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Effect of CA2+ Antagonists on Mechanical Function in the Neonatal Heart

ABSTRACT. The effect of verapamil and diltiazem on mechanical function was studied in the isolated arterially perfused neonatal and adult rabbit heart. The negative inotropic effect of these drugs in the newborn was significantly greater than in the adult. At concentrations 10−7 M of verapamil and 10−6 M of diltiazem, resting tension was significantly increased in the newborn, but not in the adult. In both age groups, verapamil and diltiazem inhibited the positive inotropy of staircase, but did not alter the inotropic effect of hyperosmolarity (116 mM mannitol). The positive inotropy of paired electrical stimulation was eliminated by these drugs in the newborn, but not in the adult. These data suggest that the neonatal heart as compared with the adult heart is more dependent on transsarcolemmal calcium influx for contraction and transsarcolemmal calcium efflux for relaxation.