Gram-negative endotoxemia: effects on cardiac Na-Ca exchange and stoichiometry

We studied the acute effects of gram-negative endotoxemia on Na-Ca exchange activity and stoichiometry in cardiac sarcolemmal (SL) vesicles isolated from pentobarbital-anesthetized dogs. Dogs were given either endotoxin (ET; 1.5 mg/kg IV) or saline vehicle (C; n = 4 dogs/group). Characteristic of endotoxemia, endotoxin produced a decrease in mean arterial pressure from 120 to 60 mmHg, an increase in packed cell volume from 38% to 60%, and an increase in heart rate from 130 to 190 bpm. After 2 hr, hearts were removed and SL vesicles were prepared from left and right ventricular tissue. For ET and C, Na-dependent Ca2+ uptake (left ventricle) was 3.13 and 3.44 (2 sec) and 18.60 and 19.42 (60 sec) nmole Ca2+/mg protein, respectively; ET group values were not significantly different from corresponding C values in either left or right ventricles. The stoichiometry of Na-Ca exchange was determined in left ventricular vesicles by a previously described thermodynamic approach utilizing a K+-valinomycin gradient opposed by Na+ equilibrium potentials (Reeves and Hale: J Biol Chem 259:7733-7739, 1984). The stoichiometry of exchange of Na+ for Ca2+ was 2.84 +/- 0.09 and 2.74 +/- 0.14 for ET and C, respectively. We conclude that during the developmental phase (2 hr) of endotoxemia, there were no ET-mediated changes in cardiac Na-Ca exchange activity in SL vesicles from either left or right ventricular tissue and the exchange process remained electrogenic with a stoichiometry of 3Na+ for 1Ca2+.