ABSTRACT
Porcine hypodynamic shock was induced by continuous infusion of 5 micrograms lipopolysaccharide/kg per hour. This resulted in a decrease of cardiac 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-group (n = 6 animals). Pretreatment with the H1-antagonist dimethindene (2 mg/kg) in a second group (n = 6) significantly prevented these effects. Furthermore animals pretreated with the H1-antagonist showed a stable mean arterial blood pressure, whereas the control endotoxin-treated 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 ameliorated by the H1-antagonist in hypodynamic shock. Gastrointestinal mucosal pH (pHi), which indicates oxygenation of the mucosa, was decreased by endotoxin-infusion (7.45 +/- .32 baseline value to 6.92 +/- .24 after 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 H1-antagonist-pretreatment on endotoxin-induced deterioration of the microcirculation. Furthermore our results clearly demonstrated that only pretreatment before endotoxemia with H1-antagonism is effective, since infusion of H1-antagonist in hypodynamic shock 45 min after addition of endotoxin (n = 6 animals) did not improve the cardiovascular system or the microcirculation.
Subject(s)
Cardiac Output, Low/drug therapy , Histamine H1 Antagonists/pharmacology , Hypokinesia/drug therapy , Intestinal Mucosa/drug effects , Shock, Septic/drug therapy , Animals , Blood Pressure/drug effects , Cardiac Output, Low/chemically induced , Cardiac Output, Low/metabolism , Heart Rate/drug effects , Hydrogen-Ion Concentration , Hypokinesia/chemically induced , Hypokinesia/metabolism , Intestinal Mucosa/metabolism , Lung Diseases/chemically induced , Lung Diseases/drug therapy , Lung Diseases/metabolism , Male , Microcirculation/drug effects , Shock, Septic/chemically induced , Shock, Septic/metabolism , Swine , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The definite role of histamine in early hyperdynamic septic shock is not yet clear. Therefore a randomized, controlled, blind trial was performed to investigate the effect of the H1-antagonist dimethindene in hyperdynamic porcine shock. Lipopolysaccharide (LPS) infusion (5 micrograms/kg/h) in anesthetized pigs (n = 6) in the control-group induced a hyperdynamic shock state with a decrease in mean arterial blood pressure, and systemic vascular resistance (SVR), and an increase in mean arterial 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 pulmonary function, as measured by the oxygenation ratio (PaO2/FiO2) in LPS-treated animals, was reduced by the H1-antagonist (p = .01). Tissue oxygenation was ameliorated by the H1-antagonist treatment, as demonstrated by plasma lactate levels and base excess values (p < .05, control group versus dimethindene group). The increase in tumor necrosis factor alpha by LPS infusion was not influenced by H1-antagonist pretreatment. The early decrease in SVR did not correlate with an enhanced nitric oxide formation, as measured by nitrate/nitrite plasma levels.
