Role of hypervolemic hemodilution in focal cerebral ischemia of rats

Abstract

This study was designed to better define a protocol for hypervolemic hemodilution in acute cerebral ischemia and investigate the mechanism of action of this therapy. Anesthetized rats (n = 40) were subjected to 6 h of middle cerebral artery (MCA) occlusion. At 45 min after MCA occlusion, each rat received one of the following treatment modalities: (1) control, (2) isovolemic hemodilution, (3) hypervolemic nonhemodilution (whole blood), (4) hypervolemic hemodilution (normal saline), and (5) hypervolemic hemodilution (hetastarch). Local cerebral blood flow (CBF) was determined with hydrogen clearance technique, and cardiac output was assessed by measuring the descending aorta blood flow (DAF). Infarction volume was estimated by 2,3,5-triphenyltetrazolium chloride staining method. Hetastarch infusion increased both DAF and local CBF more than the other treatments, by 98% and by 89%, respectively. Hetastarch also reduced infarction volume the most to 71 +/- 19 mm3 (p < 0.01 versus control 117 +/- 32 mm3). A significant correlation between percent (%) changes in local CBF and % changes in DAF existed in ischemic brain regions, and the hetastarch infusion improved local CBF more prominently in profoundly ischemic regions in contrast to isovolemic hemodilution. These data demonstrated the superiority of hypervolemic hemodilution with hetastarch as compared to other similar treatment modalities for acute cerebral ischemia, and indicate that cardiac output augmentation may be more responsible than decreased blood viscosity for the beneficial effect of hypervolemic hemodilution on local CBF in profoundly ischemic regions, as such ischemic brain tissue can severely lose its regulatory control of CBF to alterations in cardiac output.