H1-antagonism improves intestinal mucosal pH and heart function in porcine hypodynamic endotoxic shock.
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.
Dimmeler
S
S
Medical Clinic IV, University of Frankfurt, Germany.
Kum
C K
CK
Troost
C
C
Auweiler
M
M
Lechleuthner
A
A
Nagelschmidt
M
M
Neugebauer
E
E
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002303:Cardiac Output, Low / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D018476:Hypokinesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006634:Histamine H1 Antagonists; D014409:Tumor Necrosis Factor-alpha