The effect of high extracellular sodium concentration ((Na](0)) on myocardial mechanical function was determined in the isolated, arterially perfused newborn and adult rabbit heart. The muscles were initially perfused with hyperosmolar solutions containing 116 mM mannitol and all subsequent manipulations were done without changing the osmolarity. The inotropic effect of hyperosmolarity in the newborn was significantly greater than that in the adult. Solutions containing 200 mM [Na](0) caused immediate depression in myocardial contractility and this was followed by a partial recovery. The transient depression and recovery of myocardial contractility induced by 200 mM [Na](0) in the newborn were both significantly greater than that in the adult. When [Ca](0) alone was reduced so that the[Ca](0)/[Na)o ratio was equal to that of 200 mM [Na]0 solutions, the decrease in myocardial contractility in the newborn was greater than that in the adult. These data suggest that: (1)the negative inotropic effect of high [Na](0) is due to Na—Ca competition for external membrane binding sites, this effect in the newborn is greater than that in the adult; (2) the increased [Na](i) stimulates Na-Ca exchange and increases Ca influx, this effect in the newborn is greater than that in the adult, and (3) the age-related difference in the effect of high[Na](0) on myocardial contractility is, at least in part, related to the difference in the effect of calcium on mechanical function.

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