Early Exercise Training Normalizes Myofilament Function and Attenuates Left Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction

Waard, Monique C. de; Velden, Jolanda van der; Bito, Virginie; Özdemir, Semir; Biesmans, Liesbeth; Boontje, Nicky M.; Dekkers, Dick H. W.; Schoonderwoerd, Kees; Schuurbiers, Hans; Crom, Rini de; Stienen, G. J. M.; Sipido, Karin R.; Lamers, Jos M. J.; Duncker, Dirk J.

doi:10.1161/01.res.0000262655.16373.37

Cited by 111 publications

(134 citation statements)

References 62 publications

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“…Both diseases are also characterized by a high incidence of VT and SCD. Interestingly, exercise training after myocardial infarction, which normalizes the increased myofilament Ca 2+ sensitivity (47), also has been shown to reduce mortality and the rate of ventricular arrhythmias in animal (48,49) and human studies (50). Further, treatment with the Ca 2+ sensitizer levosimendan significantly increased the incidence of VT in patients with heart failure (51).…”

Section: Discussionmentioning

confidence: 99%

Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice

Baudenbacher¹,

Schober²,

Pinto³

et al. 2008

J. Clin. Invest.

177

235

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In human cardiomyopathy, anatomical abnormalities such as hypertrophy and fibrosis contribute to the risk of ventricular arrhythmias and sudden death. Here we have shown that increased myofilament Ca 2+ sensitivity, also a common feature in both inherited and acquired human cardiomyopathies, created arrhythmia susceptibility in mice, even in the absence of anatomical abnormalities. In mice expressing troponin T mutants that cause hypertrophic cardiomyopathy in humans, the risk of developing ventricular tachycardia was directly proportional to the degree of Ca 2+ sensitization caused by the troponin T mutation. Arrhythmia susceptibility was reproduced with the Ca 2+ -sensitizing agent EMD 57033 and prevented by myofilament Ca 2+ desensitization with blebbistatin. Ca 2+ sensitization markedly changed the shape of ventricular action potentials, resulting in shorter effective refractory periods, greater beat-to-beat variability of action potential durations, and increased dispersion of ventricular conduction velocities at fast heart rates. Together these effects created an arrhythmogenic substrate. Thus, myofilament Ca 2+ sensitization represents a heretofore unrecognized arrhythmia mechanism. The protective effect of blebbistatin provides what we believe to be the first direct evidence that reduction of Ca 2+ sensitivity in myofilaments is antiarrhythmic and might be beneficial to individuals with hypertrophic cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice

Baudenbacher¹,

Schober²,

Pinto³

et al. 2008

J. Clin. Invest.

177

235

View full text Add to dashboard Cite

show abstract

“…Hemodynamic parameters are determined in terminal experiments in anesthetized and ventilated mice (238,551) or rats (540) by advancing a micro-tipped pressure transducer or a combined pressure-volume catheter through the right common carotid artery into the ascending aorta and subsequently into the LV. The positive and negative rates of pressure development and the systolic and enddiastolic pressures may be used as sensitive indicators of thyroid hormone-dependent changes in expression of contractile proteins and proteins involved in intracellular calcium homeostasis.…”

Section: And Recommendation 50bmentioning

confidence: 99%

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Bianco

Anderson

Forrest

et al. 2014

Thyroid

173

106

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“…7, 17 But the molecular mechanisms that mediate the powerful cardioprotective effect of EP remain to be elucidated. Several studies have shown that EP increased the expression of some myocardial proteins, such as heat shock proteins, 18 mitochondrial and sarcolemmal ATP-sensitive potassium channels (mitoKATP or sarcKATP), 19 cyclooxygenase-2, 20 and endoplasmic reticulum stress proteins, 7 which can attenuate many types of heart injuries.…”

Section: Ep-induced Early and Late Phase Of Cardioprotection Is Assocmentioning

confidence: 99%

Exercise Preconditioning-Induced Early and Late Phase of Cardioprotection Is Associated With Protein Kinase C Epsilon Translocation

Hao

Shen

et al. 2014

Circ J

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1636HAO Z et al. Circulation JournalOfficial Journal of the Japanese Circulation Society http://www. j-circ.or.jp the EP-induced early phase of cardioprotection requires PKCδ translocation. 8 In this study, which was performed by the present team, short-term adaptation of adult rats to EP was found to markedly increase the expression of PKCδ and phosphorylation of PKCδ. However, the PKCε responsible for EP has not been identified. In the present study, it was hypothesized that EP caused an increase in PKCε expression and translocation of PKCε, and that the PKC inhibitor, chelerythrine (CHE), suppressed these events, thus attenuating the EP-mediated cardioprotection. Methods Ethical ApprovalAdult (8-week-old) male Sprague-Dawley rats (Sippr BK, Shanghai, China) were housed at a constant temperature (22±2°C) on a 12-h light/dark cycle. They were fed ad libitum on standard laboratory rat chow and had free access to tap water. The investigation conforms to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication no. 85-23, revised 1996) and was schemia/reperfusion (I/R) is one of the major causes of myocardial injury. Over the years, investigators have studied many approaches regarding the protection of the heart against I/R injury. Specifically, cardioprotection of ischemic preconditioning (IP) 1 and remote IP 2,3,4 were described as the immediate adaptation of the heart to brief sublethal ischemia but it lacking practical utility for providing protection to human. Recently, researchers have found that, like IP, exercise preconditioning (EP), which here refers to brief episodes of exercise, can also enhance the tolerance of the heart to subsequent ischemic insult. 5,6 It is demonstrated here that EP has 2 distinct protective phases, the early phase, which occurs immediately after the exercise, and a late phase, which peaks 24 h after exercise. 6-9 Although the powerful cardioprotective effect of EP has been proved, the intracellular mechanisms involved in this EP-conferred cardioprotection remain unclear. Recent evidence supports the contention that acute exercise directly enhances myocardial tolerance to ischemia in the hearts of rats through a protein kinase C (PKC)-mediated mechanism. 5 However, studies investigating the role of isoform-specific alterations in PKC after EP are still rare. One recent study clearly demonstrated that Background: Exercise preconditioning (EP) can provide powerful protection to the heart. Evidence supports the contention that EP directly enhances myocardial tolerance to ischaemia through a protein kinase C (PKC)-mediated mechanism. However, studies investigating the role of isoform-specific PKC after EP are lacking.

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Early Exercise Training Normalizes Myofilament Function and Attenuates Left Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction

Cited by 111 publications

References 62 publications

Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice

Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Exercise Preconditioning-Induced Early and Late Phase of Cardioprotection Is Associated With Protein Kinase C Epsilon Translocation

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