An evaluation of naloxone as a gastric cytoprotective agent during hemorrhagic shock.
Administration of naloxone, an opiate antagonist, is known to improve survival from hemorrhagic shock and to reverse the effects of septicemia on gastric mucosal O2 tension and potential difference (PD). We tested these potentially cytoprotective actions in the ex-vivo canine gastric chamber model with acid, bile, and hemorrhagic hypotension. Naloxone (2 mg/kg IV bolus, then 2 mg/kg/hr IV) was given before or during shock. Naloxone did not affect oxygen consumption, the bile-induced drop in PD, or the transmucosal oxygen consumption, the bile-induced drop in PD, or the transmucosal movements of H+, Na+, K+, and fluid. The reduction in average mucosal lesion formation with naloxone pretreatment (5.4 +/- 1.2 vs. 2.8 +/- 0.5%) was not statistically significant (p = 0.07). Similarly, administration of naloxone after the onset of shock also failed to protect the mucosa from stress ulceration. We conclude: 1) naloxone does not inhibit the effects of topical bile on the gastric mucosal barrier; 2) naloxone has no apparent effect on local gastric vascular resistance during hemorrhagic shock; and 3) the therapeutic potential of naloxone as an anti-ulcer drug is questionable. 24GM 23095
D000208:Acute Disease; D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy*; D013270:Stomach / Q000503:physiopathology; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications; D014882:Water-Electrolyte Balance
D001647:Bile Acids and Salts; D009270:Naloxone