Hyperglycemia and the vascular effects of cerebral ischemia

Background and Purpose A well-demarcated infarct was observed after 4 hours of rat middle cerebral artery (MCA) occlusion with xylazine/ketamine but not pentobarbital or isoflurane anesthesia. This study examined whether this reflected vascular changes and, because xylazine induces hyperglycemia, whether glucose could cause similar vascular effects in cerebral ischemia. Methods To examine the effects of anesthetics, rats were anesthetized for thread occlusion of the MCA with either xylazine/ketamine, pentobarbital, or isoflurane. To evaluate the effects of glycemia, acute hyperglycemia was induced by glucose injection. In both experiments, cerebral plasma volume (CPV) was determined using H-3-inulin after 4 hours of permanent occlusion, and cerebral blood flow was measured using [C-14]iodoantipyrine following 2 hours of reperfusion after 2 or 4 hours of occlusion. The presence of cerebral hemorrhage after reperfusion was checked macroscopically and infarct volume with 2,3,5-triphenyltetrazolium staining. Results The ischemic CPV was about 50% of the contralateral values with xylazine/ketamine but not with the other anesthetics. On reperfusion, ischemic cerebral blood flow with xylazine/ketamine anesthesia was approximately half that with pentobarbital. Use of xylazine/ketamine also resulted in more frequent hemorrhagic infarcts and a larger infarct volume. Induced hyperglycemia resulted in a CPV decrease in the ischemic compared with nonischemic tissue (4.0+/-0.5 versus 7.4+/-0.2 mu L/g; P<.001). Hyperglycemia also caused poor reperfusion and increased the occurrence of hemorrhagic infarction (hyperglycemia, 15 of 20; normoglycemia, 1 of 11; P<.01). Conclusions Hyperglycemia induces marked cerebrovascular changes, both during ischemia and during reperfusion, that may exacerbate tissue damage. Change in CPV during ischemia may be a useful clinical indicator in predicting poor hemodynamic recovery and occurrence of hemorrhagic infarction after reperfusion therapy.