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Defibrillation depresses heart sarcoplasmic reticulum calcium pump: a mechanism of postshock dysfunction
1Department of Physiology, University of Western Ontario, London, Canada.
Insights
Defibrillation shocks impair cardiac sarcoplasmic reticulum (SR) Ca2+ uptake, leading to poor heart contractility. This study reveals shocks disrupt SR Ca2+ transport, explaining post-shock heart dysfunction.
Area of Science:
- Cardiology
- Biochemistry
- Physiology
Background:
- Ventricular fibrillation therapy relies on high-voltage shocks.
- Post-defibrillation myocardial dysfunction, characterized by poor cardiac contractility, remains mechanistically unexplained.
- Intracellular calcium (Ca2+) handling by the sarcoplasmic reticulum (SR) is critical for cardiac contractility.
Purpose of the Study:
- To investigate the hypothesis that defibrillation shocks interfere with the Ca2+ transport function of cardiac SR.
- To elucidate the mechanisms underlying post-shock myocardial dysfunction.
Main Methods:
- Transthoracic shocks were delivered to anesthetized rats.
- SR-enriched membrane vesicles were isolated from rat hearts.
- ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase activity of SR vesicles were measured.
- Cardiac contractility and relaxation were assessed in Langendorff-perfused hearts.
Main Results:
- Defibrillation shocks caused a significant decline in ATP-dependent Ca2+ uptake by cardiac SR.
- Ca2+-stimulated ATPase activity of SR remained unaltered post-shock.
- Shock delivery decreased cardiac contractility and slowed relaxation in Langendorff hearts.
- SR polypeptide composition was unchanged between control and shocked groups.
Conclusions:
- Defibrillation shocks impair the Ca2+-pumping function of cardiac SR by uncoupling ATP hydrolysis from Ca2+ transport.
- Shock-induced dysfunction of the SR Ca2+ pump may be a key mechanism contributing to post-shock myocardial dysfunction.
Abstract:
Presently, the only therapy for ventricular fibrillation is delivery of high-voltage shocks. Despite "successful defibrillation," patients may have poor cardiac contractility, the mechanisms of which are unknown. Intracellular Ca2+ handling by the sarcoplasmic reticulum (SR) plays a major role in contractility. We tested the hypothesis that defibrillation shocks interfere with Ca2+ transport function of cardiac SR. Rats anesthetized with pentobarbital sodium had bilateral electrodes implanted subcutaneously for transthoracic shocks. A series of 10 shocks, 10 s apart, at 0-250 V was delivered from a trapezoidal defibrilator. The hearts were rapidly removed, SR-enriched membrane vesicles were isolated, and ATP-dependent Ca2+ uptake and Ca(2+)-stimulated ATP hydrolysis were determined. There was a marked, shock-related decline in Ca2+ uptake, whereas adenosinetriphosphatase activity remained unaltered. The polypeptide compositions were similar in control and shocked SR. In Langendorff hearts, shocks also decreased contractility and slowed relaxation. These data indicate that shocks with current densities similar to defibrillation depress Ca(2+)-pumping function of cardiac SR because of uncoupling of ATP hydrolysis and Ca2+ transport. Shock-induced impairment of Ca2+ pump function may underlie postshock myocardial dysfunction.