We propose to study the effects of isovolemic hemodilution achieved by phlebotomy and infusions of low molecular weight dextran in a dog model of cerebral ischemia. Our hypothesis is that isovolemic hemodilution, by reducing viscosity and thus improving microcirculation, will result in a smaller infarct size when treated animals are compared with controls. One hundred dogs will be used over a three-year period. The animals will be divided into two groups of 50 animals. All dogs will be splenectomized 1 week prior to initiation of the study. One group of animals (Group A) will be studied acutely. In this group, 40 dogs will undergo temporary (6 hours) ligation of the distal internal carotid artery (ICA) and the proximal middle cerebral artery (MCA). Of these animals, one-half will have isovolemic hemodilution by phlebotomy and dextran injections immediately after arterial ligation. In addition, 10 dogs will be sham-operated. Of these, 5 will be subjected to isovolemic hemodilution and 5 will not. Regional cerebral blood flow, as determined by radionculide labeled microsperes, will be measured immediately after arterial ligation. 1 hour after hemodilution or at an equivalent time in non-hemodiluted animals, and one-half hour after termination of temporary occlusion (removal of the arterial clips 6 hours after initial placement). After the last injection of microspheres the animals will be perfused with tetrazolium chloride (TTC) and then will be sacrificed. Volume of brain infarction as determined by lack of staining with TTC will be estimated by planimetry. The second group of 50 animals (Group B) will also be divided into 40 dogs who will undergo temporary (6 hours) occlusion of the distal ICA and the proximal MCA and 10 dogs who will be sham-operated. Again, one-half of the dogs in each of these sub-groups will be subjected to isovolemic hemodilution immediately after arterial occlusion. These animals in Group B will not undergo blood flow measurements, but rather will be kept for a week for daily neurologic observation and then will be perfused with fluorescein and sacrificed at the end of the week for definitive histopathologic examination of the brains to determine the size of infarction. In all animals, hemodynamic and hematologic parameters to be monitored and then compared and correlated will include the following: intracranial pressure, systemic mean arterial pressure and pulse pressure, arterial blood gases, hematocrit, fibrinogen level, blood viscosity, central venous pressure, pulmonary artery pressure, cardiac output, blood volume, bleeding time, prothrombin time, and partial thromboplastin time.
