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Effects of stimulation frequency on calcium transients in noninfarcted myocardium: modulation by chronic captopril
1Cardiovascular Division, Salt Lake City Veterans Affairs Medical Center, University of Utah, USA.
Background:
Angiotensin-converting enzyme (ACE) inhibition produces beneficial effects in patients and experimental animals after myocardial infarction (MI). However, the mechanisms accounting for these effects are incompletely understood.
Methods And Results:
We recorded contractile force and intracellular calcium (Ca2+i) transients in papillary muscles from sham-operated rats (n = 8), untreated rats with heart failure after MI (MI; n = 7), and MI rats receiving captopril treatment for 5 weeks (n = 4). All studies were performed 6 weeks after MI or sham surgery. In muscles from sham-operated rats, increasing stimulation frequency from 0.33 to 3.0 Hz was associated with no change in the peak amplitude or the time to the peak of the Ca2+i transients. In contrast, in muscles from MI rats, stimulation at 3.0 Hz caused a marked increase in the amplitude of the Ca2+i transients (170% of baseline), prolongation of the time to the peak of the Ca2+i transient (54 +/- 2 to 84 +/- 8 * ms), and a prominent alternans pattern. Tissue hypoxia did not appear to be responsible for the abnormal response to rapid stimulation in the myocardium from infarcted hearts because bubbling the bath solution with 95% N2/5% CO2 resulted in no change in the amplitude of the Ca2+i transients in muscles from both groups. Muscles from captopril-treated MI rats responded like sham-operated controls, with no change in the amplitude or time course of the Ca2+i transients during rapid stimulation.
Conclusion:
In myocardium isolated from rats with postinfarction heart failure, increasing stimulation frequency causes marked increases in peak Ca2+i , prolongation of the time course of the Ca2+i transient, and Ca2+i alternans. Despite the increased Ca2+i transients, contractility declined during rapid pacing. We hypothesize that these changes could be explained by a frequency-related decline in intracellular pH and/or a decrease in sarcolemmal Ca2+ extrusion. The frequency-dependent abnormalities of cellular Ca2+ regulation in the infarcted heart are prevented by long-term treatment with an ACE inhibitor.