H-1-ANTAGONISM IMPROVES INTESTINAL MUCOSAL PH AND HEART FUNCTION IN PORCINE HYPODYNAMIC ENDOTOXIC-SHOCK

Porcine hypodynamic shock was induced by continuous infusion of 5 mu g lipopolysaccharide/kg per hour. This resulted in a decrease of cardia c output from baseline values of 3.5 +/- .9 L/min to 1.5 +/- .8 L/min and a reduced left ventricular stroke work index in the endotoxin-grou p (n = 6 animals). Pretreatment with the H-1-antagonist dimethindene ( 2 mg/kg) in a second group (n = 6) significantly prevented these effec ts, Furthermore animals pretreated with the H-1-antagonist showed a st able mean arterial blood pressure, whereas the control endotoxin-treat ed group revealed a drastic reduction in mean arterial blood pressure (99 +/- 4.7 mmHg versus 65.8 +/- 10 mmHg after 240 min, respectively). Pulmonary function and systemic vascular resistance were not ameliora ted by the H-1-antagonist in hypodynamic shock, Gastrointestinal mucos al pH (pHi), which indicates oxygenation of the mucosa, was decreased by endotoxin-infusion (7.45 +/- .32 baseline value to 6.92 +/- .24 aft er 120 min). This parameter as well as base excess values and lactate levels were significantly improved by dimethindene-pretreatment (p < . 05). These results may indicate a beneficial effect of H-1-antagonist- pretreatment on endotoxin-induced deterioration of the microcirculatio n. Furthermore our results clearly demonstrated that only pretreatment before endotoxemia with H-1-antagonism is effective, since infusion o f H-1-antagonist in hypodynamic shock 45 min after addition of endotox in (n = 6 animals) did not improve the cardiovascular system or the mi crocirculation.