Thermal injury alters myocardial sarcoplasmic reticulum calcium channel function

Background We have previously shown that a major cutaneous thermal injury p roduces profound cardiac contractile dysfunction despite adequate resuscita tion. While the molecular basis of this dysfunction is unknown, recent work has suggested that alterations in calcium flux between the myocyte sarcopl asmic reticulum (SR) to the cytoplasm may play a role. Materials and methods. To determine if thermal injury-induced contractile d ysfunction is related to intracellular calcium transport across the SR memb rane, we accessed myocardial microsomal preparations from scalded (43% TBSA ) guinea pigs for the ability of the cardiac calcium efflux channel to bind radiolabeled ryanodine. Intracellular calcium flux was assessed by fluores cence spectrophotometry. Results. Thermal injury resulted in severe cardiac contractile deficit char acterized by loss of LVP and +/-dP/dt despite resuscitation. Analysis of is olated myocyte cultures showed a twofold increase in cytoplasmic [Ca2+](1) by 24 h postburn. Competitive binding and Scatchard analysis demonstrated a single, high-affinity binding site present in both sham and burn animal he arts. Myocardial membrane vesicles revealed a significantly enhanced number of calcium efflux channels in the open configuration at both 8 and 24 h fo llowing thermal injury compared to time-matched shams (1.07 +/- 0.01 and 0. 95 +/- 0.06 vs 0.85 +/- 0.01 pmol bound/mg protein, P < 0.05). The data ind icate that altered function of the myocardial transmembrane SR calcium effl ux channel following thermal injury was associated with elevated [Ca2+](1) and contractile dysfunction. Conclusions. We conclude that postburn cardiac dysfunction may partly be a result of elevated cytoplasmic calcium concentrations and diminished regula tion of SR calcium efflux channel activity. (C) 1999 Academic Press.