Inotropic effects of calcium antagonists in the cardiomyopathic Syrian hamster

The inotropic responses of papillary muscles isolated from the BIO 14.6 cardiomyopathic Syrian hamster were compared with those of age-matched F1B controls. Length-tension curves revealed the preservation of contractile function at 1-2 months of age and significant loss of function at 4-6 months of age. Papillary muscles prepared from 4-6-month-old myopathic hamsters were significantly less sensitive to increasing frequency of stimulation than were controls (p less than 0.05). There were no differences in the responses to nifedipine, Bay K 8644, diltiazem, or gallopamil. Only verapamil demonstrated a biphasic inotropic response in the cardiomyopathic hamster with a low-dose positive inotropic effect (131 +/- 4% at 4 +/- 2 x 10(-7) M) and a 50-fold higher IC50 for negative inotropy compared with F1B controls (200 +/- 30 vs. 4.0 +/- 1.0 microM). Verapamil is also a less potent negative inotrope in 1-2-month-old myopathic papillary muscles compared with controls (IC50, 280 +/- 70 vs. 32 +/- 10 microM; p less than 0.05). These inotropic effects are not shared by the other calcium channel modulators studied (i.e., nifedipine, Bay K 8644, diltiazem, gallopamil). These findings do not support the presence of a functional defect in the sarcolemmal L-type calcium channel in the cardiomyopathic Syrian hamster. The mechanism of action of verapamil in the cardiomyopathic Syrian hamster remains to be elucidated.