MYOCARDIAL RESERVE AND CALCIUM TOLERANCE IN THE CARDIOMYOPATHIC HAMSTER

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While the cardiomyopathic hamster (CMH), BIO14.6 strain, develops congestive heart failure with aging, the evolution of compromised myocardial reserve, calcium intolerance, and response to catecholamines prior to overt failure remains to be fully understood and is investigated in this project. We used hearts from 28-52 day old male CMH and age-matched F1B strain control (C) hearts. Isolated, isovolumic and AV blocked hearts were perfused with Hepes buffer at constant pressure and stimulated at 2 Hz at 37 degrees C to investigate the effects of (1) an increasing in bathing [Ca(2+)] (1-10 mM; n = 10 of each), beta-adrenergic (isoproterenol, 1 nm - l micromM; n = 10 of each), 3) alpha-adrenergic (phenylephrine, 0.1 - 10 micromM; n = 10 of each) agonists, and (4) Ca(2+) channel agonist (BAYK8644, 5 nm - 1 microM; n = 10 of each) on contractile properties. In CMH, the peak developed pressure response saturates at a significantly (p < 0.001) smaller developed pressure and declines from maximum occurs at a significantly lower concentrations of alpha- or beta-agonist, Za(2+) channel agonist or of perfusate [Ca(2+)] compared to control. The rise in end-diastolic pressure with increasing in drug or perfusate [Ca(2+)] concentration in CMH is also significantly (p < 0.001) greater than control. These results suggest that myocardium shows enhanced response to Ca(2+) per se, and also that myocardial cell Ca(2+) loading in response to catecholamines greater in CMH than in C hearts.