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Sun Ho Lee, Roberto C. Heros, John C. Mullan, and Kazuyoshi Korosue

✓ The ability of hemodilution to lower blood viscosity and increase cerebral blood flow has been proven experimentally; however, the optimum hematocrit for maximum oxygen delivery to ischemic brain tissue is not known, and a study was designed to determine this. Fifty dogs were selected for inclusion in the study using criteria based on changes in somatosensory evoked potentials at the time of arterial occlusion, which were found in a previous study to predict the development of a moderate infarction of relatively constant size. Infarctions were induced by permanent occlusion of the left middle cerebral artery and the azygous anterior cerebral artery. The animals selected for inclusion were divided into five groups of 10 dogs each: 1) a control group; 2) a group with 25% hematocrit; 3) a group with 30% hematocrit; 4) a group with 35% hematocrit; and 5) a group with 40% hematocrit. Isovolemic hemodilution was accomplished 1 hour after occlusion of vessels using dextran infusion and blood withdrawal. The animals were sacrificed after 6 days and infarction volume was determined from fluorescein-stained sections. Statistical analysis was performed using Student's t-test and one-way analysis of variance.

Mean infarction volume for each group, expressed as a percentage of total hemispheric volume ± 1 standard error of the mean, was 28.3% ± 2.8% for the control group, 33.6% ± 3.4% for the 25% hematocrit group, 17.1% ± 2.2% for the 30% hematocrit group, 29.2% ± 4.3% for the 35% hematocrit group, and 29.9% ± 2.1% for the 40% hematocrit group. The 30% hematocrit group showed the smallest average infarction size and this size differed significantly (p = 0.02) from the average infarction size in the control animals. These results show that, in this model of focal ischemia, a hematocrit of approximately 30% is optimum for protecting the brain.

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Kazuyoshi Korosue, Roberto C. Heros, Christopher S. Ogilvy, Akio Hyodo, Yong-Kwang Tu, and Robert Graichen

✓ Forty dogs were subjected to 6 hours of occlusion of the left internal carotid and middle cerebral arteries. They were divided into two “hemodilution groups” of 13 dogs each and a control “nonhemodiluted group” of 14 dogs. Thirty minutes after arterial occlusion, isovolemic hemodilution was performed by phlebotomy and infusions of low-molecular weight (MW) dextran in one group and of lactated Ringer's solution in the other group. The animals were sacrificed 1 week after temporary arterial occlusion.

Hemodilution reduced the hematocrit to a level of 33% to 34%, which lasted throughout the week in both groups. After hemodilution there was a very significant reduction in blood viscosity, plasma total protein content, and fibrinogen levels in both groups in the acute stage; these levels gradually returned to baseline by the end of the week. In the group with lactated Ringer's solution hemodilution, both osmotic and oncotic pressures were decreased by hemodilution in the acute stage. In the control and low-MW dextran groups, osmotic and oncotic pressure remained unaltered throughout the week. Hemodilution resulted in a slight decrease in mean arterial blood pressure in all groups in the acute stage, but there were no significant changes in central venous, pulmonary arterial, or pulmonary wedge pressures. During the week of study, there were no differences in the cardiac index and total blood volume between the groups, and no significant changes in hematological parameters with the exception of a slight increase in bleeding time immediately after hemodilution with low-MW dextran.

Daily neurological assessment showed consistently poorer condition during the first 5 days in the group with lactated Ringer's solution compared to either the control group or the group receiving low-MW dextran. Based on Mann-Whitney U-testing, the infarct volume of the lactated Ringer's solution recipients, expressed as a percentage of the total volume of that hemisphere (median 15.7%, range 6.6% to 25.2%) was significantly larger than that of the group receiving low-MW dextran (median 2.2%, range 0% to 15.8%) and that of the control group (median 11.9%, range 0% to 39.9%). The results indicate that, in this model, hemodilution with colloids was beneficial, whereas hemodilution with crystalloids was deleterious. It is likely that the decrease in oncotic pressure observed after hemodilution with lactated Ringer's solution is one of the most important reasons for its detrimental effect.