Inotropic Effects of Calcium Antagonists in the Cardiomyopathic Syrian Hamster

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Abstract
The inotropic responses of papillary muscles isolated from the BIO 14.6 cardiomyopathic Syrian hamster were compared with those of age-matched F, B 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 < 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 × 10 -7M) and a 50-fold higher IC50 for negative inotropy compared with F1B controls (200 ± 30 vs. 4.0 ± 1.0 μM). 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 μM; p < 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 sarcolem-mal L-type calcium channel in the cardiomyopathic Syrian hamster. The mechanism of action of verapamil in the cardiomyopathic Syrian hamster remains to be elucidated.

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