Inhibition of ion transport in septic rat heart: 133Cs+ as an NMR active K+ analog.

Sepsis, the systemic response to severe infection, and the resulting multiorgan failure it induces are major contributors to intensive care unit morbidity and mortality. A number of abnormalities in ion transport processes and intracellular free Na+ ([Na+]i) and K+ ([K+]i) concentrations have been reported to occur during sepsis/endotoxemia. An effect of sepsis on the NA(+)-K(+)-ATPase may be an important contribution to changes in intracellular ion balance and the resultant pathophysiology of the disorder. The purpose of this study was to examine the effect of sepsis on the Na(+)-K(+)-ATPase in the isolated perfused rat heart using 133Cs+ nuclear magnetic resonance (NMR). Cs+ is a K+ analog, and 133Cs-NMR offers the opportunity to examine Na(+)-K(+)-ATPase activity in the intact organ via tracer kinetics. Sepsis was induced in halothane-anesthetized male Sprague-Dawley rats using the cecal ligation and perforation (CLP) model. Twenty-four to thirty-six hours after surgery, hearts from CLP or sham-operated rats were perfused with Krebs-Henseleit buffer containing 1.25 mM Cs+. The influx rate constant for Cs+ was decreased by 24% in septic rat hearts, i.e., 0.25 +/- 0.08 (SD) min 1 for controls and 0.19 +/- 0.04 (SD) min-1 for septic animals (P = 0.003). There was no difference for Cs+ efflux [0.005 +/- 0.001 (SD) min-1 for controls and 0.005 +/- 0.002 (SD) min-1 for septic animals; P = 0.8]. These results are consistent with an inhibition of the Na(+)-K(+)-ATPase pump during sepsis/endotoxemia. A decrease in the activity of the Na(+)-K(+)-ATPase pump may be responsible for or contribute to the changes in [Na+]i and [K+]i during the disorder.