Increased oxygen cost of contractility in the endotoxemic porcine left ventricle

Objective - Myocardial oxygen consumption (MVO2) in the septic myocardium is comparatively high in relation to the sepsis-induced reduction in ventricular work. Our previous studies indicate that this energetic inefficiency is due to increased energy consumption in excitation - contraction (EC) coupling, i.e. myocardial calcium handling. Design - To further confirm this observation, we assessed the oxygen cost of contractility in anesthetized pigs before and 2 h after induction of endotoxemia ( 1 mug/kg endotoxin infusion over 1 h, Escherichia coli toxin, n = 6). Baroreceptor reflexes were blocked by hexamethonium. Contractility was increased by stepwise dopamine infusions at baseline and 2 h after induction of endotoxemia. Oxygen cost of contractility was assessed as the relationship between myocardial contractility (E-es or elastance) and non-mechanical oxygen consumption ( unloaded MVO2), a measure of energy consumption in EC coupling or calcium handling. Results - Non-mechanical oxygen consumption ( unloaded MVO2) was higher after endotoxin infusions than at baseline (0.641 +/- 0.05 vs 0.383 +/- 0.07 J/beat/ 100 g, p < 0.05). The relationship between unloaded MVO2 and Ees, constructed by the dopamine response, was highly linear both at baseline and endotoxemia ( r(2) = 0.76 - 0.99). However, endotoxin increased oxygen cost of contractility by ∼ 45% ( baseline 0.06 +/- 0.03 vs endotoxin 0.09 +/- 0.04 J ml/mmHg/beat/100 g). Conclusion - Acute endotoxemia increases oxygen cost of contractility, a measure of energy consumed in EC coupling or myocardial calcium handling.