INTRODUCTION: Cardiomyocyte sodium accumulation after burn injury precedes the development of myocardial contractile dysfunction. This study examined the effects of burn injury on Na,K-ATPase activity in adult rat hearts after major burn injury and explored the hypothesis that burn related changes in myocardial Na,K-ATPase activity were PKC dependent. METHODS: A 3° burn injury (or sham burn) was given over 40% total body surface area and rats received lactated Ringers solution, 4 ml/kg/% burn. Subgroups of rats were sacrificed either 2, 4, or 24 hrs post burn (n=6 rats/time period), hearts were homogenized and Na,K-ATPase activity determined from ouabain-sensitive phosphate generation from ATP by cardiac sarcolemmal vesicles. Additional groups of rats were studied at several times post burn to determine the time course of myocyte sodium loading and the time course of myocardial dysfunction. Additional groups of sham and burned rats were given calphostin, an inhibitor of PKC; and Na,K-ATPase activity/cell Na⁺/myocardial function were measured. RESULTS: Burn injury caused a progressive rise in cardiomyocyte Na⁺ and myocardial Na,K-ATPase activity progressively decreased after burn while PKC activity progressively rose. Administration of calphostin to inhibit PKC activity prevented both the burn-related decrease in myocardial Na,K-ATPase and the rise in intracellular Na⁺ and improved post burn myocardial contractile performance. CONCLUSIONS: Burn-related inhibition of Na,K-ATPase likely contributes to the cardiomyocyte accumulation of intracellular sodium. Since intracellular Na⁺ is one determinate of electrical-mechanical recovery after insults such as burn injury, burn-related inhibition of the Na,K-ATPase may be critical in post burn recovery of myocardial contractile function.