Protection of focal cerebral ischemia by alkalinization of systemic pH

OBJECT: It has been demonstrated in many studies that intracellular brain acidosis during cerebral ischemia is a significant factor, in perpetuating the cycle of cellular dysfunction, leading to neuronal injury. The purpose of this study was to determine whether preischemic administration of alkalotic agents could reduce neuronal injury. after focal cerebral ischemia. METHODS; Fifteen fasted rabbits under 1.0% halothane anesthesia were randomized into three groups: Group 1 rabbits were ischemic controls (n = 5) that underwent 4 hours of focal cerebral ischemia. Groups 2 and 3 rabbits underwent a paradigm similar to that of Group 1, except that they were pretreated with either sodium bicarbonate or Carbicarb at similar buffering capacities. Intracellular brain pH (pH(i));, regional cortical blood flow (rCBF), and intrinsic reduced nicotinamide adenine dinucleotide (NADH) fluorescence were measured with in vivo. fluorescence imaging. At the end of each experiment, infarct volume expressed as a percentage of hemispheric, volume was measured by triphenyltetrazolium chloride staining. RESULTS: Preischemic alkalinization did not alter brain pHi, rCBF, or NADH fluorescence. After 4 hours of ischemia, brain pHi, rCBF,NADH fluorescence, and infarct, volume measured 6.40 +/- 0.09 (mean standard error), 11 +/- 2 ml/100 g/min, 165 +/- 8% of baseline control, and 37 +/- 3% in ischemic controls, respectively. In-Group 2 animals treated with sodium bicarbonate, brain pHi, rCBF, NADH. fluorescence, and infarct volume improved significantly (P < 0.05, analysis of variance) to 6.74 +/- 0.08, 24 +/- 6 ml/100 g/min, 137 +/- 6% of baseline control, and 22 +/- 4% respectively. Group 3 Carbicarb animals demonstrated improvements in brain pHi, rCBF, and NADH fluorescence, with a significant reduction in infarct volume. CONCLUSION: These findings suggest that pretreatment with alkalinizing agents may be a useful :intervention to provide intraoperative cerebral protection from ischemic injury.