Isovolemic hemodilution normalizes the prolonged passage of red cells and plasma through cerebral microvessels in the partially ischemic forebrain of rats

Abstract

The objective of this study was to determine whether hemodilution could normalize the mean transit times of red blood cells (Tr) and plasma (Tp) through cerebral microvessels in a partially ischemic brain. Wistar-Kyoto (WKY) rats, aged 30-40 weeks, were divided randomly into three groups. The first group was the nonocclusion, nonhemodilution (NN) normal control group. The second group was the occlusion, nonhemodilution (ON) group, in which animals were treated with bilateral carotid artery ligation. The third group was the occlusion-hemodilution (OH) group, in which animals were treated with bilateral common carotid artery ligation and, then, isovolemic hemodilution by replacing blood with the same volume of 3% modified fluid gelatin. Local cerebral blood flow (ICBF) and microvascular volumes of red blood cells (Vr) and plasma (Vp) in 14 brain structures were measured using 14C- iodoantipyrine, iron-55-labeled red blood cells, and 14C-inulin, respectively. The amount of oxygen delivered to local brain structures (OD), cerebral microvascular blood volume (Vb), mean transit time of blood (Tb), Tr, and Tp through cerebral microvessels were calculated from the data. Two hours after carotid artery ligation, ICBF decreased by ~38% in forebrain structures, 22% in rostral hindbrain areas, and 8% in the caudal hindbrain (29% for all 14 structures). The decreases in ODs were parallel with those of ICBFs, at 33, 17, and 2% in the three regions, respectively (24% for all structures). In contrast, Vb increased by 68, 37, and 16% in the three regions, respectively (48% for all structures). Tr and Tp were markedly prolonged (180% for Tr and 154% for Tp) in the forebrain regions, moderately (91% for Tr and 73% for Tp) in the rostral hindbrain, and mildly (60% for Tr and 13% for Tp) in the caudal hindbrain, with a mean increase of 136% for Tr and 111% for Tp in all structures. When data in the OH and NN groups were compared, ICBF values tended to be slightly higher and Vb values were significantly higher (p < 0.05) in the OH group. ODs in the eight forebrain structures were all significantly less (p < 0.05) in the OH group than the NN group. Tr and Tp values in the forebrain were similar between the OH and the NN groups. In conclusion, occlusion of the bilateral common carotid arteries in WKY rats causes partial forebrain ischemia, in which both Tr and Tp are prolonged. These prolongations of Tr and Tp can be normalized by isovolemic hemodilution. However, the ischemic forebrain remains hypoxic after hemodilution.