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Effects of Postnatal Maturation on Myocardial Contractile Responses to Calcium Antagonists and Changes in Contraction Frequency

Summary: The inotropic responses to verapamil and nitrendipine (5.0 × 10−8−1.0 × 10−5 M) were compared in right ventricular papillary muscles isolated from immature (14–21 days of age) and adult rabbits. In addition, the effects of changing the contraction frequency (force-frequency response) were studied in both age groups in the presence and absence of the calcium antagonists. Immature myocardium exhibited a greater sensitivity to the negative inotropic effect of both calcium antagonists. The concentrations of verapamil which reduced basal developed tension by 50% were 0.70 × 10−6 M in the immature rabbit and 4.51 × 10−6 M in the adult (p < 0.05). For nitrendipine, these values were 0.48 × 10−6 M in the immature rabbit and 1.21 × 10−6 M in the adult (p < 0.05). Raising the contraction frequency increased the contractile force (positive staircase) in both age groups, and verapamil abolished the positive staircase in both groups. Nitrendipine preserved but attenuated the positive staircase in the adult, but, in contrast, augmented the positive-staircase response in the immature myocardium. These age-related differences suggest that the mechanisms regulating calcium influx across the sarcolemma undergo postnatal maturation.