Mechanisms of cimetidine protection following thermal injury

Experimental studies have shown that treatment with cimetidine within 30 minutes of severe thermal injury decreases resuscitative fluid volume requirements by 70 percent. In treated animals, marked hemodynamic improvement was shown as compared with the untreated animals. Administration of the histamine (H2)-receptor antagonist ranitidine was not effective in reducing resuscitative fluid volume, leading to the hypothesis that cimetidine acts via predominantly non-H2-receptor antagonist mechanisms. Evidence is presented for a multifactorial mechanism by which cimetidine offers protection from burn shock. The mechanisms under investigation include inhibition of the hepatic cytochrome P-450 enzymes, cimetidine/copper scavenging of oxygen free radicals, inhibition of thromboxane synthesis, and imidazole buffering capacity. Acting via one or all of these mechanisms, cimetidine may protect against the vascular permeability changes and circulatory collapse that can follow severe thermal injury.