imaging Tool for Characterizing Anthracycline-Induced Myocardial Remodeling.

    PubMed

    Nguyen, Kim-Lien; Hu, Peng; Ennis, Daniel B; Shao, Jiaxin; Pham, Kimberly A; Chen, Joseph J

    2016-08-01

    Cardiovascular side effects of cancer therapeutics are the leading causes of morbidity and mortality in cancer survivors. Anthracyclines (AC) serve as the backbone of many anti-cancer treatment strategies, but dose-dependent myocardial injury limits their use. Cumulative AC exposure can disrupt the dynamic equilibrium of the myocardial microarchitecture while repeated injury and repair leads to myocyte loss, interstitial myocardial fibrosis, and impaired contractility. Although children are assumed to have greater myocardial plasticity, AC exposure at a younger age portends worse prognosis. In older patients, there is lower overall survival once they develop cardiovascular disease. Because aberrations in the myocardial architecture predispose the heart to a decline in function, early detection with sensitive imaging tools is crucial and the implications for resource utilization are substantial. As a comprehensive imaging modality, cardiac magnetic resonance (CMR) imaging is able to go beyond quantification of ejection fraction and myocardial deformation to characterize adaptive microstructural and microvascular changes that are important to myocardial tissue health. Herein, we describe CMR as an established translational imaging tool that can be used clinically to characterize AC-associated myocardial remodeling. PMID:27292153

  10. Contractile dysfunction of the shoulder (rotator cuff tendinopathy): an overview

    PubMed Central

    Littlewood, Chris

    2012-01-01

    It is now over a decade since the features defining a contractile dysfunction of the shoulder were first reported. Since this time, some progress has been made to better understand this mechanical syndrome. In response to these developments, this narrative review will explore current understanding in relation to pathology, diagnosis, treatment, and prognosis of this syndrome with reference to literature specifically relating to contractile dysfunction but also literature relating to rotator cuff tendinopathy where necessary. The review not only identifies the strengths of the mechanical diagnosis and therapy approach with reference to a contractile dysfunction of the shoulder but also identifies where further progress needs to be made. PMID:24179329

  11. Maintaining PGC-1α expression following pressure overload-induced cardiac hypertrophy preserves angiogenesis but not contractile or mitochondrial function

    PubMed Central

    Pereira, Renata O.; Wende, Adam R.; Crum, Ashley; Hunter, Douglas; Olsen, Curtis D.; Rawlings, Tenley; Riehle, Christian; Ward, Walter F.; Abel, E. Dale

    2014-01-01

    During pathological hypertrophy, peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) is repressed in concert with reduced mitochondrial oxidative capacity and fatty acid oxidation (FAO). We therefore sought to determine if maintaining or increasing PGC-1α levels in the context of pressure overload hypertrophy (POH) would preserve mitochondrial function and prevent contractile dysfunction. Pathological cardiac hypertrophy was induced using 4 wk of transverse aortic constriction (TAC) in mice overexpressing the human PGC-1α genomic locus via a bacterial artificial chromosome (TG) and nontransgenic controls (Cont). PGC-1α levels were increased by 40% in TG mice and were sustained following TAC. Although TAC-induced repression of FAO genes and oxidative phosphorylation (oxphos) genes was prevented in TG mice, mitochondrial function and ATP synthesis were equivalently impaired in Cont and TG mice after TAC. Contractile function was also equally impaired in Cont and TG mice following TAC, as demonstrated by decreased +dP/dt and ejection fraction and increased left ventricular developed pressure and end diastolic pressure. Conversely, capillary density was preserved, in concert with increased VEGF expression, while apoptosis and fibrosis were reduced in TG relative to Cont mice after TAC. Hence, sustaining physiological levels of PGC-1α expression following POH, while preserving myocardial vascularity, does not prevent mitochondrial and contractile dysfunction.—Pereira, R. O., Wende, A. R., Crum, A., Hunter, D., Olsen, C. D., Rawlings, T., Riehle, C., Ward, W. F., Abel, E. D. Maintaining PGC-1α expression following pressure overload-induced cardiac hypertrophy preserves angiogenesis but not contractile or mitochondrial function. PMID:24776744

  12. The increasing burden of depression.

    PubMed

    Lépine, Jean-Pierre; Briley, Mike

    2011-01-01

    Recent epidemiological surveys conducted in general populations have found that the lifetime prevalence of depression is in the range of 10% to 15%. Mood disorders, as defined by the World Mental Health and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, have a 12-month prevalence which varies from 3% in Japan to over 9% in the US. A recent American survey found the prevalence of current depression to be 9% and the rate of current major depression to be 3.4%. All studies of depressive disorders have stressed the importance of the mortality and morbidity associated with depression. The mortality risk for suicide in depressed patients is more than 20-fold greater than in the general population. Recent studies have also shown the importance of depression as a risk factor for cardiovascular death. The risk of cardiac mortality after an initial myocardial infarction is greater in patients with depression and related to the severity of the depressive episode. Greater severity of depressive symptoms has been found to be associated with significantly higher risk of all-cause mortality including cardiovascular death and stroke. In addition to mortality, functional impairment and disability associated with depression have been consistently reported. Depression increases the risk of decreased workplace productivity and absenteeism resulting in lowered income or unemployment. Absenteeism and presenteeism (being physically present at work but functioning suboptimally) have been estimated to result in a loss of $36.6 billion per year in the US. Worldwide projections by the World Health Organization for the year 2030 identify unipolar major depression as the leading cause of disease burden. This article is a brief overview of how depression affects the quality of life of the subject and is also a huge burden for both the family of the depressed patient and for society at large. PMID:21750622

  13. The PPAR-α activator fenofibrate fails to provide myocardial protection in ischemia and reperfusion in pigs

    PubMed Central

    Xu, Ya; Lu, Li; Greyson, Clifford; Rizeq, Mona; Nunley, Karin; Wyatt, Beata; Bristow, Michael R.; Long, Carlin S.; Schwartz, Gregory G.

    2010-01-01

    Rodent studies suggest that peroxisome proliferator-activated receptor-α (PPAR-α) activation reduces myocardial ischemia-reperfusion (I/R) injury and infarct size; however, effects of PPAR-α activation in large animal models of myocardial I/R are unknown. We determined whether chronic treatment with the PPAR-α activator fenofibrate affects myocardial I/R injury in pigs. Domestic farm pigs were assigned to treatment with fenofibrate 50 mg·kg−1 ·day−1 orally or no drug treatment, and either a low-fat (4% by weight) or a high-fat (20% by weight) diet. After 4 wk, 66 pigs underwent 90 min low-flow regional myocardial ischemia and 120 min reperfusion under anesthetized open-chest conditions, resulting in myocardial stunning. The high-fat group received an infusion of triglyceride emulsion and heparin during this terminal experiment to maintain elevated arterial free fatty acid (FFA) levels. An additional 21 pigs underwent 60 min no-flow ischemia and 180 min reperfusion, resulting in myocardial infarction. Plasma concentration of fenofibric acid was similar to the EC50 for activation of PPAR-α in vitro and to maximal concentrations achieved in clinical use. Myocardial expression of PPAR-α mRNA was prominent but unaffected by fenofibrate treatment. Fenofibrate increased expression of carnitine palmitoyltransferase (CPT)-I mRNA in liver and decreased arterial FFA and lactate concentrations (each P < 0.01). However, fenofibrate did not affect myocardial CPT-I expression, substrate uptake, lipid accumulation, or contractile function during low-flow I/R in either the low- or high-fat group, nor did it affect myocardial infarct size. Despite expression of PPAR-α in porcine myocardium and effects of fenofibrate on systemic metabolism, treatment with this PPAR-α activator does not alter myocardial metabolic or contractile responses to I/R in pigs. PMID:16339839

  14. Multimodality imaging in the assessment of myocardial viability

    PubMed Central

    Partington, Sara L.; Kwong, Raymond Y.

    2014-01-01

    The prevalence of heart failure due to coronary artery disease continues to increase, and it portends a worse prognosis than non-ischemic cardiomyopathy. Revascularization improves prognosis in these high-risk patients who have evidence of viability; therefore, optimal assessment of myocardial viability remains essential. Multiple imaging modalities exist for differentiating viable myocardium from scar in territories with contractile dysfunction. Given the multiple modalities available, choosing the best modality for a specific patient can be a daunting task. In this review, the physiology of myocardial hibernation and stunning will be reviewed. All the current methods available for assessing viability including echocardiography, cardiac magnetic resonance imaging, nuclear imaging with single photon emission tomography and positron emission tomography imaging and cardiac computed tomography will be reviewed. The effectiveness of the various techniques will be compared, and the limitations of the current literature will be discussed. PMID:21069458

  15. Idiopathic calcified myocardial mass

    PubMed Central

    Patterson, David; Gibson, Derek; Gomes, Ricardo; McDonald, Lawson; Olsen, Eckhardt; Parker, John; Ross, Donald

    1974-01-01

    Patterson, D., Gibson, D., Gomes, R., McDonald, L., Olsen, E., Parker, J., and Ross, D. (1974).Thorax,29, 589-594. Idiopathic calcified myocardial mass. Myocardial calcification can be subdivided into three groups—metastatic, dystrophic or an extension inwards from the pericardium. This case in which the calcified myocardial mass was initially delineated by radiography and by echocardiography and subsequently removed does not fit into any subdivision and has been termed idiopathic. Images PMID:4279467

  16. Optimum periodicity of repeated contractile actions applied in mass transport

    NASA Astrophysics Data System (ADS)

    Ahn, Sungsook; Lee, Sang Joon

    2015-01-01

    Dynamically repeated periodic patterns are abundant in natural and artificial systems, such as tides, heart beats, stock prices, and the like. The characteristic repeatability and periodicity are expected to be optimized in effective system-specific functions. In this study, such optimum periodicity is experimentally evaluated in terms of effective mass transport using one-valve and multi-valve systems working in contractile fluid flows. A set of nanoscale gating functions is utilized, operating in nanocomposite networks through which permeates selectively pass under characteristic contractile actions. Optimized contractile periodicity exists for effective energy impartment to flow in a one-valve system. In the sequential contractile actions for a multi-valve system, synchronization with the fluid flow is critical for effective mass transport. This study provides fundamental understanding on the various repeated periodic patterns and dynamic repeatability occurring in nature and mechanical systems, which are useful for broad applications.

  17. Geometrical Origins of Contractility in Disordered Actomyosin Networks

    NASA Astrophysics Data System (ADS)

    Lenz, Martin

    2014-10-01

    Movement within eukaryotic cells largely originates from localized forces exerted by myosin motors on scaffolds of actin filaments. Although individual motors locally exert both contractile and extensile forces, large actomyosin structures at the cellular scale are overwhelmingly contractile, suggesting that the scaffold serves to favor contraction over extension. While this mechanism is well understood in highly organized striated muscle, its origin in disordered networks such as the cell cortex is unknown. Here, we develop a mathematical model of the actin scaffold's local two- or three-dimensional mechanics and identify four competing contraction mechanisms. We predict that one mechanism dominates, whereby local deformations of the actin break the balance between contraction and extension. In this mechanism, contractile forces result mostly from motors plucking the filaments transversely rather than buckling them longitudinally. These findings shed light on recent in vitro experiments and provide a new geometrical understanding of contractility in the myriad of disordered actomyosin systems found in vivo.

  18. Optimum periodicity of repeated contractile actions applied in mass transport

    PubMed Central

    Ahn, Sungsook; Lee, Sang Joon

    2015-01-01

    Dynamically repeated periodic patterns are abundant in natural and artificial systems, such as tides, heart beats, stock prices, and the like. The characteristic repeatability and periodicity are expected to be optimized in effective system-specific functions. In this study, such optimum periodicity is experimentally evaluated in terms of effective mass transport using one-valve and multi-valve systems working in contractile fluid flows. A set of nanoscale gating functions is utilized, operating in nanocomposite networks through which permeates selectively pass under characteristic contractile actions. Optimized contractile periodicity exists for effective energy impartment to flow in a one-valve system. In the sequential contractile actions for a multi-valve system, synchronization with the fluid flow is critical for effective mass transport. This study provides fundamental understanding on the various repeated periodic patterns and dynamic repeatability occurring in nature and mechanical systems, which are useful for broad applications. PMID:25622949

  19. [Myocardial responses to ischemia].

    PubMed

    Borisenko, V G; Gubareva, E A; Kade, A Kh

    2010-01-01

    The paper details the types of a myocardial response to impaired blood flow, such as myocardial stunning, hibernation, ischemic preconditioning, warm-up phenomenon, ischemic postconditioning, remodeling, and infarction. According to the pathogenesis, the authors identify several types of myocardial dysfunction in transient ischemic attack--uptake, delivery; and a mixed one. It is concluded the myocardial response to damage depends on a combination of influencing factors, a number of pathophysiological processes starting in the acute phase of ischemia achieve its peak in the late period. PMID:20564927

  20. Maternal Age and Contractility of Human Myometrium in Pregnancy.

    PubMed

    Crankshaw, Denis J; O'Brien, Yvonne M; Crosby, David A; Morrison, John J

    2015-10-01

    There is controversy as to whether maternal age exerts an influence on the contractility of human myometrium in pregnancy. The aim of this study was to examine a series of functional contractile parameters of human myometrium in vitro, over a broad range of maternal ages. Myometrial tissue specimens were obtained at cesarean delivery from 32 women with maternal ages ranging from 28 to 52 years. Using in vitro recordings, a number of contractile parameters including maximal amplitude, mean contractile force, time to maximal amplitude, maximum rate of rise, and occurrence of simple and complex (biphasic and multiphasic) contractions were examined for spontaneous and induced contractile activity. The relationship between maternal age and individual parameters was evaluated using linear regression analysis. For all contractile parameters examined, for both spontaneous and induced contractions, no significant correlation was observed with maternal age between 28 and 52 years. The mean maximum amplitude values for spontaneous and oxytocin-induced contractions were 23 ± 3 and 43 ± 5 mN, respectively. The mean contractile forces for spontaneous and oxytocin-induced contractions were 1.5 ± 0.2 and 6.5 ± 0.9 mN, respectively. There was no variation in the proportion of biphasic or multiphasic contractions with maternal age. These results indicate there is no significant functional impairment of uterine contractility and no lack in responsiveness of myometrium in vitro, in the older mother. These findings do not support the concept that there may be a biological basis for dysfunctional labor or increased cesarean delivery rates in older parturients. PMID:25759369

  1. Effects of regular exercise training on skeletal muscle contractile function

    NASA Technical Reports Server (NTRS)

    Fitts, Robert H.

    2003-01-01

    Skeletal muscle function is critical to movement and one's ability to perform daily tasks, such as eating and walking. One objective of this article is to review the contractile properties of fast and slow skeletal muscle and single fibers, with particular emphasis on the cellular events that control or rate limit the important mechanical properties. Another important goal of this article is to present the current understanding of how the contractile properties of limb skeletal muscle adapt to programs of regular exercise.

  2. Considerations for Contractile Electroactive Materials and Actuators

    SciTech Connect

    Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Carl; Bernasek, Stephen L.; Abelev, Esta

    2010-02-19

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

  3. Tensile Properties of Contractile and Synthetic Vascular Smooth Muscle Cells

    NASA Astrophysics Data System (ADS)

    Miyazaki, Hiroshi; Hasegawa, Yoshitaka; Hayashi, Kozaburo

    Tensile properties of vascular smooth muscle cells (VSMCs) of synthetic and contractile phenotypes were determined using a newly developed tensile test system. Synthetic and contractile VSMCs were isolated from the rabbit thoracic aorta with an explant and an enzymatic digestion method, respectively. Each cell floated in Hanks' balanced salt solution of 37°C was attached to the fine tips of a pair of micropipettes with a cell adhesive and, then, stretched at the rate of 6µm/sec by moving one of the micropipettes with a linear actuator. Load applied to the cell was measured with a cantilever-type load cell; its elongation was determined from the distance between the micropipette tips using a video dimension analyzer. The synthetic and contractile VSMCs were not broken even at the tensile force of 2.4µN and 3.4µN, respectively. Their stiffness was significantly higher in contractile phenotype (0.17N/m) than in synthetic one (0.09N/m). The different tensile properties between synthetic and contractile cells are attributable to the differences in cytoskeletal structures and contractile apparatus.

  4. [ECG-gated myocardial SPECT with 99mTc-MIBI in patients with right ventricular infarction].

    PubMed

    Kumita, S; Mizumura, S; Cho, K; Kijima, T; Kumazaki, T; Tetsuou, Y; Sakai, S; Sano, J; Kusama, Y; Munakata, K

    1996-06-01

    Although 99mTc-pyrophosphate (PYP) myocardial scintigraphy has so far been widely used for the diagnosis of right ventricular infarction, PYP accumulation disappears within one week or so. To evaluate the myocardial condition of the right ventricle alternatively, myocardial SPECT with 99mTc-MIBI was performed in 16 patients with acute inferior left ventricular infarction, and ECG-gated myocardial SPECT data acquisition was accompanied in 14 of 16 patients. Right ventricular perfusion defect was observed in 4 of 16 patients (RVI (+) group), and the remains were negative (RVI (-) group). Then, right ventricular count increase rate (RV %WT) of MIBI from end-diastole to end-systole was calculated using an automated method which was developed for quantification of wall thickening in our laboratory. The RV %WT was conceived to be an objective index representing right ventricular contractility. RVI (+) group (n = 3) as compared with RVI (-) group (n = 11) had significant lower RV %WT (26.7 +/- 3.2 vs. 49.6 +/- 14.2; p < 0.01). In conclusion, ECG-gated myocardial SPECT with MIBI was considered to be useful for assessment of myocardial perfusion and contractility of right ventricle. PMID:8741508

  5. Asymptomatic myocardial infarction in Kawasaki disease: Long-term prognosis

    SciTech Connect

    Shiraishi, I.; Onouchi, Z.; Hayano, T.; Hamaoka, K.; Kiyosawa, N. )

    1991-04-01

    Eight patients with Kawasaki disease who had sustained asymptomatic myocardial infarction 8-15 years ago (mean, 13.1 years) were reexamined by various noninvasive cardiac function tests to assess long-term prognosis. At present, electrocardiograms (ECGs) are normal in six patients. However, all eight patients had a prolonged preejection period (PEP) to left ventricular ejection time (LVET) ratio 30 s after amylnitrate (AN) inhalation. Six patients had perfusion defects by exercise thallium-201 myocardial scintigraphy, and two patients developed ST segment depression in treadmill exercise testing. These patients are symptom-free even though their physical activity has not been restricted. Yet they proved to have serious abnormalities suggesting sequelae of myocardial infarction or existing myocardial ischemia. Judging from the results of noninvasive cardiac function tests and recently performed coronary angiography, five of the eight patients require coronary bypass surgery.

  6. Energy Drinks and Myocardial Ischemia: A Review of Case Reports.

    PubMed

    Lippi, Giuseppe; Cervellin, Gianfranco; Sanchis-Gomar, Fabian

    2016-07-01

    The use and abuse of energy drinks (EDs) is constantly increasing worldwide. We performed a systematic search in Medline, Scopus and Web of Science to identify evidence about the potential link between these beverages and myocardial ischemia. Overall, 8 case reports could be detected, all of which described a realistic association between large intake of EDs and episodes of myocardial ischemia. Interestingly, no additional triggers of myocardial ischemia other than energy drinks could be identified in the vast majority of cases. Some plausible explanations can be brought in support of this association. Most of the biological effects of EDs are seemingly mediated by a positive inotropic effect on cardiac function, which entails increase in heart rate, cardiac output and contractility, stroke volume and arterial blood pressure. Additional biological abnormalities reported after EDs intake include increased platelet aggregation, endothelial dysfunction, hyperglycemia as well as an increase in total cholesterol, triglycerides and low-density lipoprotein cholesterol. Although a causal relationship between large consumption of EDs and myocardial ischemia cannot be definitely established so far, concerns about the cardiovascular risk of excessive consumption of these beverages are seemingly justified. PMID:26320007

  7. Sum of effects of myocardial ischemia followed by electrically induced tachycardia on myocardial function

    PubMed Central

    Díez, José Luis; Hernándiz, Amparo; Cosín-Aguilar, Juan; Aguilar, Amparo; Portolés, Manuel

    2013-01-01

    Background The alteration of contractile function after tachyarrhythmia ceases is influenced by the type of prior ischemia (acute coronary syndrome or ischemia inherent in a coronary revascularization procedure). We aimed to analyze cardiac dysfunction in an acute experimental model of supraphysiological heart rate preceded by different durations and types of ischemia. Material/Methods Twenty-four pigs were included in: (S1) series of ventricular pacing; (S2, A and B) series with 10 or 20 min, respectively, of coronary occlusion previous to ventricular pacing; S3 with 20 brief, repeated ischemia/reperfusion processes prior to ventricular pacing and; (S4) control series. Overall cardiac function parameters and regional myocardial contractility at the apex and base of the left ventricle were recorded, as were oxidative stress markers (glutathione and lipid peroxide serum levels). Left ventricular pacing at 60% over baseline heart rate was performed for 2 h followed by 1 h of recovery. Results High ventricular pacing rates preceded by short, repeated periods of coronary ischemia/reperfusion resulted in worse impairment of overall cardiac and regional function that continued to be altered 1 h after tachycardia ceased. There was significant reduction of stroke volume (26.9±5.3 basal vs. 16±6.2 ml; p<0.05), LVP; dP/dt and LAD flow (13.1±1.5 basal vs. 8.4±1.6 ml/min; p<0.05); the base contractility remained altered when recovering compared to baseline (base SF: 5.6±2.8 vs. 2.2±0.7%; p<0.05); and LPO levels were higher than less aggressive series at the end of recovery. Conclusions Ischemia and tachycardia accumulate their effects, with increased cardiac involvement depending on the type of ischemia. PMID:23722244

  8. The intrinsic circadian clock within the cardiomyocyte directly regulates myocardial gene expression, metabolism, and contractile function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology remains unknown. We hypothesized that the circadian clock within the cardiomyocyte plays a role in regulating myo...

  9. Genistein stimulates myocardial contractility in guinea pigs by different subcellular mechanisms.

    PubMed

    Li, Hongfang; Zhang, Yingfu; Tian, Zhifeng; Qiu, Xiaoqing; Gu, Jing; Wu, Jinxia

    2008-11-12

    The purpose of this study was to investigate the mechanisms involved in the excitatory effect induced by genistein in isolated guinea pig left ventricular papillary muscles and to determine relationship of genistein action with the tyrosine kinase pathway and phosphatidylinositol 3-kinase (PI3K) activity, the cyclic adenosine 5'-monophosphate (cAMP) signal system and the sarcoplasmic reticulum Ca2+ mobilization. Genistein (1-100 microM) significantly increased contraction of left ventricular papillary muscles from male and female guinea pigs in a concentration-dependent manner and its action had no obvious gender differences. Prior treatment with an L-type Ca2+ channel blocker verapamil hydrochloride, beta-adrenoceptor inhibitors propranolol and atenolol, an inhibitor of Na+-Ca2+ reverse exchanger Kb-r7943 or the blocker of estrogen receptor ICI 182,780 failed to alter the positive inotropic effect induced by genistein in papillary muscles. However, tyrosine phosphatase inhibitor, sodium orthovanadate or a potent phosphotyrosine phosphatase inhibitor bpV (phen) could partly but significantly reduce the stimulatory action of genistein. Interestingly, insulin-like growth factor-1, a known PI3K activator could also decrease the stimulatory action of genistein obviously, but the PI3K inhibitor LY294002 had no significant effect on the stimulatory action of genistein. The excitatory effect of genistein was markedly attenuated not only after treatment with an inhibitor of cAMP synthesis Sq 22536, carbachol or an inhibitor of specific protein kinase A H-89, but also after the inhibition of sarcoplasmic reticulum Ca2+ mobilization by ruthenium red, ryanodine or the inhibitor of sarcoplasmic reticulum Ca2+-ATPase thapsigargin. All these results indicate that the excitatory effects of genistein in papillary muscles are due to the inhibition of tyrosine kinase pathway and PI3K activity, thereby locally activating cAMP signal transduction and facilitating intracellular Ca2+ mobilization, but are not related to the activation of beta-adrenoceptor, the Na+-Ca2+ reverse exchange and the estrogen receptor. PMID:18793631

  10. The intrinsic circadian clock within the cardiomyocyte directly regulates myocardial gene expression, metabolism, and contractile function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology remains unknown. We hypothesized that circadian clock within the cardiomyocyte plays a role in regulating myocardia...

  11. Changes in Myocardial Contractility and Electromechanical Interval During the First Month of Life in Healthy Neonates.

    PubMed

    Kahr, Peter C; Kahr, Maike K; Dabral, Himanshu; Agarwal, Ramesh; Kothari, Shyam S; Saxena, Anita; Ramakrishnan, Sivasubramanian

    2016-02-01

    This study aims at documenting the changes in ventricular tissue velocities, longitudinal strain and electromechanical coupling during the first month of life. During the neonatal period, when the ventricular myocardium is not yet fully maturated, the heart is subjected to significant hemodynamic changes. We studied the ventricular performance of 16 healthy neonates at three time points over the first month of life: on days 2 (IQR [2;2]), 13 [12;14] and 27 [25;29]. We found that systolic and diastolic tissue velocities increased significantly in both left and right ventricle (by 1.2-1.7 times, p < 0.001). Congruently, we found that peak systolic longitudinal strain of the right and left ventricles increased significantly. However, no significant changes in longitudinal strain rate were observed. Finally, QS-intervals shortened during the neonatal period: being measured at 12 points throughout the left ventricle, time to peak systolic velocity decreased on average to 89 % in the second and to 80 % in the fourth week of life (22.3 ± 0.2 vs. 19.8 ± 0.3 vs. 17.8 ± 0.5 ms, r = -0.564, p < 0.001). When comparing opposing walls of the left ventricle, no dyssynchrony in left ventricular contraction was found. In addition to increasing systolic and diastolic tissue velocities during the first month of life, the time to peak systolic contraction shortens in the neonatal heart, which may reflect an increasing efficiency of the excitation-contraction coupling in the maturing myocardium. While there appears to be no dyssynchrony in ventricular contraction, these findings may extend our appreciation of the immature neonatal heart and certain disease states. PMID:26499358

  12. Myocyte repolarization modulates myocardial function in aging dogs.

    PubMed

    Sorrentino, Andrea; Signore, Sergio; Qanud, Khaled; Borghetti, Giulia; Meo, Marianna; Cannata, Antonio; Zhou, Yu; Wybieralska, Ewa; Luciani, Marco; Kannappan, Ramaswamy; Zhang, Eric; Matsuda, Alex; Webster, Andrew; Cimini, Maria; Kertowidjojo, Elizabeth; D'Alessandro, David A; Wunimenghe, Oriyanhan; Michler, Robert E; Royer, Christopher; Goichberg, Polina; Leri, Annarosa; Barrett, Edward G; Anversa, Piero; Hintze, Thomas H; Rota, Marcello

    2016-04-01

    Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions. PMID:26801307

  13. Chronic sodium depletion increases myocardial calcium content in normotensive rats.

    PubMed

    Rossi, G; Bond, M; Fouad-Tarazi, F M

    1989-03-01

    Increased myocardial contractility was found in the perfused heart isolated from sodium depleted Sprague-Dawley rats. Previously, it was reported that in vitro exposure of different cardiac preparations to low Na+ buffers was associated with both an increased contractility and an increased Ca2+ content in the cells. Therefore, this study was designed to examine increases in ventricular Ca2+ content in the hearts of chronically sodium depleted rats. Two groups of 12-week-old Sprague-Dawley rats were studied. One group (n = 5) received furosemide (5 mg/kg/day IP for 4 days), a low Na+ diet and distilled drinking water for 6 weeks (low sodium plus diuretics group = LSD). The other group (n = 5) received the same low Na+ diet, but 0.5% NaCl was supplemented in drinking water (regular sodium group = RS). Body weight and blood pressure were measured weekly during the dietary period in all rats. At the end of the 6 weeks, heart weight as well as water and electrolyte contents of the heart were measured in all animals. Results showed that both body weight and heart weight were significantly lower in LSD than in RS. Moreover, ventricular Na+ content was reduced while ventricular Ca2+ content was doubled in LSD compared to RS (8.2 +/- 0.2 units vs. 9.2 +/- 0.3 units, p less than .05 and 0.45 +/- 0.13 units vs. 0.23 +/- 0.01 units, p less than .01, respectively). We conclude that in vivo sodium depletion induces an increase in ventricular calcium content; this increased myocardial calcium may be related to the increased in vitro cardiac contractility observed after chronic in vivo sodium depletion, but its distribution between intracellular and extracellular compartments needs to be determined. PMID:2923136

  14. Depression - elderly

    MedlinePlus

    ... highest risk. Families should pay close attention to elderly relatives who are depressed and who live alone. ... health care provider. Alternative Names Depression in the elderly Images Depression among the elderly References Abbasi O, ...

  15. Postpartum depression

    MedlinePlus

    Depression - postpartum; Postnatal depression; Postpartum psychological reactions ... The exact causes of postpartum depression are unknown. Changes in hormone levels during and after pregnancy may affect a woman’s mood. Many non-hormonal factors may also ...

  16. Caregiver Depression

    MedlinePlus

    ... will not sell or share your name. Caregiver Depression Tweet Bookmark this page | Email | Print Many caregivers ... depression See your doctor Treatment Coping Symptoms of depression Caregiving is hard — and can lead to feelings ...

  17. THE CONTRACTILE PROCESS IN THE CILIATE, STENTOR COERULEUS

    PubMed Central

    Huang, B.; Pitelka, D. R.

    1973-01-01

    The structural basis for the function of microtubules and filaments in cell body contractility in the ciliate Stentor coeruleus was investigated. Cells in the extended state were obtained for ultrastructural analysis by treatment before fixation with a solution containing 10 mM EGTA, 50–80 mM Tris, 3 mM MgSO4, 7.5 mM NH4Cl, 10 mM phosphate buffer (pH 7.1). The response of Stentor to changes in the divalent cation concentrations in this solution suggests that Ca+2 and Mg+2 are physiologically important in the regulation of ciliate contractility. The generation of motive force for changes in cell length in Stentor resides in two distinct longitudinal cortical fiber systems, the km fibers and myonemes. Cyclic changes in cell length are associated with (a) the relative sliding of parallel, overlapping microtubule ribbons in the km fibers, and (b) a distinct alteration in the structure of the contractile filaments constituting the myonemes. The microtubule and filament systems are distinguished functionally as antagonistic contractile elements. The development of motive force for cell extension is accomplished by active microtubule-to-microtubule sliding generated by specific intertubule bridges. Evidence is presented which suggests that active shortening of contractile filaments, reflected in a reversible structural transformation of dense 4-nm filaments to tubular 10–12-nm filaments, provides the basis for rapid cell contraction. PMID:4633444

  18. Effects of Hindlimb Unweighting on Arterial Contractile Responses in Mice

    NASA Technical Reports Server (NTRS)

    Ma, Jia; Ren, Xin-Ling; Purdy, Ralph E.

    2003-01-01

    The aim of this work was to determine if hindlimb unweighting in mice alters arterial contractile responses. Sixteen male C57B/6 mice and 16 male Chinese Kunming mice were divided into control and 3 weeks hindlimb unweighting groups, respectively. Using isolated arterial rings from different arteries of mouse, effects of 3 weeks hindlimb unweighting on arterial contractile responsiveness were examined in vitro. The results showed that, in arterial rings from both C57B/6 and Chinese Kunming mice, maximum isometric contractile tensions evoked by either KCl or phenylephrine were significantly lower in abdominal aortic, mesenteric arterial and femoral arterial rings from hindlimb unweighting, compared to control mice. However, the maximal contractile responses of common carotid rings to KCl and PE were not significantly different between control and hindlimb unweighting groups. The sensitivity (EC(sub 50)) of all arteries to KCl or PE showed no significant differences between control and hindlimb unweighting mice. These data indicated that 3 weeks hindlimb unweighting results in a reduced capacity of the arterial smooth muscle of the hindquarter to develop tension. In addition, the alterations in arterial contractile responses caused by hindlimb unweighting in mice are similar as those in rats. Our work suggested that hindlimb unweighting mouse model may be used as a model for the study of postflight cardiovascular deconditioning.

  19. Contractile cell forces deform macroscopic cantilevers and quantify biomaterial performance.

    PubMed

    Allenstein, U; Mayr, S G; Zink, M

    2015-07-01

    Cells require adhesion to survive, proliferate and migrate, as well as for wound healing and many other functions. The strength of contractile cell forces on an underlying surface is a highly relevant quantity to measure the affinity of cells to a rigid surface with and without coating. Here we show with experimental and theoretical studies that these forces create surface stresses that are sufficient to induce measurable bending of macroscopic cantilevers. Since contractile forces are linked to the formation of focal contacts, results give information on adhesion promoting qualities and allow a comparison of very diverse materials. In exemplary studies, in vitro fibroblast adhesion on the magnetic shape memory alloy Fe-Pd and on the l-lysine derived plasma-functionalized polymer PPLL was determined. We show that cells on Fe-Pd are able to induce surface stresses three times as high as on pure titanium cantilevers. A further increase was observed for PPLL, where the contractile forces are four times higher than on the titanium reference. In addition, we performed finite element simulations on the beam bending to back up the calculation of contractile forces from cantilever bending under non-homogenous surface stress. Our findings consolidate the role of contractile forces as a meaningful measure of biomaterial performance. PMID:26027952

  20. Effect of gender on rat upper airway muscle contractile properties.

    PubMed

    Cantillon, D; Bradford, A

    1998-08-01

    Obstructive sleep apnoea arises due to upper airway (UA) collapse which is normally counteracted by contraction of UA muscles such as the sternohyoids and geniohyoids. The disorder has a marked male predominance but the effect of gender on UA muscle contractile properties is unknown and these properties have not been compared for the sternohyoid and geniohyoid muscles in the same species. Isometric contractile characteristics were determined using strips of sternohyoid and geniohyoid muscle from male and female rats in Krebs solution at 30 degrees C. For both muscles, there were no differences between male and female contractile kinetics, twitch or tetanic tension, tension-length or tension-frequency relationship or endurance. In both males and females, sternohyoid twitch and tetanic tension was greater than geniohyoid. Sternohyoid endurance was less than geniohyoid but contractile kinetics, tension-length and tension-frequency relationships were similar. Therefore, gender does not affect UA muscle contractile properties and sternohyoid tension is greater and endurance less than that of the geniohyoid. PMID:9832233

  1. Changes of smooth muscle contractile filaments in small bowel atresia

    PubMed Central

    Gfroerer, Stefan; Fiegel, Henning; Ramachandran, Priya; Rolle, Udo; Metzger, Roman

    2012-01-01

    AIM: To investigate morphological changes of intestinal smooth muscle contractile fibres in small bowel atresia patients. METHODS: Resected small bowel specimens from small bowel atresia patients (n = 12) were divided into three sections (proximal, atretic and distal). Standard histology hematoxylin-eosin staining and enzyme immunohistochemistry was performed to visualize smooth muscle contractile markers α-smooth muscle actin (SMA) and desmin using conventional paraffin sections of the proximal and distal bowel. Small bowel from age-matched patients (n = 2) undergoing Meckel’s diverticulum resection served as controls. RESULTS: The smooth muscle coat in the proximal bowel of small bowel atresia patients was thickened compared with control tissue, but the distal bowel was unchanged. Expression of smooth muscle contractile fibres SMA and desmin within the proximal bowel was slightly reduced compared with the distal bowel and control tissue. There were no major differences in the architecture of the smooth muscle within the proximal bowel and the distal bowel. The proximal and distal bowel in small bowel atresia patients revealed only minimal differences regarding smooth muscle morphology and the presence of smooth muscle contractile filament markers. CONCLUSION: Changes in smooth muscle contractile filaments do not appear to play a major role in postoperative motility disorders in small bowel atresia. PMID:22791945

  2. Micropost arrays for measuring stem cell-derived cardiomyocyte contractility.

    PubMed

    Beussman, Kevin M; Rodriguez, Marita L; Leonard, Andrea; Taparia, Nikita; Thompson, Curtis R; Sniadecki, Nathan J

    2016-02-01

    Stem cell-derived cardiomyocytes have the potential to be used to study heart disease and maturation, screen drug treatments, and restore heart function. Here, we discuss the procedures involved in using micropost arrays to measure the contractile forces generated by stem cell-derived cardiomyocytes. Cardiomyocyte contractility is needed for the heart to pump blood, so measuring the contractile forces of cardiomyocytes is a straightforward way to assess their function. Microfabrication and soft lithography techniques are utilized to create identical arrays of flexible, silicone microposts from a common master. Micropost arrays are functionalized with extracellular matrix protein to allow cardiomyocytes to adhere to the tips of the microposts. Live imaging is used to capture videos of the deflection of microposts caused by the contraction of the cardiomyocytes. Image analysis code provides an accurate means to quantify these deflections. The contractile forces produced by a beating cardiomyocyte are calculated by modeling the microposts as cantilever beams. We have used this assay to assess techniques for improving the maturation and contractile function of stem cell-derived cardiomyocytes. PMID:26344757

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

    PubMed

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

    2016-07-01

    Inotropic medications are routinely used to increase cardiac output and arterial blood pressure during critical illness. However, few comparative data exist between these medications, particularly independent of their effects on venous capacitance and systemic vascular resistance. We hypothesized that an isolated working heart model that maintained constant left atrial pressure and aortic blood pressure could identify load-independent differences between inotropic medications. In an isolated heart preparation, the aorta and left atrium of Sprague Dawley rats were cannulated and placed in working mode with fixed left atrial and aortic pressure. Hearts were then exposed to common doses of a catecholamine (dopamine, epinephrine, norepinephrine, or dobutamine), milrinone, or triiodothyronine (n = 10 per dose per combination). Cardiac output, contractility (dP/dtmax), diastolic performance (dP/dtmin and tau), stroke work, heart rate, and myocardial oxygen consumption were compared during each 10-min infusion to an immediately preceding baseline. Of the catecholamines, dobutamine increased cardiac output, contractility, and diastolic performance more than clinically equivalent doses of norepinephrine (second most potent), dopamine, or epinephrine (P < 0.001). The use of triiodothyronine and milrinone was not associated with significant changes in cardiac output, contractility or diastolic function, either alone or added to a baseline catecholamine infusion. Myocardial oxygen consumption was closely related to dP/dtmax (r(2) = 0.72), dP/dtmin (r(2) = 0.70), and stroke work (r(2) = 0.53). In uninjured, isolated working rodent hearts under constant ventricular loading conditions, dobutamine increased contractility and cardiac output more than clinically equivalent doses of norepinephrine, dopamine, and epinephrine; milrinone and triiodothyronine did not have significant effects on contractility. PMID:27150829

  4. Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure.

    PubMed

    Coggan, Andrew R; Peterson, Linda R

    2016-08-01

    Heart failure (HF) patients suffer from exercise intolerance that diminishes their ability to perform normal activities of daily living and hence compromises their quality of life. This is due largely to detrimental changes in skeletal muscle mass, structure, metabolism, and function. This includes an impairment of muscle contractile performance, i.e., a decline in the maximal force, speed, and power of muscle shortening. Although numerous mechanisms underlie this reduction in contractility, one contributing factor may be a decrease in nitric oxide (NO) bioavailability. Consistent with this, recent data demonstrate that acute ingestion of NO3 (-)-rich beetroot juice, a source of NO via the NO synthase-independent enterosalivary pathway, markedly increases maximal muscle speed and power in HF patients. This review discusses the role of muscle contractile dysfunction in the exercise intolerance characteristic of HF, and the evidence that dietary NO3 (-) supplementation may represent a novel and simple therapy for this currently underappreciated problem. PMID:27271563

  5. Lateral hypothalamic lesions cause gastric injury by stimulating gastric contractility.

    PubMed

    Garrick, T; Grijalva, C V; Trauner, M

    1993-07-01

    Changes in gastric contractility following lateral hypothalamic (LH) lesions with and without bilateral cervical vagotomy were measured in urethan-anesthetized rats. LH lesions were induced with direct current passed through stereotaxically placed electrodes. Gastric contractility was recorded continuously for 4 h with acutely implanted strain gauge force transducers and analyzed by computer. LH lesions consistently stimulated gastric contractility and caused more gastric mucosal injury than control conditions. Vagotomy blocked both gastric mucosal injury and high-amplitude gastric contractions. In rats with LH lesions and exogenously infused intragastric hydrochloric acid, atropine methyl nitrate inhibited high-amplitude gastric contractions and gastric erosions. These findings indicate that LH lesions stimulate vagally mediated high-amplitude gastric contractions, which, in the presence of hydrochloric acid, cause gastric mucosal erosions. PMID:8338162

  6. Characterization of nontransmural myocardial infarction by positron-emission tomography

    SciTech Connect

    Geltman, E.M.; Biello, D.; Welch, M.J.; Ter-Pogossian, M.M.; Roberts, R.; Sobel, B.E.

    1982-04-01

    The present study was performed to determine whether positron emission tomography (PET) performed after i.v. 11C-palmitate permits detection and characterization of nontransmural myocardial infarction. PET was performed after the i.v. injection of 11C-palmitate in 10 normal subjects, 24 patients with initial nontransmural myocardial infarction (defined electrocardiographically), and 22 patients with transmural infarction. Depressed accumulation of 11C-palmitate was detected with sagittal, coronal and transverse reconstructions, and quantified based on 14 contiguous transaxial reconstructions. Defects with homogeneously intense depression of accumulation of tracer were detected in all 22 patients with transmural infarction (100%). Abnormalities of the distribution of 11C-palmitate in the myocardium were detected in 23 patients with nontransmural infarction (96%). Thallium scintigrams were abnormal in only 11 of 18 patients with nontransmural infarction (61%). Tomographically estimated infarct size was greater among patients with transmural infarction (50.4 +/- 7.8 PET-g-Eq/m2 (+/- SEM SEM)) compared with those with nontransmural infarction (19 +/- 4 PET-g-Eq, p less than 0.01). Residual accumulation of 11C-palmitate within regions of infarction was more intensely depressed among patients with transmural compared to nontransmural infarction (33 +/- 1 vs 39 +/- 1% maximal myocardial radioactivity, p less than 0.01). Thus, PET and metabolic imaging with 11C-palmitate is a sensitive means of detecting, quantifying and characterizing nontransmural and transmural myocardial infarction.

  7. Effects of traumatic brain injury on intestinal contractility

    PubMed Central

    OLSEN, A. B.; HETZ, R. A.; XUE, H.; AROOM, K. R.; BHATTARAI, D.; JOHNSON, E.; BEDI, S.; COX, C. S.; URAY, K.

    2014-01-01

    Background Patients with traumatic brain injury (TBI) often suffer from gastrointestinal dysfunction including intolerance to enteral feedings. However, it is unclear how TBI affects small intestinal contractile activity. The purpose of this study was to determine if TBI affects intestinal smooth muscle function. Methods Sprague–Dawley rats were subjected to controlled cortical impact injury (TBI). Sham animals underwent a similar surgery but no injury (SHAM). Animals were sacrificed 1, 3, and 7 days after TBI and intestinal smooth muscle tissue was collected for measurement of contractile activity and transit, NF-kB activity, and cytokine levels. Brains were collected after sacrifice to determine volume loss due to injury. Key Results Contractile activity decreased significantly in ileum, but not jejunum, in the TBI group 7 days after injury compared with SHAM. Brain volume loss increased significantly 7 days after injury compared with 3 days and correlated significantly with the contractile activity 1 day after injury. In the intestinal smooth muscle, NF-kB activity increased significantly in the TBI group 3 and 7 days after injury vs SHAM. Wet to dry weight ratio, indicating edema, also increased significantly in the TBI group. Interleukin- 1α, -1β, and -17 increased significantly in the TBI group compared with SHAM. Conclusions & Inferences Traumatic brain injury causes a delayed but significant decrease in intestinal contractile activity in the ileum leading to delayed transit. The decreased intestinal contractile activity is attributed to secondary inflammatory injury as evidenced by increased NF-kB activity, increased edema, and increased inflammatory cytokines in the intestinal smooth muscle. PMID:23551971

  8. Impaired Insulin Signaling Accelerates Cardiac Mitochondrial Dysfunction After Myocardial Infarction

    PubMed Central

    Sena, Sandra; Hu, Ping; Zhang, Dongfang; Wang, Xiaohui; Wayment, Benjamin; Olsen, Curtis; Avelar, Erick; Abel, E. Dale; Litwin, Sheldon E

    2009-01-01

    Diabetes increases mortality and accelerates left ventricular (LV) dysfunction following myocardial infarction (MI). This study sought to determine the impact of impaired myocardial insulin signaling, in the absence of diabetes, on the development of LV dysfunction following MI. Mice with cardiomyocyte-restricted knock out of the insulin receptor (CIRKO) and wild type (WT) mice were subjected to proximal left coronary artery ligation (MI) and followed for 14 days. Despite equivalent infarct size, mortality was increased in CIRKO-MI vs. WT-MI mice (68 % vs. 40 %, respectively). In surviving mice, LV ejection fraction and dP/dt were reduced by > 40% in CIRKO-MI vs. WT-MI. Relative to shams, isometric developed tension in LV papillary muscles increased in WT-MI but not in CIRKO-MI. Time to peak tension and relaxation times were prolonged in CIRKO-MI vs. WT-MI suggesting impaired, load-independent myocardial contractile function. To elucidate mechanisms for impaired LV contractility, mitochondrial function was examined in permeabilized cardiac fibers. Whereas maximal ADP-stimulated mitochondrial O2 consumption rates (VADP) with palmitoyl carnitine were unchanged in WT-MI mice relative to sham-operated animals, VADP was significantly reduced in CIRKO-MI (13.17 ± 0.94 vs. 9.14 ± 0.88 nmol O2/min/mgdw, p<0.05). Relative to WT-MI, expression levels of GLUT4, PPAR-α, SERCA2, and the FA-Oxidation genes MCAD, LCAD, CPT2 and the electron transfer flavoprotein ETFDH were repressed in CIRKO-MI. Thus reduced insulin action in cardiac myocytes accelerates post-MI LV dysfunction, due in part to a rapid decline in mitochondrial FA oxidative capacity, which combined with limited glucose transport capacity may reduce substrate utilization and availability. PMID:19249310

  9. Nandrolone-pretreatment enhances cardiac beta(2)-adrenoceptor expression and reverses heart contractile down-regulation in the post-stress period of acute-stressed rats.

    PubMed

    Penna, Claudia; Abbadessa, Giuliana; Mancardi, Daniele; Spaccamiglio, Angela; Racca, Silvia; Pagliaro, Pasquale

    2007-10-01

    To investigate whether nandrolone decanoate (ND)-pretreatment can modulate (1) beta-adrenoceptor expression and (2) myocardial contractility in response to beta-adrenoceptors stimulation with isoproterenol (ISO), in hearts of both normal and stressed rats. Rats were treated with 15 mg/(kgday) of Deca-Durabolin (ND, 1 ml i.m.) or with vehicle (oil) for 14 days. The day after the last injection, the dose-response to ISO (1 x 10(-8), 5 x 10(-8) and 10(-7)M), was studied in isolated rat hearts harvested from unstressed animals (unstressed+vehicle (control) or unstressed+ND) or from stressed animals (stressed+vehicle or stressed+ND): acute stress protocol consisted in restrain for 1h immediately before sacrifice. ND-pretreatment increased beta(2)-adrenoceptor expression. In baseline conditions all hearts had a similar left ventricular developed pressure (LVDP) and maximum rate of increase of LVDP (dP/dt(max)). In hearts of unstressed+vehicle or unstressed+ND, ISO caused a similar increase in LVDP (+90-100%) and dP/dt(max) (+120-150%). However, hearts of stressed+vehicle animals showed a marked depression of inotropic response to ISO (i.e. for ISO 1 x 10(-8),-55% in LVDP response versus unstressed). Yet, in hearts of stressed+ND-animals the effect of stress was reversed, showing the highest response to ISO (i.e. for ISO 1 x 10(-7), +30% LVDP response versus unstressed). The ND-induced beta(2)-adrenoceptor overexpression does not affect ISO-response in unstressed animals. However, acute stress induces a down-regulation of ISO-response, which is reversed by ND-pretreatment. Since the physiological post-stress down-regulation of adrenergic-response is absent after nandrolone treatment, the heart may be exposed to a sympathetic over-stimulation. This might represent a risk for cardiovascular incidents in anabolic steroid addicts under stressing conditions. PMID:17611100

  10. ORM-3819 promotes cardiac contractility through Ca(2+) sensitization in combination with selective PDE III inhibition, a novel approach to inotropy.

    PubMed

    Nagy, László; Pollesello, Piero; Haikala, Heimo; Végh, Ágnes; Sorsa, Tia; Levijoki, Jouko; Szilágyi, Szabolcs; Édes, István; Tóth, Attila; Papp, Zoltán; Papp, Julius Gy

    2016-03-15

    This study is the first pharmacological characterization of the novel chemical entity, ORM-3819 (L-6-{4-[N'-(4-Hydroxi-3-methoxy-2-nitro-benzylidene)-hydrazino]-phenyl}-5-methyl-4,5-dihydro-2H-pyridazin-3-one), focusing primarily on its cardiotonic effects. ORM-3819 binding to cardiac troponin C (cTnC) was confirmed by nuclear magnetic resonance spectroscopy, and a selective inhibition of the phosphodiesterase III (PDE III) isozyme (IC50=3.88±0.3nM) was revealed during in vitro enzyme assays. The Ca(2+)-sensitizing effect of ORM-3819 was demonstrated in vitro in permeabilized myocyte-sized preparations from left ventricles (LV) of guinea pig hearts (ΔpCa50=0.12±0.01; EC50=2.88±0.14µM). ORM-3819 increased the maximal rate of LV pressure development (+dP/dtmax) (EC50=8.9±1.7nM) and LV systolic pressure (EC50=7.63±1.74nM) in Langendorff-perfused guinea pig hearts. Intravenous administration of ORM-3819 increased LV+dP/dtmax (EC50=0.13±0.05µM/kg) and improved the rate of LV pressure decrease (-dP/dtmax); (EC50=0.03±0.02µM/kg) in healthy guinea pigs. In an in vivo dog model of myocardial stunning, ORM-3819 restored the depressed LV+dP/dtmax and improved % segmental shortening (%SS) in the ischemic area (to 18.8±3), which was reduced after the ischaemia-reperfusion insult (from 24.1±2.1 to 11.0±2.4). Our data demonstrate ORM-3819 as a potent positive inotropic agent exerting its cardiotonic effect by a cTnC-dependent Ca(2+)-sensitizing mechanism in combination with the selective inhibition of the PDE III isozyme. This dual mechanism of action results in the concentration-dependent augmentation of the contractile performance under control conditions and in the postischemic failing myocardium. PMID:26872993

  11. Assessment of the Contractile Properties of Permeabilized Skeletal Muscle Fibers.

    PubMed

    Claflin, Dennis R; Roche, Stuart M; Gumucio, Jonathan P; Mendias, Christopher L; Brooks, Susan V

    2016-01-01

    Permeabilized individual skeletal muscle fibers offer the opportunity to evaluate contractile behavior in a system that is greatly simplified, yet physiologically relevant. Here we describe the steps required to prepare, permeabilize and preserve small samples of skeletal muscle. We then detail the procedures used to isolate individual fiber segments and attach them to an experimental apparatus for the purpose of controlling activation and measuring force generation. We also describe our technique for estimating the cross-sectional area of fiber segments. The area measurement is necessary for normalizing the absolute force to obtain specific force, a measure of the intrinsic force-generating capability of the contractile system. PMID:27492182

  12. Myocardial infarction and marijuana.

    PubMed

    Charles, R; Holt, S; Kirkham, N

    1979-04-01

    Myocardial infarction in the virtual absence of risk factors occurred in a 25-year old man shortly after smoking a cigarette containing marijuana. Subsequent coronary arteriography was normal. PMID:466984

  13. Controversies in cardiovascular care: silent myocardial ischemia

    NASA Technical Reports Server (NTRS)

    Hollenberg, N. K.

    1987-01-01

    The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.

  14. Experimental myocardial infarction

    PubMed Central

    Kumar, Raj; Joison, Julio; Gilmour, David P.; Molokhia, Farouk A.; Pegg, C. A. S.; Hood, William B.

    1971-01-01

    The hemodynamic effects of tachycardia induced by atrial pacing were investigated in left ventricular failure of acute and healing experimental myocardial infarction in 20 intact, conscious dogs. Myocardial infarction was produced by gradual inflation of a balloon cuff device implanted around the left anterior descending coronary artery 10-15 days prior to the study. 1 hr after acute myocardial infarction, atrial pacing at a rate of 180 beats/min decreased left ventricular end-diastolic pressure from 19 to 8 mm Hg and left atrial pressure from 17 to 12 mm Hg, without change in cardiac output. In the healing phase of myocardial infarction 1 wk later, atrial pacing decreased left ventricular end-diastolic pressure from 17 to 9 mm Hg and increased the cardiac output by 37%. This was accompanied by evidence of peripheral vasodilation. In two dogs with healing anterior wall myocardial infarction, left ventricular failure was enhanced by partial occlusion of the circumflex coronary artery. Both the dogs developed pulmonary edema. Pacing improved left ventricular performance and relieved pulmonary edema in both animals. In six animals propranolol was given after acute infarction, and left ventricular function deteriorated further. However the pacing-induced augmentation of cardiac function was unaltered and, hence, is not mediated by sympathetics. The results show that the spontaneous heart rate in left ventricular failure of experimental canine myocardial infarction may be less than optimal and that maximal cardiac function may be achieved at higher heart rates. Images PMID:4395910

  15. Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat

    PubMed Central

    Elmes, Matthew; Szyszka, Alexandra; Pauliat, Caroline; Clifford, Bethan; Daniel, Zoe; Cheng, Zhangrui; Wathes, Claire; McMullen, Sarah

    2015-01-01

    Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2α, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhibited by YOUNG rats was threefold greater than OLDER animals (P < 0.027) but maternal age had no significant effect on myometrial CAP expression, lipid profiles, or pregnancy-related hormones. OLDER myometrium increased contractile activity in response to PGF2α, phenylephrine, and carbachol, a response absent in YOUNG rats (all P < 0.002). Microarray analysis identified that maternal age affected expression of genes related to immune and inflammatory responses, lipid transport and metabolism, steroid metabolism, tissue remodeling, and smooth muscle contraction. In conclusion YOUNG laboring rat myometrium seems primed to contract maximally, whereas activity is blunted in OLDER animals and requires stimulation to meet contractile potential. Further work investigating maternal age effects on myometrial function is required with focus on lipid metabolism and inflammatory pathways. PMID:25876907

  16. Multifunctional MR monitoring of the healing process after myocardial infarction.

    PubMed

    Bönner, Florian; Jacoby, Christoph; Temme, Sebastian; Borg, Nadine; Ding, Zhaoping; Schrader, Jürgen; Flögel, Ulrich

    2014-01-01

    Healing of the myocardium after infarction comprises a variety of local adaptive processes which contribute to the functional outcome after the insult. Therefore, we aimed to establish a setting for concomitant assessment of regional alterations in contractile function, morphology, and immunological state to gain prognostic information on cardiac recovery after infarction. For this, mice were subjected to myocardial ischemia/reperfusion (I/R) and monitored for 28 days by cine MRI, T2 mapping, late gadolinium enhancement (LGE), and (19)F MRI. T2 values were calculated from gated multi-echo sequences. (19)F-loaded nanoparticles were injected intravenously for labelling circulating monocytes and making them detectable by (19)F MRI. In-house developed software was used for regional analysis of cine loops, T2 maps, LGE, and (19)F images to correlate local wall movement, tissue damage as well as monocyte recruitment over up to 200 sectors covering the left ventricle. This enabled us to evaluate simultaneously zonal cardiac necrosis, oedema, and inflammation patterns together with sectional fractional shortening (FS) and global myocardial function. Oedema, indicated by a rise in T2, showed a slightly better correlation with FS than LGE. Regional T2 values increased from 19 ms to above 30 ms after I/R. In the course of the healing process oedema resolved within 28 days, while myocardial function recovered. Infiltrating monocytes could be quantitatively tracked by (19)F MRI, as validated by flow cytometry. Furthermore, (19)F MRI proved to yield valuable insight on the outcome of myocardial infarction in a transgenic mouse model. In conclusion, our approach permits a comprehensive surveillance of key processes involved in myocardial healing providing independent and complementary information for individual prognosis. PMID:25098936

  17. Role of cytokines in myocardial ischemia and reperfusion.

    PubMed

    Sharma, H S; Das, D K

    1997-01-01

    Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia-reperfusion injury. Furthermore, ischemia-reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-alpha) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart. PMID:18472818

  18. Myofilament calcium sensitization delays decompensated hypertrophy differently between the sexes following myocardial infarction

    PubMed Central

    Shioura, Krystyna M.; Farjah, Mariam; Geenen, David L.; Solaro, R. John

    2011-01-01

    Contractile dysfunction is common to many forms of cardiovascular disease. Approaches directed at enhancing cardiac contractility at the level of the myofilaments during heart failure (HF) may provide a means to improve overall cardiovascular function. We are interested in gender-based differences in cardiac function and the effect of sarcomere activation agents that increase contractility. Thus, we studied the effect of gender and time on integrated arterial-ventricular function (A-V relationship) following myocardial infarction (MI). In addition, transgenic mice that overexpress the slow skeletal troponin I isoform were used to determine the impact of increased myofilament Ca2+ sensitivity following MI. Based on pressure-volume (P-V) loop measurements, we used derived parameters of cardiovascular function to reveal the effects of sex, time, and increased myofilament Ca2+ sensitivity among groups of post-MI mice. Analysis of the A-V relationship revealed that the initial increase was similar between the sexes, but the vascular unloading of the heart served to delay the decompensated stage in females. Conversely, the vascular response at 6 and 10 wk post-MI in males contributed to the continuous decline in cardiovascular function. Increasing the myofilament Ca2+ sensitivity appeared to provide sufficient contractile support to improve contractile function in both male and female transgenic mice. However, the improved contractile function was more beneficial in males as the concurrent vascular response contributed to a delayed decompensated stage in female transgenic mice post-MI. This study represents a quantitative approach to integrating the vascular-ventricular relationship to provide meaningful and diagnostic value following MI. Consequently, the data provide a basis for understanding how the A-V relationship is coupled between males and females and the enhanced ability of the cardiovascular system to tolerate pathophysiological stresses associated with HF in

  19. Myocardial Noncompaction Presenting With Myocardial Bridge

    PubMed Central

    Shen, Yuechun; Li, Xinchun; Lu, Dongfeng; Xiao, Aiyi; Li, Jun

    2015-01-01

    Abstract Myocardial noncompaction, namly isolated noncompaction of the left ventricular myocardium (NVM), is a rare congenital disease. It can be either seen in the absence of other cardiac anomalies, or associated with other congenital cardiac defects, mostly stenotic lesions of the left ventricular outflow tract. A myocardial bridge (MB) is thought being associated with coronary heart disease, such as coronary spasm, arrhythmia, and so on. The significance of MB in association with other congenital cardiac conditions is unknown. We report a novel case who was presented NVM and MB. A 34-year-old man complained of chest prickling-like pain and dizzy for 1 year. His blood pressure was 110/70 mm Hg. Echocardiograph revealed increased trabeculations below the level of papillary muscle of left ventricle (LV); deep intertrabecular recesses in the endocardial wall of LV particularly in apex free wall; and LV ejection fraction of 57%. A coronary computerized tomography scan showed that part, 38.9 cm, of left descending artery tunnel was surrounding by cardiac muscles rather than resting on top of the myocardium. The therapeutics interventions included lifestyle cares, agents of anti-ischemia and improvement myocardial cell metabolism. The patient was followed up for 2.6 years, and his general condition was stable. This case indicates that NVM can be developed with MB, and the complete diagnosis of NVM and MB should be made by different image studies. PMID:26356695

  20. PPAR-γ activation fails to provide myocardial protection in ischemia and reperfusion in pigs

    PubMed Central

    Xu, Ya; Gen, Michael; Lu, Li; Fox, Jennifer; Weiss, Sara O.; Brown, R. Dale; Perlov, Daniel; Ahmad, Hasan; Zhu, Peili; Greyson, Clifford; Long, Carlin S.; Schwartz, Gregory G.

    2010-01-01

    Peroxisome proliferator-activated receptor (PPAR)-γ modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (I/R), thiazolidinedione PPAR-γ activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-γ activator that has been shown to be protective in I/R in large animals. However, because troglitazone contains both α-tocopherol and thiazolidinedione moieties, whether PPAR-γ activation per se is protective in myocardial I/R in large animals remains uncertain. To address this question, 56 pigs were treated orally for 8 wk with troglitazone (75 mg·kg−1 ·day−1), rosiglitazone (3 mg·kg−1 ·day−1), or α-tocopherol (73 mg·kg−1 ·day−1, equimolar to troglitazone dose) or received no treatment. Pigs were then anesthetized and subjected to 90 min of low-flow regional myocardial ischemia and 90 min of reperfusion. Myocardial expression of PPAR-γ, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (Frank-Starling relations), substrate uptake, or expression of proinflammatory cytokines during I/R compared with untreated pigs. In contrast, preservation of myocardial contractile function and lactate uptake were greater and cytokine expression was attenuated in pigs treated with troglitazone or α-tocopherol compared with untreated pigs. Multivariate analysis indicated that presence of an α-tocopherol, but not a thiazolidinedione, moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-γ activation is not protective in a porcine model of myocardial I/R. Protective effects of troglitazone are attributable to its α-tocopherol moiety. These findings, in conjunction with prior rat studies, suggest

  1. Human colonic smooth muscle: electrical and contractile activity in vitro.

    PubMed Central

    Gill, R C; Cote, K R; Bowes, K L; Kingma, Y J

    1986-01-01

    Extracellular electrical and contractile activities were recorded in vitro from strips of human colonic smooth muscle obtained at the time of surgery. Serosal electrical activity of longitudinally oriented strips from the taenia and intertaenial region was characterised by continuous oscillation at a frequency of 28 +/- 1/min. Contractions were marked electrically by a series of oscillations upon which spikes were superimposed. The electrical activity recorded from the submucosal surface of circularly oriented strips exhibited oscillations at 24 +/- 4/min, a frequency significantly lower (p less than 0.001) than that recorded from the serosal surface of similar preparations. The contractile force and frequency was dependent upon the part of the colon from which the strip originated; the most powerful contractions were recorded from strips of sigmoid colon. The contractile frequency of circularly oriented strips from the right colon was 6.3 +/- 0.6/min, significantly higher (p less than 0.001) than that of strips from the left colon (3.4 +/- 0.3/min). Stretching these strips caused an increase in contractile frequency to that of the electrical oscillation. PMID:3699550

  2. Sarcoplasmic reticulum function and muscle contractile character following fatiguing exercise in humans

    PubMed Central

    Hill, Christopher A; Thompson, Martin W; Ruell, Patricia A; Thom, Jeanette M; White, Michael J

    2001-01-01

    This study examined the alterations in calcium release, calcium uptake and calcium ATPase activity of skeletal muscle sarcoplasmic reticulum in response to a bout of intense dynamic knee extensor exercise, and the relationship between these changes and alterations in muscle contractile characteristics in the human quadriceps. In biopsy samples taken from the vastus lateralis, sarcoplasmic reticulum calcium release and calcium uptake were significantly depressed (P < 0.01 and 0.05, respectively) immediately following the exercise with no alteration in the sarcoplasmic reticulum Ca2+-ATPase activity. A 33 % reduction in the maximum voluntary isometric torque was found following the exercise, with reduced torques from electrically evoked isometric contractions at low frequencies of stimulation (10 and 20 Hz) but not at higher frequencies (50 and 100 Hz). The depressed calcium release was correlated (P < 0.05) with a decreased ratio of torques generated at 20:50 Hz, indicating an involvement in low frequency fatigue; however, no correlations between the muscle relaxation times or rates of change of torque and calcium uptake were observed. PMID:11251066

  3. Identification of contractile vacuole proteins in Trypanosoma cruzi.

    PubMed

    Ulrich, Paul N; Jimenez, Veronica; Park, Miyoung; Martins, Vicente P; Atwood, James; Moles, Kristen; Collins, Dalis; Rohloff, Peter; Tarleton, Rick; Moreno, Silvia N J; Orlando, Ron; Docampo, Roberto

    2011-01-01

    Contractile vacuole complexes are critical components of cell volume regulation and have been shown to have other functional roles in several free-living protists. However, very little is known about the functions of the contractile vacuole complex of the parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, other than a role in osmoregulation. Identification of the protein composition of these organelles is important for understanding their physiological roles. We applied a combined proteomic and bioinfomatic approach to identify proteins localized to the contractile vacuole. Proteomic analysis of a T. cruzi fraction enriched for contractile vacuoles and analyzed by one-dimensional gel electrophoresis and LC-MS/MS resulted in the addition of 109 newly detected proteins to the group of expressed proteins of epimastigotes. We also identified different peptides that map to at least 39 members of the dispersed gene family 1 (DGF-1) providing evidence that many members of this family are simultaneously expressed in epimastigotes. Of the proteins present in the fraction we selected several homologues with known localizations in contractile vacuoles of other organisms and others that we expected to be present in these vacuoles on the basis of their potential roles. We determined the localization of each by expression as GFP-fusion proteins or with specific antibodies. Six of these putative proteins (Rab11, Rab32, AP180, ATPase subunit B, VAMP1, and phosphate transporter) predominantly localized to the vacuole bladder. TcSNARE2.1, TcSNARE2.2, and calmodulin localized to the spongiome. Calmodulin was also cytosolic. Our results demonstrate the utility of combining subcellular fractionation, proteomic analysis, and bioinformatic approaches for localization of organellar proteins that are difficult to detect with whole cell methodologies. The CV localization of the proteins investigated revealed potential novel roles of these organelles in phosphate metabolism

  4. Actomyosin contractility spatiotemporally regulates actin network dynamics in migrating cells.

    PubMed

    Okeyo, Kennedy Omondi; Adachi, Taiji; Sunaga, Junko; Hojo, Masaki

    2009-11-13

    Coupling interactions among mechanical and biochemical factors are important for the realization of various cellular processes that determine cell migration. Although F-actin network dynamics has been the focus of many studies, it is not yet clear how mechanical forces generated by actomyosin contractility spatiotemporally regulate this fundamental aspect of cell migration. In this study, using a combination of fluorescent speckle microscopy and particle imaging velocimetry techniques, we perturbed the actomyosin system and examined quantitatively the consequence of actomyosin contractility on F-actin network flow and deformation in the lamellipodia of actively migrating fish keratocytes. F-actin flow fields were characterized by retrograde flow at the front and anterograde flow at the back of the lamellipodia, and the two flows merged to form a convergence zone of reduced flow intensity. Interestingly, activating or inhibiting actomyosin contractility altered network flow intensity and convergence, suggesting that network dynamics is directly regulated by actomyosin contractility. Moreover, quantitative analysis of F-actin network deformation revealed that the deformation was significantly negative and predominant in the direction of cell migration. Furthermore, perturbation experiments revealed that the deformation was a function of actomyosin contractility. Based on these results, we suggest that the actin cytoskeletal structure is a mechanically self-regulating system, and we propose an elaborate pathway for the spatiotemporal self-regulation of the actin cytoskeletal structure during cell migration. In the proposed pathway, mechanical forces generated by actomyosin interactions are considered central to the realization of the various mechanochemical processes that determine cell motility. PMID:19665125

  5. (1) Coronary Events Caused by Myocardial Bridge

    PubMed Central

    Yoko, Kawawa; Ehiichi, Kohda; Toshiharu, Ishii

    2009-01-01

    Myocardial bridge (MB), which covers a part of the left anterior descending coronary artery (LAD), is a normal anatomical variant structure (45% in frequency by autopsy) in LAD. MB contraction plays the role of a “double-edged sword” on the coronary events, suppressing coronary atherosclerosis under the MB, yet generating abnormal blood flow associated with coronary heart diseases (CHDs). High shear stress driven by MB compression causes the suppression of vascular permeability and vasoactive protein expression such as e-NOS and endothelin-1, which leads to the suppression of atherosclerosis in the LAD segment under the MB. However, despite the prevalent view of MB as benignancy by conventional coronary angiography (5-6% in frequency), with advance of imaging technique such as multislice spiral computed tomography [(MSCT); 16% in frequency], cardiologists are now frequently aware of symptomatic MB occurring not only in hospitalized patients, but also in young athletes free from atherosclerosis. Moreover, the large mass volume of MB muscle induces atherosclerosis evolution at the settled site in LAD proximal to MB and contributes to the occurrence of myocardial infarction. These events upon the coronary events result from the different pathophysiological mechanisms induced by contractile force of MB, which is solely determined just by the integration of anatomical properties of MB, such as the location, length and thickness of MB in an individual LAD. A recent MSCT provides the objective quantification of the anatomical variables that correlate with the histopathological results in relation to the occurrence of CHD. In this review, we therefore discuss the necessity to explore MB as a inherent chance anatomical risk factor for CHD. PMID:23555365

  6. Hydrogen sulfide alleviates cardiac contractile dysfunction in an Akt2-knockout murine model of insulin resistance: role of mitochondrial injury and apoptosis

    PubMed Central

    Hu, Nan; Dong, Maolong

    2014-01-01

    Hydrogen sulfide (H2S) is a toxic gas now being recognized as an endogenous signaling molecule in multiple organ systems, in particular, the cardiovascular system. H2S is known to regulate cardiac function and protect against ischemic injury. However, little information is available regarding the effect of H2S on cardiac function in insulin resistance. This study was designed to examine the impact of H2S supplementation on cardiac function using an Akt2 knockout model of insulin resistance. Wild-type and Akt2 knockout mice were treated with NaHS (50 μM·kg−1·day−1 ip for 10 days) prior to evaluation of echocardiographic, cardiomyocyte contractile, and intracellular Ca2+ properties, apoptosis, and mitochondrial damage. Our results revealed that Akt2 ablation led to overtly enlarged ventricular end-systolic diameter, reduced myocardial and cardiomyocyte contractile function, and disrupted intracellular Ca2+ homeostasis and apoptosis, the effects of which were ameliorated by H2S. Furthermore, Akt2 knockout displayed upregulated apoptotic protein markers (Bax, caspase-3, caspase-9, and caspace-12) and mitochondrial damage (reduced aconitase activity and NAD+, elevated cytochrome-c release from mitochondria) along with reduced phosphorylation of PTEN, Akt, and GSK3β in the absence of changes in pan protein expression, the effects of which were abolished or significantly ameliorated by H2S treatment. In vitro data revealed that H2S-induced beneficial effect against Akt2 ablation was obliterated by mitochondrial uncoupling. Taken together, our findings suggest the H2S may reconcile Akt2 knockout-induced myocardial contractile defect and intracellular Ca2+ mishandling, possibly via attenuation of mitochondrial injury and apoptosis. PMID:24622975

  7. Postpartum Depression

    MedlinePlus

    ... do not need treatment. The symptoms of postpartum depression last longer and are more severe. You may ... treatment right away, often in the hospital. Postpartum depression can begin anytime within the first year after ...

  8. Teen Depression

    MedlinePlus

    ... shown that certain types of talk therapy or psychotherapy can help teens deal with depression. These include ... behaviors, and feelings related to depression, and interpersonal psychotherapy, which focuses on working on relationships. Read more ...

  9. Postpartum depression

    MedlinePlus

    ... therapy if you have postpartum depression. Having good social support from family, friends, and coworkers may help reduce ... Having good social support from family, friends, and coworkers may ... seriousness of postpartum depression, but may not prevent it. ...

  10. Postpartum Depression

    MedlinePlus

    ... and do not need treatment. The symptoms of postpartum depression last longer and are more severe. You may ... get treatment right away, often in the hospital. Postpartum depression can begin anytime within the first year after ...

  11. Depression - overview

    MedlinePlus

    Depression may be described as feeling sad, blue, unhappy, miserable, or down in the dumps. Most of ... one time or another for short periods. Clinical depression is a mood disorder in which feelings of ...

  12. Cardiac Function Is Regulated by B56α-mediated Targeting of Protein Phosphatase 2A (PP2A) to Contractile Relevant Substrates*

    PubMed Central

    Kirchhefer, Uwe; Brekle, Christiane; Eskandar, John; Isensee, Gunnar; Kučerová, Dana; Müller, Frank U.; Pinet, Florence; Schulte, Jan S.; Seidl, Matthias D.; Boknik, Peter

    2014-01-01

    Dephosphorylation of important myocardial proteins is regulated by protein phosphatase 2A (PP2A), representing a heterotrimer that is comprised of catalytic, scaffolding, and regulatory (B) subunits. There is a multitude of B subunit family members directing the PP2A holoenzyme to different myocellular compartments. To gain a better understanding of how these B subunits contribute to the regulation of cardiac performance, we generated transgenic (TG) mice with cardiomyocyte-directed overexpression of B56α, a phosphoprotein of the PP2A-B56 family. The 2-fold overexpression of B56α was associated with an enhanced PP2A activity that was localized mainly in the cytoplasm and myofilament fraction. Contractility was enhanced both at the whole heart level and in isolated cardiomyocytes of TG compared with WT mice. However, peak amplitude of [Ca]i did not differ between TG and WT cardiomyocytes. The basal phosphorylation of cardiac troponin inhibitor (cTnI) and the myosin-binding protein C was reduced by 26 and 35%, respectively, in TG compared with WT hearts. The stimulation of β-adrenergic receptors by isoproterenol (ISO) resulted in an impaired contractile response of TG hearts. At a depolarizing potential of −5 mV, the ICa,L current density was decreased by 28% after administration of ISO in TG cardiomyocytes. In addition, the ISO-stimulated phosphorylation of phospholamban at Ser16 was reduced by 27% in TG hearts. Thus, the increased PP2A-B56α activity in TG hearts is localized to specific subcellular sites leading to the dephosphorylation of important contractile proteins. This may result in higher myofilament Ca2+ sensitivity and increased basal contractility in TG hearts. These effects were reversed by β-adrenergic stimulation. PMID:25320082

  13. Sensorless control for a sophisticated artificial myocardial contraction by using shape memory alloy fibre.

    PubMed

    Shiraishi, Y; Yambe, T; Saijo, Y; Sato, F; Tanaka, A; Yoshizawa, M; Sugai, T K; Sakata, R; Luo, Y; Park, Y; Uematsu, M; Umezu, M; Fujimoto, T; Masumoto, N; Liu, H; Baba, A; Konno, S; Nitta, S; Imachi, K; Tabayashi, K; Sasada, H; Homma, D

    2008-01-01

    The authors have been developing an artificial myocardium, which is capable of supporting natural contractile function from the outside of the ventricle. The system was originally designed by using sophisticated covalent shape memory alloy fibres, and the surface did not implicate blood compatibility. The purpose of our study on the development of artificial myocardium was to achieve the assistance of myocardial functional reproduction by the integrative small mechanical elements without sensors, so that the effective circulatory support could be accomplished. In this study, the authors fabricated the prototype artificial myocardial assist unit composed of the sophisticated shape memory alloy fibre (Biometal), the diameter of which was 100 microns, and examined the mechanical response by using pulse width modulation (PWM) control method in each unit. Prior to the evaluation of dynamic characteristics, the relationship between strain and electric resistance and also the initial response of each unit were obtained. The component for the PWM control was designed in order to regulate the myocardial contractile function, which consisted of an originally-designed RISC microcomputer with the input of displacement, and its output signal was controlled by pulse wave modulation method. As a result, the optimal PWM parameters were confirmed and the fibrous displacement was successfully regulated under the different heat transfer conditions simulating internal body temperature as well as bias tensile loading. Then it was indicated that this control theory might be applied for more sophisticated ventricular passive or active restraint by the artificial myocardium on physiological demand. PMID:19162754

  14. Relationship between myocardial uptake and actions in heart failure of methyldigoxin.

    PubMed Central

    Hayward, R; Greenwood, H; Stephens, J; Hamer, J

    1983-01-01

    1 Problems have been encountered in recent years in confirming useful benefit to patients with heart failure and sinus rhythm from acute exposure to digitalis glycosides, though effectiveness of these preparations upon cardiac contractile performance is indisputable. Undesired effects such as those upon systemic vascular resistance have been invoked to explain this. 2 Detailed haemodynamic responses have been studied by cardiac catheterisation in nine such patients for 30 min after intravenous methyldigoxin infusion. Myocardial glycoside uptake was simultaneously assessed. 3 Methyldigoxin uptake by the heart was rapid, passing its peak within 20 min, and was followed by substantial elution. 4 A small progressive and significant increase in cardiac output was observed, though left ventricular filling pressures were not significantly reduced after methyldigoxin. Cardiac contractile function as assessed by left ventricular maximum dP/dt, measured in six patients, showed consistent improvement. PMID:6849743

  15. Micropatterned nanostructures: a bioengineered approach to mass-produce functional myocardial grafts

    NASA Astrophysics Data System (ADS)

    Serpooshan, Vahid; Mahmoudi, Morteza

    2015-02-01

    Cell-based therapies are a recently established path for treating a wide range of human disease. Tissue engineering of contractile heart muscle for replacement therapy is among the most exciting and important of these efforts. However, current in vitro techniques of cultivating functional mature cardiac grafts have only been moderately successful due to the poor capability of traditional two-dimensional cell culture systems to recapitulate necessary in vivo conditions. In this issue, Kiefer et al [1] introduce a laser-patterned nanostructured substrate (Al/Al2O3 nanowires) for efficient maintenance of oriented human cardiomyocytes, with great potential to open new roads to mass-production of contractile myocardial grafts for cardiovascular tissue engineering.

  16. Biomarkers detect involvement of acute myocardial injury in a paediatric haemolytic-uraemic syndrome patient.

    PubMed

    Palanca Arias, Daniel; López Ramón, Marta; Jiménez Montañés, Lorenzo

    2016-06-01

    Although extrarenal manifestations of haemolytic-uraemic syndrome are not frequent, myocardial dysfunction should be given special consideration because of the importance of proper early haemodynamic management and potential complications. We report the case of a 21-month-old child with haemolytic-uraemic syndrome who developed clinical signs of poor myocardial function with depressed myocardial function noted by bedside echocardiography and significant elevation of biomarkers. Early intervention and supportive treatment for the patient were crucial during the acute phase of cardiac failure, and repeated monitoring of biomarkers and ecocardiography were useful diagnostic tools that provided relevant information throughout the patient's evolution. PMID:26838960

  17. Regional Myocardial Perfusion Rates in Patients with Coronary Artery Disease

    PubMed Central

    Cannon, Paul J.; Dell, Ralph B.; Dwyer, Edward M.

    1972-01-01

    Regional myocardial perfusion rates were estimated from the myocardial washout of 133Xenon in 24 patients with heart disease whose coronary arteriograms were abnormal and 17 similar subjects whose coronary arteriograms were judged to be normal. Disappearance rates of 133Xe from multiple areas of the heart were monitored externally with a multiple-crystal scintillation camera after the isotope had been injected into a coronary artery and local myocardial perfusion rates were calculated by the Kety formula. The mean myocardial perfusion rates in the left ventricle exceeded those in the right ventricle or atrial regions in subjects without demonstrable coronary artery disease. In this group there was a significant lack of homogeneity of local perfusion rates in left ventricular myocardium; the mean coefficient of variation of left ventricular local perfusion rates was 15.8%. In the patients with radiographically demonstrable coronary artery disease, a variety of myocardial perfusion patterns were observed. Local capillary blood flow rates were depressed throughout the myocardium of patients with diffuse coronary disease but were subnormal only in discrete myocardial regions of others with localized occlusive disease. Local myocardial perfusion rates were similar to those found in the group with normal coronary arteriograms in patients with slight degrees of coronary disease and in those areas of myocardium distal to marked coronary constrictions or occlusions which were well supplied by collateral vessels. In subjects with right coronary disease, the mean right ventricular perfusion rates were significantly subnormal; in seven subjects of this group perfusion of the inferior left ventricle by a dominant right coronary artery was absent or depressed. The average mean left ventricular perfusion rate of 12 subjects with significant disease of two or more branches of the left coronary artery was significantly lower than that of the group with normal left coronary

  18. Adolescent Depression.

    ERIC Educational Resources Information Center

    Evans, Dina M.

    Affective disorder is characterized by maladaptive changes in mood, attitudes, energy level, and physical status. These changes constitute the basic dimensions of depression. Depression results from a combination of genetic and experiential factors. There are sex differences and age differences with regard to depression, and there is a high…

  19. Perinatal depression

    PubMed Central

    Alhusen, Jeanne L.; Alvarez, Carmen

    2016-01-01

    Abstract: Perinatal depression is a common condition with significant adverse maternal, fetal, neonatal, and early childhood outcomes. The perinatal period is an opportune time to screen, diagnose, and treat depression. Improved recognition of perinatal depression, particularly among low-income women, can lead to improved perinatal health outcomes. PMID:26934457

  20. [Occupational stress and myocardial infarction].

    PubMed

    Consoli, Silla M

    2015-01-01

    Besides the best-known role of depressed mood, occupational stress deserves to be taken as a coronary risk factor. There are two basic models to define occupational stress: Karasek's model (high job psychological demands associated with low decision latitude, or even low social support at work) and Siegrist's model (imbalance between efforts and rewards received). The combination of the two models better reflects the coronary risk than each model alone. Occupational stress appears both as a risk factor and a prognostic factor after the occurrence of myocardial infarction. The relevance of the models is best in men or in younger age subjects. In women, role conflicts (occupational/domestic), the existence of excessive "intrinsic" efforts (job over investment) and association with marital stress provide more specific information. Burnout, particularly among health professionals, and bullying at work are also linked to cardiovascular risk. Occupational stress is a collective indicator of health at work, valuable to the employer. At an individual level, it can lead to therapeutic preventive approaches. PMID:26150284

  1. Patterns of disturbed myocardial perfusion in patients with coronary artery disease. Regional myocardial perfusion in angina pectoris

    SciTech Connect

    Selwyn, A.P.; Forse, G.; Fox, K.; Jonathan, A.; Steiner, R.

    1981-07-01

    Fifty patients who presented with angina pectoris were studied to examine the disturbances of regional myocardial perfusion during stress. Each patient underwent 16-point precordial mapping of the ECG during an exercise test, and coronary and left ventricular angiography. Regional myocardial perfusion was assessed using an atrial pacing test and a short-lived radionuclide, krypton-81m. Eleven patients had negative exercise tests and uniform increases in myocardial activity of krypton-81m of 98 +/- 18.0% during pacing. Ten patients performed 30,000-43,000 J in positive exercise tests. These patients showed abnormal coronary anatomy and increases in myocardial activity of krypton-81m to remote and jeopardized myocardium at the onset of pacing. However, further pacing produced a decrease in activity in the affected segment of 68.0 +/- 9.0% accompanied by ST-segment depression and angina. Twelve patients achieved 26,000-32,000 J in positive exercise tests and had significant coronary artery disease. Atrial pacing produced increased activity of krypton-81m to remote myocardium. The jeopardized segment at first showed no change and then a decrease in regional activity of krypton-81m (89.0 +/- 17%) accompanied by ST-segment depression and chest pain. Seventeen patients achieved only 7000-22,000 J in positive exercise tests. These patients showed abnormal coronary anatomy and developed decreases in regional activity of krypton-81m to the affected segment of myocardium starting at the onset of atrial pacing and decreasing by 88 +/- 0 7.0% below control. We conclude that different patterns of disturbed myocardial distribution of krypton-81m are present during stress-induced ischemia in patients with coronary artery disease. There was a close temporal relationship between these disturbances and ST-segment depression.

  2. Myocardial diseases of animals.

    PubMed Central

    Van Vleet, J. F.; Ferrans, V. J.

    1986-01-01

    In this review we have attempted a comprehensive compilation of the cardiac morphologic changes that occur in spontaneous and experimental myocardial diseases of animals. Our coverage addresses diseases of mammals and birds and includes these diseases found in both domesticated and wild animals. A similar review of the myocardial diseases in this broad range of animal species has not been attempted previously. We have summarized and illustrated the gross, microscopic, and ultrastructural alterations for these myocardial diseases; and, whenever possible, we have reviewed their biochemical pathogenesis. We have arranged the myocardial diseases for presentation and discussion according to an etiologic classification with seven categories. These include a group of idiopathic or primary cardiomyopathies recognized in man (hypertrophic, dilated, and restrictive types) and a large group of secondary cardiomyopathies with known causes, such as inherited tendency; nutritional deficiency; toxicity; physical injury and shock; endocrine disorders, and myocarditides of viral, bacterial, and protozoal causation. Considerable overlap exists between each of the etiologic groups in the spectrum of pathologic alterations seen in the myocardium. These include various degenerative changes, myocyte necrosis, and inflammatory lesions. However, some diseases show rather characteristic myocardial alterations such as vacuolar degeneration in anthracycline cardiotoxicity, myofibrillar lysis in furazolidone cardiotoxicity, calcification in calcinosis of mice, glycogen accumulation in the glycogenoses, lipofuscinosis in cattle, fatty degeneration in erucic acid cardiotoxicity, myofiber disarray in hypertrophic cardiomyopathy, and lymphocytic inflammation with inclusion bodies in canine parvoviral myocarditis. The myocardial diseases represent the largest group in the spectrum of spontaneous cardiac diseases of animals. Pericardial and endocardial diseases and congential cardiac diseases are

  3. Myocardial imaging in dogs treated with grisorixin: relationship between thallium-201 uptake and coronary blood flow

    SciTech Connect

    Moins, N.; Gachon, P.; Maublant, J.

    1982-04-01

    Thallium-201 myocardial imaging was performed in dogs after pretreatment with grisorixin, which appeared to increase the myocardial uptake of Tl-201. This effect of grisorixin was found to be dose dependent, with an optimal dose of 60 ..mu..g/kg. The myocardial-to-background ratio, which was 1.92 in the control dogs, rose to 4.45. The increase in the absolute myocardial uptake was demonstrated in guinea pigs that received Tl-201 after similar pretreatment with grisorixin. In the animals treated with 500 ..mu..g/kg, the uptake of Tl-201 by the heart was 35% over the control value. With 60 ..mu..g/kg grisorixin, the coronary blood flow increased from 40 to 176 ml/min 5 min after the injection. This dose, optimal for imaging, induced the maximum vasodilator effect with only a very slight concomitant increase in the left-ventricular pressure and myocardial contractility. Above 60 ..mu..g/kg, grisorixin appeared to be a potent inotropic agent, whereas below this dose it showed only coronary vasodilator properties. Some evidence for an inophore effect of this compound was found in dogs pretreated with 60 ..mu..g/kg. In these the radionuclide was injected when the coronary vasodilation had become insignificant, but a significant improvement of the M/B ratio was still evident.

  4. Effect of hypokinesia on contractile function of cardiac muscle

    NASA Technical Reports Server (NTRS)

    Meyerson, F. Z.; Kapelko, V. I.; Trikhpoyeva, A. M.; Gorina, M. S.

    1980-01-01

    Rats were subjected to hypokinesia for two months and the contractile function of isolated papillary muscle was studied. Hypokinesia reduced significantly the isotonic contraction rate which depended on the ATPase activity of the myofibrils; it also reduced the rate and index of relaxation which depended on the functional capacity of the Ca(++) pump of the sarcoplasmic reticulum. The maximum force of isometric contraction determined by the quantity of actomyosin bridges in the myofibrils did not change after hypokinesia. This complex of changes is contrary to that observed in adaptation to exercise when the rate of isotonic contraction and relaxation increases while the force of isometric contraction does not change. The possible mechanism of this stability of the contractile force during adaptation and readaptation of the heart is discussed.

  5. Spontaneous Oscillations of Elastic Contractile Materials with Turnover

    NASA Astrophysics Data System (ADS)

    Dierkes, Kai; Sumi, Angughali; Solon, Jérôme; Salbreux, Guillaume

    2014-10-01

    Single and collective cellular oscillations driven by the actomyosin cytoskeleton have been observed in numerous biological systems. Here, we propose that these oscillations can be accounted for by a generic oscillator model of a material turning over and contracting against an elastic element. As an example, we show that during dorsal closure of the Drosophila embryo, experimentally observed changes in actomyosin concentration and oscillatory cell shape changes can, indeed, be captured by the dynamic equations studied here. We also investigate the collective dynamics of an ensemble of such contractile elements and show that the relative contribution of viscous and friction losses yields different regimes of collective oscillations. Taking into account the diffusion of force-producing molecules between contractile elements, our theoretical framework predicts the appearance of traveling waves, resembling the propagation of actomyosin waves observed during morphogenesis.

  6. Lidocaine decreases the xylazine-evoked contractility in pregnant cows.

    PubMed

    Piccinno, M; Rizzo, A; Mutinati, M; D'Onghia, G; Sciorsci, R L

    2016-08-01

    The objective of this in vitro study was to evaluate and compare the effects of xylazine on basal uterine contractility of bovine pregnant uterine strips and that of lidocaine on xylazine-sensitized bovine pregnant uterine strips, at different stages of pregnancy. Basal contractility was evaluated in an isolated organ bath and the functionality of the strips throughout the experiment was evaluated using a dose of carbachol (10(-5)M). Uterine motility, expressed with amplitude, frequency of contractions as well as the area under the curve, was recorded in different stages of pregnancy and data were collected at 15-min intervals (5-min before and 5-min after xylazine administration and 5-min after lidocaine addition on the plateau contraction induced by xylazine). Uterine motility increased in all the stages of pregnancy after xylazine addition and gradually decreased after treatment with lidocaine. These data suggest that lidocaine might decrease the tonic effect induced by xylazine on bovine pregnant uteri. PMID:27474006

  7. In Vivo Assessment of Muscle Contractility in Animal Studies.

    PubMed

    Iyer, Shama R; Valencia, Ana P; Hernández-Ochoa, Erick O; Lovering, Richard M

    2016-01-01

    In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Animal models provide unmitigated access to histological samples, which provide a "direct measure" of damage. However, even with unconstrained access to tissue morphology and biochemistry assays, the findings typically do not account for loss of muscle function. Thus, the most comprehensive measure of the overall health of the muscle is assessment of its primary function, which is to produce contractile force. The majority of animal models testing contractile force have been limited to the muscle groups moving the ankle, with advantages and disadvantages depending on the equipment. Here, we describe in vivo methods to measure torque, to produce a reliable muscle injury, and to follow muscle function within the same animal over time. We also describe in vivo methods to measure tension in the leg and thigh muscles. PMID:27492180

  8. An Optogenetic Method to Modulate Cell Contractility during Tissue Morphogenesis.

    PubMed

    Guglielmi, Giorgia; Barry, Joseph D; Huber, Wolfgang; De Renzis, Stefano

    2015-12-01

    Morphogenesis of multicellular organisms is driven by localized cell shape changes. How, and to what extent, changes in behavior in single cells or groups of cells influence neighboring cells and large-scale tissue remodeling remains an open question. Indeed, our understanding of multicellular dynamics is limited by the lack of methods allowing the modulation of cell behavior with high spatiotemporal precision. Here, we developed an optogenetic approach to achieve local modulation of cell contractility and used it to control morphogenetic movements during Drosophila embryogenesis. We show that local inhibition of apical constriction is sufficient to cause a global arrest of mesoderm invagination. By varying the spatial pattern of inhibition during invagination, we further demonstrate that coordinated contractile behavior responds to local tissue geometrical constraints. Together, these results show the efficacy of this optogenetic approach to dissect the interplay between cell-cell interaction, force transmission, and tissue geometry during complex morphogenetic processes. PMID:26777292

  9. Redox regulation of muscle adaptations to contractile activity and aging

    PubMed Central

    2015-01-01

    Superoxide and nitric oxide are generated by skeletal muscle, and these species are increased by contractile activity. Mitochondria have long been assumed to play the primary role in generation of superoxide in muscle, but recent studies indicate that, during contractile activity, membrane-localized NADPH oxidase(s) rapidly generate(s) superoxide that plays a role in redox signaling. This process is important in upregulation of rapid and specific cytoprotective responses that aid maintenance of cell viability following contractile activity, but the overall extent to which redox signaling contributes to regulation of muscle metabolism and homeostasis following contractile activity is currently unclear, as is identification of key redox-sensitive protein targets involved in these processes. Reactive oxygen and nitrogen species have also been implicated in the loss of muscle mass and function that occurs with aging, although recent work has questioned whether oxidative damage plays a key role in these processes. A failure of redox signaling occurs in muscle during aging and may contribute to the age-related loss of muscle fibers. Whether such changes in redox signaling reflect primary age-related changes or are secondary to the fundamental mechanisms is unclear. For instance, denervated muscle fibers within muscles from aged rodents or humans appear to generate large amounts of mitochondrial hydrogen peroxide that could influence adjacent innervated fibers. Thus, in this instance, a “secondary” source of reactive oxygen species may be potentially generated as a result of a primary age-related pathology (loss of neurons), but, nevertheless, may contribute to loss of muscle mass and function during aging. PMID:25792715

  10. Protrusive and Contractile Forces of Spreading Human Neutrophils.

    PubMed

    Henry, Steven J; Chen, Christopher S; Crocker, John C; Hammer, Daniel A

    2015-08-18

    Human neutrophils are mediators of innate immunity and undergo dramatic shape changes at all stages of their functional life cycle. In this work, we quantified the forces associated with a neutrophil's morphological transition from a nonadherent, quiescent sphere to its adherent and spread state. We did this by tracking, with high spatial and temporal resolution, the cell's mechanical behavior during spreading on microfabricated post-array detectors printed with the extracellular matrix protein fibronectin. Two dominant mechanical regimes were observed: transient protrusion and steady-state contraction. During spreading, a wave of protrusive force (75 ± 8 pN/post) propagates radially outward from the cell center at a speed of 206 ± 28 nm/s. Once completed, the cells enter a sustained contractile state. Although post engagement during contraction was continuously varying, posts within the core of the contact zone were less contractile (-20 ± 10 pN/post) than those residing at the geometric perimeter (-106 ± 10 pN/post). The magnitude of the protrusive force was found to be unchanged in response to cytoskeletal inhibitors of lamellipodium formation and myosin II-mediated contractility. However, cytochalasin B, known to reduce cortical tension in neutrophils, slowed spreading velocity (61 ± 37 nm/s) without significantly reducing protrusive force. Relaxation of the actin cortical shell was a prerequisite for spreading on post arrays as demonstrated by stiffening in response to jasplakinolide and the abrogation of spreading. ROCK and myosin II inhibition reduced long-term contractility. Function blocking antibody studies revealed haptokinetic spreading was induced by β2 integrin ligation. Neutrophils were found to moderately invaginate the post arrays to a depth of ∼1 μm as measured from spinning disk confocal microscopy. Our work suggests a competition of adhesion energy, cortical tension, and the relaxation of cortical tension is at play at the onset of

  11. Effects of nicotine on rat sternohyoid muscle contractile properties.

    PubMed

    O'Halloran, Ken D

    2006-02-28

    Obstructive sleep apnoea (OSA) is a major clinical disorder characterised by recurring episodes of pharyngeal collapse during sleep. At present, there remains no satisfactory treatment for OSA. Pharmacological therapies as a potential treatment for the disorder are an attractive option and include agents that increase the contractility of the pharyngeal muscles. The aim of the present study was to examine the effects of nicotine on upper airway muscle contractile properties. In vitro isometric contractile properties were determined using strips of rat sternohyoid muscle in physiological salt solution containing nicotine (0-100 microg/ml) at 25 degrees C. Isometric twitch and tetanic tension, contraction time, half-relaxation time and tension-frequency relationship were determined by electrical field stimulation with platinum electrodes. Fatigue was induced by stimulation at 40 Hz with 300 ms trains at a frequency of 0.5 Hz for 5 min. Nicotine at a concentration of 1 microg/ml was associated with a significant increase in sternohyoid muscle specific tension compared to control data. Dose-dependent increases in contractile tension were not observed. Nicotine had effects on tension-frequency relationship and endurance properties of the sternohyoid muscle at some but not all doses. A leftward shift in the tension-frequency relationship was observed at low stimulus frequencies (20-30 Hz) for nicotine at a concentration of 1 and 5 microg/ml and a significant increase in fatigue resistance was observed with nicotine at a concentration of 10 microg/ml. As fatigue of the upper airway muscles has been implicated in obstructive airway conditions, a pharmacological agent that improves muscle endurance may prove useful as a potential treatment for such disorders. Therefore, further studies of the effects of nicotinic agonists on upper airway function are warranted. PMID:15994135

  12. Protrusive and Contractile Forces of Spreading Human Neutrophils

    PubMed Central

    Henry, Steven J.; Chen, Christopher S.; Crocker, John C.; Hammer, Daniel A.

    2015-01-01

    Human neutrophils are mediators of innate immunity and undergo dramatic shape changes at all stages of their functional life cycle. In this work, we quantified the forces associated with a neutrophil’s morphological transition from a nonadherent, quiescent sphere to its adherent and spread state. We did this by tracking, with high spatial and temporal resolution, the cell’s mechanical behavior during spreading on microfabricated post-array detectors printed with the extracellular matrix protein fibronectin. Two dominant mechanical regimes were observed: transient protrusion and steady-state contraction. During spreading, a wave of protrusive force (75 ± 8 pN/post) propagates radially outward from the cell center at a speed of 206 ± 28 nm/s. Once completed, the cells enter a sustained contractile state. Although post engagement during contraction was continuously varying, posts within the core of the contact zone were less contractile (−20 ± 10 pN/post) than those residing at the geometric perimeter (−106 ± 10 pN/post). The magnitude of the protrusive force was found to be unchanged in response to cytoskeletal inhibitors of lamellipodium formation and myosin II-mediated contractility. However, cytochalasin B, known to reduce cortical tension in neutrophils, slowed spreading velocity (61 ± 37 nm/s) without significantly reducing protrusive force. Relaxation of the actin cortical shell was a prerequisite for spreading on post arrays as demonstrated by stiffening in response to jasplakinolide and the abrogation of spreading. ROCK and myosin II inhibition reduced long-term contractility. Function blocking antibody studies revealed haptokinetic spreading was induced by β2 integrin ligation. Neutrophils were found to moderately invaginate the post arrays to a depth of ∼1 μm as measured from spinning disk confocal microscopy. Our work suggests a competition of adhesion energy, cortical tension, and the relaxation of cortical tension is at play at the

  13. Recovery in skeletal muscle contractile function after prolonged hindlimb immobilization

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Brimmer, C. J.

    1985-01-01

    The effect of three-month hindlimb immobilization (IM) in rats on contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus, and fast-twitch superficial region of the vastus lateralis were measured after 0, 14, 28, 60, and 90 days of recovery on excized, horizontally suspended muscles stimulated electrically to maximal twitch tension. IM caused decreases in muscle-to-body weight ratios for all muscles, with no complete recovery even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than those of the slow-twitch SOL. The SOL isometric twitch duration was shortened, due to reduced contraction and half-relaxation time, both of which returned to control levels after 14 days of recovery. The peak tetanic tension, P(O), g/sq cm,, decreased with IM by 46 percent in the SOL, but recovered by the 28th day. The maximum shortening velocity was not altered by IM in any of the muscles. Thus, normal contractile function could recover after prolonged limb IM.

  14. Multicellular contractility contributes to the emergence of mesothelioma nodules

    NASA Astrophysics Data System (ADS)

    Czirok, Andras

    Malignant pleural mesothelioma (MPM) nodules arise from the mesothelial lining of the pleural cavity by a poorly understood mechanism. We demonstrate that macroscopic multicellular aggregates, reminiscent of the MPM nodules found in patients, develop when MPM cell lines are cultured at high cell densities for several weeks. Surprisingly, the nodule-like aggregates do not arise by excessive local cell proliferation, but by myosin II-driven cell contractility. Contractile nodules contain prominent actin cables that can span several cells. Several features of the in vitro MPM nodule development can be explained by a computational model that assumes uniform and steady intercellular contractile forces within a monolayer of cells, and a mechanical load-dependent lifetime of cell-cell contacts. The model behaves as a self-tensioned Maxwell fluid and exhibits an instability that leads to pattern formation. Altogether, our findings suggest that inhibition of the actomyosin system may provide a hitherto not utilized therapeutic approach to affect MPM growth. NIH R01-GM102801.

  15. Collective cancer cell invasion induced by coordinated contractile stresses.

    PubMed

    Jimenez Valencia, Angela M; Wu, Pei-Hsun; Yogurtcu, Osman N; Rao, Pranay; DiGiacomo, Josh; Godet, Inês; He, Lijuan; Lee, Meng-Horng; Gilkes, Daniele; Sun, Sean X; Wirtz, Denis

    2015-12-22

    The physical underpinnings of fibrosarcoma cell dissemination from a tumor in a surrounding collagen-rich matrix are poorly understood. Here we show that a tumor spheroid embedded in a 3D collagen matrix exerts large contractile forces on the matrix before invasion. Cell invasion is accompanied by complex spatially and temporally dependent patterns of cell migration within and at the surface of the spheroids that are fundamentally different from migratory patterns of individual fibrosarcoma cells homogeneously distributed in the same type of matrix. Cells display a continuous transition from a round morphology at the spheroid core, to highly aligned elongated morphology at the spheroid periphery, which depends on both β1-integrin-based cell-matrix adhesion and myosin II/ROCK-based cell contractility. This isotropic-to-anisotropic transition corresponds to a shift in migration, from a slow and unpolarized movement at the core, to a fast, polarized and persistent one at the periphery. Our results also show that the ensuing collective invasion of fibrosarcoma cells is induced by anisotropic contractile stresses exerted on the surrounding matrix. PMID:26528856

  16. Surgical Treatment of Concomitant Atrial Fibrillation: Focus onto Atrial Contractility

    PubMed Central

    Loardi, Claudia; Alamanni, Francesco; Galli, Claudia; Naliato, Moreno; Veglia, Fabrizio; Zanobini, Marco; Pepi, Mauro

    2015-01-01

    Background. Maze procedure aims at restoring sinus rhythm (SR) and atrial contractility (AC). This study evaluated multiple aspects of AC recovery and their relationship with SR regain after ablation. Methods. 122 mitral and fibrillating patients underwent radiofrequency Maze. Rhythm check and echocardiographic control of biatrial contractility were performed at 3, 6, 12, and 24 months postoperatively. A multivariate Cox analysis of risk factors for absence of AC recuperation was applied. Results. At 2-years follow-up, SR was achieved in 79% of patients. SR-AC coexistence increased from 76% until 98%, while biatrial contraction detection augmented from 84 to 98% at late stage. Shorter preoperative arrhythmia duration was the only common predictor of SR-AC restoring, while pulmonary artery pressure (PAP) negatively influenced AC recuperation. Early AC restoration favored future freedom from arrhythmia recurrence. Minor LA dimensions correlated with improved future A/E value and vice versa. Right atrial (RA) contractility restoring favored better left ventricular (LV) performance and volumes. Conclusions. SR and left AC are two interrelated Maze objectives. Factors associated with arrhythmia “chronic state” (PAP and arrhythmia duration) are negative predictors of procedural success. Our results suggest an association between postoperative LA dimensions and “kick” restoring and an influence of RA contraction onto LV function. PMID:26229956

  17. Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity

    PubMed Central

    Hinz, Boris; Celetta, Giuseppe; Tomasek, James J.; Gabbiani, Giulio; Chaponnier, Christine

    2001-01-01

    To evaluate whether α-smooth muscle actin (α-SMA) plays a role in fibroblast contractility, we first compared the contractile activity of rat subcutaneous fibroblasts (SCFs), expressing low levels of α-SMA, with that of lung fibroblasts (LFs), expressing high levels of α-SMA, with the use of silicone substrates of different stiffness degrees. On medium stiffness substrates the percentage of cells producing wrinkles was similar to that of α-SMA–positive cells in each fibroblast population. On high stiffness substrates, wrinkle production was limited to a subpopulation of LFs very positive for α-SMA. In a second approach, we measured the isotonic contraction of SCF- and LF-populated attached collagen lattices. SCFs exhibited 41% diameter reduction compared with 63% by LFs. TGFβ1 increased α-SMA expression and lattice contraction by SCFs to the levels of LFs; TGFβ-antagonizing agents reduced α-SMA expression and lattice contraction by LFs to the level of SCFs. Finally, 3T3 fibroblasts transiently or permanently transfected with α-SMA cDNA exhibited a significantly higher lattice contraction compared with wild-type 3T3 fibroblasts or to fibroblasts transfected with α-cardiac and β- or γ-cytoplasmic actin. This took place in the absence of any change in smooth muscle or nonmuscle myosin heavy-chain expression. Our results indicate that an increased α-SMA expression is sufficient to enhance fibroblast contractile activity. PMID:11553712

  18. Contractile dynamics change before morphological cues during florescence illumination

    PubMed Central

    Knoll, S. G.; Ahmed, W. W.; Saif, T. A.

    2015-01-01

    Illumination can have adverse effects on live cells. However, many experiments, e.g. traction force microscopy, rely on fluorescence microscopy. Current methods to assess undesired photo-induced cell changes rely on qualitative observation of changes in cell morphology. Here we utilize a quantitative technique to identify the effect of light on cell contractility prior to morphological changes. Fibroblasts were cultured on soft elastic hydrogels embedded with fluorescent beads. The adherent cells generated contractile forces that deform the substrate. Beads were used as fiducial markers to quantify the substrate deformation over time, which serves as a measure of cell force dynamics. We find that cells exposed to moderate fluorescence illumination (λ = 540–585 nm, I = 12.5 W/m2, duration = 60 s) exhibit rapid force relaxation. Strikingly, cells exhibit force relaxation after only 2 s of exposure, suggesting that photo-induced relaxation occurs nearly immediately. Evidence of photo-induced morphological changes were not observed for 15–30 min after illumination. Force relaxation and morphological changes were found to depend on wavelength and intensity of excitation light. This study demonstrates that changes in cell contractility reveal evidence of a photo-induced cell response long before any morphological cues. PMID:26691776

  19. Actomyosin contractility controls cell surface area of oligodendrocytes

    PubMed Central

    Kippert, Angelika; Fitzner, Dirk; Helenius, Jonne; Simons, Mikael

    2009-01-01

    Background To form myelin oligodendrocytes expand and wrap their plasma membrane multiple times around an axon. How is this expansion controlled? Results Here we show that cell surface area depends on actomyosin contractility and is regulated by physical properties of the supporting matrix. Moreover, we find that chondroitin sulfate proteoglycans (CSPG), molecules associated with non-permissive growth properties within the central nervous system (CNS), block cell surface spreading. Most importantly, the inhibitory effects of CSPG on plasma membrane extension were completely prevented by treatment with inhibitors of actomyosin contractility and by RNAi mediated knockdown of myosin II. In addition, we found that reductions of plasma membrane area were accompanied by changes in the rate of fluid-phase endocytosis. Conclusion In summary, our results establish a novel connection between endocytosis, cell surface extension and actomyosin contractility. These findings open up new possibilities of how to promote the morphological differentiation of oligodendrocytes in a non-permissive growth environment. See related minireview by Bauer and ffrench-Constant: PMID:19781079

  20. Bovine myocardial epithelial inclusions.

    PubMed

    Baker, D C; Schmidt, S P; Langheinrich, K A; Cannon, L; Smart, R A

    1993-01-01

    Light microscopic, histochemical, immunohistochemical, and ultrastructural methods were used to examine myocardial epithelial masses in the hearts of ten cattle. The tissues consisted of paraffin-embedded or formalin-fixed samples from eight hearts that were being inspected in slaughter houses and from two hearts from calves that died of septicemia. The ages of the cattle ranged from 4 days to 12 years; the breeds were unspecified for all but one Hereford female and the two Holstein calves; and there were three males, four females, and three steers. The masses in these cases were compared with similar appearing lesions found in other animal species. The lesions in the bovine hearts were single to multiple, well circumscribed, found in the left ventricle wall, and composed of squamous to cuboidal epithelial cells that formed tubular, ductular, and acinar structures with lumens that were void or filled with amorphous protein globules. Electron microscopic examination revealed epithelial cells that had sparse apical microvilli, tight apical intercellular junctions, perinuclear bundles of filaments, and rare cilia. Almost half of the bovine epithelial masses (4/9) had occasional diastase-resistant periodic acid-Schiff-positive granules in their cytoplasm, and few had hyaluronidase-resistant alcian blue-positive granules (2/9) or colloidal iron-positive granules (1/9). All myocardial masses had abundant collagen surrounding the tubular and acinar structures, and 2/9 had elastin fibers as well. None of the myocardial masses had Churukian-Schenk or Fontana Masson's silver staining granules in epithelial cells. Immunohistochemically, all bovine myocardial tumors stained positively for cytokeratin (8/8), and occasional masses stained positively for vimentin (3/8) or carcinoembryonic antigen (3/8). None of the masses stained positively for desmin. The myocardial epithelial tumors most likely represent endodermal rests of tissue misplaced during organogenesis. PMID:7680178

  1. Severe coronary tortuosity or myocardial bridging in patients with chest pain, normal coronary arteries, and reversible myocardial perfusion defects.

    PubMed

    Gaibazzi, Nicola; Rigo, Fausto; Reverberi, Claudio

    2011-10-01

    We reviewed patients with normal or near-normal coronary angiograms enrolled in the SPAM contrast stress echocardiographic diagnostic study in which 400 patients with chest pain syndrome of suspected cardiac origin with a clinical indication to coronary angiography were enrolled. Patients underwent dipyridamole contrast stress echocardiography (cSE) with sequential analysis of wall motion, myocardial perfusion, and Doppler coronary flow reserve before elective coronary angiography. Ninety-six patients with normal or near-normal epicardial coronary arteries were screened for the presence of 2 prespecified findings: severely tortuous coronary arteries and myocardial bridging. Patients were divided in 2 groups based on the presence (false-positive results, n = 37) or absence (true-negative results, n = 59) of reversible myocardial perfusion defects during cSE and compared for history and clinical and angiographic characteristics. Prevalence of severely tortuous coronary arteries (35% vs 5%, p <0.001) or myocardial bridging (13% vs 2%, p <0.05) was 7 times higher in patients who demonstrated reversible perfusion defects at cSE compared to those without reversible perfusion defects. No significant differences were found between the 2 groups for the main demographic variables and risk factors. Patients in the false-positive group more frequently had a history of effort angina (p <0.001) and ST-segment depression at treadmill electrocardiography (p <0.001). In conclusion, we hypothesize that patients with a positive myocardial perfusion finding at cSE but without obstructive epicardial coronary artery disease have a decreased myocardial blood flow reserve, which may be caused by a spectrum of causes other than obstructive coronary artery disease, among which severely tortuous coronary arteries/myocardial bridging may play a significant role. PMID:21784382

  2. AP180-mediated trafficking of Vamp7B limits homotypic fusion of Dictyostelium contractile vacuoles.

    PubMed

    Wen, Yujia; Stavrou, Irene; Bersuker, Kirill; Brady, Rebecca J; De Lozanne, Arturo; O'Halloran, Theresa J

    2009-10-01

    Clathrin-coated vesicles play an established role in endocytosis from the plasma membrane, but they are also found on internal organelles. We examined the composition of clathrin-coated vesicles on an internal organelle responsible for osmoregulation, the Dictyostelium discoideum contractile vacuole. Clathrin puncta on contractile vacuoles contained multiple accessory proteins typical of plasma membrane-coated pits, including AP2, AP180, and epsin, but not Hip1r. To examine how these clathrin accessory proteins influenced the contractile vacuole, we generated cell lines that carried single and double gene knockouts in the same genetic background. Single or double mutants that lacked AP180 or AP2 exhibited abnormally large contractile vacuoles. The enlarged contractile vacuoles in AP180-null mutants formed because of excessive homotypic fusion among contractile vacuoles. The SNARE protein Vamp7B was mislocalized and enriched on the contractile vacuoles of AP180-null mutants. In vitro assays revealed that AP180 interacted with the cytoplasmic domain of Vamp7B. We propose that AP180 directs Vamp7B into clathrin-coated vesicles on contractile vacuoles, creating an efficient mechanism for regulating the internal distribution of fusion-competent SNARE proteins and limiting homotypic fusions among contractile vacuoles. Dictyostelium contractile vacuoles offer a valuable system to study clathrin-coated vesicles on internal organelles within eukaryotic cells. PMID:19692567

  3. Measurement of contractile forces generated by individual fibroblasts on self-standing fiber scaffolds.

    PubMed

    Jeon, Hojeong; Kim, Eunpa; Grigoropoulos, Costas P

    2011-02-01

    Contractility of cells in wound site is important to understand pathological wound healing and develop therapeutic strategies. In particular, contractile force generated by cells is a basic element for designing artificial three-dimensional cell culture scaffolds. Direct assessment of deformation of three-dimensional structured materials has been used to calculate contractile forces by averaging total forces with respect to the cell population number. However, macroscopic methods have offered only lower bounds of contractility due to experimental assumptions and the large variance of the spatial and temporal cell response. In the present study, cell contractility was examined microscopically in order to measure contractile forces generated by individual cells on self-standing fiber scaffolds that were fabricated via femtosecond laser-induced two-photon polymerization. Experimental assumptions and calculation errors that arose in previous studies of macroscopic and microscopic contractile force measurements could be reduced by adopting a columnar buckling model on individual, standing fiber scaffolds. Via quantifying eccentric critical loads for the buckling of fibers with various diameters, contractile forces of single cells were calculated in the range between 30-116 nN. In the present study, a force magnitude of approximately 200 nN is suggested as upper bound of the contractile force exerted by single cells. In addition, contractile forces by multiple cells on a single fiber were calculated in the range between 241-709 nN. PMID:20862610

  4. Perioperative Assessment of Myocardial Deformation

    PubMed Central

    Duncan, Andra E.; Alfirevic, Andrej; Sessler, Daniel I.; Popovic, Zoran B.; Thomas, James D.

    2014-01-01

    Evaluation of left ventricular performance improves risk assessment and guides anesthetic decisions. However, the most common echocardiographic measure of myocardial function, the left ventricular ejection fraction (LVEF), has important limitations. LVEF is limited by subjective interpretation which reduces accuracy and reproducibility, and LVEF assesses global function without characterizing regional myocardial abnormalities. An alternative objective echocardiographic measure of myocardial function is thus needed. Myocardial deformation analysis, which performs quantitative assessment of global and regional myocardial function, may be useful for perioperative care of surgical patients. Myocardial deformation analysis evaluates left ventricular mechanics by quantifying strain and strain rate. Strain describes percent change in myocardial length in the longitudinal (from base to apex) and circumferential (encircling the short-axis of the ventricle) direction and change in thickness in the radial direction. Segmental strain describes regional myocardial function. Strain is a negative number when the ventricle shortens longitudinally or circumferentially and is positive with radial thickening. Reference values for normal longitudinal strain from a recent meta-analysis using transthoracic echocardiography are (mean ± SD) −19.7 ± 0.4%, while radial and circumferential strain are 47.3 ± 1.9 and −23.3 ± 0.7%, respectively. The speed of myocardial deformation is also important and is characterized by strain rate. Longitudinal systolic strain rate in healthy subjects averages −1.10 ± 0.16 sec−1. Assessment of myocardial deformation requires consideration of both strain (change in deformation), which correlates with LVEF, and strain rate (speed of deformation), which correlates with rate of rise of left ventricular pressure (dP/dt). Myocardial deformation analysis also evaluates ventricular relaxation, twist, and untwist, providing new and noninvasive methods to

  5. Effects of glutamine treatment on myocardial damage and cardiac function in rats after severe burn injury

    PubMed Central

    Yan, Hong; Zhang, Yong; Lv, Shang-jun; Wang, Lin; Liang, Guang-ping; Wan, Qian-xue; Peng, Xi

    2012-01-01

    Treatment with glutamine has been shown to reduce myocardial damage associated with ischemia/reperfusion injury. However, the cardioprotective effect of glutamine specifically after burn injury remains unclear. The present study explores the ability of glutamine to protect against myocardial damage in rats that have been severely burned. Seventy-two Wistar rats were randomly divided into three groups: normal controls (C), burned controls (B) and a glutamine-treated group (G). Groups B and G were subjected to full thickness burns comprising 30% of total body surface area. Group G was administered 1.5 g/ (kg•d) glutamine and group B was given the same dose of alanine via intragastric administration for 3 days. Levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and blood lactic acid were measured, as well as myocardial ATP and glutathione (GSH) contents. Cardiac function indices and histopathological changes were analyzed at 12, 24, 48 and 72 post-burn hours. In both burned groups, levels of serum CK, LDH, AST and blood lactic acid increased significantly, while myocardial ATP and GSH contents decreased. Compared with group B, CK, LDH, and AST levels were lower and blood lactic acid, myocardial ATP and GSH levels were higher in group G. Moreover, cardiac contractile function inhibition and myocardial histopathological damage were significantly reduced in group G compared to B. Taken together, these results show that glutamine supplementation protects myocardial structure and function after burn injury by improving energy metabolism and by promotedthe synthesis of ATP and GSH in cardiac myocytes. PMID:22977661

  6. Effect of Acute Xanthine Oxidase Inhibition on Myocardial Energetics During Basal and Very High Cardiac Workstates

    PubMed Central

    Lee, Joseph; Hu, Qingsong; Mansoor, Abdul; Kamdar, Forum

    2014-01-01

    Myocardial ischemia is associated with reduced myocardial adenosine triphosphate (ATP) and increased free adenosine diphosphate (ADP) similar to the normal heart at very high cardiac workstates (HCW). We examined whether acute xanthine oxidase inhibition (XOI) in vivo can decrease myocardial free ADP in normal hearts functioning at basal cardiac workstates (BCW) or very HCW (catecholamine-induced). Myocardial high-energy phosphate (31P magnetic resonance spectroscopy), blood flow (radioactive microspheres), and oxygen consumption (MVO2) were measured in an open-chest canine model before and after infusion of vehicle or an XO inhibitor (allopurinol or febuxostat; n= 10 in each group) during BCW and infusion of dobutamine + dopamine to induce a very HCW. During BCW, both allopurinol and febuxostat resulted in higher phosphocreatine (PCr)/ATP, corresponding to lower ADP levels. During vehicle infusion, HCW caused a decrease of PCr/ATP and an increase in myocardial free ADP. Although XOI did not prevent an increase in free ADP during catecholamine infusion, the values in the allopurinol or febuxostat groups (0.141±0.012 and 0.136±0.011 μmol/g dry wt, respectively) remained significantly less than in the vehicle group (0.180±0.017; P<0.05). Thus, at a given rate of ATP synthesis, XOI decreased the free ADP level needed to drive ATP synthesis, suggesting a more energy-efficient status. As contractile dysfunction in ischemia is characterized by increase of myocardial free ADP and energy deficiency, the data suggest that XOI might be a potential therapy for improving energy efficiency during myocardial ischemia. PMID:21584861

  7. Creatine kinase overexpression improves ATP kinetics and contractile function in postischemic myocardium

    PubMed Central

    Akki, Ashwin; Su, Jason; Yano, Toshiyuki; Gupta, Ashish; Wang, Yibin; Leppo, Michelle K.; Chacko, Vadappuram P.; Steenbergen, Charles

    2012-01-01

    Reduced myofibrillar ATP availability during prolonged myocardial ischemia may limit post-ischemic mechanical function. Because creatine kinase (CK) is the prime energy reserve reaction of the heart and because it has been difficult to augment ATP synthesis during and after ischemia, we used mice that overexpress the myofibrillar isoform of creatine kinase (CKM) in cardiac-specific, conditional fashion to test the hypothesis that CKM overexpression increases ATP delivery in ischemic-reperfused hearts and improves functional recovery. Isolated, retrograde-perfused hearts from control and CKM mice were subjected to 25 min of global, no-flow ischemia and 40 min of reperfusion while cardiac function [rate pressure product (RPP)] was monitored. A combination of 31P-nuclear magnetic resonance experiments at 11.7T and biochemical assays was used to measure the myocardial rate of ATP synthesis via CK (CK flux) and intracellular pH (pHi). Baseline CK flux was severalfold higher in CKM hearts (8.1 ± 1.0 vs. 32.9 ± 3.8, mM/s, control vs. CKM; P < 0.001) with no differences in phosphocreatine concentration [PCr] and RPP. End-ischemic pHi was higher in CKM hearts than in control hearts (6.04 ± 0.12 vs. 6.37 ± 0.04, control vs. CKM; P < 0.05) with no differences in [PCr] and [ATP] between the two groups. Post-ischemic PCr (66.2 ± 1.3 vs. 99.1 ± 8.0, %preischemic levels; P < 0.01), CK flux (3.2 ± 0.4 vs. 14.0 ± 1.2 mM/s; P < 0.001) and functional recovery (13.7 ± 3.4 vs. 64.9 ± 13.2%preischemic RPP; P < 0.01) were significantly higher and lactate dehydrogenase release was lower in CKM than in control hearts. Thus augmenting cardiac CKM expression attenuates ischemic acidosis, reduces injury, and improves not only high-energy phosphate content and the rate of CK ATP synthesis in postischemic myocardium but also recovery of contractile function. PMID:22886411

  8. Exacerbation of myocardial dysfunction and autonomic imbalance contribute to the estrogen-dependent chronic hypotensive effect of ethanol in female rats

    PubMed Central

    El-Mas, Mahmoud M.; Abdel-Rahman, Abdel A.

    2012-01-01

    Our previous studies showed that the hypotensive effect of chronic ethanol in female rats is reduced by ovariectomy (OVX) rats and was restored after estrogen replacement (OVXE2). Further, in randomly cycling rats, chronic ethanol increased cardiac parasympathetic dominance and subsequently reduced myocardial contractility and blood pressure (BP). In this study, we tested the hypothesis that alterations in myocardial contractility and sympathovagal control account for the E2 exacerbation of the hemodynamic effects of ethanol. BP, myocardial contractility (+dP/dtmax), and spectral cardiovascular autonomic profiles were evaluated in radiotelemetered OVX, and OVXE2 rats receiving liquid diet with or without ethanol (5%, w/v) for 13 weeks. In OVX rats, ethanol caused modest hypotension along with significant increases in +dP/dtmax during weeks 2–5. The high-frequency (IBIHF, 0.75–3 Hz) and low-frequency (IBILF, 0.25–0.75 Hz) bands of interbeat intervals were briefly increased and decreased, respectively, by ethanol. Compared with its effects in OVX rats, chronic treatment of OVXE2 rats with ethanol elicited significantly greater and more sustained reductions in systolic (SBP) and diastolic (DBP) blood pressures and +dP/dtmax. Altered sympathovagal balance and parasympathetic overactivity were more evident in ethanol-treated OVXE2 rats as suggested by the sustained: (i) increases in high-frequency bands of interbeat intervals (IBIHF, 0.75–3 Hz), and (ii) decreases in low-frequency IBI bands (IBILF, 0.25–0.75 Hz), IBILF/HF ratio and +dP/dtmax. The plasma ethanol concentration was not affected by changes in the hormonal milieu. These findings suggest that estrogen exacerbates the ethanol-evoked reductions in myocardial contractility and BP and the associated parasympathetic overactivity in female rats. PMID:22305881

  9. Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

    PubMed

    Wang, Qingjie; Yang, Hui; Bai, Aobing; Jiang, Wei; Li, Xiuya; Wang, Xinhong; Mao, Yishen; Lu, Chao; Qian, Ruizhe; Guo, Feng; Ding, Tianling; Chen, Haiyan; Chen, Sifeng; Zhang, Jianyi; Liu, Chen; Sun, Ning

    2016-10-01

    With the advent of induced pluripotent stem cells and directed differentiation techniques, it is now feasible to derive individual-specific cardiac cells for human heart tissue engineering. Here we report the generation of functional engineered human cardiac patches using human induced pluripotent stem cells-derived cardiac cells and decellularized natural heart ECM as scaffolds. The engineered human cardiac patches can be tailored to any desired size and shape and exhibited normal contractile and electrical physiology in vitro. Further, when patching on the infarct area, these patches improved heart function of rats with acute myocardial infarction in vivo. These engineered human cardiac patches can be of great value for normal and disease-specific heart tissue engineering, drug screening, and meet the demands for individual-specific heart tissues for personalized regenerative therapy of myocardial damages in the future. PMID:27509303

  10. Acute myocardial infarction.

    PubMed

    Rischpler, Christoph

    2016-09-01

    Inflammatory processes after myocardial infarction have gained major interest in recent cardiovascular research. It is believed that not only the degree of cell recruitment to the heart plays a pivotal role in the quality of wound healing after myocardial infarction, but also the balance between different types or even subtypes of cells. It is also this balance which is thought to control key processes in tissue repair, such as apoptosis and neoangiogenesis. In this paper, we aim to review imaging strategies (with a special focus on nuclear molecular imaging strategies) that target cells and processes involved in postischemic inflammation and that have a high potential to be translated into clinic or that are already being used and evaluated in humans. PMID:27225319

  11. Age- and exercise-related sympathetic activity in untrained volunteers, trained athletes and patients with impaired left-ventricular contractility.

    PubMed

    Lehmann, M; Schmid, P; Keul, J

    1984-11-01

    To study the influence of training, aging and left-ventricular contractility on the sympathetic nervous system, responses of plasma catecholamines and density of adrenoreceptors on intact blood cells were evaluated in 21 dynamically trained subjects, 8 statically trained weight lifters, 15 healthy young and 15 old control subjects, and 55 post-infarction patients. Plasma catecholamines are indicators of the overall sympathetic tone, while the density of adrenoreceptors is a cellular indicator of the sensitivity to catecholamines. Static and dynamic training result in lower catecholamine response at identical work loads during incremental ergometric tests. Higher density of beta 2 receptors on intact leucocytes and higher sensitivity to isoproterenol are seen in the dynamically trained test subjects. Higher density of alpha 2 receptors on intact thrombocytes is found in the weight lifters. Despite the training-dependent control of the sympathetic activity bradycardia occurs only in endurance-trained subjects, indicating an additionally increased vagal control. The exercise-related tachycardia of the weight lifters, on the other hand, points to an insufficient vagal control of the cardiac sinus rate. Decrease of physical fitness, as related to aging, a deficit in physical training and impaired left-ventricular contractility are connected with a higher sympathetic activity at identical work loads and a lower beta-receptor density on intact blood cells and, in cardiac patients, on myocardial cells as well (Bristow et al. 1982). Changes in the sympathetic system may amplify the age- and disease-dependent decrease of the cardiac function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6526026

  12. Cell motion, contractile networks, and the physics of interpenetrating reactive flow

    SciTech Connect

    Dembo, M.; Harlow, F.

    1986-07-01

    In this paper the authors propose a physical model of contractile biological polymer networks based on the notion of reactive interpenetrating flow. They show how their model leads to a mathematical formulation of the dynamical laws governing the behavior of contractile networks. They also develop estimates of the various parameters that appear in their equations, and discuss some elementary predictions of the model concerning the general scaling principles that pertain to the motions of contractile networks.

  13. Cell motion, contractile networks, and the physics of interpenetrating reactive flow.

    PubMed Central

    Dembo, M; Harlow, F

    1986-01-01

    In this paper we propose a physical model of contractile biological polymer networks based on the notion of reactive interpenetrating flow. We show how our model leads to a mathematical formulation of the dynamical laws governing the behavior of contractile networks. We also develop estimates of the various parameters that appear in our equations, and we discuss some elementary predictions of the model concerning the general scaling principles that pertain to the motions of contractile networks. PMID:3730497

  14. Relations between contractile responses and. beta. -adrenoceptors in gastric fundus of diabetic rats

    SciTech Connect

    Sakai, Yasushi; Inazu, Masato; Aihara, Kazuo; Inoue, Kazuaki; Homma, Ikuo )

    1991-01-01

    Contractile responses to norepinephrine (NE), and the population of {beta}-adrenoceptors, were determined in gastric fundus smooth muscle from rats with diabetes induced by streptozotocin(STZ), and age-matched controls. Relaxation and/or contraction of fundus strips of controls and diabetics were induced by 10{sup {minus}5}M NE. Responses to NE were mainly relaxation in gastric fundus isolated from controls, and contraction in fundus isolated from diabetics. Contraction was blocked by 10{sup {minus}8}M prazosin and relaxation was blocked by 10{sup {minus}6}M propranolol. Relaxation by isoproterenol of contraction induced by 10{sup {minus}6}M acetylcholine was significantly less in fundus from diabetics than in that from controls. The number of {beta}-adrenoceptors, measured with ({sup 125}I)iodocyanopindorol as a ligand, was significantly less in gastic fundus membrane isolated from diabetics than in that from controls, but affinity was no different. The level of plasma catecholamine was higher in diabetics than in controls. Results suggest that depression of gastric fundus relaxation and increase of contraction by NE in diabetics could be due to fewer {beta}-adrenoceptor binding sites caused by down-regulation by higher catecholamine level in diabetic rats.

  15. Single cell contractility studies based on compact moiré system over periodic gratings

    NASA Astrophysics Data System (ADS)

    Zheng, Xiaoyu; Surks, Howard; Zhang, Xin

    2010-05-01

    Abnormal vascular cell contractile performance is a hallmark of cardiovascular diseases. Conventional cell force measurement technique requires individually tracking the sensing units and complex computation efforts for further studying cell contractility. We developed instead a robust and simple compact optical moiré system that measures phase changes encoded in carrier moiré patterns generated from two layers of gratings. Cell mechanics study including cell contractile forces and stress and strain distributions during normal and abnormal cell contractions can thus be conveniently analyzed. The distinct signals from moiré patterns in longitudinal and transverse directions revealed abnormal cell mechanical contractility linked to cardiovascular disease.

  16. Abnormalities in intracellular calcium regulation and contractile function in myocardium from dogs with pacing-induced heart failure.

    PubMed Central

    Perreault, C L; Shannon, R P; Komamura, K; Vatner, S F; Morgan, J P

    1992-01-01

    24 d of rapid ventricular pacing induced dilated cardiomyopathy with both systolic and diastolic dysfunction in conscious, chronically instrumented dogs. We studied mechanical properties and intracellular calcium (Ca2+i) transients of trabeculae carneae isolated from 15 control dogs (n = 32) and 11 dogs with pacing-induced cardiac failure (n = 26). Muscles were stretched to maximum length at 30 degrees C and stimulated at 0.33 Hz; a subset (n = 17 control, n = 17 myopathic) was loaded with the [Ca2+]i indicator aequorin. Peak tension was depressed in the myopathic muscles, even in the presence of maximally effective (i.e., 16 mM) [Ca2+] in the perfusate. However, peak [Ca2+]i was similar (0.80 +/- 0.13 vs. 0.71 +/- 0.05 microM; [Ca2+]o = 2.5 mM), suggesting that a decrease in Cai2+ availability was not responsible for the decreased contractility. The time for decline from the peak of the Cai2+ transient was prolonged in the myopathic group, which correlated with prolongation of isometric contraction and relaxation. However, similar end-diastolic [Ca2+]i was achieved in both groups (0.29 +/- 0.05 vs. 0.31 +/- 0.02 microM), indicating that Cai2+ homeostasis can be maintained in myopathic hearts. The inotropic response of the myopathic muscles to milrinone was depressed compared with the controls. However, when cAMP production was stimulated by pretreatment with forskolin, the response of the myopathic muscles to milrinone was improved. Our findings provide direct evidence that abnormal [Ca2+]i handling is an important cause of contractile dysfunction in dogs with pacing-induced heart failure and suggest that deficient production of cAMP may be an important cause of these changes in excitation-contraction coupling. PMID:1311723

  17. Abnormalities in intracellular calcium regulation and contractile function in myocardium from dogs with pacing-induced heart failure

    NASA Technical Reports Server (NTRS)

    Perreault, C. L.; Shannon, R. P.; Komamura, K.; Vatner, S. F.; Morgan, J. P.

    1992-01-01

    24 d of rapid ventricular pacing induced dilated cardiomyopathy with both systolic and diastolic dysfunction in conscious, chronically instrumented dogs. We studied mechanical properties and intracellular calcium (Ca2+i) transients of trabeculae carneae isolated from 15 control dogs (n = 32) and 11 dogs with pacing-induced cardiac failure (n = 26). Muscles were stretched to maximum length at 30 degrees C and stimulated at 0.33 Hz; a subset (n = 17 control, n = 17 myopathic) was loaded with the [Ca2+]i indicator aequorin. Peak tension was depressed in the myopathic muscles, even in the presence of maximally effective (i.e., 16 mM) [Ca2+] in the perfusate. However, peak [Ca2+]i was similar (0.80 +/- 0.13 vs. 0.71 +/- 0.05 microM; [Ca2+]o = 2.5 mM), suggesting that a decrease in Cai2+ availability was not responsible for the decreased contractility. The time for decline from the peak of the Cai2+ transient was prolonged in the myopathic group, which correlated with prolongation of isometric contraction and relaxation. However, similar end-diastolic [Ca2+]i was achieved in both groups (0.29 +/- 0.05 vs. 0.31 +/- 0.02 microM), indicating that Cai2+ homeostasis can be maintained in myopathic hearts. The inotropic response of the myopathic muscles to milrinone was depressed compared with the controls. However, when cAMP production was stimulated by pretreatment with forskolin, the response of the myopathic muscles to milrinone was improved. Our findings provide direct evidence that abnormal [Ca2+]i handling is an important cause of contractile dysfunction in dogs with pacing-induced heart failure and suggest that deficient production of cAMP may be an important cause of these changes in excitation-contraction coupling.

  18. Effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury: an overview.

    PubMed

    Zughaib, M E; Sun, J Z; Bolli, R

    1993-01-01

    There are multiple mechanisms whereby ACE inhibitors could be beneficial during myocardial ischemia and reperfusion, including: i) reduced formation of angiotensin II, ii) decreased metabolism of bradykinin, iii) antioxidant activity, and iv) possibly other unknown mechanisms. Reduced formation of angiotensin II should be beneficial because this peptide exerts several actions that are potentially detrimental to the ischemic/reperfused myocardium, including vasoconstriction, increased release of norepinephrine, stimulation of phospholipase C and/or A2, and increased afterload with an attendant increase in oxygen demands. Reduced metabolism of bradykinin could be beneficial by increasing myocardial glucose uptake, by causing vasodilation, and by stimulating production of endothelium-derived relaxing factor and prostacyclin. Although earlier studies suggested that sulfhydryl-containing ACE inhibitors scavenge superoxide anions, recent data have shown that these drugs scavenge hydroxyl radical and hypochlorous acid with no effect on superoxide anion. Studies in isolated hearts have demonstrated that ACE inhibitors attenuate the metabolic, arrhythmic, and contractile dearrangements associated with ischemia and reperfusion, and have suggested that such beneficial effects are mediated by potentiation of bradykinin and/or increased synthesis of prostacyclin. Studies in models of myocardial stunning after brief (15-min) ischemia in vivo (anesthetized dogs) suggest that ACE inhibitors enhance the recovery of contractile function after a single brief ischemic episode. No data are available regarding the effect of these drugs on myocardial stunning after a prolonged, partly reversible episode, after multiple consecutive brief ischemic episodes, and after global ischemia. The mechanism for the salutary effects of ACE inhibitors on stunning remains a mystery. It may involve an antioxidant action (in the case of thiol-containing molecules) or potentiation of prostaglandins (in

  19. Caveolin-3 Promotes a Vascular Smooth Muscle Contractile Phenotype

    PubMed Central

    Gutierrez-Pajares, Jorge L.; Iturrieta, Jeannette; Dulam, Vipin; Wang, Yu; Pavlides, Stephanos; Malacari, Gabriella; Lisanti, Michael P.; Frank, Philippe G.

    2015-01-01

    Epidemiological studies have demonstrated the importance of cardiovascular diseases in Western countries. Among the cell types associated with a dysfunctional vasculature, smooth muscle (SM) cells are believed to play an essential role in the development of these illnesses. Vascular SM cells are key regulators of the vascular tone and also have an important function in the development of atherosclerosis and restenosis. While in the normal vasculature, contractile SM cells are predominant, in atherosclerotic vascular lesions, synthetic cells migrate toward the neointima, proliferate, and synthetize extracellular matrix proteins. In the present study, we have examined the role of caveolin-3 in the regulation of SM cell phenotype. Caveolin-3 is expressed in vivo in normal arterial SM cells, but its expression appears to be lost in cultured SM cells. Our data show that caveolin-3 expression in the A7r5 SM cell line is associated with increased expression of contractility markers such as SM α-actin, SM myosin heavy chain but decreased expression of the synthetic phenotype markers such as p-Elk and Klf4. Moreover, we also show that caveolin-3 expression can reduce proliferation upon treatment with LDL or PDGF. Finally, we show that caveolin-3-expressing SM cells are less sensitive to apoptosis than control cells upon treatment with oxidized LDL. Taken together, our data suggest that caveolin-3 can regulate the phenotypic switch between contractile and synthetic SM cells. A better understanding of the factors regulating caveolin-3 expression and function in this cell type will permit the development of a better comprehension of the factors regulating SM function in atherosclerosis and restenosis. PMID:26664898

  20. The role of microtubules in contractile ring function

    NASA Technical Reports Server (NTRS)

    Conrad, A. H.; Paulsen, A. Q.; Conrad, G. W.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    During cytokinesis, a cortical contractile ring forms around a cell, constricts to a stable tight neck and terminates in separation of the daughter cells. At first cleavage, Ilyanassa obsoleta embryos form two contractile rings simultaneously. The cleavage furrow (CF), in the animal hemisphere between the spindle poles, constricts to a stable tight neck and separates the daughter cells. The third polar lobe constriction (PLC-3), in the vegetal hemisphere below the spindle, constricts to a transient tight neck, but then relaxes, allowing the polar lobe cytoplasm to merge with one daughter cell. Eggs exposed to taxol, a drug that stabilizes microtubules, before the CF or the PLC-3 develop, fail to form CFs, but form stabilized tight PLCs. Eggs exposed to taxol at the time of PLC-3 formation develop varied numbers of constriction rings in their animal hemispheres and one PLC in their vegetal hemisphere, none of which relax. Eggs exposed to taxol after PLC-3 initiation form stabilized tight CFs and PLCs. At maximum constriction, control embryos display immunolocalization of nonextractable alpha-tubulin in their CFs, but not in their PLCs, and reveal, via electron microscopy, many microtubules extending through their CFs, but not through their PLCs. Embryos which form stabilized tightly constricted CFs and PLCs in the presence of taxol display immunolocalization of nonextractable alpha-tubulin in both constrictions and show many polymerized microtubules extending through both CFs and PLCs. These results suggest that the extension of microtubules through a tight contractile ring may be important for stabilizing that constriction and facilitating subsequent cytokinesis.

  1. Cholesterol Depletion Alters Cardiomyocyte Subcellular Signaling and Increases Contractility

    PubMed Central

    McIntosh, Victoria J.; Abou Samra, Abdul B.; Mohammad, Ramzi M.; Lasley, Robert D.

    2016-01-01

    Membrane cholesterol levels play an important factor in regulating cell function. Sarcolemmal cholesterol is concentrated in lipid rafts and caveolae, which are flask-shaped invaginations of the plasma membrane. The scaffolding protein caveolin permits the enrichment of cholesterol in caveolae, and caveolin interactions with numerous proteins regulate their function. The purpose of this study was to determine whether acute reductions in cardiomyocyte cholesterol levels alter subcellular protein kinase activation, intracellular Ca2+ and contractility. Methods: Ventricular myocytes, isolated from adult Sprague Dawley rats, were treated with the cholesterol reducing agent methyl-β-cyclodextrin (MβCD, 5 mM, 1 hr, room temperature). Total cellular cholesterol levels, caveolin-3 localization, subcellular, ERK and p38 mitogen activated protein kinase (MAPK) signaling, contractility, and [Ca2+]i were assessed. Results: Treatment with MβCD reduced cholesterol levels by ~45 and shifted caveolin-3 from cytoskeleton and triton-insoluble fractions to the triton-soluble fraction, and increased ERK isoform phosphorylation in cytoskeletal, cytosolic, triton-soluble and triton-insoluble membrane fractions without altering their subcellular distributions. In contrast the primary effect of MβCD was on p38 subcellular distribution of p38α with little effect on p38 phosphorylation. Cholesterol depletion increased cardiomyocyte twitch amplitude and the rates of shortening and relaxation in conjunction with increased diastolic and systolic [Ca2+]i. Conclusions: These results indicate that acute reductions in membrane cholesterol levels differentially modulate basal cardiomyocyte subcellular MAPK signaling, as well as increasing [Ca2+]i and contractility. PMID:27441649

  2. [Mortality of myocardial infarction].

    PubMed

    Bonnefoy, E; Kirkorian, G

    2011-12-01

    Coronary disease is a major cause of death and disability. From 1975 to 2000, coronary mortality was reduced by half. Better treatments and reduction of risk factors are the main causes. This phenomenon is observed in most developed countries, but mortality from coronary heart disease continues to increase in developing countries. In-hospital mortality of ST elevation myocardial infarction (STEMI) is in the range of 7 to 10% in registries. In infarction without ST segment elevation (NSTEMI), in-hospital mortality is around 5%. More recent studies found a similar in-hospital mortality for STEMI and NSTEMI. Because of patient selection and monitoring, mortality in clinical trials is much lower. After adjustment for the extent of coronary disease, age, risk factors, history of myocardial infarction, the excess mortality observed in women is fading. Many clinical, biological and laboratory parameters are associated with mortality in myocardial infarction. They refer to the immediate risk of death (ventricular rhythm disturbances, shock…), the extent of infarction (number of leads with ST elevation on the ECG, release of biomarkers, ejection fraction…), the presence of heart failure, the failure of reperfusion and the patient's baseline risk (age, renal function…). Risk scores, and more specifically the GRACE risk score, synthesize these different markers to predict the risk of death in a given patient. However, their use for the treatment of myocardial only concerns NSTEMI. Only a limited number of mechanical or pharmacological interventions reduces mortality of heart attack. The main benefits are observed with reperfusion by thrombolysis or primary angioplasty in STEMI, aspirin, heparin, beta-blockers, angiotensin converting enzyme inhibitors. Some medications such as bivalirudin and fondaparinux reduce mortality by decreasing the incidence of hemorrhagic complications. The guidelines classify interventions according to their benefit and especially their ability

  3. Myocardial Cell Pattern on Piezoelectric Nanofiber Mats for Energy Harvesting

    NASA Astrophysics Data System (ADS)

    Liu, X.; Wang, X.; Zhao, H.; Du, Y.

    2014-11-01

    The paper presents in vitro contractile myocardial cell pattern on piezoelectric nanofiber mats with applications in energy harvesting. The cell-based energy harvester consists of myocardial cell sheet and a PDMS substrate with a PVDF nanofiber mat on. Experimentally, cultured on specifically distributed nanofiber mats, neonatal rat ventricular cardiomyocytes are characterized with the related morphology and contraction. Previously, we have come up with the concept of energy harvesting from heart beating using piezoelectric material. A bio-hybrid energy harvester combined living cardiomyocytes, PDMS polymer substrate and piezoelectric PVDF film with the electrical output of peak current 87.5nA and peak voltage 92.3mV. However, the thickness of the cardiomyocyte cultured on a two-dimensional substrate is much less than that of the piezoelectric film. The Micro Contact Printing (μCP) method used in cell pattern on the PDMS thin film has tough requirement for the film surface. As such, in this paper we fabricated nanofiber-constructed PDMS thin film to realize cell pattern due to PVDF nanofibers with better piezoelectricity and microstructures of nanofiber mats guiding cell distribution. Living cardiomyocytes patterned on those distributed piezoelectric nanofibers with the result of the same distribution as the nanofiber pattern.

  4. Effect of prophylactic digitalization on the development of myocardial hypertrophy.

    PubMed

    Cutilletta, A F; Rudnik, M; Arcilla, R A; Straube, R

    1977-11-01

    The effect of prophylactic digitalization on the development of left ventricular hypertrophy was studied in adult rats. Digitoxin, 0.1 mg/100 g body wt or solvent was given daily for 1 wk prior to either aortic constriction or sham operation and was continued until the animals were killed, either 1 or 4 wk after surgery. A hemodynamic study was done in those animals killed 1 wk after surgery; hearts of all animals were examined for evidence of myocardial hypertrophy. Constriction of the ascending aorta had no significant effect on cardiac output but did reduce peak flow velocity and flow acceleration. An increase in left ventricular mass, RNA, and hydroxyproline was found in the animals with aortic constriction. Digitoxin treatment did not alter peak flow velocity or flow acceleration, but did significantly increase isovolumic (dP/dt)P-1. Digitoxin had no effect on body weight, heart weight, RNA, or hydroxyproline in either the sham-operated animals or in the animals with aortic constriction. Therefore, despite plasma digitoxin levels sufficient to affect myocardial contractility, left ventricular hypertrophy still developed after aortic constriction. PMID:144440

  5. Myocardial Infarction: Symptoms and Treatments.

    PubMed

    Lu, Lei; Liu, Min; Sun, RongRong; Zheng, Yi; Zhang, Peiying

    2015-07-01

    Myocardial infarction (MI) is a term used for an event of heart attack which is due to formation of plaques in the interior walls of the arteries resulting in reduced blood flow to the heart and injuring heart muscles because of lack of oxygen supply. The symptoms of MI include chest pain, which travels from left arm to neck, shortness of breath, sweating, nausea, vomiting, abnormal heart beating, anxiety, fatigue, weakness, stress, depression, and other factors. The immediate treatment of MI include, taking aspirin, which prevents blood from clotting, and nitro-glycerin to treat chest pain and oxygen. The heart attack can be prevented by taking an earlier action to lower those risks by controlling diet, fat, cholesterol, salt, smoking, nicotine, alcohol, drugs, monitoring of blood pressure every week, doing exercise every day, and loosing body weight. The treatment of MI includes, aspirin tablets, and to dissolve arterial blockage injection of thrombolytic or clot dissolving drugs such as tissue plasminogen activator, streptokinase or urokinase in blood within 3 h of the onset of a heart attack. The painkillers such as morphine or meperidine can be administered to relieve pain. Nitroglycerin and antihypertensive drugs such as beta-blockers, ACE inhibitors or calcium channel blockers may also be used to lower blood pressure and to improve the oxygen demand of heart. The ECG, coronary angiography and X-ray of heart and blood vessels can be performed to observe the narrowing of coronary arteries. In this article the causes, symptoms and treatments of MI are described. PMID:25638347

  6. High-throughput screening for modulators of cellular contractile force†

    PubMed Central

    Park, Chan Young; Zhou, Enhua H.; Tambe, Dhananjay; Chen, Bohao; Lavoie, Tera; Dowell, Maria; Simeonov, Anton; Maloney, David J.; Marinkovic, Aleksandar; Tschumperlin, Daniel J.; Burger, Stephanie; Frykenberg, Matthew; Butler, James P.; Stamer, W. Daniel; Johnson, Mark; Solway, Julian; Fredberg, Jeffrey J.

    2015-01-01

    When cellular contractile forces are central to pathophysiology, these forces comprise a logical target of therapy. Nevertheless, existing high-throughput screens are limited to upstream signalling intermediates with poorly defined relationships to such a physiological endpoint. Using cellular force as the target, here we report a new screening technology and demonstrate its applications using human airway smooth muscle cells in the context of asthma and Schlemm's canal endothelial cells in the context of glaucoma. This approach identified several drug candidates for both asthma and glaucoma. We attained rates of 1000 compounds per screening day, thus establishing a force-based cellular platform for high-throughput drug discovery. PMID:25953078

  7. Regulation of the uterine contractile apparatus and cytoskeleton

    PubMed Central

    Morgan, Kathleen G

    2007-01-01

    Parturition at term, the end stage of a successful pregnancy occurs as a result of powerful, co-ordinated and periodic contractions of uterine smooth muscle (myometrium). To occur in a propitious manner, a high degree of control over the activation of a myometrial cell is required. We review the molecular mechanisms and structural composition of myometrial cells that may contribute to their increased contractile capacity at term. We focus attention on pathways that lead to the activation of filamentous networks traditionally labeled ‘contractile’ or ‘cytoskeletal’ yet draw attention to the fact that functional discrimination between these systems is not absolute. PMID:17582796

  8. Caffeine reduces dipyridamole-induced myocardial ischemia

    SciTech Connect

    Smits, P.; Aengevaeren, W.R.; Corstens, F.H.; Thien, T. )

    1989-10-01

    The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-{sup 201}Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed nodepressions, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging.

  9. Interactions of ethanol and quinidine on contractility and myocyte action potential in the rat ventricle.

    PubMed

    Guthrie, S K; Wilde, D W; Brown, R A; Savage, A O; Bleske, B

    1995-01-01

    The combined effects of ethanol and quinidine on cardiac electromechanical coupling are unknown, but both drugs affect cardiac conduction and can cause myocardial depression. Isolated left ventricular papillary and ventricular myocytes were used to assess the combined effects of quinidine and ethanol on the electrophysiologic and mechanical properties of rat myocardium. The combination of quinidine (1-300 microM) and ethanol (120-240 mg/dL) depressed active papillary muscle tension within the clinically useful concentration range. In electrophysiologic studies of isolated ventricular myocytes, quinidine prolonged the action potential duration at 50% (APD50) and 90% (APD90) repolarization, the absolute refractory period, and the relative refractory period, but decreased the maximum rate of change of depolarization in phase 0 (Vmax). When cells were exposed to ethanol (240 mg/dL) and quinidine (1.5 microM) together, a significant decrease in the quinidine-induced prolongation of the absolute refractory and relative refractory periods was seen. Additional changes in action potential parameters from the quinidine values included slight reductions in Vmax and in APD50 and APD90, but these reductions were not consistently displayed, nor were they statistically significant. PMID:7897336

  10. Increased smooth muscle contractility in mice deficient for neuropilin 2.

    PubMed

    Bielenberg, Diane R; Seth, Abhishek; Shimizu, Akio; Pelton, Kristine; Cristofaro, Vivian; Ramachandran, Aruna; Zwaans, Bernadette M M; Chen, Cheng; Krishnan, Ramaswamy; Seth, Meetu; Huang, Lin; Takashima, Seiji; Klagsbrun, Michael; Sullivan, Maryrose P; Adam, Rosalyn M

    2012-08-01

    Neuropilins (NRPs) are transmembrane receptors that bind class 3 semaphorins and VEGF family members to regulate axon guidance and angiogenesis. Although expression of NRP1 by vascular smooth muscle cells (SMCs) has been reported, NRP function in smooth muscle (SM) in vivo is unexplored. Using Nrp2(+/LacZ) and Nrp2(+/gfp) transgenic mice, we observed robust and sustained expression of Nrp2 in the SM compartments of the bladder and gut, but no expression in vascular SM, skeletal muscle, or cardiac muscle. This expression pattern was recapitulated in vitro using primary human SM cell lines. Alterations in cell morphology after treatment of primary visceral SMCs with the NRP2 ligand semaphorin-3F (SEMA3F) were accompanied by inhibition of RhoA activity and myosin light chain phosphorylation, as well as decreased cytoskeletal stiffness. Ex vivo contractility testing of bladder muscle strips exposed to electrical stimulation or soluble agonists revealed enhanced tension generation of tissues from mice with constitutive or SM-specific knockout of Nrp2, compared with controls. Mice lacking Nrp2 also displayed increased bladder filling pressures, as assessed by cystometry in conscious mice. Together, these findings identify Nrp2 as a mediator of prorelaxant stimuli in SMCs and suggest a novel function for Nrp2 as a regulator of visceral SM contractility. PMID:22688055

  11. Type VI secretion system: secretion by a contractile nanomachine

    PubMed Central

    Basler, Marek

    2015-01-01

    The type VI secretion systems (T6SS) are present in about a quarter of all Gram-negative bacteria. Several key components of T6SS are evolutionarily related to components of contractile nanomachines such as phages and R-type pyocins. The T6SS assembly is initiated by formation of a membrane complex that binds a phage-like baseplate with a sharp spike, and this is followed by polymerization of a long rigid inner tube and an outer contractile sheath. Effectors are preloaded onto the spike or into the tube during the assembly by various mechanisms. Contraction of the sheath releases an unprecedented amount of energy, which is used to thrust the spike and tube with the associated effectors out of the effector cell and across membranes of both bacterial and eukaryotic target cells. Subunits of the contracted sheath are recycled by T6SS-specific unfoldase to allow for a new round of assembly. Live-cell imaging has shown that the assembly is highly dynamic and its subcellular localization is in certain bacteria regulated with a remarkable precision. Through the action of effectors, T6SS has mainly been shown to contribute to pathogenicity and competition between bacteria. This review summarizes the knowledge that has contributed to our current understanding of T6SS mode of action. PMID:26370934

  12. [Contractile proteins in chemical signal transduction in plant microspores].

    PubMed

    Roshchina, V V

    2005-01-01

    Involvement of contractile components in chemical signal transduction from the cell surface to the organelles was studied using unicellular systems. Neurotransmitters dopamine and serotonin as well as active forms of oxygen hydrogen peroxide and tert-butyl peroxide were used as chemical signals. Experiments were carried out on vegetative microspores of field horsetail Equisetum arvense and generative microspores (pollen) of amaryllis Hippeastrum hybridum treated with cytochalasin B (an inhibitor of actin polymerization in microfilaments), colchicine, and vinblastine (inhibitors of tubulin polymerization in microtubules). Both types of thus treated microspores demonstrated suppressed development, particularly, for cytochalasin B treatment. At the same time, an increased typical blue fluorescence of certain cell regions (along the cell wall and around nuclei and chloroplasts) where the corresponding contractile proteins could reside was observed. In contrast to anticontractile agents, dopamine, serotonin B, and the peroxides stimulated microspore germination. Microspore pretreatment with cytochalasin B and colchicine followed by the treatment with serotonin, dopamine, or the peroxides decreased the germination rate. Involvement of actin and tubulin in chemical signal transduction from the cell surface to the nucleus is proposed. PMID:16004258

  13. Human Engineered Heart Tissue: Analysis of Contractile Force.

    PubMed

    Mannhardt, Ingra; Breckwoldt, Kaja; Letuffe-Brenière, David; Schaaf, Sebastian; Schulz, Herbert; Neuber, Christiane; Benzin, Anika; Werner, Tessa; Eder, Alexandra; Schulze, Thomas; Klampe, Birgit; Christ, Torsten; Hirt, Marc N; Huebner, Norbert; Moretti, Alessandra; Eschenhagen, Thomas; Hansen, Arne

    2016-07-12

    Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). This study describes the generation of 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM and their physiological and pharmacological properties. CM were differentiated from hiPSC by a growth factor-based three-stage protocol. EHTs were generated and analyzed histologically and functionally. HiPSC-CM in EHTs showed well-developed sarcomeric organization and alignment, and frequent mitochondria. Systematic contractility analysis (26 concentration-response curves) reveals that EHTs replicated canonical response to physiological and pharmacological regulators of inotropy, membrane- and calcium-clock mediators of pacemaking, modulators of ion-channel currents, and proarrhythmic compounds with unprecedented precision. The analysis demonstrates a high degree of similarity between hiPSC-CM in EHT format and native human heart tissue, indicating that human EHTs are useful for preclinical drug testing and disease modeling. PMID:27211213

  14. Priming and polymerization of a bacterial contractile tail structure.

    PubMed

    Zoued, Abdelrahim; Durand, Eric; Brunet, Yannick R; Spinelli, Silvia; Douzi, Badreddine; Guzzo, Mathilde; Flaugnatti, Nicolas; Legrand, Pierre; Journet, Laure; Fronzes, Rémi; Mignot, Tâm; Cambillau, Christian; Cascales, Eric

    2016-03-01

    Contractile tails are composed of an inner tube wrapped by an outer sheath assembled in an extended, metastable conformation that stores mechanical energy necessary for its contraction. Contraction is used to propel the rigid inner tube towards target cells for DNA or toxin delivery. Although recent studies have revealed the structure of the contractile sheath of the type VI secretion system, the mechanisms by which its polymerization is controlled and coordinated with the assembly of the inner tube remain unknown. Here we show that the starfish-like TssA dodecameric complex interacts with tube and sheath components. Fluorescence microscopy experiments in enteroaggregative Escherichia coli reveal that TssA binds first to the type VI secretion system membrane core complex and then initiates tail polymerization. TssA remains at the tip of the growing structure and incorporates new tube and sheath blocks. On the basis of these results, we propose that TssA primes and coordinates tail tube and sheath biogenesis. PMID:26909579

  15. Implementing cell contractility in filament-based cytoskeletal models.

    PubMed

    Fallqvist, B

    2016-02-01

    Cells are known to respond over time to mechanical stimuli, even actively generating force at longer times. In this paper, a microstructural filament-based cytoskeletal network model is extended to incorporate this active response, and a computational study to assess the influence on relaxation behaviour was performed. The incorporation of an active response was achieved by including a strain energy function of contractile activity from the cross-linked actin filaments. A four-state chemical model and strain energy function was adopted, and generalisation to three dimensions and the macroscopic deformation field was performed by integration over the unit sphere. Computational results in MATLAB and ABAQUS/Explicit indicated an active cellular response over various time-scales, dependent on contractile parameters. Important features such as force generation and increasing cell stiffness due to prestress are qualitatively predicted. The work in this paper can easily be extended to encompass other filament-based cytoskeletal models as well. © 2016 Wiley Periodicals, Inc. PMID:26899417

  16. Dipyridamole thallium-201 myocardial scintigraphy

    SciTech Connect

    Not Available

    1988-09-01

    Thallium-201 (/sup 201/Tl) myocardial scintigraphy is a sensitive technique for detecting coronary artery disease. Standardized exercise testing is the most common method for inducing myocardial stress for /sup 201/Tl imaging. Unfortunately, a significant number of patients are unable to undergo adequate treadmill or bicycle exercise. In these patients, pharmacologic stress with dipyridamole provides a safe, efficacious, and reliable alternative.

  17. Ultrasound-mediated microbubble destruction enhances the therapeutic effect of intracoronary transplantation of bone marrow stem cells on myocardial infarction

    PubMed Central

    Chang, Xuefeng; Liu, Jiaqing; Liao, Xudong; Liu, Guohui

    2015-01-01

    Objective: The combination of intracoronary transplantation and ultrasound-mediated microbubble destruction may promote effective and accurate delivery of bone marrow stem cells (BMSCs) into the infarct zone. To test this hypothesis in this study we examined the effectiveness of ultrasound-mediated microbubble destruction in combination with intracoronary transplantation of BMSCs for the treatment of myocardial infarction in canine model of acute myocardial infarction. Method: The dogs were randomly assigned to four groups: PBS, ultrasound-mediated microbubble destruction, BMSCs, BMSCs together with ultrasound-mediated microbubble destruction. At 28 days post-surgery, cardiac function and the percentage of perfusion defect area to total left ventricular perfusion area (DA%) were determined by myocardial contrast echocardiography. Nitro blue tetrazolium staining was performed to determine myocardial infarct size, hematoxylin and eosin staining for assessing microvascular injury, Masson’s staining for analyzing myocardial tissue collagen, immunohistochemical analysis of α-actin to measure cardiac contractile function and of BrdU-labeled myocardial cells to measure the number of the BMSCs homing to the infarcted region. Results: The transplantation of BMSCs significantly improved heart function and DA% (P < 0.05). The group that received ultrasound-mediated microbubble destruction with BMSCs transplantation showed the most improvement in heart function and DA% (P < 0.05). This group also showed a denser deposition of BMSCs in the coronary artery and more BrdU positive cells in the infarcted region, had the maximum number of α-actin positive cells, showed the smallest myocardial infarct area compared to other groups (P< 0.05). Conclusion: Ultrasound-mediated microbubble destruction increases the homing of BMSCs in the target area following intracoronary transplantation, which allows more BMSCs to differentiate into functional cardiomyocytes, thereby reducing

  18. Complete regression of myocardial involvement associated with lymphoma following chemotherapy

    PubMed Central

    Vinicki, Juan Pablo; Cianciulli, Tomás F; Farace, Gustavo A; Saccheri, María C; Lax, Jorge A; Kazelian, Lucía R; Wachs, Adolfo

    2013-01-01

    Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We describe the case of a 26 year old man who had initially been diagnosed with myocardial infiltration on an echocardiogram, presenting with a testicular mass and unilateral peripheral facial paralysis. On admission, electrocardiograms (ECG) revealed negative T-waves in all leads and ST-segment elevation in the inferior leads. On two-dimensional echocardiography, there was infiltration of the pericardium with mild effusion, infiltrative thickening of the aortic walls, both atria and the interatrial septum and a mildly depressed systolic function of both ventricles. An axillary biopsy was performed and reported as a T-cell lymphoblastic lymphoma (T-LBL). Following the diagnosis and staging, chemotherapy was started. Twenty-two days after finishing the first cycle of chemotherapy, the ECG showed regression of T-wave changes in all leads and normalization of the ST-segment elevation in the inferior leads. A follow-up Two-dimensional echocardiography confirmed regression of the myocardial infiltration. This case report illustrates a lymphoma presenting with testicular mass, unilateral peripheral facial paralysis and myocardial involvement, and demonstrates that regression of infiltration can be achieved by intensive chemotherapy treatment. To our knowledge, there are no reported cases of T-LBL presenting as a testicular mass and unilateral peripheral facial paralysis, with complete regression of myocardial involvement. PMID:24109501

  19. Complete regression of myocardial involvement associated with lymphoma following chemotherapy.

    PubMed

    Vinicki, Juan Pablo; Cianciulli, Tomás F; Farace, Gustavo A; Saccheri, María C; Lax, Jorge A; Kazelian, Lucía R; Wachs, Adolfo

    2013-09-26

    Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We describe the case of a 26 year old man who had initially been diagnosed with myocardial infiltration on an echocardiogram, presenting with a testicular mass and unilateral peripheral facial paralysis. On admission, electrocardiograms (ECG) revealed negative T-waves in all leads and ST-segment elevation in the inferior leads. On two-dimensional echocardiography, there was infiltration of the pericardium with mild effusion, infiltrative thickening of the aortic walls, both atria and the interatrial septum and a mildly depressed systolic function of both ventricles. An axillary biopsy was performed and reported as a T-cell lymphoblastic lymphoma (T-LBL). Following the diagnosis and staging, chemotherapy was started. Twenty-two days after finishing the first cycle of chemotherapy, the ECG showed regression of T-wave changes in all leads and normalization of the ST-segment elevation in the inferior leads. A follow-up Two-dimensional echocardiography confirmed regression of the myocardial infiltration. This case report illustrates a lymphoma presenting with testicular mass, unilateral peripheral facial paralysis and myocardial involvement, and demonstrates that regression of infiltration can be achieved by intensive chemotherapy treatment. To our knowledge, there are no reported cases of T-LBL presenting as a testicular mass and unilateral peripheral facial paralysis, with complete regression of myocardial involvement. PMID:24109501

  20. Investigation in patients with previous myocardial infarction who present with chest pain

    SciTech Connect

    Selwyn, A.P.; Fox, K.; Forse, G.; Pratt, T.; Steiner, R.

    1981-12-01

    Thirty-five patients who presented with chest pain underwent mapping of the ECG with exercise and angiocardiography. Krypton-81m was used to assess regional myocardial perfusion before, during and after atrial pacing. Twelve of the 35 patients had negative exercise tests. Eight of these 12 had normal coronary arteries and four had less than or equal to 50% stenosis of at least one major coronary artery. All 12 patients had uniform increases in regional myocardial perfusion (98 plus/minus 14.0%) during atrial pacing. Thirteen of the 35 patients had a history of myocardial infarction and precordial areas of Q waves. During exercise, all 13 patients complained of chest pain and showed precordial areas of both ST-segment elevation and depression. These 13 patients had greater than or equal to 70% stenosis of at least one major coronary artery. Myocardial blood flow studies showed fixed defects of perfusion corresponding to the Q waves and ST-segment elevation. In addition, there were separate transient decreases of regional myocardial perfusion (70 plus/minus 9.0%) during atrial pacing corresponding to ST-segment depression and chest pain. Ten of the 35 patients had a history of myocardial infarction and precordial areas of Q waves. These areas showed no changes during atrial pacing. All the patients showed at least one remote region of myocardium that increased perfusion (74 plus/minus 170%) throughout pacing. Patients with a history of myocardial infarction may present with chest pain. In this study, ST-segment elevation during an exercise ECG was not associated with chest pain or detectable myocardial ischemia. Regional perfusion in infarcted segments of myocardium did not change with atrial pacing.

  1. Inhibition of Histone Deacetylases Preserves Myocardial Performance and Prevents Cardiac Remodeling through Stimulation of Endogenous Angiomyogenesis

    PubMed Central

    Zhang, Ling; Qin, Xin; Zhao, Yu; Fast, Loren; Zhuang, Shougang; Liu, Paul; Cheng, Guangmao

    2012-01-01

    We have previously shown that the inhibition of histone deacetylases (HDACs) protects the heart against acute myocardial ischemia and reperfusion injury. We also demonstrated that HDAC inhibition stimulates myogenesis and angiogenesis in a cultured embryonic stem cell model. We investigate whether in vivo inhibition of HDAC preserves cardiac performance and prevents cardiac remodeling in mouse myocardial infarction (MI) through the stimulation of endogenous regeneration. MI was created by ligation of the left descending artery. Animals were divided into three groups: 1) sham group, animals that underwent thoracotomy without MI; 2) MI, animals that underwent MI; and 3) MI + trichostatin A (TSA), MI animals that received a daily intraperitoneal injection of TSA. In addition, infarcted mice received a daily intraperitoneal injection of TSA (0.1 mg/kg), a selective HDAC inhibitor. 5-Bromo-2-deoxyuridine (50 mg/kg) was delivered every other day to pulse-chase label in vivo endogenous cardiac replication. Eight weeks later, the MI hearts showed a reduction in ventricular contractility. HDAC inhibition increased the improvement of myocardial functional recovery after MI, which was associated with the prevention of myocardial remodeling and reduction of myocardial and serum tumor necrosis factor α. HDAC inhibition enhanced the formation of new myocytes and microvessels, which was consistent with the robust increase in proliferation and cytokinesis in the MI hearts. An increase in angiogenic response was demonstrated in MI hearts receiving TSA treatment. It is noteworthy that TSA treatment significantly inhibited HDAC activity and increased phosphorylation of Akt-1, but decreased active caspase 3. Taken together, our results indicate that HDAC inhibition preserves cardiac performance and mitigates myocardial remodeling through stimulating cardiac endogenous regeneration. PMID:22271820

  2. Role of endogenous testosterone in myocardial proinflammatory and proapoptotic signaling after acute ischemia-reperfusion.

    PubMed

    Wang, Meijing; Tsai, Ben M; Kher, Ajay; Baker, Lauren B; Wairiuko, G Mathenge; Meldrum, Daniel R

    2005-01-01

    Myocardial ischemia is the leading cause of death in both men and women; however, very little information exists regarding the effect of testosterone on the response of myocardium to acute ischemic injury. We hypothesized that testosterone may exert deleterious effects on myocardial inflammatory cytokine production, p38 MAPK activation, apoptotic signaling, and myocardial functional recovery after acute ischemia-reperfusion (I/R). To study this, isolated, perfused rat hearts (Langendorff) from adult males, castrated males, and males treated with a testosterone receptor blocker (flutamide) were subjected to 25 min of ischemia followed by 40 min of reperfusion. Myocardial contractile function (left ventricular developed pressure, left ventricular end-diastolic pressure, positive and negative first derivative of pressure) was continuously recorded. After reperfusion, hearts were analyzed for expression of tissue TNF-alpha, IL-1beta, and IL-6 (ELISA) and activation of p38 MAPK, caspase-1, caspase-3, caspase-11, and Bcl-2 (Western blot). All indices of postischemic myocardial functional recovery were significantly higher in castrated males or flutamide-treated males compared with untreated males. After I/R, castrated male and flutamide-treated male hearts had decreased TNF-alpha, IL-1beta, and IL-6; decreased activated p38 MAPK; decreased caspase-1, caspase-3, and caspase-11; and increased Bcl-2 expression compared with untreated males. These results show that blocking the testosterone receptor (flutamide) or depleting testosterone (castration) in normal males improves myocardial function after I/R. These effects may be attributed to the proinflammatory and/or the proapoptotic properties of endogenous testosterone. Further understanding may allow therapeutic manipulation of sex hormone signaling mechanisms in the treatment of acute I/R. PMID:15374831

  3. Major depression.

    PubMed

    Bentley, Susan M; Pagalilauan, Genevieve L; Simpson, Scott A

    2014-09-01

    Major depression is a common, disabling condition seen frequently in primary care practices. Non-psychiatrist ambulatory providers are increasingly responsible for diagnosing, and primarily managing patients suffering from major depressive disorder (MDD). The goal of this review is to help primary care providers to understand the natural history of MDD, identify practical tools for screening, and a thoughtful approach to management. Clinically challenging topics like co-morbid conditions, treatment resistant depression and pharmacotherapy selection with consideration to side effects and medication interactions, are also covered. PMID:25134869

  4. Spiral MR myocardial tagging.

    PubMed

    Ryf, Salome; Kissinger, Kraig V; Spiegel, Marcus A; Börnert, Peter; Manning, Warren J; Boesiger, Peter; Stuber, Matthias

    2004-02-01

    In the present study, complementary spatial modulation of magnetization (CSPAMM) myocardial tagging was extended with an interleaved spiral imaging sequence. The use of a spiral sequence enables the acquisition of grid-tagged images with a tagline distance as low as 4 mm in a single breath-hold. Alternatively, a high temporal resolution of 77 frames per second was obtained with 8-mm grid spacing. Ten healthy adult subjects were studied. With this new approach, high-quality images can be obtained and the tags persist throughout the entire cardiac cycle. PMID:14755646

  5. Assessment of myocardial viability.

    PubMed

    Travin, Mark I; Bergmann, Steven R

    2005-01-01

    The prevalence of left ventricular (LV) dysfunction and resultant congestive heart failure is increasing. Patients with this condition are at high risk for cardiac death and usually have significant limitations in their lifestyles. Although there have been advances in medical therapy resulting in improved survival and well being, the best and most definitive therapy, when appropriate, is revascularization. In the setting of coronary artery disease, accounting for approximately two thirds of cases of congestive heart failure, LV dysfunction often is not the result of irreversible scar but rather caused by impairment in function and energy use of still viable-myocytes, with the opportunity for improved function if coronary blood flow is restored. Patients with LV dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischemia but at the same time benefit most from revascularization. It is important to identify viable myocardium in these patients, and radionuclide myocardial scintigraphy is an excellent tool for this. Single-photon emission computed tomography perfusion scintigraphy, whether using thallium-201, Tc-99m sestamibi, or Tc-99m tetrofosmin, in stress and/or rest protocols, has consistently been shown to be an effective modality for identifying myocardial viability and guiding appropriate management. Metabolic imaging with positron emission tomography radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularization, including some patients referred instead for cardiac transplantation. Other noninvasive modalities, such as stress echocardiography, also facilitate the assessment of myocardial viability, but there are advantages and disadvantages compared with the nuclear techniques. Nuclear imaging appears to require fewer viable cells for detection, resulting in a higher sensitivity but a lower specificity than stress

  6. Effects of glycyl-glutamine dipeptide supplementation on myocardial damage and cardiac function in rats after severe burn injury

    PubMed Central

    Zhang, Yong; Yan, Hong; Lv, Shang-Gun; Wang, Lin; Liang, Guang-Ping; Wan, Qian-Xue; Peng, Xi

    2013-01-01

    Glutamine decreases myocardial damage in ischemia/reperfusion injury. However, the cardioprotective effect of glutamine after burn injury remains unclear. Present study was to explore the protective effect of glycyl-glutamine dipeptide on myocardial damage in severe burn rats. Seventy-two Wistar rats were randomly divided into three groups: normal control (C), burned control (B) and glycyl-glutamine dipeptide-treated (GG) groups. B and GG groups were inflicted with 30% total body surface area of full thickness burn. The GG group was given 1.5 g/kg glycyl-glutamine dipeptide per day and the B group was given the same dose of alanine via intraperitoneal injection for 3 days. The serum CK, LDH, AST, and, blood lactic acid levels, as well as the myocardium ATP and GSH contents, were measured. The indices of cardiac contractile function and histopathological change were analyzed at 12, 24, 48, and 72 post-burn hours (PBH). The serum CK, LDH, AST and blood lactic acid levels increased, and the myocardium ATP and GSH content decreased in both burned groups. Compared with B group, the CK, LDH, AST and blood lactic acid levels reduced, myocardium ATP and GSH content increased in GG group. Moreover, the inhibition of cardiac contractile function and myocardial histopathological damage were reduced significantly in GG group. We conclude that myocardial histological structure and function were damaged significantly after burn injury, glycyl-glutamine dipeptide supplementation is beneficial to myocardial preservation by improving cardiocyte energy metabolism, increasing ATP and glutathione synthesis. PMID:23638213

  7. Recovery of regional myocardial dysfunction after successful coronary angioplasty early after a non-Q wave myocardial infarction

    SciTech Connect

    Suryapranata, H.; Serruys, P.W.; Beatt, K.; De Feyter, P.J.; van den Brand, M.; Roelandt, J. )

    1990-08-01

    More aggressive therapy has been suggested for patients who have a non-Q wave myocardial infarction (MI) because of the frequency of subsequent unstable angina, recurrent MI, and high mortality rate compared to patients with Q wave MI. The present study was undertaken to investigate the effect of coronary angioplasty on regional myocardial function of the infarct zone in patients with angina early after a non-Q wave MI. The study population consisted of 36 patients undergoing successful coronary angioplasty within 30 days of a non-Q wave MI, in whom sequential left ventricular angiograms of adequate quality were obtained before the initial procedure and at follow-up angiography. The global ejection fraction increased significantly from 60 +/- 9% to 67 +/- 6% (p = 0.0003). This significant increase in the global ejection fraction was primarily due to a significant improvement in the regional myocardial function of the infarct zone. The results of the present study show not only that ischemic attacks early after a non-Q wave MI may lead to prolonged regional myocardial dysfunction but more important that this depressed myocardium has the potential to achieve normal contraction after successful coronary angioplasty.

  8. Major depression

    MedlinePlus

    ... is very severe, you may have hallucinations and delusions (false beliefs). This condition is called depression with ... This helps relieve your symptoms. If you have delusions or hallucinations, your provider may prescribe additional medicines. ...

  9. Detecting cardiac contractile activity in the early mouse embryo using multiple modalities

    PubMed Central

    Chen, Chiann-Mun; Miranda, António M. A.; Bub, Gil; Srinivas, Shankar

    2015-01-01

    The heart is one of the first organs to develop during mammalian embryogenesis. In the mouse, it starts to form shortly after gastrulation, and is derived primarily from embryonic mesoderm. The embryonic heart is unique in having to perform a mechanical contractile function while undergoing complex morphogenetic remodeling. Approaches to imaging the morphogenesis and contractile activity of the developing heart are important in understanding not only how this remodeling is controlled but also the origin of congenital heart defects (CHDs). Here, we describe approaches for visualizing contractile activity in the developing mouse embryo, using brightfield time lapse microscopy and confocal microscopy of calcium transients. We describe an algorithm for enhancing this image data and quantifying contractile activity from it. Finally we describe how atomic force microscopy can be used to record contractile activity prior to it being microscopically visible. PMID:25610399

  10. Characteristics of bovine early puerperal uterine contractility recorded under farm conditions.

    PubMed

    Bajcsy, Arpád Csaba; Szenci, Ottó; Doornenbal, Arie; van der Weijden, Gijsbert C; Csorba, Csaba; Kocsis, László; Szucs, Imre; Ostgard, Stig; Taverne, Marcel A M

    2005-07-01

    A non-invasive, digital technique was used to measure and quantify intrauterine pressure (IUP) changes in early postpartum dairy cows kept under farm conditions in order to document physiological changes in uterine contractility after uncomplicated calvings. In addition, possible relationships between characteristics of uterine contractility and blood ionized calcium (Ca(2+))-concentrations were investigated. Recordings of uterine contractility were made by using a transcervically inserted open tip catheter in 12 healthy cows during their first 48h after calving. The IUP recording technique appeared easily applicable under farm conditions. Although mean frequency (FREQ), amplitude (AMP) and area under the curve (AUC) of the myometrial contractions significantly decreased due to time, untreated early postpartum cows showed a high variability in characteristics of uterine contractility. There was no correlation between blood Ca2+ -concentrations and any of the contractility parameters. PMID:15935846

  11. Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles

    PubMed Central

    Park, Ki Ho; Brotto, Leticia; Lehoang, Oanh; Brotto, Marco; Ma, Jianjie; Zhao, Xiaoli

    2012-01-01

    Described here is a method to measure contractility of isolated skeletal muscles. Parameters such as muscle force, muscle power, contractile kinetics, fatigability, and recovery after fatigue can be obtained to assess specific aspects of the excitation-contraction coupling (ECC) process such as excitability, contractile machinery and Ca2+ handling ability. This method removes the nerve and blood supply and focuses on the isolated skeletal muscle itself. We routinely use this method to identify genetic components that alter the contractile property of skeletal muscle though modulating Ca2+ signaling pathways. Here, we describe a newly identified skeletal muscle phenotype, i.e., mechanic alternans, as an example of the various and rich information that can be obtained using the in vitro muscle contractility assay. Combination of this assay with single cell assays, genetic approaches and biochemistry assays can provide important insights into the mechanisms of ECC in skeletal muscle. PMID:23149471

  12. Valsartan after myocardial infarction.

    PubMed

    Güleç, Sadi

    2014-12-01

    One of the important problems of the patients undergoing acute myocardial infarction (MI) is early development of heart failure. It has been revealed in various studies that renin-angiotensin-aldosterone system (RAAS) has a significant role in this process. The studies conducted with angiotensin converting enzyme (ACE) inhibitors have resulted in decreased mortality rate. Another RAAS blocker which was discovered about ten years later than other ACE inhibitors in historical process is angiotensin receptor blockers (ARB) inhibiting the efficiency of angiotensin 2 by binding to angiotensin 1 receptor. Valsartan is one of the molecules of this group, which has higher number of large-scale randomized clinical studies. In this review, following presentation of a general overview on heart failure after acute MI, the efficiency of ARBs in this patient group will be discussed. This discussion will mostly emphasize the construction, outcomes and clinical importance of VALIANT (VALsartan In Acute myocardial iNfarcTion), which is the study on valsartan after acute MI heart failure. PMID:25604205

  13. Trauma Induced Myocardial Infarction

    PubMed Central

    Lolay, Georges A.; Abdel-Latef, Ahmed K.

    2016-01-01

    Chest Trauma in athletes is a common health problem. However, myocardial infarction secondary to coronary dissection in the setting of blunt chest trauma is extremely rare. We report a case of acute inferior wall myocardial infarction following blunt chest trauma. A 32-year-old male with no relevant medical problems was transferred to our medical center for retrosternal chest pain after being elbowed in the chest during a soccer game. Few seconds later, he started experiencing sharp retrosternal chest pain that was severe to that point where he called the emergency medical service. Upon arrival to the Trauma department patient was still complaining of chest pain. ECG demonstrated ST segment elevation in the inferior leads with reciprocal changes in the lateral leads all consistent with active ischemia. After rolling out Aortic dissection, patient was loaded with ASA, ticagerlor, heparin and was emergently taken to the cardiac catheterization lab. Coronary angiography demonstrated 100% thrombotic occlusion in the distal right coronary artery with TIMI 0 flow distally. After thrombus aspiration, a focal dissection was noted on the angiogram that was successfully stented. Two days after admission patient was discharged home. Echocardiography prior to discharge showed inferior wall akinesis, normal right ventricular systolic function and normal overall ejection fraction. PMID:26490501

  14. Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass†

    PubMed Central

    Aass, Terje; Stangeland, Lodve; Moen, Christian Arvei; Salminen, Pirjo-Riitta; Dahle, Geir Olav; Chambers, David J.; Markou, Thomais; Eliassen, Finn; Urban, Malte; Haaverstad, Rune; Matre, Knut; Grong, Ketil

    2016-01-01

    OBJECTIVES Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model. METHODS Twenty anaesthetized young pigs, 42 ± 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure–conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples. RESULTS Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross-clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 ± 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 ± 70 mmHg/s, after 180 min of reperfusion (P = 0

  15. Myocardial imaging in dogs treated with grisorixin: relationship between /sup 201/Tl uptake and coronary blood flow

    SciTech Connect

    Moins, N.; Gachon, P.; Maublant, J.

    1982-04-01

    /sup 201/Tl myocardial imaging was performed in dogs after pretreatment with grisorixin, which appeared to increase the myocardial uptake of /sup 201/Tl. This effect of grisorixin was found to be dose dependent, with an optimal dose of 60 microgram/kg. The myocardial-to-background ratio, which was 1.92 in the control dogs, rose to 4.45. The increase in the absolute myocardial uptake was demonstrated in guinea pigs that received /sup 201/Tl after similar pretreatment with grisorixin. In the animals treated with 500 microgram/kg, the uptake of /sup 201/Tl by the heart was 35% over the control value. With 60 microgram/kg grisorixin, the coronary blood flow increased from 40 to 176 ml/min 5 min after the injection. This dose, optimal for imaging, induced the maximum vasodilator effect with only a very slight concomitant increase in the left-ventricular pressure and myocardial contractility. Above 60 microgram/kg, grisorixin appeared to be a potent inotropic agent, whereas below this dose it showed only coronary vasodilator properties. Some evidence for an ionophore effect of this compound was found in dogs pretreated with 60 microgram/kg. In these the radionuclide was injected when the coronary vasodilatation had become insignificant, but a significant improvement of the M/B ratio was still evident.

  16. Procedures for rat in situ skeletal muscle contractile properties.

    PubMed

    MacIntosh, Brian R; Esau, Shane P; Holash, R John; Fletcher, Jared R

    2011-01-01

    There are many circumstances where it is desirable to obtain the contractile response of skeletal muscle under physiological circumstances: normal circulation, intact whole muscle, at body temperature. This includes the study of contractile responses like posttetanic potentiation, staircase and fatigue. Furthermore, the consequences of disease, disuse, injury, training and drug treatment can be of interest. This video demonstrates appropriate procedures to set up and use this valuable muscle preparation. To set up this preparation, the animal must be anesthetized, and the medial gastrocnemius muscle is surgically isolated, with the origin intact. Care must be taken to maintain the blood and nerve supplies. A long section of the sciatic nerve is cleared of connective tissue, and severed proximally. All branches of the distal stump that do not innervate the medial gastrocnemius muscle are severed. The distal nerve stump is inserted into a cuff lined with stainless steel stimulating wires. The calcaneus is severed, leaving a small piece of bone still attached to the Achilles tendon. Sonometric crystals and/or electrodes for electromyography can be inserted. Immobilization by metal probes in the femur and tibia prevents movement of the muscle origin. The Achilles tendon is attached to the force transducer and the loosened skin is pulled up at the sides to form a container that is filled with warmed paraffin oil. The oil distributes heat evenly and minimizes evaporative heat loss. A heat lamp is directed on the muscle, and the muscle and rat are allowed to warm up to 37°C. While it is warming, maximal voltage and optimal length can be determined. These are important initial conditions for any experiment on intact whole muscle. The experiment may include determination of standard contractile properties, like the force-frequency relationship, force-length relationship, and force-velocity relationship. With care in surgical isolation, immobilization of the origin of the

  17. Angina and Mental Stress-Induced Myocardial Ischemia

    PubMed Central

    Pimple, Pratik; Shah, Amit J.; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon; Ibeanu, Ijeoma; Raggi, Paolo; Vaccarino, Viola

    2015-01-01

    Objective Mental stress-induced myocardial ischemia is a common phenomenon in patients with coronary artery disease (CAD) and an emerging prognostic factor. Mental stress ischemia is correlated with ambulatory ischemia. However, whether it is related to angina symptoms during daily life has not been examined. Methods We assessed angina-frequency (past month) in 98 post-myocardial infarction (MI) subjects (age 18-60 years) using the Seattle Angina Questionnaire. Patients underwent [99mTc]sestamibi SPECT perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed-difference score (SDS), the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. Results The mean age was 50 years, 50% were female and 60% were non-white. After adjustment for age, sex, smoking, CAD-severity, depressive, anger and anxiety symptoms, each 1-point increase in mental-stress SDS was associated with 1.73-unit increase in the angina-frequency score (95% CI: 0.09-3.37) and 17% higher odds of being in a higher angina-frequency category (OR: 1.17, 95% CI: 1.00-1.38). Depressive symptoms were associated with 12% higher odds of being in a higher angina-frequency category (OR: 1.12, 95% CI: 1.03-1.21). In contrast, exercise/pharmacological stress-induced SDS was not associated with angina-frequency. Conclusion Among young and middle-aged post-MI patients, myocardial ischemia induced by mental stress in the lab, but not by exercise/pharmacological stress, is associated with higher frequency of retrospectively reported angina during the day. Psychosocial stressors related to mental stress ischemia may be important contributory factor to daily angina. PMID:25727240

  18. Cellular Polarization and Contractility in Collective Cell Migration

    NASA Astrophysics Data System (ADS)

    Utuje, Kazage J. Christophe; Notbohm, Jacob; Banerjee, Shiladitya; Gweon, Bomi; Jang, Hwanseok; Park, Yongdoo; Shin, Jennifer; Butler, James P.; Fredberg, Jeffrey J.; Marchetti, M. Cristina

    Collective cell migration drives many biological processes such as metastasis, morphogenesis and wound healing. These coordinated motions are driven by active forces. The physical nature of these forces and the mechanisms by which they generate collective cell migration are still not fully understood. We have developed a minimum physical model of a cell monolayer as an elastic continuum whose deformation field is coupled to two internal degrees of freedom: the concentration of a chemical signal, controlling cell Contractility, and the polarization field controlling the direction of local cell motion. By combining theory with experiments, we show that these two internal variables account for the sloshing waves and the systematic deviations of the direction of cell polarization from that of local cell velocity observed in confined cell monolayers. KJCU and MCM were supported by the Simons Foundation.

  19. [Polyamines antagonizing angiotensin II contractile effects in isolated rat aorta].

    PubMed

    Costuleanu, Natalia; Foia, Liliana; Slătineanu, Simona Mihaela; Indrei, L L; Costuleanu, M; Petrescu, Gh

    2003-01-01

    Our study showed that the administration in pre-treatment of some polyamines (especially spermine and spermidine and almost null agmatine, putrescine and cadaverine) reduced the contractile effects of angiotensin II (Ang II) in isolated rat aorta. These effects might not be associated to the interference of clathrin coated vesicles (coated pits) formation or caveolae interaction (and thus to Ang II internalization through AT1 receptors). In contrast, these effects seem to be due to the interaction with voltage-gated membrane Ca2+ channels. Therefore, the alteration of transmembrane Ca2+ fluxes does not exclude the involvement of internalization process through coated pits or caveolae, since the endocytosis mediated by these phenomena essentially needs Ca2+. In addition, the inhibitory effects are dependent on the number of positive charges of the polyamine molecules. PMID:14755941

  20. Dynamic regulation of β1 subunit trafficking controls vascular contractility

    PubMed Central

    Leo, M. Dennis; Bannister, John P.; Narayanan, Damodaran; Nair, Anitha; Grubbs, Jordan E.; Gabrick, Kyle S.; Boop, Frederick A.; Jaggar, Jonathan H.

    2014-01-01

    Ion channels composed of pore-forming and auxiliary subunits control physiological functions in virtually all cell types. A conventional view is that channels assemble with their auxiliary subunits before anterograde plasma membrane trafficking of the protein complex. Whether the multisubunit composition of surface channels is fixed following protein synthesis or flexible and open to acute and, potentially, rapid modulation to control activity and cellular excitability is unclear. Arterial smooth muscle cells (myocytes) express large-conductance Ca2+-activated potassium (BK) channel α and auxiliary β1 subunits that are functionally significant modulators of arterial contractility. Here, we show that native BKα subunits are primarily (∼95%) plasma membrane-localized in human and rat arterial myocytes. In contrast, only a small fraction (∼10%) of total β1 subunits are located at the cell surface. Immunofluorescence resonance energy transfer microscopy demonstrated that intracellular β1 subunits are stored within Rab11A-postive recycling endosomes. Nitric oxide (NO), acting via cGMP-dependent protein kinase, and cAMP-dependent pathways stimulated rapid (≤1 min) anterograde trafficking of β1 subunit-containing recycling endosomes, which increased surface β1 almost threefold. These β1 subunits associated with surface-resident BKα proteins, elevating channel Ca2+ sensitivity and activity. Our data also show that rapid β1 subunit anterograde trafficking is the primary mechanism by which NO activates myocyte BK channels and induces vasodilation. In summary, we show that rapid β1 subunit surface trafficking controls functional BK channel activity in arterial myocytes and vascular contractility. Conceivably, regulated auxiliary subunit trafficking may control ion channel activity in a wide variety of cell types. PMID:24464482

  1. Role of Peripheral Vascular Resistance for the Association Between Major Depression and Cardiovascular Disease

    PubMed Central

    Bouzinova, Elena V.; Wiborg, Ove; Aalkjaer, Christian

    2015-01-01

    Abstract: Major depression and cardiovascular diseases are 2 of the most prevalent health problems in Western society, and an association between them is generally accepted. Although the specific mechanism behind this comorbidity remains to be elucidated, it is clear that it has a complex multifactorial character including a number of neuronal, humoral, immune, and circulatory pathways. Depression-associated cardiovascular abnormalities associate with cardiac dysfunctions and with changes in peripheral resistance. Although cardiac dysfunction in association with depression has been studied in detail, little attention was given to structural and functional changes in resistance arteries responsible for blood pressure control and tissue perfusion. This review discusses recent achievements in studies of depression-associated abnormalities in resistance arteries in humans and animal experimental models. The changes in arterial structure, contractile and relaxing functions associated with depression symptoms are discussed, and the role of these abnormalities for the pathology of major depression and cardiovascular diseases are suggested. PMID:25469807

  2. An unusual myocardial infarction

    PubMed Central

    Di Michele, Sara; Mirabelli, Francesca; Mankad, Sunil

    2014-01-01

    Summary We present a 74-year-old male with a chondrosarcoma, who presented with chest pain. The history, electrocardiogram (ECG), and biomarkers established the diagnosis of myocardial infarction (MI); angiography did not show coronary atherosclerosis and, both initial transthoracic echocardiogram and chest computed tomography (CT), did not demonstrate any cardiac abnormalities. A second echocardiogram following a routine ECG showed presence of a mass involving the right ventricle and the cardiac apex that was confirmed by chest CT scan. We underline the importance of considering cardiac tumors in the clinical arena of MI management. Learning points Cardiac tumors cause ECG changes similar to ischemic heart diseases.Keep in mind cardiac tumors when performing transthoracic echocardiogram (TTE) in the setting of suspected MI.TTE is the technique of choice in detecting cardiac tumors. PMID:26693309

  3. Masquerades of myocardial infarction.

    PubMed Central

    Bean, W. B.

    1976-01-01

    I summarize these observations in Figure 1. It represents every person in a hypothetical population who has myocardial infarction. A large but unknown number, some believe almost half, never get help. Mobile coronary care units are reducing this group, but so far only a little. When the diagnosis is not understood the disease is not recognized. Then come discovery and popularization. Hereafter masquerades hide some cases and the diagnosis is missed. Somewhere fairly early the diagnostic fad leads to false positive diagnosis. As new techniques are discovered, perfected and mastered, false positive errors and masquerades leading to oversights diminish but still exist. All the skill and technical virtuosity in the world will not be applied if we do not think of the disease. When we think of it, even obscure cases may be resolved easily. PMID:960416

  4. CARD9 knockout ameliorates myocardial dysfunction associated with high fat diet-induced obesity.

    PubMed

    Cao, Li; Qin, Xing; Peterson, Matthew R; Haller, Samantha E; Wilson, Kayla A; Hu, Nan; Lin, Xin; Nair, Sreejayan; Ren, Jun; He, Guanglong

    2016-03-01

    Obesity is associated with chronic inflammation which plays a critical role in the development of cardiovascular dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) in macrophages regulates innate immune responses via activation of pro-inflammatory cytokines, we hypothesize that CARD9 mediates the pro-inflammatory signaling associated with obesity en route to myocardial dysfunction. C57BL/6 wild-type (WT) and CARD9(-/-) mice were fed normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5months. At the end of 5-month HFD feeding, cardiac function was evaluated using echocardiography. Cardiomyocytes were isolated and contractile properties were measured. Immunofluorescence was performed to detect macrophage infiltration in the heart. Heart tissue homogenates, plasma, and supernatants from isolated macrophages were collected to measure the concentrations of pro-inflammatory cytokines using ELISA kits. Western immunoblotting analyses were performed on heart tissue homogenates and isolated macrophages to explore the underlying signaling mechanism(s). CARD9 knockout alleviated HFD-induced insulin resistance and glucose intolerance, prevented myocardial dysfunction with preserved cardiac fractional shortening and cardiomyocyte contractile properties. CARD9 knockout also significantly decreased the number of infiltrated macrophages in the heart with reduced myocardium-, plasma-, and macrophage-derived cytokines including IL-6, IL-1β and TNFα. Finally, CARD9 knockout abrogated the increase of p38 MAPK phosphorylation, the decrease of LC3BII/LC3BI ratio and the up-regulation of p62 expression in the heart induced by HFD feeding and restored cardiac autophagy signaling. In conclusion, CARD9 knockout ameliorates myocardial dysfunction associated with HFD-induced obesity, potentially through reduction of macrophage infiltration, suppression of p38 MAPK phosphorylation, and preservation of autophagy in the heart. PMID

  5. Factors released from endocardium of the ferret and pig modulate myocardial contraction.

    PubMed Central

    Smith, J A; Shah, A M; Lewis, M J

    1991-01-01

    1. In isolated heart muscle preparations, selective removal of the endocardium results in a characteristic and unusual negative inotropic effect. Possible mechanisms for this effect were investigated in this study. 2. In endocardium-intact preparations of ferret papillary muscle, 8-bromo-cyclic GMP, sodium nitroprusside, atrial natriuretic peptide (ANP) and substance P each induced changes in contractile behaviour similar to selective endocardial removal, and each significantly elevated myocardial cyclic GMP levels. Substance P failed to elevate myocardial cyclic GMP levels following removal of endocardium or in the presence of haemoglobin, suggesting that it may act by releasing endothelium-derived relaxing factor (EDRF) from endocardium. However, there was no change in myocardial cyclic GMP levels following endocardium removal alone. 3. In cascade bioassay experiments, it was confirmed that porcine cultured endocardial cells released an unstable humoral agent whose effects on an endothelium-denuded pig coronary artery were indistinguishable from EDRF. 4. The negative inotropic effects of endocardium removal were reversed in bioassay experiments where an endocardium-denuded papillary muscle was exposed to the effluent from a column of porcine cultured endocardial cells on microcarrier beads. This demonstrates for the first time the release of a 'contraction prolonging factor' from endocardium, the tonic release of which would explain the negative inotropic effect of endocardium removal. 5. It is concluded that elevation of ferret papillary muscle cyclic GMP (as for example with EDRF) produces changes in contractile performance similar to those induced by endocardium removal. We also demonstrate that superfused porcine cultured endocardial cells release a humoral agent (provisionally named 'endocardin') which causes reversal of the changes in mechanical properties seen after endocardial removal. PMID:1716674

  6. Modeling to link regional myocardial work, metabolism and blood flows

    PubMed Central

    Bassingthwaighte, James B.; Beard, Daniel A; Carlson, Brian E.; Dash, Ranjan K.; Vinnakota, Kalyan

    2012-01-01

    Given the mono-functional, highly coordinated processes of cardiac excitation and contraction, the observations that regional myocardial blood flows, rMBF, are broadly heterogeneous has provoked much attention, but a clear explanation has not emerged. In isolated and in vivo heart studies the total coronary flow is found to be proportional to the rate-pressure product (systolic mean blood pressure times heart rate), a measure of external cardiac work. The same relationship might be expected on a local basis: more work requires more flow. The validity of this expectation has never been demonstrated experimentally. In this article we review the concepts linking cellular excitation and contractile work to cellular energetics and ATP demand, substrate utilization, oxygen demand, vasoregulation, and local blood flow. Mathematical models of these processes are now rather well developed. We propose that the construction of an integrated model encompassing the biophysics, biochemistry and physiology of cardiomyocyte contraction, then combined with a detailed three-dimensional structuring of the fiber bundle and sheet arrangements of the heart as a whole will frame an hypothesis that can be quantitatively evaluated to settle the prime issue: Does local work drive local flow in a predictable fashion that explains the heterogeneity? While in one sense one can feel content that work drives flow is irrefutable, there are no cardiac contractile models that demonstrate the required heterogeneity in local strain-stress-work; quite the contrary, cardiac contraction models have tended toward trying to show that work should be uniform. The object of this review is to argue that uniformity of work does not occur, and is impossible in any case, and that further experimentation and analysis are necessary to test the hypothesis. PMID:22915334

  7. Inhibition by sildenafil of contractility of isolated non-pregnant human myometrium

    PubMed Central

    Winston, Aruldhas Blessed; Vazhudhi, Kaysina; Sen, Sumalya; Thomas, Elsy; Benjamin, Santhosh; Peedicayil, Jacob

    2015-01-01

    Objective: To investigate the ability of sildenafil to inhibit the contractility of isolated non pregnant human myometrium. Materials and Methods: The inhibitory effect of three concentrations (3, 10, and 30 µM) of sildenafil on 55 mM KCl-induced contractility of isolated non-pregnant human myometrium was studied. The ability of the guanylyl cyclase inhibitor ODQ (10 µM), the adenylyl cyclase inhibitor MDL-12,330A (10 µM), the non-specific potassium channel blocker TEA (2 mM), and the calcium-sensitive potassium (BKCa) channel blocker iberiotoxin (100 nM) to reverse the inhibition of 10 µM sildenafil on KCl-induced myometrial contractility was also studied. Results: Sildenafil produced a concentration-dependent inhibition of KCl-induced myometrial contractility that was statistically significant at all three concentrations of sildenafil used. The inhibition by 10 µM sildenafil of KCl-induced myometrial contractility was not reversed by the concurrent administration of ODQ or MDL-12,330A. The inhibition of 10 µM sildenafil of myometrial contractility was partially reversed by concurrent administration of TEA and totally and significantly reversed by the concurrent administration of iberiotoxin. Conclusions: These results suggest that sildenafil inhibits the contractility of isolated non-pregnant human myometrium. The results suggest that sildenafil does so by opening BKCa channels. PMID:26311996

  8. Junb regulates arterial contraction capacity, cellular contractility, and motility via its target Myl9 in mice.

    PubMed

    Licht, Alexander H; Nübel, Tobias; Feldner, Anja; Jurisch-Yaksi, Nathalie; Marcello, Marco; Demicheva, Elena; Hu, Jun-Hao; Hartenstein, Bettina; Augustin, Hellmut G; Hecker, Markus; Angel, Peter; Korff, Thomas; Schorpp-Kistner, Marina

    2010-07-01

    Cellular contractility and, thus, the ability to alter cell shape are prerequisites for a number of important biological processes such as cytokinesis, movement, differentiation, and substrate adherence. The contractile capacity of vascular smooth muscle cells (VSMCs) is pivotal for the regulation of vascular tone and thus blood pressure and flow. Here, we report that conditional ablation of the transcriptional regulator Junb results in impaired arterial contractility in vivo and in vitro. This was exemplified by resistance of Junb-deficient mice to DOCA-salt-induced volume-dependent hypertension as well as by a decreased contractile capacity of isolated arteries. Detailed analyses of Junb-deficient VSMCs, mouse embryonic fibroblasts, and endothelial cells revealed a general failure in stress fiber formation and impaired cellular motility. Concomitantly, we identified myosin regulatory light chain 9 (Myl9), which is critically involved in actomyosin contractility and stress fiber assembly, as a Junb target. Consistent with these findings, reexpression of either Junb or Myl9 in Junb-deficient cells restored stress fiber formation, cellular motility, and contractile capacity. Our data establish a molecular link between the activator protein-1 transcription factor subunit Junb and actomyosin-based cellular motility as well as cellular and vascular contractility by governing Myl9 transcription. PMID:20551518

  9. Junb regulates arterial contraction capacity, cellular contractility, and motility via its target Myl9 in mice

    PubMed Central

    Licht, Alexander H.; Nübel, Tobias; Feldner, Anja; Jurisch-Yaksi, Nathalie; Marcello, Marco; Demicheva, Elena; Hu, Jun-Hao; Hartenstein, Bettina; Augustin, Hellmut G.; Hecker, Markus; Angel, Peter; Korff, Thomas; Schorpp-Kistner, Marina

    2010-01-01

    Cellular contractility and, thus, the ability to alter cell shape are prerequisites for a number of important biological processes such as cytokinesis, movement, differentiation, and substrate adherence. The contractile capacity of vascular smooth muscle cells (VSMCs) is pivotal for the regulation of vascular tone and thus blood pressure and flow. Here, we report that conditional ablation of the transcriptional regulator Junb results in impaired arterial contractility in vivo and in vitro. This was exemplified by resistance of Junb-deficient mice to DOCA-salt–induced volume-dependent hypertension as well as by a decreased contractile capacity of isolated arteries. Detailed analyses of Junb-deficient VSMCs, mouse embryonic fibroblasts, and endothelial cells revealed a general failure in stress fiber formation and impaired cellular motility. Concomitantly, we identified myosin regulatory light chain 9 (Myl9), which is critically involved in actomyosin contractility and stress fiber assembly, as a Junb target. Consistent with these findings, reexpression of either Junb or Myl9 in Junb-deficient cells restored stress fiber formation, cellular motility, and contractile capacity. Our data establish a molecular link between the activator protein–1 transcription factor subunit Junb and actomyosin-based cellular motility as well as cellular and vascular contractility by governing Myl9 transcription. PMID:20551518

  10. Thin filament incorporation of an engineered cardiac troponin C variant (L48Q) enhances contractility in intact cardiomyocytes from healthy and infarcted hearts

    PubMed Central

    Feest, Erik R.; Korte, F. Steven; Tu, An-yue; Dai, Jin; Razumova, Maria V.; Murry, Charles E.; Regnier, Michael

    2014-01-01

    Many current pharmaceutical therapies for systolic heart failure target intracellular [Ca2+] ([Ca2+]i) metabolism, or cardiac troponin C (cTnC) on thin filaments, and can have significant side-effects, including arrhythmias or adverse effects on diastolic function. In this study, we tested the feasibility of directly increasing the Ca2+ binding properties of cTnC to enhance contraction independent of [Ca2+]i in intact cardiomyocytes from healthy and myocardial infarcted (MI) hearts. Specifically, cardiac thin filament activation was enhanced through adenovirus-mediated over-expression of a cardiac troponin C (cTnC) variant designed to have increased Ca2+ binding affinity conferred by single amino acid substitution (L48Q). In skinned cardiac trabeculae and myofibrils we and others have shown that substitution of L48Q cTnC for native cTnC increases Ca2+ sensitivity of force and the maximal rate of force development. Here we introduced L48Q cTnC into myofilaments of intact cardiomyocytes via adeno-viral transduction to deliver cDNA for the mutant or wild type (WT) cTnC protein. Using video-microscopy to monitor cell contraction, relaxation, and intracellular Ca2+ transients (Fura-2), we report that incorporation of L48Q cTnC significantly increased contractility of cardiomyocytes from healthy and MI hearts without adversely affecting Ca2+ transient properties or relaxation. The improvements in contractility from L48Q cTnC expression are likely the result of enhanced contractile efficiency, as intracellular Ca2+ transient amplitudes were not affected. Expression and incorporation of L48Q cTnC into myofilaments was confirmed by Western blot analysis of myofibrils from transduced cardiomyocytes, which indicated replacement of 18±2% of native cTnC with L48Q cTnC. These experiments demonstrate the feasibility of directly targeting cardiac thin filament proteins to enhance cardiomyocyte contractility that is impaired following MI. PMID:24690333

  11. The diagnosis and treatment of the no-reflow phenomenon in patients with myocardial infarction undergoing percutaneous coronary intervention

    PubMed Central

    Ramjane, Khalill; Han, Lei; Jin, Chang

    2008-01-01

    OBJECTIVE To review the diagnosis and treatment available for myocardial infarction patients having no-reflow in the setting of percutaneous coronary intervention (PCI). DATA SOURCES Data for the present review were obtained from searches in PubMed (1997 to 2007) using the following key terms: “acute myocardial infarction”, “no-reflow phenomenon”, “myocardial contrast echocardiography”, “coronary angiography” and “cardioprotection devices”. STUDY SELECTION Mainly original articles and critical reviews written by major research pioneers in interventional cardiology were selected. RESULTS Despite a fully patent coronary artery post-PCI for myocardial infarction, patients may experience inadequate myocardial perfusion through a given segment of the coronary circulation without angiographic evidence of mechanical vessel obstruction. This phenomenon is defined as no-reflow and is a growing problem in the field of interventional cardiology. Although voluminous clinical trial data are available, the exact mechanisms involved and which treatment should be administered as first-line therapy are currently unknown. The different techniques used to diagnose no-reflow also have their pros and cons; myocardial contrast echocardiography and coronary angiography are the most reliable techniques. In cases when no-reflow was successfully reversed, patient recovery was associated with favourable left ventricular remodelling and increased left ventricular ejection fraction, even in the absence of significant improvement in regional contractile function. CONCLUSION Based on the trials in the literature, myocardial contrast echocardiography is the gold standard for the diagnosis of no-reflow. If no-reflow occurs following PCI, treatment with intracoronary adenosine or verapamil should be administered, because this form of therapy is inexpensive and safe, improves flow in the target vessel and may reduce infarct size. PMID:19343126

  12. Effects of lactic acid and catecholamines on contractility in fast-twitch muscles exposed to hyperkalemia.

    PubMed

    Hansen, Anders Krogh; Clausen, Torben; Nielsen, Ole Baekgaard

    2005-07-01

    Intensive exercise is associated with a pronounced increase in extracellular K+ ([K+]o). Because of the ensuing depolarization and loss of excitability, this contributes to muscle fatigue. Intensive exercise also increases the level of circulating catecholamines and lactic acid, which both have been shown to alleviate the depressing effect of hyperkalemia in slow-twitch muscles. Because of their larger exercise-induced loss of K+, fast-twitch muscles are more prone to fatigue caused by increased [K+]o than slow-twitch muscles. Fast-twitch muscles also produce more lactic acid. We therefore compared the effects of catecholamines and lactic acid on the maintenance of contractility in rat fast-twitch [extensor digitorum longus (EDL)] and slow-twitch (soleus) muscles. Intact muscles were mounted on force transducers and stimulated electrically to evoke short isometric tetani. Elevated [K+]o (11 and 13 mM) was used to reduce force to approximately 20% of control force at 4 mM K+. In EDL, the beta2-agonist salbutamol (10(-5) M) restored tetanic force to 83 +/- 2% of control force, whereas in soleus salbutamol restored tetanic force to 93 +/- 1%. In both muscles, salbutamol induced hyperpolarization (5-8 mV), reduced intracellular Na+ content and increased Na+-K+ pump activity, leading to an increased K+ tolerance. Lactic acid (24 mM) restored force from 22 +/- 4% to 58 +/- 2% of control force in EDL, an effect that was significantly lower than in soleus muscle. These results amplify and generalize the concept that the exercise-induced acidification and increase in plasma catecholamines counterbalance fatigue arising from rundown of Na+ and K+ gradients. PMID:15743886

  13. Effect of alterations in the thyroid state on the intrinsic contractile properties of isolated rat skeletal muscle

    PubMed Central

    Gold, Herman K.; Spann, James F.; Braunwald, Eugene

    1970-01-01

    Contractile properties of soleus muscles isolated from 31 euthyroid (EU), 20 hyperthyroid (HT), and 18 myxedematous (MY) rats were studied in a myograph. At 100 stimuli/sec maximum isometric tension was essentially identical in EU (17.2 ±0.5 g/mm2) and HT (17.7 ±0.5 g/mm2) muscles, but was significantly depressed in MY muscles (11.5 ±0.7 g/mm2). The rate of tension development was increased in HT (103 ±4.5 g/sec per mm2) as compared to both EU (86.2 ±4.6 g/sec per mm2) and MY (38.4 ±2.2 g/sec per mm2) muscles, while the duration of the active state was shortened in HT (77.1 ±2.3 msec) as compared to EU (105.1 ±1.1 msec) muscles and was prolonged in MY muscles (153.3 ±6.0 msec). The mean rate of isometric relaxation was 26.5 ±4.9 g/mm2 per sec in EU muscles, more rapid in HT muscles (33.1 ±1.3 g/sec per mm2), and slower in MY muscles (16.0 ± g/mm2 per sec). The fusion frequency was greater in HT muscles, averaging 68.5 ±3.6 stimuli/sec compared to EU muscles (38.1 ±1.2 stimuli/sec) and to MY muscles (33.3 ±4.0 stimuli/sec). At 40 stimuli/sec tension averaged 16.4 ±0.8 g/mm2 in EU muscles while at the same frequency tension was reduced in HT muscle, averaging 14.2 ±0.5 g/mm2. All differences were significant (P < 0.01). In conclusion, HT and MY result in profound alterations in the intrinsic contractile properties of skeletal muscle. While tension in HT muscles is maintained in vitro at a stimulus frequency of 100 stimuli/sec, the reduction in duration of active state may lower tension in vivo by preventing complete fusion of contractile events. In MY tension is reduced as a consequence of the lowered intensity of the active state. These changes explain, at least in part, the weakness of muscle activity in both HT and MY. PMID:5443184

  14. Single acute stress-induced progesterone and ovariectomy alter cardiomyocyte contractile function in female rats

    PubMed Central

    Kalász, Judit; Tóth, Enikő Pásztor; Bódi, Beáta; Fagyas, Miklós; Tóth, Attila; Pal, Bhattoa Harjit; Vári, Sándor G.; Balog, Marta; Blažetić, Senka; Heffer, Marija; Papp, Zoltán; Borbély, Attila

    2014-01-01

    Aim To assess how ovarian-derived sex hormones (in particular progesterone) modify the effects of single acute stress on the mechanical and biochemical properties of left ventricular cardiomyocytes in the rat. Methods Non-ovariectomized (control, n = 8) and ovariectomized (OVX, n = 8) female rats were kept under normal conditions or were exposed to stress (control-S, n = 8 and OVX-S, n = 8). Serum progesterone levels were measured using a chemiluminescent immunoassay. Left ventricular myocardial samples were used for isometric force measurements and protein analysis. Ca2+-dependent active force (Factive), Ca2+-independent passive force (Fpassive), and Ca2+-sensitivity of force production were determined in single, mechanically isolated, permeabilized cardiomyocytes. Stress- and ovariectomy-induced alterations in myofilament proteins (myosin-binding protein C [MyBP-C], troponin I [TnI], and titin) were analyzed by sodium dodecyl sulfate gel electrophoresis using protein and phosphoprotein stainings. Results Serum progesterone levels were significantly increased in stressed rats (control-S, 35.6 ± 4.8 ng/mL and OVX-S, 21.9 ± 4.0 ng/mL) compared to control (10 ± 2.9 ng/mL) and OVX (2.8 ± 0.5 ng/mL) groups. Factive was higher in the OVX groups (OVX, 25.9 ± 3.4 kN/m2 and OVX-S, 26.3 ± 3.0 kN/m2) than in control groups (control, 16.4 ± 1.2 kN/m2 and control-S, 14.4 ± 0.9 kN/m2). Regarding the potential molecular mechanisms, Factive correlated with MyBP-C phosphorylation, while myofilament Ca2+-sensitivity inversely correlated with serum progesterone levels when the mean values were plotted for all animal groups. Fpassive was unaffected by any treatment. Conclusion Stress increases ovary-independent synthesis and release of progesterone, which may regulate Ca2+-sensitivity of force production in left ventricular cardiomyocytes. Stress and female hormones differently alter Ca2+-dependent cardiomyocyte contractile

  15. Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction.

    PubMed

    Mapanga, Rudo F; Rajamani, Uthra; Dlamini, Nonkululeko; Zungu-Edmondson, Makhosazane; Kelly-Laubscher, Roisin; Shafiullah, Mohammed; Wahab, Athiq; Hasan, Mohamed Y; Fahim, Mohamed A; Rondeau, Philippe; Bourdon, Emmanuel; Essop, M Faadiel

    2012-01-01

    Diabetes constitutes a major health challenge. Since cardiovascular complications are common in diabetic patients this will further increase the overall burden of disease. Furthermore, stress-induced hyperglycemia in non-diabetic patients with acute myocardial infarction is associated with higher in-hospital mortality. Previous studies implicate oxidative stress, excessive flux through the hexosamine biosynthetic pathway (HBP) and a dysfunctional ubiquitin-proteasome system (UPS) as potential mediators of this process. Since oleanolic acid (OA; a clove extract) possesses antioxidant properties, we hypothesized that it attenuates acute and chronic hyperglycemia-mediated pathophysiologic molecular events (oxidative stress, apoptosis, HBP, UPS) and thereby improves contractile function in response to ischemia-reperfusion. We employed several experimental systems: 1) H9c2 cardiac myoblasts were exposed to 33 mM glucose for 48 hr vs. controls (5 mM glucose); and subsequently treated with two OA doses (20 and 50 µM) for 6 and 24 hr, respectively; 2) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mM glucose vs. controls (11 mM glucose) for 60 min, followed by 20 min global ischemia and 60 min reperfusion ± OA treatment; 3) In vivo coronary ligations were performed on streptozotocin treated rats ± OA administration during reperfusion; and 4) Effects of long-term OA treatment (2 weeks) on heart function was assessed in streptozotocin-treated rats. Our data demonstrate that OA treatment blunted high glucose-induced oxidative stress and apoptosis in heart cells. OA therapy also resulted in cardioprotection, i.e. for ex vivo and in vivo rat hearts exposed to ischemia-reperfusion under hyperglycemic conditions. In parallel, we found decreased oxidative stress, apoptosis, HBP flux and proteasomal activity following ischemia-reperfusion. Long-term OA treatment also improved heart function in streptozotocin-diabetic rats. These findings are

  16. Plasticity of TOM complex assembly in skeletal muscle mitochondria in response to chronic contractile activity.

    PubMed

    Joseph, Anna-Maria; Hood, David A

    2012-03-01

    We investigated the assembly of the TOM complex within skeletal muscle under conditions of chronic contractile activity-induced mitochondrial biogenesis. Tom40 import into mitochondria was increased by chronic contractile activity, as was its time-dependent assembly into the TOM complex. These changes coincided with contractile activity-induced augmentations in the expression of key protein import machinery components Tim17, Tim23, and Tom22, as well as the cytosolic chaperone Hsp90. These data indicate the adaptability of the TOM protein import complex and suggest a regulatory role for the assembly of this complex in exercise-induced mitochondrial biogenesis. PMID:22142511

  17. Implication of advanced glycation end products (Ages) and their receptor (Rage) on myocardial contractile and mitochondrial functions.

    PubMed

    Neviere, Remi; Yu, Yichi; Wang, Lei; Tessier, Frederic; Boulanger, Eric

    2016-08-01

    Advanced glycation end products (AGEs) play an important role for the development and/or progression of cardiovascular diseases, mainly through induction of oxidative stress and inflammation. AGEs are a heterogeneous group of molecules formed by non-enzymatic reaction of reducing sugars with amino acids of proteins, lipids and nucleic acids. AGEs are mainly formed endogenously, while recent studies suggest that diet constitutes an important exogenous source of AGEs. The presence and accumulation of AGEs in various cardiac cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes up regulation of the transcription factor nuclear factor-κB and its target genes. of the RAGE engagement stimulates oxidative stress, evokes inflammatory and fibrotic reactions, which all contribute to the development and progression of devastating cardiovascular disorders. This review discusses potential targets of glycation in cardiac cells, and underlying mechanisms that lead to heart failure with special interest on AGE-induced mitochondrial dysfunction in the myocardium. PMID:27277623

  18. Paroxetine Is a Direct Inhibitor of G Protein-Coupled Receptor Kinase 2 and Increases Myocardial Contractility

    SciTech Connect

    Thal, David M.; Homan, Kristoff T.; Chen, Jun; Wu, Emily K.; Hinkle, Patricia M.; Huang, Z. Maggie; Chuprun, J. Kurt; Song, Jianliang; Gao, Erhe; Cheung, Joseph Y.; Sklar, Larry A.; Koch, Walter J.; Tesmer, John J.G.

    2012-08-10

    G protein-coupled receptor kinase 2 (GRK2) is a well-established therapeutic target for the treatment of heart failure. In this paper we identify the selective serotonin reuptake inhibitor (SSRI) paroxetine as a selective inhibitor of GRK2 activity both in vitro and in living cells. In the crystal structure of the GRK2·paroxetine–Gβγ complex, paroxetine binds in the active site of GRK2 and stabilizes the kinase domain in a novel conformation in which a unique regulatory loop forms part of the ligand binding site. Isolated cardiomyocytes show increased isoproterenol-induced shortening and contraction amplitude in the presence of paroxetine, and pretreatment of mice with paroxetine before isoproterenol significantly increases left ventricular inotropic reserve in vivo with no significant effect on heart rate. Neither is observed in the presence of the SSRI fluoxetine. Our structural and functional results validate a widely available drug as a selective chemical probe for GRK2 and represent a starting point for the rational design of more potent and specific GRK2 inhibitors.

  19. Understanding Depression (For Parents)

    MedlinePlus

    ... daylight are shorter; for example, during winter months. Bipolar disorder (also called manic depression or bipolar depression) is ... to a Therapist Anxiety Disorders Cutting Word! Depression Bipolar Disorder Why Am I So Sad? Sadness and Depression ...

  20. Thoracic epidural anesthesia improves functional recovery from myocardial stunning in conscious dogs.

    PubMed

    Rolf, N; Van de Velde, M; Wouters, P F; Möllhoff, T; Weber, T P; Van Aken, H K

    1996-11-01

    The effects of thoracic epidural anesthesia (TEA) on the contractile performance of ischemic and postischemic myocardium have not been well investigated. The purpose of this investigation was to examine the effects of TEA on severity and duration of myocardial stunning in an experimental model for sublethal acute myocardial ischemia. Seven dogs were chronically instrumented for measurement of heart rate (HR), left atrial (LAP), aortic and left ventricular pressure (LVP), LV dP/dtmax' and myocardial wall-thickening fraction (WTF). An occluder around the left anterior descending artery (LAD) allowed induction of reversible LAD ischemia. TEA was performed with lidocaine 4 mg/kg through a chronically implanted epidural catheter at the second thoracic level. Regional myocardial blood flow was determined with colored microspheres. Two experiments were performed in a cross-over design on separate days: Experiment 1, induction of 10 min of LAD ischemia without TEA; and Experiment 2, induction of 10 min of LAD ischemia with TEA. WTF was measured at baseline (BL) and predetermined time points until complete recovery from ischemic dysfunction occurred. LAD ischemia caused a significant decrease of LAD-WTF with (-28% +/- 5.1% versus BL) and without TEA (-15.5% +/- 5.3% versus BL). After 3 h of reperfusion, WTF as percent of BL values was significantly higher with TEA (P < 0.001). BL values of WTF were reached after 24 h with TEA and after more than 48 h without TEA (P < 0.05). There were no significant differences for mean arterial pressure (MAP), heart rate (HR), LVP, LAP, and LVdP/dtmax between the groups during ischemia and reperfusion. In nonischemic myocardium TEA caused an increase of subendocardial blood flow. During ischemia neither the subendocardial/subepicardial nor the occluded/ normal zone blood flow was affected by TEA. TEA attenuates myocardial stunning in conscious dogs. This finding is consistent with data regarding a reduction of infarct size due to TEA. PMID

  1. Wave Propagation of Myocardial Stretch: Correlation with Myocardial Stiffness

    PubMed Central

    Pislaru, Cristina; Pellikka, Patricia A.; Pislaru, Sorin V.

    2015-01-01

    The mechanism of flow propagation during diastole in the left ventricle (LV) has been well described. Little is known about the associated waves propagating along the heart wall s. These waves may have a mechanism similar to pulse wave propagation in arteries. The major goal of the study was to evaluate the effect of myocardial stiffness and preload on this wave transmission. Methods Longitudinal late diastolic deformation and wave speed (Vp) of myocardial stretch in the anterior LV wall were measured using sonomicrometry in sixteen pigs. Animals with normal and altered myocardial stiffness (acute myocardial infarction) were studied with and without preload alterations. Elastic modulus estimated from Vp (EVP; Moens-Korteweg equation) was compared to incremental elastic modulus obtained from exponential end -diastolic stress-strain relation (ESS). Myocardial distensibility and α-and β-coefficients of stress-strain relations were calculated. Results Vp was higher at reperfusion compared to baseline (2.6±1.3 m/s vs. 1.3±0.4 m/s; p=0.005) and best correlated with ESS (r 2=0.80, p<0.0001), β-coefficient (r2=0.78, p<0.0001), distensibility (r2=0.47, p=0.005), and wall thickness/diameter ratio (r2=0.42, p=0.009). Elastic moduli (EVP and ESS) were strongly correlated (r2=0.83, p<0.0001). Increasing preload increased Vp and EVP and decreased distensibility. At multivariate analysis, ESS, wall thickness, and end-diastolic and systolic LV pressures were independent predictors of Vp (r2model=0.83, p<0.0001). Conclusions The main determinants of wave propagation of longitudinal myocardial stretch were myocardial stiffness and LV geometry and pressure. This local wave speed could potentially be measured noninvasively by echocardiography. PMID:25193091

  2. Anterior ST depression with acute transmural inferior infarction due to posterior infarction. A vectorcardiographic and scintigraphic study

    SciTech Connect

    Mukharji, J.; Murray, S.; Lewis, S.E.; Croft, C.H.; Corbett, J.R.; Willerson, J.T.; Rude, R.E.

    1984-07-01

    The hypothesis that anterior ST segment depression represents concomitant posterior infarction was tested in 49 patients admitted with a first transmural inferior myocardial infarction. Anterior ST depression was defined as 0.1 mV or more ST depression in leads V1, V2 or V3 on an electrocardiogram recorded within 18 hours of infarction. Serial vectorcardiograms and technetium pyrophosphate scans were obtained. Eighty percent of the patients (39 of 49) had anterior ST depression. Of these 39 patients, 34% fulfilled vectorcardiographic criteria for posterior infarction, and 60% had pyrophosphate scanning evidence of posterior infarction. Early anterior ST depression was neither highly sensitive (84%) nor specific (20%) for the detection of posterior infarction as defined by pyrophosphate imaging. Of patients with persistent anterior ST depression (greater than 72 hours), 87% had posterior infarction detected by pyrophosphate scan. In patients with inferior myocardial infarction, vectorcardiographic evidence of posterior infarction correlated poorly with pyrophosphate imaging data. Right ventricular infarction was present on pyrophosphate imaging in 40% of patients with pyrophosphate changes of posterior infarction but without vectorcardiographic evidence of posterior infarction. It is concluded that: 1) the majority of patients with acute inferior myocardial infarction have anterior ST segment depression; 2) early anterior ST segment depression in such patients is not a specific marker for posterior infarction; and 3) standard vectorcardiographic criteria for transmural posterior infarction may be inaccurate in patients with concomitant transmural inferior myocardial infarction or right ventricular infarction, or both.

  3. Modification of aortic contractility in the cardiomyopathic hamster.

    PubMed Central

    Dumont, E. C.; Lambert, C.; Lamontagne, D.

    1996-01-01

    1. The functional arterial response in the cardiomyopathic hamster compared with inbred control, was investigated in thoracic aortae. For this purpose, vessels were cut into 6-mm rings and mounted in 20-ml organ baths. 2. In a first experimental series, the function of the endothelium was evaluated. Dose-response curves to acetylcholine (0.1 nM-10 microM) on phenylephrine (0.3 microM)-preconstricted rings of cardiomyopathic hamsters and inbred age-matched controls were comparable (log[EC50] of -7.08 +/- 0.12 and -7.18 +/- 0.12, respectively; n = 4). 3. Changes in contractility of cardiomyopathic hamster endothelium-denuded aortae were investigated. Dose-response curves to phenylephrine (1 nM-0.1 mM), angiotensin II (10 pM-0.3 microM), 5-hydroxytryptamine (5-HT) (1 nM-0.1 mM) and KCl (1 mM-0.1 M) were performed. Increased sensitivity in cardiomyopathic hamster aortae, compared to controls, was observed with phenylephrine (log[EC50] of -7.25 +/- 0.05 and -6.83 +/- 0.05, respectively, n = 6, P < 0.001) and angiotensin II (log[EC50] of -8.67 +/- 0.07 and -8.26 +/- 0.06, respectively, n = 6, P = 0.001) but not with 5-HT or KCl. A decreased maximum response in cardiomyopathic, compared to control, was observed with 5-HT (1.28 +/- 0.06 g vs 1.56 +/- 0.07 g, respectively, n = 6, P = 0.03). Comparable results were found in aortae with an intact endothelium. 4. No difference in the maximum contractile response to the G-protein activator, NaF (3, 10 and 30 mM) was observed in either group of animals. 5. Phorbol 12-myristate 13-acetate (PMA, 1-10 microM) was used to assess changes in the activity of protein kinase C (PKC). Contractility to PMA was increased in cardiomyopathic hamster aortae compared to controls (0.22 +/- 0.02 g vs 0.07 +/- 0.03 g at 3 microM, respectively, n = 6, P = 0.003). 6. Finally, cardiomyopathic hamsters aortae were found to be less sensitive when exposed to increasing concentrations of Ca2+ (10 microM-1 mM) in KCl-depolarized rings (0.58 +/- 0.04 g in

  4. Cortical actin regulation modulates vascular contractility and compliance in veins

    PubMed Central

    Saphirstein, Robert J; Gao, Yuan Z; Lin, Qian Qian; Morgan, Kathleen G

    2015-01-01

    Abstract The literature on arterial mechanics is extensive, but far less is known about mechanisms controlling mechanical properties of veins. We use here a multi-scale approach to identify subcellular sources of venous stiffness. Portal vein tissue displays a severalfold decrease in passive stiffness compared to aortic tissues. The α-adrenergic agonist phenylephrine (PE) increased tissue stress and stiffness, both attenuated by cytochalasin D (CytoD) and PP2, inhibitors of actin polymerization and Src activity, respectively. We quantify, for the first time, cortical cellular stiffness in freshly isolated contractile vascular smooth muscle cells using magnetic microneedle technology. Cortical stiffness is significantly increased by PE and CytoD inhibits this increase but, surprisingly, PP2 does not. No detectable change in focal adhesion size, measured by immunofluorescence of FAK and zyxin, accompanies the PE-induced changes in cortical stiffness. Probing with phospho-specific antibodies confirmed activation of FAK/Src and ERK pathways and caldesmon phosphorylation. Thus, venous tissue stiffness is regulated both at the level of the smooth muscle cell cortex, via cortical actin polymerization, and by downstream smooth muscle effectors of Src/ERK signalling pathways. These findings identify novel potential molecular targets for the modulation of venous capacitance and venous return in health and disease. Key points Most cardiovascular research focuses on arterial mechanisms of disease, largely ignoring venous mechanisms. Here we examine ex vivo venous stiffness, spanning tissue to molecular levels, using biomechanics and magnetic microneedle technology, and show for the first time that venous stiffness is regulated by a molecular actin switch within the vascular smooth muscle cell in the wall of the vein. This switch connects the contractile apparatus within the cell to adhesion structures and facilitates stiffening of the vessel wall, regulating blood flow return

  5. Non-invasive technology that improves cardiac function after experimental myocardial infarction: Whole Body Periodic Acceleration (pGz).

    PubMed

    Uryash, Arkady; Bassuk, Jorge; Kurlansky, Paul; Altamirano, Francisco; Lopez, Jose R; Adams, Jose A

    2015-01-01

    Myocardial infarction (MI) may produce significant inflammatory changes and adverse ventricular remodeling leading to heart failure and premature death. Pharmacologic, stem cell transplantation, and exercise have not halted the inexorable rise in the prevalence and great economic costs of heart failure despite extensive investigations of such treatments. New therapeutic modalities are needed. Whole Body Periodic Acceleration (pGz) is a non-invasive technology that increases pulsatile shear stress to the endothelium thereby producing several beneficial cardiovascular effects as demonstrated in animal models, normal humans and patients with heart disease. pGz upregulates endothelial derived nitric oxide synthase (eNOS) and its phosphorylation (p-eNOS) to improve myocardial function in models of myocardial stunning and preconditioning. Here we test whether pGz applied chronically after focal myocardial infarction in rats improves functional outcomes from MI. Focal MI was produced by left coronary artery ligation. One day after ligation animals were randomized to receive daily treatments of pGz for four weeks (MI-pGz) or serve as controls (MI-CONT), with an additional group as non-infarction controls (Sham). Echocardiograms and invasive pressure volume loop analysis were carried out. Infarct transmurality, myocardial fibrosis, and markers of inflammatory and anti-inflammatory cytokines were determined along with protein analysis of eNOS, p-eNOS and inducible nitric oxide synthase (iNOS).At four weeks, survival was 80% in MI-pGz vs 50% in MI-CONT (p< 0.01). Ejection fraction and fractional shortening and invasive pressure volume relation indices of afterload and contractility were significantly better in MI-pGz. The latter where associated with decreased infarct transmurality and decreased fibrosis along with increased eNOS, p-eNOS. Additionally, MI-pGz had significantly lower levels of iNOS, inflammatory cytokines (IL-6, TNF-α), and higher level of anti

  6. Non-Invasive Technology That Improves Cardiac Function after Experimental Myocardial Infarction: Whole Body Periodic Acceleration (pGz)

    PubMed Central

    Kurlansky, Paul; Altamirano, Francisco; Lopez, Jose R.

    2015-01-01

    Myocardial infarction (MI) may produce significant inflammatory changes and adverse ventricular remodeling leading to heart failure and premature death. Pharmacologic, stem cell transplantation, and exercise have not halted the inexorable rise in the prevalence and great economic costs of heart failure despite extensive investigations of such treatments. New therapeutic modalities are needed. Whole Body Periodic Acceleration (pGz) is a non-invasive technology that increases pulsatile shear stress to the endothelium thereby producing several beneficial cardiovascular effects as demonstrated in animal models, normal humans and patients with heart disease. pGz upregulates endothelial derived nitric oxide synthase (eNOS) and its phosphorylation (p-eNOS) to improve myocardial function in models of myocardial stunning and preconditioning. Here we test whether pGz applied chronically after focal myocardial infarction in rats improves functional outcomes from MI. Focal MI was produced by left coronary artery ligation. One day after ligation animals were randomized to receive daily treatments of pGz for four weeks (MI-pGz) or serve as controls (MI-CONT), with an additional group as non-infarction controls (Sham). Echocardiograms and invasive pressure volume loop analysis were carried out. Infarct transmurality, myocardial fibrosis, and markers of inflammatory and anti-inflammatory cytokines were determined along with protein analysis of eNOS, p-eNOS and inducible nitric oxide synthase (iNOS).At four weeks, survival was 80% in MI-pGz vs 50% in MI-CONT (p< 0.01). Ejection fraction and fractional shortening and invasive pressure volume relation indices of afterload and contractility were significantly better in MI-pGz. The latter where associated with decreased infarct transmurality and decreased fibrosis along with increased eNOS, p-eNOS. Additionally, MI-pGz had significantly lower levels of iNOS, inflammatory cytokines (IL-6, TNF-α), and higher level of anti

  7. [IMPROVING THE EFFICACY OF THERAPY FOR PATIENTS WITH MYOCARDIAL INFARCTION COMPLICATED BY CIRCULATORY FAILURE].

    PubMed

    Zhenilo, V M; Avsaragova, A Z; Astakhova, Z T

    2016-01-01

    The effectiveness of drug remaxol inclusion in the scheme of treatment of patients with myocardial infarction on the background of degree III - III acute cardiac insufficiency was evaluated by the analysis of clinical and laboratory data of 126 patients with newly diagnosed acute myocardial infarction including ST-segment elevation on the background of acute cardiac insufficiency. Depending on the regimen, patients were divided into two groups. The first (control) group included 60 patients who received conventional thrombolytic therapy; the second (main) group included 66 patients which, after thrombolytic therapy, received remaxol (single daily intravenous administration, 400 mL at 3 - 4 mL/min rate) with controlled central venous pressure, arterial pressure, and diuresis. The course lasted for 3 - 5 days, depending on the severity of condition. A high efficiency of the treatment regimen including remaxol was established as characterized by more rapid (in comparison to conventional therapy) stabilization of disturbed systemic hemodynamics and recovery of weakened myocardial contractility, decreased risk of cardiac arrhythmias, and relieved hyperhomocysteinemia that, in turn, reduced the risk of complications such as thrombosis and thromboembolism. PMID:27455573

  8. Sex-dependent effects of sleep deprivation on myocardial sensitivity to ischemic injury.

    PubMed

    Zoladz, Phillip R; Krivenko, Anna; Eisenmann, Eric D; Bui, Albert D; Seeley, Sarah L; Fry, Megan E; Johnson, Brandon L; Rorabaugh, Boyd R

    2016-01-01

    Sleep deprivation is associated with increased risk of myocardial infarction. However, it is unknown whether the effects of sleep deprivation are limited to increasing the likelihood of experiencing a myocardial infarction or if sleep deprivation also increases the extent of myocardial injury. In this study, rats were deprived of paradoxical sleep for 96 h using the platform-over-water method. Control rats were subjected to the same condition except the control platform was large enough for the rats to sleep. Hearts from sleep deprived and control rats were subjected to 20 min ischemia on a Langendorff isolated heart system. Infarct size and post ischemic recovery of contractile function were unaffected by sleep deprivation in male hearts. In contrast, hearts from sleep-deprived females exhibited significantly larger infarcts than hearts from control females. Post ischemic recovery of rate pressure product and + dP/dT were significantly attenuated by sleep deprivation in female hearts, and post ischemic recovery of end diastolic pressure was significantly elevated in hearts from sleep deprived females compared to control females, indicating that post ischemic recovery of both systolic and diastolic function were worsened by sleep deprivation. These data provide evidence that sleep deprivation increases the extent of ischemia-induced injury in a sex-dependent manner. PMID:26953626

  9. Myocardial Reloading after Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis

    SciTech Connect

    Kajimoto, Masaki; Priddy, Colleen M.; Ledee, Dolena; Xu, Chun; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-08-19

    Extracorporeal membrane oxygenation (ECMO) unloads the heart providing a bridge to recovery in children after myocardial stunning. Mortality after ECMO remains high.Cardiac substrate and amino acid requirements upon weaning are unknown and may impact recovery. We assessed the hypothesis that ventricular reloading modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Fourteen immature piglets (7.8-15.6 kg) were separated into 2 groups based on ventricular loading status: 8 hour-ECMO (UNLOAD) and post-wean from ECMO (RELOAD). We infused [2-13C]-pyruvate as an oxidative substrate and [13C6]-L-leucine, as a tracer of amino acid oxidation and protein synthesis into the coronary artery. RELOAD showed marked elevations in myocardial oxygen consumption above baseline and UNLOAD. Pyruvate uptake was markedly increased though RELOAD decreased pyruvate contribution to oxidative CAC metabolism.RELOAD also increased absolute concentrations of all CAC intermediates, while maintaining or increasing 13C-molar percent enrichment. RELOAD also significantly increased cardiac fractional protein synthesis rates by >70% over UNLOAD. Conclusions: RELOAD produced high energy metabolic requirement and rebound protein synthesis. Relative pyruvate decarboxylation decreased with RELOAD while promoting anaplerotic pyruvate carboxylation and amino acid incorporation into protein rather than to the CAC for oxidation. These perturbations may serve as therapeutic targets to improve contractile function after ECMO.

  10. Rate-pressure product and myocardial oxygen consumption during surgery for coronary artery bypass.

    PubMed

    Wilkinson, P L; Moyers, J R; Ports, T; Chatterjee, K; Ullyott, D; Hamilton, W K

    1979-08-01

    Rate-pressure product (RPP) is a sensitive index of myocardial oxygen consumption (mVO2) in awake people. We wished to determine whether this relationship persisted under anesthesia and in the face of concurrent large changes in myocardial contractility and left ventricular filling pressures. In 16 patients scheduled for coronary artery bypass surgery, we inserted coronary sinus and Swan-Ganz catheters, and a central aortic catheter via the brachial artery, before induction of anesthesia with either morphine (2 mg/kg) or halothane, chosen in random order. We measured aortic, pulmonary, and venous pressures, cardiac output, systolic time intervals, and thermodilution coronary sinus flow. We calculated mVO2 as coronary sinus flow times myocardial arteriovenous oxygen content difference. We found significant correlations between mVO2 and heart rate (r = 0.57), systolic blood pressure (r = 0.52), the index delta /delta T (r = 0.53, and RPP (r = 0.78). Multiple regression of RPP and delta P/delta T against mVO2 increased their correlation (r = 0.86), while multiple regression of RPP and pulmonary wedge pressure against mVo2 did not significantly improve the correlation of RPP alone (r = 0.75). We conclude that hemodynamic changes anesthesia and surgery do not decrease the sensitivity of RPP as an index of mVO2. PMID:312708

  11. Myocardial Function Improved by Electromagnetic Field Induction of Stress Protein hsp70

    PubMed Central

    George, Isaac; Geddis, Matthew S.; Lill, Zachary; Lin, Hana; Gomez, Teodoro; Blank, Martin; Oz, Mehmet C.; Goodman, Reba

    2011-01-01

    Studies on myocardial function have shown that hsp70, stimulated by an increase in temperature, leads to improved survival following ischemia reperfusion (I-R). Low frequency electromagnetic fields (EMF) also induce the stress protein hsp70, but without elevating temperature. We have examined the hemodynamic changes in concert with EMF preconditioning and the induction of hsp70 to determine whether improved myocardial function occurs following I-R injury in Sprague-Dawley rats. Animals were exposed to EMF (60Hz, 8µT) for 30 minutes prior to I-R. Ischemia was then induced by ligation of left anterior descending coronary artery (LAD) for 30 minutes, followed by 30 minutes of reperfusion. Blood and heart tissue levels for hsp70 taken at 10 minute intervals were determined by Western blot and RNA transcription by rtPCR. Significant upregulation of the HSP70 gene and increased hsp70 levels were measured in response to EMF pre-exposures. Invasive hemodynamics, as measured using a volume conductance catheter, demonstrated significant recovery of systolic contractile function after 30 minutes of reperfusion following EMF exposure. Additionally, isovolemic relaxation, a measure of ventricular diastolic function, was markedly improved in EMF-treated animals. In conclusion, noninvasive EMF induction of hsp70 preserved myocardial function and has the potential to improve tolerance to ischemic injury. PMID:18446816

  12. Myocardial Hypertrophy and Its Role in Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Heinzel, Frank R.; Hohendanner, Felix; Jin, Ge; Sedej, Simon; Edelmann, Frank

    2015-01-01

    Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load and cytokines associated with arterial hypertension, chronic kidney disease, diabetes and other co-morbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood but may include extracellular matrix changes, vascular dysfunction as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound co-morbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training on the other hand, in clinical trials improved exercise tolerance and diastolic function but did not reduce LVH. Thus, current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF. PMID:26183480

  13. Quantifying esophagogastric junction contractility with a novel HRM topographic metric, the EGJ-Contractile Integral: normative values and preliminary evaluation in PPI non-responders

    PubMed Central

    Nicodème, Frédéric; Pipa-Muniz, Maria; Khanna, Kern; Kahrilas, Peter J.; Pandolfino, John E.

    2015-01-01

    Background Despite its obvious pathophysiological relevance, the clinical utility of measures of esophagogastric junction (EGJ) contractility is unsubstantiated. High-resolution manometry (HRM) may improve upon this with its inherent ability to integrate the magnitude of contractility over time and length of the EGJ. This study aimed to develop a novel HRM metric summarizing EGJ contractility and test its ability distinguish among subgroups of proton pump inhibitor non-responders (PPI-NRs). Methods 75 normal controls and 88 PPI-NRs were studied. All underwent HRM. PPI-NRs underwent pH-impedance monitoring on PPI therapy scored in terms of acid exposure, number of reflux events, and reflux-symptom correlation and grouped as meeting All Criteria, Some Criteria, or No Criteria of abnormality. Control HRM studies were used to establish normal values for candidate EGJ contractility metrics, which were then compared in their ability to differentiate among PPI-NR subgroups. Results The EGJ contractile integral (EGJ-CI), a metric integrating contractility across the EGJ for three respiratory cycles, best distinguished the All Criteria PPI-NR subgroup from controls and other PPI-NR subgroups. Normal values (median, [IQR]) for this measure were 39 mmHg-cm [25–55 mmHg-cm]. The correlation between the EGJ-CI and a previously proposed metric, the lower esophageal sphincter-pressure integral, that used a fixed 10s time frame and an atmospheric as opposed to gastric pressure reference was weak. Conclusion Among HRM metrics tested, the EGJ-CI was best in distinguishing PPI-NRs meeting All Criteria of abnormality on pH-impedance testing. Future prospective studies are required to explore its utility in management of broader groups of GERD patients. PMID:24460814

  14. Effect of trimebutine maleate on the contractile response of the isolated ileum from diabetic rats.

    PubMed

    Uchida, M; Iwata, T; Takagi, S; Sugiyama, Y; Ishitani, K; Honda, H; Sakai, Y

    1994-05-01

    1. Tension of the isolated ileum from diabetic rats induced by streptozotocin was measured isometrically to study the mode of action of trimebutine maleate (TMB). 2. The hyperreactivity of contractile response to KCl was observed in the isolated ileum from diabetic rats. TMB inhibited the contraction induced by KCl and acetylcholine (ACh) in normal solution. 3. In Ca2+ free solution, the hyperreactivity of contractile response to KCl was attenuated, and TMB did not inhibit the contraction induced by KCl. In contrast, TMB inhibited the contraction induced by ACh even in Ca2+ free solution. 4. These results suggest that the hyperreactivity of contractile response to KCl in the ileum from diabetic rats is due to the enhancement of Ca2+ influx through voltage-dependent Ca2+ channel and that TMB inhibits the hyperreactivity of contractile response through the inhibition of Ca2+ movement by the cell. PMID:7926598

  15. CAD of myocardial perfusion

    NASA Astrophysics Data System (ADS)

    Storm, Corstiaan J.; Slump, Cornelis H.

    2007-03-01

    Our purpose is in the automated evaluation of the physiological relevance of lesions in coronary angiograms. We aim to extract as much as possible quantitative information about the physiological condition of the heart from standard angiographic image sequences. Coronary angiography is still the gold standard for evaluating and diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. The dimensions of the stenosis can be assessed nowadays successfully with image processing based Quantitative Coronary Angiography (QCA) techniques. Our purpose is to assess the clinical relevance of the pertinent stenosis. We therefore analyze the myocardial perfusion as revealed in standard angiographic image sequences. In a Region-of-Interest (ROI) on the angiogram (without an overlaying major blood vessel) the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In order to minimize motion artifacts we select based on the recorded ECG signal end-diastolic images in both a basal and a hyperemic run in the same projection to position the ROI. We present the development of the algorithms together with results of a small study of 20 patients which have been catheterized following the standard protocol.

  16. Experimental myocardial infarction

    PubMed Central

    Hood, William B.; Bianco, Jesus A.; Kumar, Raj; Whiting, Richard B.

    1970-01-01

    Compliance of the infarcted left ventricle was studied in dogs 3-5 days after occlusion of the left anterior descending coronary artery. Compliance was assessed from postmortem pressure-volume curves and from pressure-length measurements (mercury-in-silastic segment length gauges) made both in vivo and postmortem. Postmortem pressure-volume curves showed reduced compliance compared to sham-operated animals. Postmortem pressure-length curves of infarcted and adjacent normal myocardium indicated that the diminished total compliance could be attributed to an increase in stiffness of the infarcted area. This was confirmed by in vivo end-diastolic pressure-length changes produced by transient aortic occlusion. The infarcted area was akinetic, showing neither contraction nor aneurysmal bulging. In addition, anesthetized dogs with infarcts, when compared with sham-operated animals, had similar left ventricular end-diastolic volumes (indicator dilution method), but higher left ventricular end-diastolic pressures. Taken with previous observations, which show that systolic aneurysmal bulging is uniformly present at the onset of ischemia, these results indicate that stiffening of the ischemic myocardium occurs during the first 5 days after infarction, and show that elevation of left ventricular filling pressure does not necessarily signify ventricular dilatation. The results also suggest a mechanism whereby ventricular performance may improve during recovery from acute myocardial infarction. Images PMID:4914678

  17. Skeletal Muscle Phospholipid Metabolism Regulates Insulin Sensitivity and Contractile Function.

    PubMed

    Funai, Katsuhiko; Lodhi, Irfan J; Spears, Larry D; Yin, Li; Song, Haowei; Klein, Samuel; Semenkovich, Clay F

    2016-02-01

    Skeletal muscle insulin resistance is an early defect in the development of type 2 diabetes. Lipid overload induces insulin resistance in muscle and alters the composition of the sarcoplasmic reticulum (SR). To test the hypothesis that skeletal muscle phospholipid metabolism regulates systemic glucose metabolism, we perturbed choline/ethanolamine phosphotransferase 1 (CEPT1), the terminal enzyme in the Kennedy pathway of phospholipid synthesis. In C2C12 cells, CEPT1 knockdown altered SR phospholipid composition and calcium flux. In mice, diet-induced obesity, which decreases insulin sensitivity, increased muscle CEPT1 expression. In high-fat diet-fed mice with skeletal muscle-specific knockout of CEPT1, systemic and muscle-based approaches demonstrated increased muscle insulin sensitivity. In CEPT1-deficient muscles, an altered SR phospholipid milieu decreased sarco/endoplasmic reticulum Ca(2+) ATPase-dependent calcium uptake, activating calcium-signaling pathways known to improve insulin sensitivity. Altered muscle SR calcium handling also rendered these mice exercise intolerant. In obese humans, surgery-induced weight loss increased insulin sensitivity and decreased skeletal muscle CEPT1 protein. In obese humans spanning a spectrum of metabolic health, muscle CEPT1 mRNA was inversely correlated with insulin sensitivity. These results suggest that high-fat feeding and obesity induce CEPT1, which remodels the SR to preserve contractile function at the expense of insulin sensitivity. PMID:26512026

  18. Magnetically shaped cell aggregates: from granular to contractile materials.

    PubMed

    Frasca, G; Du, V; Bacri, J-C; Gazeau, F; Gay, C; Wilhelm, C

    2014-07-28

    In recent decades, significant advances have been made in the description and modelling of tissue morphogenesis. By contrast, the initial steps leading to the formation of a tissue structure, through cell-cell adhesion, have so far been described only for small numbers of interacting cells. Here, through the use of remote magnetic forces, we succeeded at creating cell aggregates of half million cells, instantaneously and for several cell types, not only those known to form spheroids. This magnetic compaction gives access to the cell elasticity, found in the range of 800 Pa. The magnetic force can be removed at any time, allowing the cell mass to evolve spontaneously thereafter. The dynamics of contraction of these cell aggregates just after their formation (or, in contrast, their spreading for non-interacting monocyte cells) provides direct information on cell-cell interactions and allows retrieving the adhesion energy, in between 0.05 and 2 mJ m(-2), depending on the cell type tested, and in the case of cohesive aggregates. Thus, we show, by probing a large number of cell types, that cell aggregates behave like complex materials, undergoing a transition from a wet granular to contractile network, and that this transition is controlled by cell-cell interactions. PMID:24710948

  19. Cannabinoid-induced actomyosin contractility shapes neuronal morphology and growth

    PubMed Central

    Roland, Alexandre B; Ricobaraza, Ana; Carrel, Damien; Jordan, Benjamin M; Rico, Felix; Simon, Anne; Humbert-Claude, Marie; Ferrier, Jeremy; McFadden, Maureen H; Scheuring, Simon; Lenkei, Zsolt

    2014-01-01

    Endocannabinoids are recently recognized regulators of brain development, but molecular effectors downstream of type-1 cannabinoid receptor (CB1R)-activation remain incompletely understood. We report atypical coupling of neuronal CB1Rs, after activation by endo- or exocannabinoids such as the marijuana component ∆9-tetrahydrocannabinol, to heterotrimeric G12/G13 proteins that triggers rapid and reversible non-muscle myosin II (NM II) dependent contraction of the actomyosin cytoskeleton, through a Rho-GTPase and Rho-associated kinase (ROCK). This induces rapid neuronal remodeling, such as retraction of neurites and axonal growth cones, elevated neuronal rigidity, and reshaping of somatodendritic morphology. Chronic pharmacological inhibition of NM II prevents cannabinoid-induced reduction of dendritic development in vitro and leads, similarly to blockade of endocannabinoid action, to excessive growth of corticofugal axons into the sub-ventricular zone in vivo. Our results suggest that CB1R can rapidly transform the neuronal cytoskeleton through actomyosin contractility, resulting in cellular remodeling events ultimately able to affect the brain architecture and wiring. DOI: http://dx.doi.org/10.7554/eLife.03159.001 PMID:25225054

  20. Coordination of contractility, adhesion and flow in migrating Physarum amoebae.

    PubMed

    Lewis, Owen L; Zhang, Shun; Guy, Robert D; del Álamo, Juan C

    2015-05-01

    This work examines the relationship between spatio-temporal coordination of intracellular flow and traction stress and the speed of amoeboid locomotion of microplasmodia of Physarum polycephalum. We simultaneously perform particle image velocimetry and traction stress microscopy to measure the velocity of cytoplasmic flow and the stresses applied to the substrate by migrating Physarum microamoebae. In parallel, we develop a mathematical model of a motile cell which includes forces from the viscous cytosol, a poro-elastic, contractile cytoskeleton and adhesive interactions with the substrate. Our experiments show that flow and traction stress exhibit back-to-front-directed waves with a distinct phase difference. The model demonstrates that the direction and speed of locomotion are determined by this coordination between contraction, flow and adhesion. Using the model, we identify forms of coordination that generate model predictions consistent with experiments. We demonstrate that this coordination produces near optimal migration speed and is insensitive to heterogeneity in substrate adhesiveness. While it is generally thought that amoeboid motility is robust to changes in extracellular geometry and the nature of extracellular adhesion, our results demonstrate that coordination of adhesive forces is essential to producing robust migration. PMID:25904525

  1. Coordination of contractility, adhesion and flow in migrating Physarum amoebae

    PubMed Central

    Lewis, Owen L.; Zhang, Shun; Guy, Robert D.; del Álamo, Juan C.

    2015-01-01

    This work examines the relationship between spatio-temporal coordination of intracellular flow and traction stress and the speed of amoeboid locomotion of microplasmodia of Physarum polycephalum. We simultaneously perform particle image velocimetry and traction stress microscopy to measure the velocity of cytoplasmic flow and the stresses applied to the substrate by migrating Physarum microamoebae. In parallel, we develop a mathematical model of a motile cell which includes forces from the viscous cytosol, a poro-elastic, contractile cytoskeleton and adhesive interactions with the substrate. Our experiments show that flow and traction stress exhibit back-to-front-directed waves with a distinct phase difference. The model demonstrates that the direction and speed of locomotion are determined by this coordination between contraction, flow and adhesion. Using the model, we identify forms of coordination that generate model predictions consistent with experiments. We demonstrate that this coordination produces near optimal migration speed and is insensitive to heterogeneity in substrate adhesiveness. While it is generally thought that amoeboid motility is robust to changes in extracellular geometry and the nature of extracellular adhesion, our results demonstrate that coordination of adhesive forces is essential to producing robust migration. PMID:25904525

  2. Aging changes agonist induced contractile responses in permeabilized rat bladder.

    PubMed

    Durlu-Kandilci, N Tugba; Denizalti, Merve; Sahin-Erdemli, Inci

    2015-08-01

    Aging alters bladder functions where a decrease in filling, storage and emptying is observed. These changes cause urinary incontinence, especially in women. The aim of this study is to examine how aging affects the intracellular calcium movements due to agonist-induced contractions in permeabilized female rat bladder. Urinary bladder isolated from young and old female Sprague-Dawley rats were used. Small detrusor strips were permeabilized with β-escin. The contractile responses induced with agonists were compared between young and old groups. Carbachol-induced contractions were decreased in permeabilized detrusor from old rats compared to young group. Heparin and ryanodine decreased carbachol-induced contractions in young rats where only heparin inhibited these contractions in olds. Caffeine-induced contractions but not inositol triphosphate (IP3)-induced contractions were decreased in old group compared to youngs. The cumulative calcium response curves (pCa 8-4) were also decreased in old rats. Carbachol-induced calcium sensitization responses did not alter by age where GTP-β-S and GF-109203X but not Y-27632 inhibited these responses. Carbachol-induced contractions decrease with aging in rat bladder detrusor. It can be postulated as IP3-induced calcium release (IICR) is primarily responsible for the contractions in older rats where the decrease in carbachol contractions in aging may be as a result of a decrease in calcium-induced calcium release (CICR), rather than carbachol-induced calcium sensitization. PMID:26153091

  3. Contractile Force of Human Extraocular Muscle: A Theoretical Analysis.

    PubMed

    Guo, Hongmei; Gao, Zhipeng; Chen, Weiyi

    2016-01-01

    Aim. The length-contractile force relationships of six human extraocular muscles (EOMs) in primary innervations should be determined during eye movement modeling and surgery of clinical EOMs. This study aims to investigate these relationships. Method. The proposal is based on the assumption that six EOMs have similar constitutive relationships, with the eye suspended in the primary position. The constitutive relationships of EOMs are obtained by optimizing from previous experimental data and the theory of mechanical equilibrium using traditional model. Further, simulate the existing experiment of resistance force, and then compare the simulated results with the existing experimental results. Finally, the mechanical constitutive relationships of EOMs are obtained. Results. The results show that the simulated resistance forces from the other four EOMs except for the horizontal recti well agree with previous experimental results. Conclusion. The mechanical constitutive relationships of six EOMs in primary innervations are obtained, and the rationality of the constitutive relationships is verified. Whereafter, the active stress-strain relationships of the six EOMs in the primary innervations are obtained. The research results can improve the eye movement model to predict the surgical amounts of EOMs before EOM surgery more precisely. PMID:27087774

  4. Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility

    PubMed Central

    Hoying, James B.; Deymier, Pierre A.; Zhang, Donna D.; Wong, Pak Kin

    2016-01-01

    A key feature of multicellular systems is the ability of cells to function collectively in response to external stimuli. However, the mechanisms of intercellular cell signaling and their functional implications in diverse vascular structures are poorly understood. Using a combination of computational modeling and plasma lithography micropatterning, we investigate the roles of structural arrangement of endothelial cells in collective calcium signaling and cell contractility. Under histamine stimulation, endothelial cells in self-assembled and microengineered networks, but not individual cells and monolayers, exhibit calcium oscillations. Micropatterning, pharmacological inhibition, and computational modeling reveal that the calcium oscillation depends on the number of neighboring cells coupled via gap junctional intercellular communication, providing a mechanistic basis of the architecture-dependent calcium signaling. Furthermore, the calcium oscillation attenuates the histamine-induced cytoskeletal reorganization and cell contraction, resulting in differential cell responses in an architecture-dependent manner. Taken together, our results suggest that endothelial cells can sense and respond to chemical stimuli according to the vascular architecture via collective calcium signaling. PMID:27196735

  5. Regulation of contractile vacuole formation and activity in Dictyostelium.

    PubMed

    Du, Fei; Edwards, Kimberly; Shen, Zhouxin; Sun, Binggang; De Lozanne, Arturo; Briggs, Steven; Firtel, Richard A

    2008-08-01

    The contractile vacuole (CV) system is the osmoregulatory organelle required for survival for many free-living cells under hypotonic conditions. We identified a new CV regulator, Disgorgin, a TBC-domain-containing protein, which translocates to the CV membrane at the late stage of CV charging and regulates CV-plasma membrane fusion and discharging. disgorgin(-) cells produce large CVs due to impaired CV-plasma membrane fusion. Disgorgin is a specific GAP for Rab8A-GTP, which also localizes to the CV and whose hydrolysis is required for discharging. We demonstrate that Drainin, a previously identified TBC-domain-containing protein, lies upstream from Disgorgin in this pathway. Unlike Disgorgin, Drainin lacks GAP activity but functions as a Rab11A effector. The BEACH family proteins LvsA and LvsD were identified in a suppressor/enhancer screen of the disgorgin(-) large CV phenotype and demonstrated to have distinct functions in regulating CV formation. Our studies help define the pathways controlling CV function. PMID:18636095

  6. Contractile vacuole complex--its expanding protein inventory.

    PubMed

    Plattner, Helmut

    2013-01-01

    The contractile vacuole complex (CVC) of some protists serves for the osmotic equilibration of water and ions, notably Ca(2+), by chemiosmotic exploitation of a H(+) gradient generated by the organelle-resident V-type H(+)-ATPase. Ca(2+) is mostly extruded, but there is also some reflux into the cytosol via Ca(2+)-release channels. Most data available are from Dictyostelium and Paramecium. In Paramecium, the major parts of CVC contain several v-/R-SNARE (synaptobrevins) and t-/Q-SNARE (syntaxins) proteins. This is complemented by Rab-type GTPases (shown in Tetrahymena) and exocyst components (Chlamydomonas). All this reflects a multitude of membrane interactions and fusion processes. Ca(2+)/H(+) and other exchangers are to be postulated, as are aquaporins and mechanosensitive Ca(2+) channels. From the complexity of the organelle, many more proteins may be expected. For instance, the pore is endowed with its own set of proteins. We may now envisage the regulation of membrane dynamics (reversible tubulation) and the epigenetic control of organelle shape, size and positioning. New aspects about organelle function and biogenesis are sketched in Section 7. The manifold regulators currently known from CVC suggest the cooperation of widely different mechanisms to maintain its dynamic function and to drive its biogenesis. PMID:24016530

  7. Modeling the dispersion effects of contractile fibers in smooth muscles

    NASA Astrophysics Data System (ADS)

    Murtada, Sae-Il; Kroon, Martin; Holzapfel, Gerhard A.

    2010-12-01

    Micro-structurally based models for smooth muscle contraction are crucial for a better understanding of pathological conditions such as atherosclerosis, incontinence and asthma. It is meaningful that models consider the underlying mechanical structure and the biochemical activation. Hence, a simple mechanochemical model is proposed that includes the dispersion of the orientation of smooth muscle myofilaments and that is capable to capture available experimental data on smooth muscle contraction. This allows a refined study of the effects of myofilament dispersion on the smooth muscle contraction. A classical biochemical model is used to describe the cross-bridge interactions with the thin filament in smooth muscles in which calcium-dependent myosin phosphorylation is the only regulatory mechanism. A novel mechanical model considers the dispersion of the contractile fiber orientations in smooth muscle cells by means of a strain-energy function in terms of one dispersion parameter. All model parameters have a biophysical meaning and may be estimated through comparisons with experimental data. The contraction of the middle layer of a carotid artery is studied numerically. Using a tube the relationships between the internal pressure and the stretches are investigated as functions of the dispersion parameter, which implies a strong influence of the orientation of smooth muscle myofilaments on the contraction response. It is straightforward to implement this model in a finite element code to better analyze more complex boundary-value problems.

  8. Structure of the Type VI secretion system contractile sheath

    PubMed Central

    Kudryashev, Mikhail; Wang, Ray Yu-Ruei; Brackmann, Maximilian; Scherer, Sebastian; Maier, Timm; Baker, David; DiMaio, Frank; Stahlberg, Henning; Egelman, Edward H.; Basler, Marek

    2015-01-01

    Summary Bacteria use rapid contraction of a long sheath of the Type VI secretion system (T6SS) to deliver effectors into a target cell. Here we present an atomic resolution structure of a native contracted Vibrio cholerae sheath determined by cryo-electron microscopy. The sheath subunits, composed of tightly interacting proteins VipA and VipB, assemble into a six-start helix. The helix is stabilized by a core domain assembled from four β-strands donated by one VipA and two VipB molecules. The fold of inner and middle layers is conserved between T6SS and phage sheaths. However, the structure of the outer layer is distinct and suggests a mechanism of interaction of the bacterial sheath with an accessory ATPase, ClpV, that facilitates multiple rounds of effector delivery. Our results provide a mechanistic insight into assembly of contractile nanomachines that bacteria and phages use to translocate macromolecules across membranes. PMID:25723169

  9. The actions of neurotensin in rat bladder detrusor contractility

    PubMed Central

    Dong, Xingyou; Bai, Xinyu; Zhao, Jiang; Wang, Liang; Wang, Qingqing; Li, Longkun

    2015-01-01

    This study assessed the expression, distribution and function of neurotensin (NTs) and two main neurotensin receptors (NTSR), NTSR1 and NTSR2 in normal rat urinary bladders. NTs is primarily located in the suburothelium and the interstitium of smooth muscle bundles. The NTSR1 and NTSR2 receptor subtypes are found to co-localize with smooth muscle cells (SMCs). NTs not only can directly act on bladder SMCs to induce intracellular calcium mobilization by activating the phospholipase C/inositol triphosphate (PLC/IP3) pathway, promoting extracellular calcium influx through a non-selective cation channels, but may be also involved in the modulation of the cholinergic system. Nowadays, the selective antimuscarinic drugs (solifenacin) and the selective beta 3-adrenergic agonist (mirabegron) are used as the first-line pharmacotherapy for overactive bladder (OAB), but without satisfactory treatment benefits in some patients. This study provided evidence suggesting that bladder NTs may play an important role in the regulation of micturition. Further research is needed to investigate the effects of NTs on bladder contractility and the underlying mechanism, which might reveal that the administration of NTSR antagonists can potentially relieve the symptoms of OAB by coordination with antimuscarinic pharmacotherapy. PMID:26053252

  10. Intravital imaging of intestinal lacteals unveils lipid drainage through contractility

    PubMed Central

    Choe, Kibaek; Jang, Jeon Yeob; Park, Intae; Kim, Yeseul; Ahn, Soyeon; Park, Dae-Young; Hong, Young-Kwon; Alitalo, Kari; Koh, Gou Young; Kim, Pilhan

    2015-01-01

    Lacteals are lymphatic vessels located at the center of each intestinal villus and provide essential transport routes for lipids and other lipophilic molecules. However, it is unclear how absorbed molecules are transported through the lacteal. Here, we used reporter mice that express GFP under the control of the lymphatic-specific promoter Prox1 and a custom-built confocal microscope and performed intravital real-time visualization of the absorption and transport dynamics of fluorescence-tagged fatty acids (FAs) and various exogenous molecules in the intestinal villi in vivo. These analyses clearly revealed transepithelial absorption of these molecules via enterocytes, diffusive distribution over the lamina propria, and subsequent transport through lacteals. Moreover, we observed active contraction of lacteals, which seemed to be directly involved in dietary lipid drainage. Our analysis revealed that the smooth muscles that surround each lacteal are responsible for contractile dynamics and that lacteal contraction is ultimately controlled by the autonomic nervous system. These results indicate that the lacteal is a unique organ-specific lymphatic system and does not merely serve as a passive conduit but as an active pump that transports lipids. Collectively, using this efficient imaging method, we uncovered drainage of absorbed molecules in small intestinal villus lacteals and the involvement of lacteal contractibility. PMID:26436648

  11. Intravital imaging of intestinal lacteals unveils lipid drainage through contractility.

    PubMed

    Choe, Kibaek; Jang, Jeon Yeob; Park, Intae; Kim, Yeseul; Ahn, Soyeon; Park, Dae-Young; Hong, Young-Kwon; Alitalo, Kari; Koh, Gou Young; Kim, Pilhan

    2015-11-01

    Lacteals are lymphatic vessels located at the center of each intestinal villus and provide essential transport routes for lipids and other lipophilic molecules. However, it is unclear how absorbed molecules are transported through the lacteal. Here, we used reporter mice that express GFP under the control of the lymphatic-specific promoter Prox1 and a custom-built confocal microscope and performed intravital real-time visualization of the absorption and transport dynamics of fluorescence-tagged fatty acids (FAs) and various exogenous molecules in the intestinal villi in vivo. These analyses clearly revealed transepithelial absorption of these molecules via enterocytes, diffusive distribution over the lamina propria, and subsequent transport through lacteals. Moreover, we observed active contraction of lacteals, which seemed to be directly involved in dietary lipid drainage. Our analysis revealed that the smooth muscles that surround each lacteal are responsible for contractile dynamics and that lacteal contraction is ultimately controlled by the autonomic nervous system. These results indicate that the lacteal is a unique organ-specific lymphatic system and does not merely serve as a passive conduit but as an active pump that transports lipids. Collectively, using this efficient imaging method, we uncovered drainage of absorbed molecules in small intestinal villus lacteals and the involvement of lacteal contractibility. PMID:26436648

  12. Contractile Force of Human Extraocular Muscle: A Theoretical Analysis

    PubMed Central

    Guo, Hongmei; Gao, Zhipeng; Chen, Weiyi

    2016-01-01

    Aim. The length-contractile force relationships of six human extraocular muscles (EOMs) in primary innervations should be determined during eye movement modeling and surgery of clinical EOMs. This study aims to investigate these relationships. Method. The proposal is based on the assumption that six EOMs have similar constitutive relationships, with the eye suspended in the primary position. The constitutive relationships of EOMs are obtained by optimizing from previous experimental data and the theory of mechanical equilibrium using traditional model. Further, simulate the existing experiment of resistance force, and then compare the simulated results with the existing experimental results. Finally, the mechanical constitutive relationships of EOMs are obtained. Results. The results show that the simulated resistance forces from the other four EOMs except for the horizontal recti well agree with previous experimental results. Conclusion. The mechanical constitutive relationships of six EOMs in primary innervations are obtained, and the rationality of the constitutive relationships is verified. Whereafter, the active stress-strain relationships of the six EOMs in the primary innervations are obtained. The research results can improve the eye movement model to predict the surgical amounts of EOMs before EOM surgery more precisely. PMID:27087774

  13. Considerations for Contractile Electroactive Polymeric Materials and Actuators

    SciTech Connect

    Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Charles; Bernasek, Stephen L.; Abelev, Esta

    2009-06-16

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

  14. [Transesophageal atrial stimulation--a test for myocardial ischemia].

    PubMed

    Jović, A; Nekić-Borcilo, M; Troskot, R; Nekić, D; Knezević, A; Rados, G

    1994-01-01

    The aim of the present study was to determine clinical value and the feasibility of transesophageal atrial pacing (TAP) in diagnosing myocardial ischemia in patients with coronary artery disease (CAD). Forty patients with CAD and with significant ST-segment depression in a standard 12-lead ECG during bicycle-stress testing underwent TAP. Rapid atrial stimulation was performed by using a very flexible six-polar polyurethane pacing lead introduced through the nares into the esophagus and connected to the stimulator allowing selection of rate, output voltage and pulse duration. The satisfactory atrial pacing was obtained by 28 +/- 6 V output and 7 +/- 1 ms pulse duration. Of 40 patients who underwent TAP, ischemic ECG changes were induced in 35 (u = 2,24 p < 0,05) and were very similar to those that occurred during bicycle-stress testing according to their intensity and distribution and affected ECG leads with comparable peak rate-pressure products. This suggests comparable sensitivity of TAP and bicycle-stress testing in discovering myocardial ischemia in CAD patients. Four patients had negative test for myocardial ischemia and in one TAP was discontinued because of intolerable chest discomfort. In conclusion, TAP is a reliable alternative technique for the assessment of coronary artery disease. In combination with some other noninvasive methods (echocardiography, scintigraphy, i.v. digital angiography), it has become a routine diagnostic procedure in cardiac patients. PMID:8028438

  15. Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis

    PubMed Central

    Maya, Lisandro; Villarreal, Francisco J.

    2009-01-01

    In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies is termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, it is imperative the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in cardiac function are typically manifested as abnormal diastolic function that with time leads to loss of contractile function. Echocardiography based methods currently stands as the preferred diagnostic approach for diabetic cardiomyopathy, due to its wide availability and economical use. In addition to conventional techniques, magnetic resonance imaging and spectroscopy along with contrast agents are now leading new approaches in the diagnosis of myocardial fibrosis, and cardiac and hepatic metabolic changes. These strategies can be complemented with serum biomarkers so they can offer a clear picture as to diabetes-induced changes in cardiac structure/function even at very early stages of the disease. This review article intends to provide a summary of experimental and routine tools currently available to diagnose diabetic cardiomyopathy induced changes in cardiac structure/function. These tools can be reliably used in either experimental models of diabetes or for clinical applications. PMID:19595694

  16. Cell contractility arising from topography and shear flow determines human mesenchymal stem cell fate

    PubMed Central

    Sonam, Surabhi; Sathe, Sharvari R.; Yim, Evelyn K.F.; Sheetz, Michael P.; Lim, Chwee Teck

    2016-01-01

    Extracellular matrix (ECM) of the human Mesenchymal Stem Cells (MSCs) influences intracellular tension and is known to regulate stem cell fate. However, little is known about the physiological conditions in the bone marrow, where external forces such as fluid shear stress, apart from the physical characteristics of the ECM, influence stem cell response. Here, we hypothesize that substrate topography and fluid shear stress alter the cellular contractile forces, influence the genetic expression of the stem cells and hence alter their lineage. When fluid shear stress was applied, human MSCs with higher contractility (seeded on 1 μm wells) underwent osteogenesis, whereas those with lower contractility (seeded on 2 μm gratings) remained multipotent. Compared to human MSCs seeded on gratings, those seeded on wells exhibited altered alignment and an increase in the area and number of focal adhesions. When actomyosin contractility was inhibited, human MSCs did not exhibit differentiation, regardless of the topographical feature they were being cultured on. We conclude that the stresses generated by the applied fluid flow impinge on cell contractility to drive the stem cell differentiation via the contractility of the stem cells. PMID:26879739

  17. A method to test contractility of the supraspinatus muscle in mouse, rat, and rabbit.

    PubMed

    Valencia, Ana P; Iyer, Shama R; Pratt, Stephen J P; Gilotra, Mohit N; Lovering, Richard M

    2016-02-01

    The rotator cuff (RTC) muscles not only generate movement but also provide important shoulder joint stability. RTC tears, particularly in the supraspinatus muscle, are a common clinical problem. Despite some biological healing after RTC repair, persistent problems include poor functional outcomes with high retear rates after surgical repair. Animal models allow further exploration of the sequela of RTC injury such as fibrosis, inflammation, and fatty infiltration, but there are few options regarding contractility for mouse, rat, and rabbit. Histological findings can provide a "direct measure" of damage, but the most comprehensive measure of the overall health of the muscle is contractile force. However, information regarding normal supraspinatus size and contractile function is scarce. Animal models provide the means to compare muscle histology, imaging, and contractility within individual muscles in various models of injury and disease, but to date, most testing of animal contractile force has been limited primarily to hindlimb muscles. Here, we describe an in vivo method to assess contractility of the supraspinatus muscle and describe differences in methods and representative outcomes for mouse, rat, and rabbit. PMID:26586911

  18. Asymmetric division of contractile domains couples cell positioning and fate specification.

    PubMed

    Maître, Jean-Léon; Turlier, Hervé; Illukkumbura, Rukshala; Eismann, Björn; Niwayama, Ritsuya; Nédélec, François; Hiiragi, Takashi

    2016-08-18

    During pre-implantation development, the mammalian embryo self-organizes into the blastocyst, which consists of an epithelial layer encapsulating the inner-cell mass (ICM) giving rise to all embryonic tissues. In mice, oriented cell division, apicobasal polarity and actomyosin contractility are thought to contribute to the formation of the ICM. However, how these processes work together remains unclear. Here we show that asymmetric segregation of the apical domain generates blastomeres with different contractilities, which triggers their sorting into inner and outer positions. Three-dimensional physical modelling of embryo morphogenesis reveals that cells internalize only when differences in surface contractility exceed a predictable threshold. We validate this prediction using biophysical measurements, and successfully redirect cell sorting within the developing blastocyst using maternal myosin (Myh9)-knockout chimaeric embryos. Finally, we find that loss of contractility causes blastomeres to show ICM-like markers, regardless of their position. In particular, contractility controls Yap subcellular localization, raising the possibility that mechanosensing occurs during blastocyst lineage specification. We conclude that contractility couples the positioning and fate specification of blastomeres. We propose that this ensures the robust self-organization of blastomeres into the blastocyst, which confers remarkable regulative capacities to mammalian embryos. PMID:27487217

  19. Thick Filament Length and Isoform Composition Determine Self-Organized Contractile Units in Actomyosin Bundles

    PubMed Central

    Thoresen, Todd; Lenz, Martin; Gardel, Margaret L.

    2013-01-01

    Diverse myosin II isoforms regulate contractility of actomyosin bundles in disparate physiological processes by variations in both motor mechanochemistry and the extent to which motors are clustered into thick filaments. Although the role of mechanochemistry is well appreciated, the extent to which thick filament length regulates actomyosin contractility is unknown. Here, we study the contractility of minimal actomyosin bundles formed in vitro by mixtures of F-actin and thick filaments of nonmuscle, smooth, and skeletal muscle myosin isoforms with varied length. Diverse myosin II isoforms guide the self-organization of distinct contractile units within in vitro bundles with shortening rates similar to those of in vivo myofibrils and stress fibers. The tendency to form contractile units increases with the thick filament length, resulting in a bundle shortening rate proportional to the length of constituent myosin thick filament. We develop a model that describes our data, providing a framework in which to understand how diverse myosin II isoforms regulate the contractile behaviors of disordered actomyosin bundles found in muscle and nonmuscle cells. These experiments provide insight into physiological processes that use dynamic regulation of thick filament length, such as smooth muscle contraction. PMID:23442916

  20. Active contractility and motor-driven effective interactions in a model cytoskeleton

    NASA Astrophysics Data System (ADS)

    Wang, Shenshen; Wolynes, Peter

    2013-03-01

    Contractile forces are essential for many developmental processes involving cell shape change and tissue deformation. Recent experiments on reconstituted actomyosin network, the major component of the contractile machinery, have shown that active contractility occurs above a threshold motor concentration and within a window of cross-link concentration. We present a microscopic dynamic model that incorporates two essential aspects of actomyosin self-organization: the asymmetric load response of individual actin filaments and the correlated motor-driven events mimicking myosin-induced filament sliding. Using computer simulations, we examine how the concentration and susceptibility of motors contribute to their collective behavior and interplay with the network connectivity to regulate macroscopic contractility. Our model is shown to capture the formation and dynamics of contractile structures and agree with the observed dependence of active contractility on microscopic parameters. We further provide a theoretical framework to investigate the intricate interplay between local force generation, network connectivity and collective action of molecular motors. This framework is capable of accommodating both regular and heterogeneous pattern formation, arrested coarsening and macroscopic contraction in a unified manner. This work is supported by NSF via Grant PHY-0822283 and the Bullard-Welch Chair at Rice University.

  1. Dual contractile effects of ATP released by field stimulation revealed by effects of alpha,beta-methylene ATP and suramin in rat tail artery.

    PubMed Central

    Bao, J. X.; Stjärne, L.

    1993-01-01

    1. The field stimulation-induced release of endogenous ATP and noradrenaline (NA) and contractile response in rat isolated tail artery were examined. The release of ATP was studied by extracellular electrophysiological recording and that of NA by a novel voltammetrical technique. The effects of the P2-purinceptor antagonist, suramin, on these parameters were compared with those of alpha,beta-methylene ATP, a P2X-purinoceptor desensitizing agent. 2. Neither alpha,beta-methylene ATP (10 microM) nor suramin (100-500 microM) had significant effects on the extracellularly recorded nerve terminal action potential but both abolished the ATP-induced excitatory junction current caused by stimulation at 0.1 Hz. Neither agent affected significantly the voltammetrically measured release of NA induced by 10 or 100 pulses at 20 Hz. 3. Combined blockade of both postjunctional alpha 1- and alpha 2-adrenoceptors by prazosin and yohimbine (both 0.1 microM) profoundly depressed the contractile response to 10 pulses at 20 Hz. The small and fast residual contraction in the presence of these agents was abolished by alpha,beta-methylene ATP (10 microM) and inhibited by suramin in a concentration-dependent manner (10-500 microM; IC50 75 microM) and was hence probably caused by ATP or a related nucleotide. 4. When added first, alpha,beta-methylene ATP (10 microM) or suramin (100-500 microM) delayed the onset and enhanced the amplitude of the neurogenic contraction. This enhanced response was abolished by further addition of prazosin and yohimbine (both 0.1 microM). 5. The K+ channel blocker, tetraethylammonium (10 mM), dramatically enhanced the contractile response to 100 pulses at 1 Hz and caused it to become diphasic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8306081

  2. How reliable is myocardial imaging in the diagnosis of acute myocardial infarction

    SciTech Connect

    Willerson, J.T.

    1983-01-01

    Myocardial scintigraphic techniques available presently allow a sensitive and relatively specific diagnosis of acute myocardial infarction when they are used correctly, although every technique has definite limitations. Small myocardial infarcts (less than 3 gm.) may be missed, and there are temporal limitations in the usefulness of the scintigraphic techniques. The development of tomographic methodology that may be used with single-photon radionuclide emitters (including technetium and /sup 201/Tl will allow the detection of relatively small abnormalities in myocardial perfusion and regions of myocardial infarction and will help to provide a more objective interpretation of the myocardial scintigrams. The use of overlay techniques allowing simultaneous assessment of myocardial perfusion, infarct-avid imaging, and radionuclide ventriculograms will provide insight into the relevant aspects of the extent of myocardial damage, the relationship of damage to myocardial perfusion, and the functional impact of myocardial infarction on ventricular performance.

  3. [Postpartum depression].

    PubMed

    Guo, S F

    1993-09-01

    A retrospective study was carried out in Beijing, China, in 1992. Edinburgh postnatal depression scale was used to inquire the mothers at 6-12 month after delivery. A total of 550 women were investigated by mailing. 425 women replied. The positive rate of PPD in our study was 17.9%. Women who had had a history of mood disorder before pregnancy had a higher risk of PPD. Social and psychological factors such as lacking support from the women's relatives, the poor marital relationship and the bad living condition shown to be significantly associated with postnatal depression. PPD can seriously affected the physical and mental health and well-being of women, her child's early education causing delayed development and her family causing a great deal of suffering, personal distress and marital troubles even causing divorce and suicide. Thus it is important to identify the high risk women and give treatment as early as possible. PMID:8313745

  4. Electrocardiograms corresponding to the development of myocardial infarction in anesthetized WHHLMI rabbits (Oryctolagus cuniculus), an animal model for familial hypercholesterolemia.

    PubMed

    Kobayashi, Tsutomu; Ito, Takashi; Yamada, Satoshi; Kuniyoshi, Nobue; Shiomi, Masashi

    2012-10-01

    The aim of this study was to determine whether features indicative of myocardial ischemia occur in the electrocardiograms (ECG) in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for human familial hypercholesterolemia. ECG were recorded in 110 anesthetized WHHLMI rabbits (age, 10 to 39 mo) by using unipolar and bipolar limb leads with or without chest leads. We noted the following electrocardiographic changes: T wave inversion (37.4%), ST segment depression (31.8%), deep Q wave (16.3%), reduced R wave amplitude (7.3%), ST segment elevation (2.7%), and high T wave (1.8%). These ECG changes resembled those in human patients with coronary heart disease. Histopathologic examination revealed that the left ventricular wall showed acute myocardial lesions, including loss of cross-striations, vacuolar degeneration, coagulation necrosis of cardiac myocytes, and edema between myofibrils, in addition to chronic myocardial lesions such as myocardial fibrosis. The coronary arteries that caused these ECG changes were severely stenosed due to atherosclerotic lesions. Ischemic ECG changes corresponded to the locations of the myocardial lesions. Normal ECG waveforms were similar between WHHLMI rabbits and humans, in contrast to the large differences between rabbits and mice or rats. In conclusion, ischemic ECG changes in WHHLMI rabbits reflect the location of myocardial lesions, making this model useful for studying coronary heart disease. PMID:23114045

  5. Recent advances in understanding cardiac contractility in health and disease.

    PubMed

    MacLeod, Ken T

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances. PMID:27508064

  6. Recent advances in understanding cardiac contractility in health and disease

    PubMed Central

    MacLeod, Ken T.

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances. PMID:27508064

  7. α-Actinin and fimbrin cooperate with myosin II to organize actomyosin bundles during contractile-ring assembly

    PubMed Central

    Laporte, Damien; Ojkic, Nikola; Vavylonis, Dimitrios; Wu, Jian-Qiu

    2012-01-01

    The actomyosin contractile ring assembles through the condensation of a broad band of nodes that forms at the cell equator in fission yeast cytokinesis. The condensation process depends on actin filaments that interconnect nodes. By mutating or titrating actin cross-linkers α-actinin Ain1 and fimbrin Fim1 in live cells, we reveal that both proteins are involved in node condensation. Ain1 and Fim1 stabilize the actin cytoskeleton and modulate node movement, which prevents nodes and linear structures from aggregating into clumps and allows normal ring formation. Our computer simulations modeling actin filaments as semiflexible polymers reproduce the experimental observations and provide a model of how actin cross-linkers work with other proteins to regulate actin-filament orientations inside actin bundles and organize the actin network. As predicted by the simulations, doubling myosin II Myo2 level rescues the node condensation defects caused by Ain1 overexpression. Taken together, our work supports a cooperative process of ring self-organization driven by the interaction between actin filaments and myosin II, which is progressively stabilized by the cross-linking proteins. PMID:22740629

  8. Ablation of Matrix Metalloproteinase-9 Prevents Cardiomyocytes Contractile Dysfunction in Diabetics

    PubMed Central

    Prathipati, Priyanka; Metreveli, Naira; Nandi, Shyam Sundar; Tyagi, Suresh C.; Mishra, Paras K.

    2016-01-01

    Elevated expression and activity of matrix metalloproteinase-9 (MMP9) and decreased contractility of cardiomyocytes are documented in diabetic hearts. However, it is unclear whether MMP is involved in the regulation of contractility of cardiomyocytes in diabetic hearts. In the present study, we tested the hypothesis that MMP9 regulates contractility of cardiomyocytes in diabetic hearts, and ablation of MMP9 prevents impaired contractility of cardiomyocytes in diabetic hearts. To determine the specific role of MMP9 in cardiomyocyte contractility, we used 12–14 week male WT (normoglycemic sibling of Akita), Akita, and Ins2+∕−/MMP9−∕− (DKO) mice. DKO mice were generated by cross-breeding male Ins2+∕− Akita (T1D) with female MMP9 knockout (MMP9−∕−) mice. We isolated cardiomyocytes from the heart of the above three groups of mice and measured their contractility and calcium transients. Moreover, we determined mRNA and protein levels of sarco-endoplasmic reticulum calcium ATPase-2a (SERCA-2a), which is involved in calcium handling during contractility of cardiomyocytes in WT, Akita, and DKO hearts using QPCR, Western blotting and immunoprecipitation, respectively. Our results revealed that in Akita hearts where increased expression and activity of MMP9 is reported, the rates of shortening and re-lengthening (±dL/dt) of cardiomyocytes were decreased, time to 90% peak height and baseline during contractility was increased, rate of calcium decay was increased, and calcium transient was decreased as compared to WT cardiomyocytes. However, these changes in Akita were blunted in DKO cardiomyocytes. The molecular analyses of SERCA-2a in the hearts showed that it was downregulated in Akita as compared to WT but was comparatively upregulated in DKO. These results suggest that abrogation of MMP9 gene prevents contractility of cardiomyocytes, possibly by increasing SERCA-2a and calcium transients. We conclude that MMP9 plays a crucial role in the regulation

  9. Association between Anger and Mental Stress-Induced Myocardial Ischemia

    PubMed Central

    Pimple, Pratik; Shah, Amit; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon; Ibeanu, Ijeoma; Murrah, Nancy; Shallenberger, Lucy; Kelley, Mary; Raggi, Paolo; Vaccarino, Viola

    2014-01-01

    Background Mental stress-induced myocardial ischemia is associated with adverse prognosis in coronary artery disease patients. Anger is thought to be a trigger of acute coronary syndromes and is associated with increased cardiovascular risk; however, little direct evidence exists for a link between anger and myocardial ischemia. Methods [99mTc]sestamibi single-photon emission tomography was performed at rest, after mental stress (a social stressor with a speech task), and after exercise/pharmacological stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed difference score, the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. The Spielberger's State-Trait Anger Expression Inventory was used to assess different anger dimensions. Results The mean age was 50 years, 50% were female and 60% were non-white. After adjusting for demographic factors, smoking, coronary artery disease severity, depressive and anxiety symptoms, each interquartile range increment in state-anger score was associated with 0.36 units adjusted increase in ischemia as measured by the summed difference score (95% CI: 0.14-0.59); the corresponding association for trait-anger was 0.95 (95% CI: 0.21-1.69). Anger expression scales were not associated ischemia. None of the anger dimensions were related to ischemia during exercise/pharmacological stress. Conclusion Anger, both as an emotional state and as a personality trait, is significantly associated with propensity to develop myocardial ischemia during mental stress, but not during exercise/pharmacological stress. Patients with this psychological profile may be at increased risk for silent ischemia induced by emotional stress and this may translate into worse prognosis. PMID:25497256

  10. Effect of trimetazidine on early and delayed doxorubicin myocardial toxicity.

    PubMed

    Perletti, G; Monti, E; Paracchini, L; Piccinini, F

    1989-01-01

    The influence of the administration of trimetazidine on the myocardial toxicity induced by doxorubicin was studied on an in vivo model in the rat. Trimetazidine was chosen due to its ability to act as a scavenger of oxygen-derived free radicals, which have been implicated in both early and delayed cardiotoxic manifestations after doxorubicin treatment. In the present study, doxorubicin was administered as 4 weekly i.v. injections of 3 mg/kg. The cardiotoxic effects were evaluated by measuring predictive ECG parameters (QT and ST intervals) as well as the contractile performance of atria isolated from treated animals. Heart preparations were also examined by light microscopy. Trimetazidine, 2.5 mg/kg/day i.p. for 3 days before doxorubicin administration plus 2.5 mg/kg/day p.o. for 10 weeks, was unable to prevent the development of doxorubicin-induced long-term cardiotoxicity. However, a significant improvement of the early cardiotoxic signs was observed in trimetazidine-treated rats, as reported in previous investigations. The present findings suggest that different target structures may be involved in the early and delayed free radical-mediated effects of doxorubicin. PMID:2636823

  11. Myocardial infarction following bee sting.

    PubMed

    Puvanalingam, A; Karpagam, P; Sundar, C; Venkatesan, S; Ragunanthanan

    2014-08-01

    Bee stings are commonly encountered worldwide. Various manifestations after bee sting have been described. Local reactions are common. Unusually, manifestations like vomiting, diarrhoea, dyspnoea, generalised oedema, acute renal failure, hypotension and collapse may occur. Rarely vasculitis, serum sickness, neuritis and encephalitis have been described which generally develop days to weeks after a sting. Acute coronary syndromes after hymenoptera stings and other environmental exposures are referred to as the Kounis syndrome or allergic myocardial ischaemia and infarction. We report a 60 year old male who developed myocardial infarction after multiple bee stings over his body. PMID:25856951

  12. Prognostic significance of ST-T segment alterations in patients with non-Q wave myocardial infarction.

    PubMed Central

    Ramires, J. A.; Serrano, C. V.; Solimene, M. C.; Moffa, P. J.; Caramelli, B.; Pileggi, F.

    1996-01-01

    OBJECTIVE: To determine whether, among patients with non-Q wave myocardial infarction, the characteristics of the segment ST-T shifts at presentation in the diagnostic electrocardiogram can identify those with more severe coronary artery disease and predict a poor clinical outcome. DESIGN: Prospective controlled clinical trial. SETTING: Primary referral medical centre. PATIENTS: 93 patients (mean (SD) 62.0 (7.5) years) were studied: 41 with non-Q wave myocardial infarction and T wave inversion and 52 with ST segment depression. Cardiac events and mortality rates were assessed over 42 months. Age, sex, risk factors, creatinine kinase MB isoenzyme peak, and left ventricular function were comparable. RESULTS: 31 patients with T wave inversion myocardial infarction (94.6%) had total occlusion of the infarct related artery, compared with 12 patients with ST segment depression myocardial infarction (26.7%) (P < 0.05). When compared with patients with T wave inversion, patients with ST segment depression had a higher incidence of cardiac events during the first month and in the 41 subsequent months: 9.6% and 30.8% v 0% (P < 0.01) and 9.8% (P < 0.02), respectively. For the same observation periods, the mortality rates in patients with T wave inversion were 4.9% and 7.3%, and in patients with ST segment depression they were 5.8% and 9.6%, respectively. CONCLUSION: These data suggest that during a non-Q wave myocardial infarction the presence of ST segment depression is related to higher rates of short and long term cardiac events when compared with T wave inversion--possibly because of a higher incidence of residual stenosis of the infarct related artery. PMID:8697161

  13. Decreases in Electrocardiographic R-Wave Amplitude and QT Interval Predict Myocardial Ischemic Infarction in Rhesus Monkeys with Left Anterior Descending Artery Ligation

    PubMed Central

    Han, Pengfei; Xie, Yuping; Chen, Jianmin; Xiao, Ying; Kang, Y. James

    2013-01-01

    Clinical studies have demonstrated the predictive values of changes in electrocardiographic (ECG) parameters for the preexisting myocardial ischemic infarction. However, a simple and early predictor for the subsequent development of myocardial infarction during the ischemic phase is of significant value for the identification of ischemic patients at high risk. The present study was undertaken by using non-human primate model of myocardial ischemic infarction to fulfill this gap. Twenty male Rhesus monkeys at age of 2–3 years old were subjected to left anterior descending artery ligation. This ligation was performed at varying position along the artery so that it produced varying sizes of myocardial infarction at the late stage. The ECG recording was undertaken before the surgical procedure, at 2 h after the ligation, and 8 weeks after the surgery for each animal. The correlation of the changes in the ECG waves in the early or the late stage with the myocardial infarction size was analyzed. The R wave depression and the QT shortening in the early ischemic stage were found to have an inverse correlation with the myocardial infarction size. At the late stage, the R wave depression, the QT prolongation, the QRS score, and the ST segment elevation were all closely correlated with the developed infarction size. The poor R wave progression was identified at both the early ischemic and the late infarction stages. Therefore, the present study using non-human primate model of myocardial ischemic infarction identified the decreases in the R wave and the QT interval as early predictors of myocardial infarction. Validation of these parameters in clinical studies would greatly help identifying patients with myocardial ischemia at high risk for the subsequent development of myocardial infarction. PMID:23967258

  14. Muscle fatigue in frog semitendinosus: alterations in contractile function.

    PubMed

    Thompson, L V; Balog, E M; Riley, D A; Fitts, R H

    1992-06-01

    The purpose of this study was to characterize the contractile properties of the frog semitendinosus (ST) muscle before and during recovery from fatigue, to relate the observed functional changes to alterations in specific steps in the crossbridge model of muscle contraction, and to determine how fatigue affects the force-frequency relationship. The frog ST (22 degrees C) was fatigued by direct electrical stimulation with 100-ms 150-Hz trains at 1/s for 5 min. The fatigue protocol reduced peak twitch (Pt) and tetanic (Po) force to 32 and 8.5% of initial force, respectively. The decline in Pt was less than Po, in part due to a prolongation in the isometric contraction time (CT), which increased to 300% of the initial value. The isometric twitch duration was greatly prolonged as reflected by the lengthened CT and the 800% increase in the one-half relaxation time (1/2RT). Both Pt and Po showed a biphasic recovery, a rapid initial phase (2 min) followed by a slower (40 min) return to the prefatigue force. CT and 1/2RT also recovered in two phases, returning to 160 and 265% of control in the first 5 min. CT returned to the prefatigue value between 35 and 40 min, whereas even at 60 min 1/2RT was 133% of control. The maximal velocity of shortening, determined by the slack test, was significantly reduced [from 6.7 +/- 0.5 to 2.5 +/- 0.4 optimal muscle length/s] at fatigue. The force-frequency relationship was shifted to the left, so that optimal frequency for generating Po was reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1535482

  15. Muscle fatigue in frog semitendinosus: alterations in contractile function

    NASA Technical Reports Server (NTRS)

    Thompson, L. V.; Balog, E. M.; Riley, D. A.; Fitts, R. H.

    1992-01-01

    The purpose of this study was to characterize the contractile properties of the frog semitendinosus (ST) muscle before and during recovery from fatigue, to relate the observed functional changes to alterations in specific steps in the crossbridge model of muscle contraction, and to determine how fatigue affects the force-frequency relationship. The frog ST (22 degrees C) was fatigued by direct electrical stimulation with 100-ms 150-Hz trains at 1/s for 5 min. The fatigue protocol reduced peak twitch (Pt) and tetanic (Po) force to 32 and 8.5% of initial force, respectively. The decline in Pt was less than Po, in part due to a prolongation in the isometric contraction time (CT), which increased to 300% of the initial value. The isometric twitch duration was greatly prolonged as reflected by the lengthened CT and the 800% increase in the one-half relaxation time (1/2RT). Both Pt and Po showed a biphasic recovery, a rapid initial phase (2 min) followed by a slower (40 min) return to the prefatigue force. CT and 1/2RT also recovered in two phases, returning to 160 and 265% of control in the first 5 min. CT returned to the prefatigue value between 35 and 40 min, whereas even at 60 min 1/2RT was 133% of control. The maximal velocity of shortening, determined by the slack test, was significantly reduced [from 6.7 +/- 0.5 to 2.5 +/- 0.4 optimal muscle length/s] at fatigue. The force-frequency relationship was shifted to the left, so that optimal frequency for generating Po was reduced.(ABSTRACT TRUNCATED AT 250 WORDS).

  16. Purinergic and cholinergic components of bladder contractility and flow.

    PubMed

    Theobald, R J

    1995-01-01

    The role of ATP as a neurotransmitter/neuromodulator in the urinary tract has been the subject of much study, particularly whether ATP has a functional role in producing urine flow. Recent studies suggested significant species variation, specifically a variation between cat and other species. This study was performed to determine the in vivo response of cat urinary bladder to pelvic nerve stimulation (PNS) and to the exogenous administration of cholinergic and purinergic agents. In anesthetized cats, bladder contractions and fluid expulsion was measured in response to PNS and to the exogenous administration of cholinergic and purinergic agents. Fluid was instilled into the bladder and any fluid expelled by bladder contractions induced by PNS or exogenous agents was collected in a beaker. The volume was measured in a graduated cylinder and recorded. PNS, carbachol and APPCP produced sustained contractions with significant expulsion of fluid. ATP, ACh and hypogastric nerve stimulation did not produce any significant expulsion of fluid. Atropine, a cholinergic antagonist, inhibited PNS contractions and fluid expulsion with no effect on purinergic actions. There was a significant relationship between the magnitude of the contraction, duration of the contractions and volume of fluid expelled. The data and information from other studies, strongly suggests a functional role for ATP as a cotransmitter in the lower urinary tract different from ACh's role. ATP stimulation of a specific purinergic receptor plays a role in initiation of bladder contractions and perhaps in the initiation of urine flow from the bladder. ACh's role is functionally different and appears to be more involved in maintenance of contractile activity and flow. PMID:7830505

  17. The effect of heat stress on skeletal muscle contractile properties.

    PubMed

    Locke, Marius; Celotti, Carlo

    2014-07-01

    An elevated heat-shock protein (HSP) content protects cells and tissues, including skeletal muscles, from certain stressors. We determined if heat stress and the elevated HSP content that results is correlated with protection of contractile characteristics of isolated fast and slow skeletal muscles when contracting at elevated temperatures. To elevate muscle HSP content, one hindlimb of Sprague-Dawley rats (21-28 days old, 70-90 g) was subjected to a 15 min 42 °C heat-stress. Twenty-four hours later, both extensor digitorum longus (EDL) and soleus muscles were removed, mounted in either 20 °C or 42 °C Krebs-Ringer solution, and electrically stimulated. Controls consisted of the same muscles from the contra-lateral (non-stressed) hindlimbs as well as muscles from other (unstressed) animals. Isolated muscles were twitched and brought to tetanus every 5 min for 30 min. As expected, HSP content was elevated in muscles from the heat-stressed limbs when compared with controls. Regardless of prior treatment, both EDL and soleus twitch tensions were lower at 42 °C when compared with 20 °C. In addition, when incubated at 42 °C, both muscles showed a drop in twitch tension between 5 and 30 min. For tetanic tension, both muscles also showed an increase in tension between 5 and 30 min when stimulated at 20 °C regardless of treatment but when stimulated at 42 °C no change was observed. No protective effect of an elevated HSP content was observed for either muscle. In conclusion, although heat stress caused an elevation in HSP content, no protective effects were conferred to isolated contracting muscles. PMID:24264930

  18. Myocardial dysfunction in endotoxin- and E. coli-induced shock: pathophysiological mechanisms.

    PubMed

    Archer, L T

    1985-01-01

    Experimental studies have documented that myocardial dysfunction is precipitated between 3 and 6 hr after endotoxin or E. coli. This finding has now been confirmed in human septic shock. A "Hinshaw-modified" isolated working left ventricle preparation has been used to document and assess the degree of failure. It was found that the failure is often severe and reversible only temporarily by adrenergic agents but reversible by digoxin or insulin. The cause of the failure has not been identified, but evidence is presented against a myocardial depressant factor (MDF) being the causative factor. Hearts subjected to a 2-4 hr period of hypotension on the threshold of failure show no signs of failure when subjected to blood circulating from an animal in splanchnic arterial occlusion shock. Hearts from pancreatectomized animals subjected to endotoxin shock with their source of MDF removed demonstrate the typical failure in 4-6 hr. Other factors are suggested that contribute to myocardial dysfunction: hypotension or nonuniform perfusion of subendocardial regions of the heart, depressed responsiveness to inotropic and chronotropic stimuli, intracardiac ionic and fluid disturbances, and increases in heart chamber and muscle stiffness. Since steroid/antibiotic therapy increases the probability (p less than 0.05) that an animal will survive lethal sepsis, investigating the effect of this therapy on myocardial function may aid in determining whether or not this degree of heart failure contributes in the animal to irreversible shock and death. PMID:3888434

  19. Thallium-201 myocardial scintigraphy in acute myocardial infarction and ischemia

    SciTech Connect

    Wackers, F.J.

    1982-04-01

    Thallium-201 scintigraphy provides a sensitive and reliable method of detecting acute myocardial infarction and ischemia when imaging is performed with understanding of the temporal characteristics and accuracy of the technique. The results of scintigraphy are related to the time interval between onset of symptoms and time of imaging. During the first 6 hr after chest pain almost all patients with acute myocardial infarction and approximately 50% of the patients with unstable angina will demonstrate /sup 201/TI pefusion defects. Delayed imaging at 2-4 hr will permit distinction between ischemia and infarction. In patients with acute myocardial infarction, the size of the perfusion defect accurately reflects the extent of the infarcted and/or jeopardized myocardium, which may be used for prognostic stratification. In view of the characteristics of /sup 201/TI scintigraphy, the most practical application of this technique is in patients in whom myocardial infarction has to be ruled out, and for early recognition of patients at high risk for complications.

  20. Depression: What We Know.

    ERIC Educational Resources Information Center

    Lobel, Brana; Hirschfeld, Robert M. A.

    This booklet is concerned with the area of clinical depression. Questions about clinical depression are briefly answered in an overview section and are examined in greater detail in the five chapters that follow. In chapter 1, depression is defined and various types of depression are identified. The origins of depression are explored in the second…

  1. Modulation of myocardial injury and collagen deposition following ischaemia-reperfusion by linagliptin and liraglutide, and both together.

    PubMed

    Wang, Xianwei; Ding, Zufeng; Yang, Fen; Dai, Yao; Chen, Peng; Theus, Sue; Singh, Sharda; Budhiraja, Madhu; Mehta, Jawahar L

    2016-08-01

    Studies have indicated that dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists reduce infarct size after myocardial ischaemia. Whether these agents modify cardiac remodelling after ischaemia is unclear. Furthermore, it is not known if combination of the two types of drugs is superior to either agent alone. We investigated the modulatory effect of the DPP-4 inhibitor linagliptin alone, the GLP-1 activator liraglutide alone, or the two agents together on myocardial infarct size, left ventricular contractile function and cardiac remodelling signals after a brief period of left coronary artery (LCA) occlusion. C57BL/6 mice were treated with vehicle, the DPP-4 inhibitor linagliptin, the GLP-1 activator liraglutide, or both agents together for 5 days, and then subjected to LCA occlusion (1 h) and reperfusion (3 h). Ischaemia-reperfusion increased reactive oxygen species (ROS) generation and expression of NADPH oxidase (p47(phox), p22(phox) and gp91(phox) subtypes), collagens, fibronectin and proinflammatory cytokines (interleukin 6, tumour necrosis factor α and monocyte chemoattractant protein-1) in the LCA-supplied regions. Pre-treatment with linagliptin or liraglutide reduced infarct size, protected cardiomyocytes from injury and preserved cardiac contractile function in a similar fashion. It is interesting that profibrotic (collagen deposition) signals were expressed soon after ischaemia-reperfusion. Both linagliptin and liraglutide suppressed ROS generation, NADPH oxidase and proinflammatory signals, and reduced collagen deposition. Addition of linagliptin or liraglutide had no significant additive effect above and beyond that of liraglutide and linagliptin given alone. In conclusion, linagliptin and liraglutide can improve cardiac contractile function and indices of cardiac remodelling, which may be related to their role in inhibition of ROS production and proinflammatory cytokines after ischaemia. PMID:27129181

  2. Nutritional Interventions in Depression and Perinatal Depression

    PubMed Central

    Rechenberg, Kaitlyn; Humphries, Debbie

    2013-01-01

    Depression is the leading cause of mental disability worldwide. Women who are depressed during pregnancy are at a higher risk for preterm delivery, preeclampsia, birth difficulties, and postpartum depression. The treatment of depression in conventional medicine has focused on physiological factors that lead to impaired neurotransmitter function and treatments to improve neurotransmitter function. Pharmaceutical substances pose risks for pregnant and lactating women, and lower risk options are preferred. Micronutrients, including certain B vitamins, folate, and docosahexaenoic acid (DHA), play a role in the synthesis and absorption of neurotransmitters. Experimental studies suggest that supplementation with specific micronutrients may alleviate depressive symptoms and improve birth outcomes in patients with perinatal depression. Alternative treatments for depression, including nutritional supplements, are an important treatment option for depressive symptoms while limiting potential side effects and treatment costs. This article explores the biological basis of perinatal depression and reviews the potential benefits of non-pharmacological interventions. PMID:23766734

  3. Spontaneous Formation of a Globally Connected Contractile Network in a Microtubule-Motor System.

    PubMed

    Torisawa, Takayuki; Taniguchi, Daisuke; Ishihara, Shuji; Oiwa, Kazuhiro

    2016-07-26

    Microtubule (MT) networks play key roles in cell division, intracellular transport, and cell motility. These functions of MT networks occur through interactions between MTs and various associated proteins, notably motor proteins that bundle and slide MTs. Our objective in this study was to address the question of how motors determine the nature of MT networks. We conducted in vitro assays using homotetrameric kinesin Eg5, a motor protein involved in the formation and maintenance of the mitotic spindle. The mixing of Eg5 and MTs produced a range of spatiotemporal dynamics depending on the motor/filament ratio. Low motor/filament ratios produced globally connected static MT networks with sparsely distributed contractile active nodes (motor-accumulating points with radially extending MTs). Increasing the motor/filament ratio facilitated the linking of contractile active nodes and led to a global contraction of the network. When the motor/filament ratio was further increased, densely distributed active nodes formed local clusters and segmented the network into pieces with their strong contractile forces. Altering the properties of the motor through the use of chimeric Eg5, which has kinesin-1 heads, resulted in the generation of many isolated asters. These results suggest that the spatial distribution of contractile active nodes determines the dynamics of MT-motor networks. We then developed a coarse-grained model of MT-motor networks and identified two essential features for reproducing the experimentally observed patterns: an accumulation of motors that form the active nodes necessary to generate contractile forces, and a nonlinear dependency of contractile force on motor densities. Our model also enabled us to characterize the mechanical properties of the contractile network. Our study provides insight into how local motor-MT interactions generate the spatiotemporal dynamics of macroscopic network structures. PMID:27463139

  4. Stable, Covalent Attachment of Laminin to Microposts Improves the Contractility of Mouse Neonatal Cardiomyocytes

    PubMed Central

    2015-01-01

    The mechanical output of contracting cardiomyocytes, the muscle cells of the heart, relates to healthy and disease states of the heart. Culturing cardiomyocytes on arrays of elastomeric microposts can enable inexpensive and high-throughput studies of heart disease at the single-cell level. However, cardiomyocytes weakly adhere to these microposts, which limits the possibility of using biomechanical assays of single cardiomyocytes to study heart disease. We hypothesized that a stable covalent attachment of laminin to the surface of microposts improves cardiomyocyte contractility. We cultured cells on polydimethylsiloxane microposts with laminin covalently bonded with the organosilanes 3-glycidoxypropyltrimethoxysilane and 3-aminopropyltriethoxysilane with glutaraldehyde. We measured displacement of microposts induced by the contractility of mouse neonatal cardiomyocytes, which attach better than mature cardiomyocytes to substrates. We observed time-dependent changes in contractile parameters such as micropost deformation, contractility rates, contraction and relaxation speeds, and the times of contractions. These parameters were affected by the density of laminin on microposts and by the stability of laminin binding to micropost surfaces. Organosilane-mediated binding resulted in higher laminin surface density and laminin binding stability. 3-glycidoxypropyltrimethoxysilane provided the highest laminin density but did not provide stable protein binding with time. Higher surface protein binding stability and strength were observed with 3-aminopropyltriethoxysilane with glutaraldehyde. In cultured cardiomyocytes, contractility rate, contraction speeds, and contraction time increased with higher laminin stability. Given these variations in contractile function, we conclude that binding of laminin to microposts via 3-aminopropyltriethoxysilane with glutaraldehyde improves contractility observed by an increase in beating rate and contraction speed as it occurs during the

  5. The contractile wall of the caput epididymidis in men affected by congenital or postinflammatory obstructive azoospermia.

    PubMed

    Pelliccione, Fiore; Cordeschi, Giuliana; Giuliani, Valeria; D'Abrizio, Piera; Necozione, Stefano; Negri, Luciano; Mancini, Mario; Sagone, Patrizia; Francavilla, Felice; Colpi, Giovanni Maria; Francavilla, Sandro

    2004-01-01

    The transport and storage of spermatozoa in the epididymis depend on the contractile activity of its tubular wall. It is not known what differences exist in the contractile wall of the human epididymis in cases of obstructive azoospermia. The contractile wall in the tubules of the caput epididymidis was analyzed by light microscopy and transmission electron microscopy in 10 azoospermic men, 5 with a bilateral congenital absence of vas deferens (CBAVD) and 5 with a bilateral postinflammatory congestive obstruction of the epididymis. Five specimens from the same region of the caput epididymidis, obtained from fertile men who had undergone an orchidectomy because of testicular cancer, served as controls. No differences were observed between congenital and congestive obstructions. The contractile wall in caput tubules proximal to the obstructed level was strongly thickened when compared with controls (62.98 +/- 5.84 micro; 80.82 +/- 7.72 micro vs 19.59 +/- 2.23 micro, respectively, for congestive and congenital obstructions vs controls; P <.0001 vs controls), and the spindle-shaped myoid cells, which formed the contractile wall in normal cases, were replaced by large smooth muscle cells (SMCs) that showed features of coexisting contractile and secretory functions. The former included crowded cytoplasmic bundles of thin myofilaments (5-6 nm in diameter) converging to a large number of dense bodies, numerous micropinocytotic vesicles of the plasma membrane, and a continuous cell basement membrane. The presence of a developed rough endoplasmic reticulum and a Golgi complex, associated with the accumulation of thick layers of pericellular basement membrane-like material and ground substance, was indicative of a secretory phenotype of SMCs. The increased mechanical forces on the epididymal wall upstream from the obstruction might eventually activate the differentiation of myoid cells into SMCs, leading to an altered physiology of the contractile wall that could have

  6. Acute myocardial infarction

    PubMed Central

    Domes, Trustin; Szafran, Olga; Bilous, Cheryl; Olson, Odell; Spooner, G. Richard

    2006-01-01

    OBJECTIVE To assess the quality of care of acute myocardial infarction (AMI) in a rural health region. DESIGN Clinical audit employing multiple explicit criteria of care elements for emergency department and in-hospital AMI management. The audit was conducted using retrospective chart review. SETTING Twelve acute care health centres and hospitals in the East Central Health Region, a rural health region in Alberta, where medical and surgical services are provided almost entirely by family physicians. PARTICIPANTS Hospital inpatients with a confirmed discharge diagnosis of AMI (ICD-9-CM codes 410.xx) during the period April 1, 2001, to March 31, 2002, were included (177 confirmed cases). MAIN OUTCOME MEASURES Quality of AMI care was assessed using guidelines from the American College of Cardiology and the American Heart Association and the Canadian Cardiovascular Outcomes Research Team and Canadian Cardiovascular Society. Quality of care indicators at three stages of patient care were assessed: at initial recognition and AMI management in the emergency department, during in-hospital AMI management, and at preparation for discharge from hospital. RESULTS In the emergency department, the quality of care was high for most procedural and therapeutic audit elements, with the exception of rapid electrocardiography, urinalysis, and provision of nitroglycerin and morphine. Average door-to-needle time for thrombolysis was 102.5 minutes. The quality of in-hospital care was high for most elements, but low for nitroglycerin and angiotensin-converting enzyme (ACE) inhibitors, daily electrocardiography, and counseling regarding smoking cessation and diet. Few patients received counseling for lifestyle changes at hospital discharge. Male and younger patients were treated more aggressively than female and older patients. Sites that used care protocols achieved better results in initial AMI management than sites that did not. Stress testing was not readily available in the rural

  7. Myocardial contusion following nonfatal blunt chest trauma

    SciTech Connect

    Kumar, S.A.; Puri, V.K.; Mittal, V.K.; Cortez, J.

    1983-04-01

    Currently available diagnostic techniques for myocardial contusion following blunt chest trauma were evaluated. We investigated 30 patients prospectively over a period of 1 year for the presence of myocardial contusion. Among the 30 patients, eight were found to have myocardial contusion on the basis of abnormal electrocardiograms, elevated creatine phosphokinase MB fraction (CPK-MB), and positive myocardial scan. Myocardial scan was positive in seven of eight patients (87.5%). CPK-MB fraction was elevated in four of eight patients (50%). Definitive electrocardiographic changes were seen in only two of eight patients (25%). It appears that myocardial scan using technetium pyrophosphate and CPK-MB fraction determinations are the most reliable aids in diagnosis of myocardial contusion following blunt chest trauma.

  8. Use of electroconvulsive therapy in an elderly after 5 weeks of myocardial infraction with 30% cardiac output.

    PubMed

    Grover, Sandeep; Suchendra, K; Mehra, Aseem; Parkash, Vijay; Saini, Vikas; Bagga, Shiv

    2015-01-01

    There is limited literature on the use of electroconvulsive therapy (ECT) in patients with recent myocardial infarction and in those with reduced cardiac output. In this report, we describe the safe use of ECT in a 70-year-male suffering from severe depressive episode with psychotic symptoms. He had a history of poor response to adequate pharmacotherapy and had suffered from myocardial infraction (MI), about 3 weeks prior to admission to the psychiatric unit. In view of severe depression associated with marked anxiety, agitation, psychotic symptoms, and poor food intake he was started on ECT after 5 weeks of MI when his cardiac output was only 30%. He received nine sessions of ECT without any cardiac complications and his depression remitted with ECT. PMID:27212828

  9. Detection of myocardial viability by dobutamine stress echocardiography: incremental value of diastolic wall thickness measurement

    PubMed Central

    Zaglavara, T; Pillay, T; Karvounis, H; Haaverstad, R; Parharidis, G; Louridas, G; Kenny, A

    2005-01-01

    Objective: To assess the diagnostic accuracy of baseline diastolic wall thickness (DWT) alone and as an adjunct to dobutamine stress echocardiography (DSE) for prediction of myocardial viability in patients with ischaemic left ventricular (LV) dysfunction, with the recovery of resting function after revascularisation as the yardstick. Patients: 24 patients with ischaemic LV dysfunction (ejection fraction < 40%) scheduled for surgical revascularisation. Setting: Regional cardiothoracic centre. Methods: All patients underwent DSE before and resting echocardiography six months after revascularisation. DWT was measured in each of the 16 LV segments. A receiver operating characteristic (ROC) and a multi-ROC curve were generated to assess the ability of DWT alone and in combination with DSE to predict myocardial viability. Results: DWT > 0.6 cm provided a sensitivity of 80%, a specificity of 51%, and a negative predictive value of 80% for the prediction of viability in akinetic segments. DSE had an excellent specificity (92%) but a modest sensitivity (60%) in akinetic segments. A combination of improvement at DSE or DWT > 0.8 cm improved sensitivity (90% v 60%, p < 0.001) and negative predictive value (92% v 78%, p  =  0.03) in akinetic segments compared with DSE alone. This was achieved with some loss in specificity (75% v 92%, p  =  0.01) and positive predictive value (71% v 82%, p  =  0.79). Conclusions: DWT measurement may improve the sensitivity of DSE for the detection of myocardial viability. Akinetic segments with DWT > 0.8 cm have a good chance of recovery despite the absence of contractile reserve during DSE. Further testing may be required before excluding myocardial viability in these cases. PMID:15831644

  10. Improvement in Myocardial Function and Coronary Blood Flow in Ischemic Myocardium after Mannitol

    PubMed Central

    Willerson, James T.; Powell, Wm. John; Guiney, Timothy E.; Stark, James J.; Sanders, Charles A.; Leaf, Alexander

    1972-01-01

    The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery. Mannitol significantly improved the depressed ventricular function curves which occurred with left anterior descending coronary artery occlusion. Mannitol also significantly lessened the S-T segment elevation (epicardial electrocardiogram) occurring during myocardial ischemia in the isovolumic hearts and this reduction was associated with significant increases in total coronary blood flow (P < 0.005) and with increased collateral coronary blood flow to the ischemia area (P < 0.005). Thus, increases in serum osmolality produced by mannitol result in the following beneficial changes during myocardial ischemia: (a) improved myocardial function, (b) reduced S-T segment elevation, (c) increased total coronary blood flow, and (d) increased collateral coronary blood flow. PMID:4640943

  11. Spousal Adjustment to Myocardial Infarction.

    ERIC Educational Resources Information Center

    Ziglar, Elisa J.

    This paper reviews the literature on the stresses and coping strategies of spouses of patients with myocardial infarction (MI). It attempts to identify specific problem areas of adjustment for the spouse and to explore the effects of spousal adjustment on patient recovery. Chapter one provides an overview of the importance in examining the…

  12. [Sewer gas induced myocardial toxicity].

    PubMed

    Antonelli, Dante; Sabanchiev, Avi; Rosner, Ehud; Turgeman, Yoav

    2014-07-01

    We report the case of a 19 year-old worker who collapsed after acute exposure to sewer gas. He rapidly developed cardiorespiratory failure with electrocardiographic, echocardiographic and laboratory findings of myocardial involvement. The mainstay of the therapy was mainly supportive treatment with a successful outcome. PMID:25189024

  13. Thrombolysis for Acute Myocardial Infarction

    PubMed Central

    Webb, John; Thompson, Christopher

    1992-01-01

    Thrombolysis has an important role in the management of acute myocardial infarction. Early treatment can markedly reduce mortality and morbidity. This new standard of care requires knowledge of accepted indications and contraindications for thrombolysis as well as familiarity with available agents and regimens. ImagesFigure 3 PMID:21221398

  14. Three-dimensional mapping of mechanical activation patterns, contractile dyssynchrony and dyscoordination by two-dimensional strain echocardiography: Rationale and design of a novel software toolbox

    PubMed Central

    De Boeck, Bart WL; Kirn, Borut; Teske, Arco J; Hummeling, Ralph W; Doevendans, Pieter A; Cramer, Maarten J; Prinzen, Frits W

    2008-01-01

    echocardiographic deformation data into a 3-D model by dedicated software allows a comprehensive analysis of spatio-temporal distribution patterns of myocardial dyssynchrony, of the global left ventricular deformation and of newer indices that may better reflect myocardial dyscoordination and/or impaired ventricular contractile efficiency. The potential value of such an analysis is highlighted in two dyssynchronous pathologies that impose particular challenges to deformation imaging. PMID:18513412

  15. Persistent depressive disorder

    MedlinePlus

    PDD; Chronic depression; Depression - chronic ... The exact cause of persistent depressive disorder (PDD) is unknown. It tends to run in families. PDD occurs more often in women. Most people with PDD will also ...

  16. Depression after Stroke

    MedlinePlus

    ... Library CARING FOR SOMEONE WITH EMOTIONAL & BEHAVIORAL NEEDS Depression After Stroke After a stroke, your loved one ... available! Almost half of all stroke survivors have depression. Depression is a normal response to the losses ...

  17. The role of voltage-gated potassium channels in the regulation of mouse uterine contractility

    PubMed Central

    Smith, Ryan C; McClure, Marisa C; Smith, Margaret A; Abel, Peter W; Bradley, Michael E

    2007-01-01

    Background Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv) channels and large-conductance, calcium-activated potassium (BK) channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium. Methods Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots. Results The Kv channel blocker 4-aminopyridine (4-AP) caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar) but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were found in isolated myometrium

  18. Titin is a Target of MMP-2: Implications in Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Ali, Mohammad A.M.; Cho, Woo Jung; Hudson, Bryan; Kassiri, Zamaneh; Granzier, Henk; Schulz, Richard

    2010-01-01

    Background Titin is the largest mammalian (∼3000-4000 kDa) and myofilament protein which acts as a molecular spring in the cardiac sarcomere and determines systolic and diastolic function. Loss of titin in ischemic hearts has been reported, but the mechanism of titin degradation is not well understood. Matrix metalloproteinase-2 (MMP-2) is localized to the cardiac sarcomere and upon activation in ischemia/reperfusion injury proteolyzes specific myofilament proteins. Here we determine whether titin is an intracellular substrate for MMP-2 and if its degradation during ischemia/reperfusion contributes to cardiac contractile dysfunction. Methods and Results Immunohistochemistry and confocal microscopy in rat and human hearts showed discrete co-localization between MMP-2 and titin in the Z-disc region of titin and that MMP-2 is mainly localized to titin near the Z-disc of the cardiac sarcomere. Both purified titin or titin in skinned cardiomyocytes were proteolyzed when incubated with MMP-2 in a concentration-dependent manner and this was prevented by MMP inhibitors. Isolated rat hearts subjected to ischemia/reperfusion injury showed cleavage of titin in ventricular extracts by gel electrophoresis which was confirmed by reduced titin immunostaining in tissue sections. Inhibition of MMP activity with ONO-4817 prevented ischemia/reperfusion-induced titin degradation and improved the recovery of myocardial contractile function. Titin degradation was also reduced in hearts from MMP-2 knockout mice subjected to ischemia/reperfusion in vivo, compared to wild type controls. Conclusions MMP-2 localizes to titin at the Z-disc region of the cardiac sarcomere and contributes to titin degradation in myocardial ischemia/reperfusion injury. PMID:21041693

  19. Multiscale Characterization of Impact of Infarct Size on Myocardial Remodeling in an Ovine Infarct Model

    PubMed Central

    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 of the influence of infarct size on temporal and spatial alteration of myocardium during progressive myocardial remodeling. MI with three infarct sizes (15%, 25% and 35% of left ventricular wall) was created in an ovine infarction model. The progressive LV remodeling over a 12 week period was studied. Echocardiography, sonomicrometry, histological and molecular analyses were carried out to evaluate cardiac function, regional tissue contractile function and structural remodeling, and regional cardiomycyte hypertrophy and calcium handling proteins. The 15%, 25% and 35% MI groups at 12 weeks after MI 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 a 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. Significant correlation was found between myocardiocyte 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, impairment severity of cellular structure and composition, and regional contractile function at regional tissue level and LV cardiac function at organ level. PMID:26540290

  20. Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts.

    PubMed

    Rorabaugh, Boyd R; Seeley, Sarah L; Bui, Albert D; Sprague, Lisanne; D'Souza, Manoranjan S

    2016-02-15

    Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart. PMID:26683901

  1. Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction.

    PubMed

    Korf-Klingebiel, Mortimer; Reboll, Marc R; Klede, Stefanie; Brod, Torben; Pich, Andreas; Polten, Felix; Napp, L Christian; Bauersachs, Johann; Ganser, Arnold; Brinkmann, Eva; Reimann, Ines; Kempf, Tibor; Niessen, Hans W; Mizrahi, Jacques; Schönfeld, Hans-Joachim; Iglesias, Antonio; Bobadilla, Maria; Wang, Yong; Wollert, Kai C

    2015-02-01

    Paracrine-acting proteins are emerging as a central mechanism by which bone marrow cell-based therapies improve tissue repair and heart function after myocardial infarction (MI). We carried out a bioinformatic secretome analysis in bone marrow cells from patients with acute MI to identify novel secreted proteins with therapeutic potential. Functional screens revealed a secreted protein encoded by an open reading frame on chromosome 19 (C19orf10) that promotes cardiac myocyte survival and angiogenesis. We show that bone marrow-derived monocytes and macrophages produce this protein endogenously to protect and repair the heart after MI, and we named it myeloid-derived growth factor (MYDGF). Whereas Mydgf-deficient mice develop larger infarct scars and more severe contractile dysfunction compared to wild-type mice, treatment with recombinant Mydgf reduces scar size and contractile dysfunction after MI. This study is the first to assign a biological function to MYDGF, and it may serve as a prototypical example for the development of protein-based therapies for ischemic tissue repair. PMID:25581518

  2. Autophagy protects cardiomyocytes from the myocardial ischaemia-reperfusion injury through the clearance of CLP36

    PubMed Central

    Li, Shiguo; Liu, Chao; Gu, Lei; Wang, Lina; Shang, Yongliang; Liu, Qiong; Wan, Junyi; Shi, Jian; Wang, Fang; Xu, Zhiliang; Ji, Guangju

    2016-01-01

    Cardiovascular disease (CVD) is the leading cause of the death worldwide. An increasing number of studies have found that autophagy is involved in the progression or prevention of CVD. However, the precise mechanism of autophagy in CVD, especially the myocardial ischaemia-reperfusion injury (MI/R injury), is unclear and controversial. Here, we show that the cardiomyocyte-specific disruption of autophagy by conditional knockout of Atg7 leads to severe contractile dysfunction, myofibrillar disarray and vacuolar cardiomyocytes. A negative cytoskeleton organization regulator, CLP36, was found to be accumulated in Atg7-deficient cardiomyocytes. The cardiomyocyte-specific knockout of Atg7 aggravates the MI/R injury with cardiac hypertrophy, contractile dysfunction, myofibrillar disarray and severe cardiac fibrosis, most probably due to CLP36 accumulation in cardiomyocytes. Altogether, this work reveals autophagy may protect cardiomyocytes from the MI/R injury through the clearance of CLP36, and these findings define a novel relationship between autophagy and the regulation of stress fibre in heart. PMID:27512143

  3. Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

    PubMed Central

    Neubauer, S; Horn, M; Naumann, A; Tian, R; Hu, K; Laser, M; Friedrich, J; Gaudron, P; Schnackerz, K; Ingwall, J S

    1995-01-01

    The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress. PMID:7883957

  4. Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility

    PubMed Central

    García Ponce, Alexander; Citalán Madrid, Alí F.; Vargas Robles, Hilda; Chánez Paredes, Sandra; Nava, Porfirio; Betanzos, Abigail; Zarbock, Alexander; Rottner, Klemens; Vestweber, Dietmar; Schnoor, Michael

    2016-01-01

    Changes in vascular permeability occur during inflammation and the actin cytoskeleton plays a crucial role in regulating endothelial cell contacts and permeability. We demonstrated recently that the actin-binding protein cortactin regulates vascular permeability via Rap1. However, it is unknown if the actin cytoskeleton contributes to increased vascular permeability without cortactin. As we consistently observed more actin fibres in cortactin-depleted endothelial cells, we hypothesised that cortactin depletion results in increased stress fibre contractility and endothelial barrier destabilisation. Analysing the contractile machinery, we found increased ROCK1 protein levels in cortactin-depleted endothelium. Concomitantly, myosin light chain phosphorylation was increased while cofilin, mDia and ERM were unaffected. Secretion of the barrier-stabilising hormone adrenomedullin, which activates Rap1 and counteracts actomyosin contractility, was reduced in plasma from cortactin-deficient mice and in supernatants of cortactin-depleted endothelium. Importantly, adrenomedullin administration and ROCK1 inhibition reduced actomyosin contractility and rescued the effect on permeability provoked by cortactin deficiency in vitro and in vivo. Our data suggest a new role for cortactin in controlling actomyosin contractility with consequences for endothelial barrier integrity. PMID:27357373

  5. Generation of contractile actomyosin bundles depends on mechanosensitive actin filament assembly and disassembly.

    PubMed

    Tojkander, Sari; Gateva, Gergana; Husain, Amjad; Krishnan, Ramaswamy; Lappalainen, Pekka

    2015-01-01

    Adhesion and morphogenesis of many non-muscle cells are guided by contractile actomyosin bundles called ventral stress fibers. While it is well established that stress fibers are mechanosensitive structures, physical mechanisms by which they assemble, align, and mature have remained elusive. Here we show that arcs, which serve as precursors for ventral stress fibers, undergo lateral fusion during their centripetal flow to form thick actomyosin bundles that apply tension to focal adhesions at their ends. Importantly, this myosin II-derived force inhibits vectorial actin polymerization at focal adhesions through AMPK-mediated phosphorylation of VASP, and thereby halts stress fiber elongation and ensures their proper contractility. Stress fiber maturation additionally requires ADF/cofilin-mediated disassembly of non-contractile stress fibers, whereas contractile fibers are protected from severing. Taken together, these data reveal that myosin-derived tension precisely controls both actin filament assembly and disassembly to ensure generation and proper alignment of contractile stress fibers in migrating cells. PMID:26652273

  6. Generation of contractile actomyosin bundles depends on mechanosensitive actin filament assembly and disassembly

    PubMed Central

    Tojkander, Sari; Gateva, Gergana; Husain, Amjad; Krishnan, Ramaswamy; Lappalainen, Pekka

    2015-01-01

    Adhesion and morphogenesis of many non-muscle cells are guided by contractile actomyosin bundles called ventral stress fibers. While it is well established that stress fibers are mechanosensitive structures, physical mechanisms by which they assemble, align, and mature have remained elusive. Here we show that arcs, which serve as precursors for ventral stress fibers, undergo lateral fusion during their centripetal flow to form thick actomyosin bundles that apply tension to focal adhesions at their ends. Importantly, this myosin II-derived force inhibits vectorial actin polymerization at focal adhesions through AMPK-mediated phosphorylation of VASP, and thereby halts stress fiber elongation and ensures their proper contractility. Stress fiber maturation additionally requires ADF/cofilin-mediated disassembly of non-contractile stress fibers, whereas contractile fibers are protected from severing. Taken together, these data reveal that myosin-derived tension precisely controls both actin filament assembly and disassembly to ensure generation and proper alignment of contractile stress fibers in migrating cells. DOI: http://dx.doi.org/10.7554/eLife.06126.001 PMID:26652273

  7. Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility.

    PubMed

    García Ponce, Alexander; Citalán Madrid, Alí F; Vargas Robles, Hilda; Chánez Paredes, Sandra; Nava, Porfirio; Betanzos, Abigail; Zarbock, Alexander; Rottner, Klemens; Vestweber, Dietmar; Schnoor, Michael

    2016-01-01

    Changes in vascular permeability occur during inflammation and the actin cytoskeleton plays a crucial role in regulating endothelial cell contacts and permeability. We demonstrated recently that the actin-binding protein cortactin regulates vascular permeability via Rap1. However, it is unknown if the actin cytoskeleton contributes to increased vascular permeability without cortactin. As we consistently observed more actin fibres in cortactin-depleted endothelial cells, we hypothesised that cortactin depletion results in increased stress fibre contractility and endothelial barrier destabilisation. Analysing the contractile machinery, we found increased ROCK1 protein levels in cortactin-depleted endothelium. Concomitantly, myosin light chain phosphorylation was increased while cofilin, mDia and ERM were unaffected. Secretion of the barrier-stabilising hormone adrenomedullin, which activates Rap1 and counteracts actomyosin contractility, was reduced in plasma from cortactin-deficient mice and in supernatants of cortactin-depleted endothelium. Importantly, adrenomedullin administration and ROCK1 inhibition reduced actomyosin contractility and rescued the effect on permeability provoked by cortactin deficiency in vitro and in vivo. Our data suggest a new role for cortactin in controlling actomyosin contractility with consequences for endothelial barrier integrity. PMID:27357373

  8. Sodium hydrogen exchanger as a mediator of hydrostatic edema induced intestinal contractile dysfunction

    PubMed Central

    Uray, Karen S.; Shah, Shinil K.; Radhakrishnan, Ravi S.; Jimenez, Fernando; Walker, Peter A.; Stewart, Randolph H.; Laine, Glen A.; Cox, Charles S.

    2010-01-01

    Background Resuscitation-induced intestinal edema is associated with early and profound mechanical changes in intestinal tissue. We hypothesize that the sodium hydrogen exchanger (NHE), a mechano-responsive ion channel, is a mediator of edema-induced intestinal contractile dysfunction. Methods An animal model of hydrostatic intestinal edema was utilized for all experiments. NHE isoforms 1-3 mRNA and protein were evaluated. Subsequently, the effects of NHE inhibition (with 5-(N-ethyl-N-isopropyl) amiloride (EIPA)) on wet to dry ratios, signal transduction and activator of transcription (STAT)-3, intestinal smooth muscle myosin light chain (MLC) phosphorylation, intestinal contractile activity, and intestinal transit were measured. Results NHE1-3 mRNA and protein levels were significantly increased in the small intestinal mucosa with the induction of intestinal edema. Administration of EIPA, an NHE inhibitor, attenuated validated markers of intestinal contractile dysfunction induced by edema as measured by decreased STAT-3 activation, increased MLC phosphorylation, improved intestinal contractile activity, and enhanced intestinal transit. Conclusion The mechano-responsive ion channel NHE may mediate edema-induced intestinal contractile dysfunction, possibly via a STAT-3 related mechanism. PMID:20553904

  9. Inhibitory Effects of Botulinum Toxin Type A on Pyloric Cholinergic Muscle Contractility of Rat.

    PubMed

    Zhao, Peng; Sun, Hong-Xu; Chu, Min; Hou, Yi-Ping

    2016-08-31

    Botulinum toxin type A (BTX-A) selectively cleaves synaptosomal-associated protein of 25 kDa (SNAP-25) and results in inhibition of the fusion of synaptic vesicles containing neurotransmitters with the presynaptic membrane to undergo exocytosis and release. The aim of this study was to investigate whether BTX-A inhibited the pyloric smooth muscle contractility induced by acetylcholine (ACh) after BTX-A-mediated cleavage of SNAP-25 antagonized by toosendanin (TSN). Three groups of rat pyloric muscle strips were studied in vitro. All strips were allowed to equilibrate for 52 min under a basal loading tension of 1 g in Krebs solution and spontaneous contractile waves were recorded as their own controls before adding each drug. According to experimental protocols, 100 μM ACh, 1 μM atropine, 29.6 μM TSN and 10 U/ml BTX-A was added, respectively. BTX-A directly inhibited pyloric spontaneous contraction and ACh-induced contractile response. Addition of 10 U/ml BTX-A still inhibited pyloric smooth muscle contractility following incubation of TSN, while subsequent administration of 100 μM ACh had no effect. BTX-A inhibits pyloric smooth muscle contractility in our study suggesting BTX-A inhibits not only ACh release from cholinergic nerves but also muscarinic cholinergic muscular transmission. PMID:27426259

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