| Background&ObjectiveDrag-reducing polymers (DRPs) were found to decrease peripheral vascular resistance, improve organ and tissue perfusion in different animal models. In a canine model of acute flow-limiting coronary stenosis, DRPs were shown to reduce microvascular resistance and improved myocardial perfusion. Besides, recent studies have shown DRPs prolonged survival time in rats with acute myocardial infarction (MI), but their effect on cardiac function post MI remains unknown. This study sought to assess the effect of DRPs on microcirculation in vivo and to test the hypothesis that the intravenous infusion of DRPs may improve left ventricular (LV) function in rats with surgically induced MI.MethodsDRPs were prepared by using a commercial polyethylene oxide (PEO) with an average molecule weight of 5×106 Dalton and dialyzed against saline for 6 days to remove low MW impurities. The ability of PEO to reduce resistance to turbulent flow was evaluated by an in vitro circulating system. Flow rates and the corresponding driving pressures before and after PEO addition were recorded.To assess the effect of DRPs on microcirculation in vivo,20 male Sprague-Dawley rats were used for hydrodynamic study. The right spinotrapezius muscle was surgically exteriorized and prepared for microscopy obsevervation using the technique described by Gray. Vessel diameter, centerline RBC velocity, calculated arteriolar wall shear rate and shear stress in third-order vessels before and after PEO were recorded.MI was induced by ligation of the left anterior descending coronary artery in 36 Sprague-Dawley rats, and sham operations were performed in 12 animals.50μg/ml concentration of DRPs solution were then administered to 18 of the MI rats at a constant rate of 3.5 ml/h.24h after MI, echocardiograpy was used to evaluate the changes of cardiac dimensional diameters and impaired LV function. Global wall motion and myocardial perfusion were semi-quantified by indexes of wall motion score index (WSMI) and contrast score index (CSI). To determine intra-and interobserver variability of echocardiography, data from a randomly selected subset of 8 MI rats were analyzed by two independent observers. Assessment of agreement between the two examinations was performed according to the method of Bland and Altman. Viscosity and shear rate data were generated by a rheometer.ResultsThe addiction of PEO to circulating system produced a marked reduction in the pressure drop required to achieve a particular flow rate, suggesting a decrease in flow resistance. The drag reduction effect of PEOs with 5 X 106 Dalton was 33.61%, while Dextran with the same molecule weigth had no drag-reduciotn effect.Hemodynamic study showed that after administration of DRPs, RBC velocity was elevated by 16.67±4.30%％by 5min and 37.37±6.82％％by 30min. DRP was associated with a 4.92±1.52％dilation of arteriole at 5 min (P<0.05 vs baseline) and the dilation reached its peak by 7.85±1.18％at 30 min time point (P< 0.001 vs baseline). Administration of DRPs caused a markedly augmentation in blood flow, ranging from 29.33±7.38％to a maximal of 60.82±10.41%.DRPs also showed beneficial effects on calculated wall shear stress in third-order arteriole of rat spinotrapezius muscle.24h following MI, the survival rate was significantly different among the sham, MI and DRP groups (P= 0.023).24h post infarction, DRP-treated animals had marked smaller left ventricular end-systolic diameter (P< 0.01, better anterior systolic wall thickness (P< 0.001). Significant improvement of fractional shortening and ejection fraction were detected in MI rats with DRP (P＜0.001 and 0.05, respectively). Wall motion score index and contrast score index were both significantly reduced in DRP group compared with that in NS group (both P＜0.001). Reproducibility analysis of echocardiography showed the variability of both intra-and inter-observervation was smaller for LV dimensions (ranging from 3.11±3.83％to 8.77±8.91％), but relatively greater for wall thickness (ranging from 10.17±8.24% to24.3±18.3%). However, the coefficients of variability in intra-and inter-observe were greater for LV dimensions than that for.wall thickness. Comparison using pair t-test between two measurements showed no systematic error (all P>0.05).Viscosity data revealed that at the concentration of 2.5 ppm in our study, DRP had no effect on blood viscosity.ConclusionPEOs with 5×106 Dalton molecule weight were shown to have good drag reduction effect. Intravenous infusion of DRPs improved microcirculation in spinotrapezius muscle model in rats. Acute administration of DRPs improved LV function in a rat model of MI possibly by improving microvascular blood flow due to their unique hydrodynamic properties. DRPs may offer a novel approach to the treatment of coronary artery ischemic diseases. |
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