Protective effects of a novel 21-aminosteroid during splanchnic artery occlusion shock

Abstract

We investigated the effects of a novel, non-glucocorticoid 21-aminosteroid, U74006F, in the pathogenesis of splanchnic artery occlusion (SAO) shock in rats. Pentobarbital-anesthetized (40 mg/kg) rats were subjected to 40 min of occlusion of both the celiac and superior mesenteric arteries followed by reperfusion, which resulted in a severe shock state characterized by a markedly lower mean arterial blood pressure (MABP) and a survival time of 40-80 min post-reperfusion. In contrast, infusion of U74006F (22.5 mg/kg) during the occlusion period resulted in a significantly higher MABP following reperfusion which prolonged survival (117 +/- 3 min vs. 66 +/- 10, P less than .01) compared to those rats receiving only the vehicle for U74006F (0.002 N HCl). Hematocrits measured at the end of each experiment were significantly lower in the treated shock rats compared to the untreated group (55.7 +/- 1.8 vs. 63.0 +/- 1.7, P less than .01). SAO shock rats treated with U74006F also exhibited significantly attenuated plasma accumulation of cathepsin D (P less than .05) and myocardial depressant factor (MDF) (P less than .01). Six of 7 SAO shock rats treated with U74006F survived for 120 min following reperfusion, while none of 7 SAO shock rats given the vehicle survived for 120 min (P less than .01). These results suggest that U74006F has therapeutic utility in SAO shock.