PLATELET-ACTIVATING-FACTOR INHIBITION REDUCES LUNG INJURY AFTER CARDIOPULMONARY BYPASS

Because cardiopulmonary bypass (CPB) produces a diffuse inflammatory r eaction that may injure multiple organs and complicate cardiac surgica l procedures, we examined the use of a competitive inhibitor of platel et activating factor (SDZ HUL-412) in a porcine model of CPB as a mean s to ameliorate pulmonary injury after CPB. Thirteen pigs (35 to 40 kg ) underwent CPB at 28 degrees C for 2 hours, followed by 2 hours of ob servation. Group I (n = 6) received SDZ HUL-412 (a quinolinium compoun d) intravenously (3 mg/kg loading dose and 2 mg.kg(-1).h(-1) continuou s infusion) starting before sternotomy. Group II (n = 7) received a sa line vehicle. Peak airway pressure, pulmonary arterial pressure, left atrial pressure, and arterial blood gases were measured and now cytome try evaluated surface expression of adhesion molecule subunit CD18 on circulating neutrophils. Pulmonary function was significantly improved in group I. Fifteen minutes after CPB, dynamic lung compliance in gro up I was 91% +/- 12% of baseline versus 49% +/- 5.2% in group II (p = 0.06 by analysis of variance). After CPB, the arterial oxygen pressure was also significantly better in group I than in group II (425 +/- 61 versus 234 +/- 76 mm Hg) (p < 0.05). The rise in pulmonary vascular r esistance after CPB was less in group I (p < 0.05) (323 +/- 55 to 553 +/- 106 dynes.s.cm(-5)) than in group II (531 +/- 177 to 884 +/- 419 d ynes.s.cm(-5)) at the end of the observation period. CD18 up-regulatio n increased similarly in the two groups during CFB. Histologic evaluat ion revealed normal pulmonary architecture in group I, but group II ha d marked intraalveolar hemorrhage, abundant neutrophils, and edema flu id. Significant edema was present in group I fields (41.0% +/- 11.7%) versus group II fields (5.05% +/- 1.5%) (p < 0.02). This study demonst rates that platelet activating factor inhibition during CPB (1) decrea ses pulmonary vascular resistance after CPB, (2) increases the arteria l oxygen pressure, and (3) decreases histologic lung damage, but (4) h as no effect on surface expression of CD18. Platelet activating factor inhibition may have clinical applicability in the amelioration of org an damage after CPB.