Platelet-activating factor antagonism improves ventricular contractility in endotoxemia.

Abstract

Endotoxin stimulates platelet-activating factor production and also causes a decrease in myocardial contractility within a few hours in animal models of sepsis. Platelet-activating factor by itself decreases left ventricular contractility. We investigated whether platelet-activating factor contributes substantially to the decrease in left ventricular contractility seen in sepsis. Prospective, randomized, controlled animal study. University research laboratory. Twenty-two juvenile, cross-bred pigs. Anesthetized pigs were pretreated with a platelet-activating factor receptor antagonist (L-659,989) or vehicle (control), and then treated with endotoxin or saline (control). Hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter) were measured. Left ventricular contractility was assessed using the slope, or maximum elastance (Emax), of the end-systolic pressure-volume relationship. In the control/endotoxin group, 4 hrs after endotoxin administration, Emax had decreased by 41 +/- 4% (p < .05) and mean arterial pressure had decreased by 32 +/- 3% (p < .05). In the L-659,989/endotoxin group, the decreases in Emax (26 +/- 2%, p < .05) and mean arterial pressure (16 +/- 7%) were significantly attenuated compared with the control/endotoxin group (p < .05). We conclude that platelet-activating factor plays a modest but statistically significant role in the early decrease in left ventricular contractility after endotoxin administration. Inhibition of platelet-activating factor during sepsis might be beneficial for left ventricular mechanics and hemodynamics.