Effect of a proteolytic enzyme inhibitor on the cardiopulmonary response to endotoxin

Gabexate mesilate (GM), a proteolytic enzyme inhibitor, was given to 31 chronically instrumented sheep either as a pretreatment or treatment to determine its effects on the cardiopulmonary response to endotoxin (ET). Twelve sheep received GM prior to endotoxin (0.75 microgram/kg), 10 after ET and 9 received GM without ET. A typical biphasic response was noted; phase I showed increased lymph flow (QL), reduced lymph to plasma protein ratio (L/P) and increased pulmonary artery pressure (PAP). Phase II occurred two hours after ET; the lymph flow remained elevated and the L/P ratio rose slightly above control. Both phases demonstrated an elevation in total peripheral vascular resistance (TPR) and hematocrit but a reduction in cardiac output (CO). In phase II, QL was reduced 35% with pretreatment; the L/P ratio did not rise as much and the PAP was unchanged. There was also a 35% reduction in lymph flow; no change in the lymph to plasma protein ratio but there was an elevation in pulmonary microvascular pressure. Pretreatment with GM diminished the fall in CO and the rise in TPR seen with endotoxin. The values were unaffected by treatment alone.