Forebrain ischemia in the rat: Relation between duration of ischemia, use of adjunctive ganglionic blockade and long-term recovery

Abstract

The relation between duration of ischemia, use of adjunctive ganglionic blockade and longterm recovery was studied in a rat model giving reversible subtotal forebrain ischemia. Ischemia was induced by bilateral carotid artery clamping and controlled hemorrhage to a mean arterial pressure of 50 mm Hg in animals artificially ventilated under 70% N2O. After variable lengths of time, the clamps were removed and the drawn blood was reinfused. In some animals, the ganglion blocker Arfonad® was given (group A +) on induction of ischemia to facilitate hypotension. There was a strict dose-response relationship between duration of ischemia and mortality. Mortality was higher among animals not given Arfonad (group A —; 37% after 10 min of ischemia and 100% after 13 min) than ingroup A + (about 20% after 12-13 min of ischemia, 50% after 15 min and 80% after 19 min). In group A + more than half of the animals died later than 24 h after ischemia. All of them were hyperexdtable and 12% died during witnessed epileptic fits. Group A— animals regularly died within the first 24 h, with no indication of central nervous system involvement. Less blood had to be drawn to attain hypotension (mean arterial pressure 50 mm Hg) in group A+ (1.5 ± 0.3 ml/100 g b.w.) than in group A— (2.5 ± 0.2 ml/100 g b.w.). Group A+ also had less “washout” acidosis 5 min after reinfusion of the shed blood than group A — (15 min of ischemia: pH 7.24 ± 0.07 v 6.96 ± 0.06). It is concluded that the model can be used reproducibly in studies on cerebral ischemia in the rat in which survival is required. If more than 10 min of ischemia is to be studied, Arfonad supplementation is necessary to avoid a general shock response to hemorrhage, which will contribute to mortality. © 1986 American Heart Association, Inc.