Blood rheological status is studied in Wistar rats with cerebral ischemia induced by ligation of the left coronary artery and reduced blood flow via the right coronary artery. Substantial changes in blood rheology and manifestations of the sludge syndrome are noted. The results obtained are compared with clinical observations, and the informativeness of each parameter is evaluated. Key Words: cerebral ischemia; blood rheologyNumerous clinical trials show that the sludge syndrome aggravates myocardial infarction [ 1,6], ischemic stroke [10,13], essential hypertension [11], etc. Therefore, it is necessary to investigate the mechanisms of this syndrome and develop pharmacological means of correcting blood rheological disorders. The aim of the present study was to create an adequate animal model of the sludge syndrome in cerebral ischemia to analyze the interplay and informativeness of rheological parameters. MATERIALS AND METHODSExperiments were carried out on 20 male rats weighing 200-250 g. Ischemia was modeled as described previously [8]. The following parameters were measured 5, 7, and 10 days after ischemia: relative viscosity of the blood and plasma (on a VK-4 capillary viscosimeter), erythrocyte aggregation (half-time of aggregate formation, Tin, i.e., the time during which the signal amplitude decreased 2-fold), hematocrit (in an MGC-8 microcentrifuge), and plasma content of fibrinogen [2]. The results were processed using Student's t test, nonparametric Wilcoxon test, correlaInstitute of Pharmacology, Tomsk Research Center, Siberian Division -of the Russian Academy of Medical Sciences tion analysis, and a geometrical approach to evaluation of informativeness of the parameters [7]. RESULTSOn day 5 after cerebral ischemia, blood viscosity in rats with cerebral ischemia was significantly higher than in intact controls and remained at this level up to the 10th day; the tendency towards normalization (on day 7) was statistically insignificant (Table 1). The increase in blood viscosity is consistent with that occurring in patients with cerebral ischemia [5,12]. In our experiments, blood viscosity was increased due to enhanced aggregation of erythrocytes and hyperfibrinogenemia persisting throughout the experiment. This conclusion is based on the results of correlation analysis showing that blood viscosity positively correlates with both spontaneous erythrocyte aggregation (r=0.96, p=0.04) and fibrinogen content (r=0.97, p--0.03). The presence of the mechanisms responsible for the increase in blood viscosity upon enhanced erythrocyte aggregation is confirmed by the finding that erythrocyte aggregation correlates with plasma fibrinogen content (r=0.95, p=0.048). Despite sustained hyperfibrinogenemia, plasma viscosity in rats with cerebral ischemia did not differ from that in the controls. Plasma viscosity tended to decrease on days
In comparison with Wistar rats, SHR rats demonstrated significantly higher viscosity of the whole blood and plasma, fibrinogen content, and erythrocyte aggregation, but a lower erythrocyte deformability. The differences in hemorheological indices in SHR and Wistar rats correspond to the deviation of these indices in the blood hyperviscosity syndrome observed in hypertensive patients.Key Words: arterial hypertension; blood hyperviscosity syndrome; SHR rats Both essential and arterial hypertension are characterized by significant deviation of some rhealogical indices and their combinations [3,6,8,9, 11-17l, which are the manifestations of the blood hyperviscosity syndrome (BHVS) in these patients.In order to develop adequate experimental models of BHVS for the search of new hemorheological drugs, we carried out a comparative study of the hemorheological indices in Wistar and SHR rats. MATERIALS AND METHODSExperiments were carried out on 15 male Wistar and SHR rats bred from the strain of the Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences. Blood was collected from carotid artery under ether narcosis. The following parameters were measured: relative viscosity of the whole blood and plasma (in a VK-4 capillary viscosimeter), hematocrit (in an MGC-8 microcentrifuge), plasma fibrinogen [1], erythrocyte aggregation [41, and deformability 121 at a shear rate of 890 sec -I. Arterial pressure was measured before blood collection. The results were statistically analyzed using Student's t test and Wilcoxon's nonparametric test. Institute of Pharmacology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences RESULTSThe mean arterial pressure was 143+5 mm Hg in SHR rats and 95+3 mm Hg in Wistar rats.Basic hemorheological parameters were significantly different in these rats (Table 1). in SHR rats, the viscosity of the whole blood and plasma was increased by 29 and 27%, respectively. Plasma fibrinogen was increased 1.5-fold. The half-time of erythrocyte aggregation (T~/2) and erythrocyte deformability index were decreased to 68% and by 12%, respectively. A significant correlation between whole blood viscosity and erythroeyte aggregability (r=0.71), blood viscosity and plasma fibrinogen (r=0.72), erythrocyte aggregability and plasma fibrinogen (r= 0.85) was revealed in SHR rats. Direct relation of reversible erythrocyte aggregation to fibrinogen content in patients with arterial hypertension was also shown by other researchers [141.Taking the hemorheological indices in Wistar rats as the control values, the hemorheological status of SHR rats can be determined as a variant of BHVS (Type VII according to [51). Comparison of our data with clinical evidence corroborates this hypothesis.The patients with essential hypertension (EH) have increased viscosity of the whole blood, which is an integral index characterizing BHVS [3,6,10,13,17]. By its relative value this increase is similar 0007-4888/98/0008-0775520.00 01999 Kluwer Academic/Plenum Publishers
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