PLATELET-ACTIVATING-FACTOR ANTAGONISM IMPROVES VENTRICULAR CONTRACTILITY IN ENDOTOXEMIA

Objectives: Endotoxin stimulates platelet-activating factor pro ductio n 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 pla telet-activating factor contributes substantially to the decrease in l eft ventricular contractility seen in sepsis. Design: Prospective, ran domized, controlled animal study. Setting: University research laborat ory. Subjects: Twenty-two juvenile, cross-bred pigs. Interventions: An esthetized pigs were pretreated with a platelet-activating factor rece ptor antagonist (L-659,989) or vehicle (control), and then treated wit h endotoxin or saline (control). Hemodynamics and left,ventricular pre ssures (Millar catheter) and volumes (conductance catheter) were measu red. Left ventricular contractility was assessed using the slope, or m aximum elastance (E(max)), of the end systolic pressure-volume relatio nship. Measurements and Main Results: In the control/endotoxin group, 4 hrs after endotoxin administration, E(max) 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 E (26 +/- 2% , p < .05) and mean arterial pressure (16 +/- 7%) were significantly a ttenuated compared with the control/endotoxin group (P < .05). Conclus ions: We conclude that platelet-activating factor plays a modest but s tatistically significant role in the early decrease in left ventricula r contractility after endotoxin administration. Inhibition of platelet activating factor during sepsis might be beneficial for left Ventricu lar mechanics and hemodynamics.