EFFECT OF H-1-ANTAGONISM ON CARDIOVASCULAR, PULMONARY, AND IMMUNOLOGICAL DYSFUNCTION IN PORCINE ENDOTOXIC-SHOCK

The definite role of histamine in early hyperdynamic septic shock is n ot yet clear. Therefore a randomized, controlled, blind trial was perf ormed to investigate the effect of the H-1-antagonist dimethindene in hyperdynamic porcine shock. Lipopolysaccharide (LPS) infusion (5 mu g/ kg/h) in anesthetized pigs (n = 6) in the control-group induced a hype rdynamic shock state with a decrease in mean arterial blood pressure, and systemic vascular resistance (SVR), and an increase in mean arteri al pulmonary pressure and pulmonary vascular resistance (PVR). In the verum group (n = 6) dimethindene (2 mg/kg) administered 15 min before LPS application prevented the decrease in SVR significantly (p < .05) and ameliorated the increase in MPAP and PVR. The impairment in pulmon ary function, as measured by the oxygenation ratio (PaO2/FiO(2) in LPS -treated animals, was reduced by the H-1-antagonist (p = .01). Tissue oxygenation was ameliorated by the H-1-antagonist treatment, as demons trated by plasma lactate levels and base excess values (p < .05, contr ol group versus dimethindene group). The increase in tumor necrosis fa ctor alpha by LPS infusion was not influenced by H-1-antagonist pretre atment. The early decrease in SVR did not correlate with an enhanced n itric oxide formation, as measured by nitrate/nitrite plasma levels.