Because cardiopulmonary bypass (CPB) produces a diffuse inflammatory reaction that may injure multiple organs and complicate cardiac surgical procedures, we examined the use of a competitive inhibitor of platelet activating factor (SDZ HUL-412) in a porcine model of CPB as a means to ameliorate pulmonary injury after CPB. Thirteen pigs (35 to 40 kg) underwent CPB at 28°C for 2 hours, followed by 2 hours of observation. Group I (n = 6) received SDZ HUL-412 (a quinolinium compound) intravenously (3 mg/kg loading dose and 2 mg · kg-1 · h-1 continuous infusion) starting before sternotomy. Group II (n = 7) received a saline vehicle. Peak airway pressure, pulmonary arterial pressure, left atrial pressure, and arterial blood gases were measured and flow cytometry 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 group 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 resistance 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 dynes · s · cm-5) at the end of the observation period. CD18 up-regulation increased similarly in the two groups during CPB. Histologic evaluation revealed normal pulmonary architecture in group I, but group II had marked intraalveolar hemorrhage, abundant neutrophils, and edema fluid. 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 demonstrates that platelet activating factor inhibition during CPB (1) decreases pulmonary vascular resistance after CPB, (2) increases the arterial oxygen pressure, and (3) decreases histologic lung damage, but (4) has no effect on surface expression of CD18. Platelet activating factor inhibition may have clinical applicability in the amelioration of organ damage after CPB.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine