Rat model of blood hyperviscosity syndrome: Informativity of blood rheological parameters in cerebral ischemia

Abstract

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

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