Histamine-2-receptor blockade does not affect hyperemia after cerebral ischemia in young swine.

OBJECTIVE: To determine whether histamine-2 (H2) receptor antagonists can blunt the increase in cerebral blood flow after cerebral ischemia.

DESIGN: Prospective, randomized trial.

SETTING: Animal laboratory.

SUBJECTS: Piglets aged 1 to 2 wks.

INTERVENTIONS: Three groups of piglets were anesthetized with pentobarbital, mechanically ventilated, and hemodynamically monitored. Each animal was randomized to receive one of three treatments 20 mins before ischemia: famotidine (0.6 mg/kg i.v.), cimetidine (5 mg/kg i.v.), or an equivalent volume of saline (3 mL). Ischemia was maintained for 15 mins by tightening ligatures around the brachiocephalic trunk and left subclavian arteries plus the induction of hemorrhagic hypotension (50 mm Hg). Reperfusion was initiated by the reinfusion of shed blood and removal of the ligatures.

MEASUREMENTS AND MAIN RESULTS: The three groups were not different with regard to baseline arterial blood gases, cerebral perfusion pressure, microsphere-determined cerebral blood flow, or oxygen consumption (VO2). Ischemia (cerebral blood flow < 5 mL/min/100 g of tissue) was demonstrated in all brain regions for all groups during arterial ligation with hemorrhage-induced hypotension. Blood flow rates were increased compared with preischemic values in all regions at 7 mins of reperfusion. For example, mean forebrain blood flow rates increased from 36 +/- 3 to 95 +/- 14 (SEM) mL/min/100 g of tissue in the group receiving saline, from 36 +/- 3 to 102 +/- 9 mL/min/100 g of tissue in the group receiving famotidine, and from 31 +/- 4 to 119 +/- 26 mL/min/100 g in the group receiving cimetidine. Overall, the three groups did not differ in regard to blood flow rates and cerebral VO2 values during ischemia and at 30 mins of reperfusion.

CONCLUSIONS: We demonstrated that famotidine or cimetidine as compared with saline did not affect the pattern or extent of hyperemia after ischemia. This finding does not support the hypothesis that a H2-receptor mechanism is necessary for postischemic hyperemia.