Effect of H1-antagonism on cardiovascular, pulmonary, and immunological dysfunction in porcine endotoxic shock.
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.
Dimmeler
S
S
Biochemical and Experimental Division, University of Cologne, Germany.
Lechleuthner
A
A
Auweiler
M
M
Troost
C
C
Nagelschmidt
M
M
Neugebauer
E
E
D000818:Animals; D004115:Dimethindene / Q000494:pharmacology*; D005260:Female; D008070:Lipopolysaccharides; D011652:Pulmonary Circulation / Q000187:drug effects; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D016019:Survival Analysis; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014655:Vascular Resistance / Q000187:drug effects
D008070:Lipopolysaccharides; D011969:Receptors, Histamine H1; D014409:Tumor Necrosis Factor-alpha; D004115:Dimethindene