Antihistamines Block Radiation-Induced Increased Intestinal Blood Flow in Canines

Antihistamines Block Radiation-Induced Increased IntestinalBlood Flow in Canines. COCK-ERHAM, L. G., DOYLE, T. F., DONLON,M. A., AND GOSSETT-HAGERMAN, C. J. (1985). Fundam. Appl. Toxicol.5, 597–604. Radiation-induced systemic hypotension isaccompanied by increased intestinal blood flow (IBF) and anincreased hematocrit (HCT) in dogs. Histamine infusion leadsto increased IBF and intestinal edema with consequent secretionof fluid into the intestinal lumen. This study was performedto determine whether these effects could be diminished by prioradministration of H₁ and H₂ histamine blockers. Dogs were givenan iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25mg/min) for 1 hr before and for 1 hr after radiation (H₁ andH₂ blockers, respectively). Mean systemic arterial blood pressure(MBP), IBF, and HCT were monitored for 2 hr. Systemic plasmahistamine levels were determined simultaneously. Data obtainedindicated that the H₁ and H₂ blockers, given simultaneously,were successful in blocking the increased IBF and the increasedHCT seen after 100 Gy, whole-body, radiation. However, thepostradiation hypotension was only somewhat affected, with theMBP falling to a level 28% below the preradiation level. Plasmahistamine levels reached a sharp peak, as much as 20% abovebaseline, at 4 min postradiation. These findings implicate histaminein the radiation-induced increase in IBF and HCT but not forthe gradual decrease in postradiation blood pressure