NITRIC-OXIDE SYNTHASE INHIBITION PARTIALLY PREVENTS DECREASED LV CONTRACTILITY DURING ENDOTOXEMIA

Decreased contractility of myocytes after cytokine exposure can be pre vented by nitric oxide synthase inhibition. Whether this is true in an intact animal model of sepsis is unknown. Anesthetized pigs were pret reated with saline or a nitric oxide synthase inhibitor, N-omega-nitro -L-arginine, and then treated with saline or endotoxin. We measured he modynamics and left ventricular pressures (Millar catheter) and volume s (conductance catheter). Left ventricular contractility was assessed using the slope (E(max)) of the end-systolic pressure-volume relations hip. Four hours after endotoxin infusion, E(max) had decreased by 44 /- 5% (P < 0.05) and mean arterial pressure had decreased by 30 +/- 10 % (P < 0.05). Pretreatment with N-omega-nitro-L-arginine significantly reduced the decrease in E(max) to 28 +/- 3% (P < 0.05) and prevented the decrease in mean arterial pressure. However, it also raised pulmon ary arterial pressure. We conclude that nitric oxide contributes to th e early decrease in left ventricular contractility after endotoxin in the intact animal. However the vascular effects of nitric oxide syntha se inhibition increase right and left ventricular afterloads, which we re detrimental to cardiac function.