| With the improvement of people's living standards and the aging tendency of population, the prevalence of the coronary heart disease has been increasing. The number of patients with coronary heart disease accounted for 30% of all the hospitalized patients with heart diseases and the coronary heart disease was in the second place of all death causes in 1990s. The extensive applications of revascularization therapies such as thrombolysis, percutaneous coronary intervention(PCI), coronary artery bypass grafting(CABG) and so on have made the mortality and disability rate of the acute coronary syndrome(ACS) decrease significantly, thus improved patients'living quality.It is well known that revascularization has brought great benefits to patients with acute myocardial infarction, but after successful opening of infarction-related coronary arteries, the microcirculatory perfusion of related cardiac muscles in as high as 80% of patients can not be completely back to normal. There happen cardiovascular events in 5%-6% of patients during 30-day of follow-up. The extent of microcirculation damage is directly related to the mortality and complications of acute myocardial infarction. In other words, the blood flow of large epicardial coronary arteries can be restored and high scores of blood flow grading can be obtained by revascularization treatment, but the damage of microcirculation, which is in the cardiac muscle areas dominated by "crime" blood vessels, make the related cardiac muscle can not be fully perfused, and low perfusion and no-reflow phenomenon of cardiac muscle after revascularization remain the heated topics in the treatment researches of acute coronary syndrome.The microcirculation dysfunction after reperfusion is usually caused by ischemical reperfusion injuries which include such factors as embolism caused by platelet thrombus and its derivates, microvascular contraction, calcium overload, leukocyte adhesion, endothelial dysfunction local edema and so on. For the treatment of acute coronary syndrome, opening the large epicardial coronary arteries as soon as possible has been resolved, but how we can deal with the microcirculation low perfusion and no-reflow phenomenon caused by reperfusion injury? So how to improve the microcirculation perfusion has become an urgent problem needed to be solved.In 1950s Toms was the first person to report that under the condition of unchanged driving pressures, adding a small amount of high molecular polymer into fluid can lower the force of resistance and increase the flow rate of fluid significantly, moreover it had no impact on the viscosity and density of the fluid when the polymer was in its effective concentration. This phenomenon is named "Toms effect", and those high molecular polymer is called "drag reducing polymers, DRPs". DRPs applications in the biomedical field have been under people's great attention.DRPs used in biological fields are a kind of large molecules with linear structure (usually more than 106 Da), which are water-soluble and fat-soluble and have no toxic effects on the body. DRPs also have the characteristics of good biocompatibility and slow degradation in vivo. Commonly used DRPs include polyethylene oxide(PEO), Aloe vera derived DRP (AVP), polyethylene lycol(PEG), polyacrylamide(PAM), poly-N-vinylformamide (PNVF).Preliminary studies have found that DRPs can increase blood perfusion of the tissues and organs without affecting the vascular tone and blood viscosity, they can also increase the volume of blood flow of narrow arteries without changing the perfusion pressure, improve microcirculation perfusion of shock animals to antagonize shock, prevent or delay the formation of atherosclerosis, be diuretic and improve renal function, reduce the damage of mechanical action on the red blood cells and so on.Foreign studies have shown that DRPs can improve the survival rate of rats with acute myocardial infarction, lower the myocardial capillary resistance of dogs and increase the flow rate of the red blood cells in the microcirculation. After establishing the rat model of the acute myocardial infarction, my research group made used of echocardiogram and contrast ultrasound to evaluate the effects of DRPs on the function of left ventricular after the acute myocardial infarction, and the results showed that DRPs can significantly improve the perfusion of acute ischemic myocardium and cardiac function of rats, but its mechanism remains to be further explored.Based on the actions of DRPs mentioned above, we think that DRPs may have important values to improve reperfusion injury after revascularization for the acute coronary syndrome. Therefore, by studying the effects of PEO on the red blood cell velocity of rat cremaster micro-circulation and myocardial ischemia-reperfusion injury, we try to elaborate the mechanism of PEO and observe its impact on myocardial ischemia-reperfusion injury.Objectives:The purpose of present Study was to investigate the drag-reducing effect of polyethylene oxide (PEO) on the velocity of red blood cells in rat cremaster microcirculation. Methods:Six Wistar male rats (100-110 g) were studied. and the blood samples were collected from their post-orbital venous plexus. The red blood cells were separated by centrifugation and labeled by fluorescinisothiocyate (FITC).After the successful establishment of cremaster model, the labeled red blood cells were injected into jugular vein, and then microcirculation was observed and recorded under the fluorescence microscope. Hemodynamic parameters and microcirculation video was record repeatly every 4 min since 4 min before PEO or normal saline injection. Both PEO (10 ppm) and normal saline was injected into the same rat in random sequence. One between PEO and normal saline was injected continually at a constant rate of 3.5 ml-h"1 for 20 min, and additional 20 min observation was continued. After that, the remained one was given in the same way. The volecity of the labeled-red blood cells was determined by IPP 6.0 software.Results:Compared with normal saline, PEO could increase significantly the velocity of the red blood cells in the rat cremaster microcirculation (498.7±182.89μm/s vs 773.54±308.27μm/s, P=0.012). There were no significant changes in terms of heart rate and arterial blood pressure (P=0.836, P=0.420).Conclusion:PEO that was at a extremely low concentration could increase significantly the velocity of the red blood cells in the rat cremaster microcirculation and had no significant impact on the heart rate and arterial blood pressure.[Objective] To investigate into the effects of PEO on the microcirculation perfusion of rat cardiac muscle and its mechanism by observing the protective effects of PEO, a long-chain high molecular polymer which plays the drag-reducing effect in the blood vessels, on the myocardial ischemia-reperfusion injury of rats.[Methods] Six Wistar male rats were randomly divided into four groups:treatment group I (rats were given PEO immediately after coronary artery ligation); treatment group II (rats were given PEO immediately after reperfusion); control group I (rats were given normal saline immediately after coronary artery ligation); control group II (rats were given normal saline immediately after reperfusion). After the successful establishment of the rat model with acute myocardial infarction, the rats in the treatment groups were given PEO (lOppm) through the jugular vein continually for 30 minutes at the speed of 5ml·h-1 and the rats in the control groups were given normal saline through the jugular vein continually for 30 minutes at the speed of 5ml-h-1. By detecting the left ventricular pressure, electrocardiogram, the cardiac blood flow quantification, markers of myocardial infarction and reperfusion injury, and myocardial infarction areas, we aim to evaluate the protective effects of PEO on the myocardial ischemia-reperfusion injury of rats.[Results] In comparison with the control group I, the incidence of reperfusion VT,VF and mortality rate were lower (χ2=11.221,P=0.001;χ2=4.571, P=0.033;χ2= 4.571, P=0.033); parameter+dp/dtmax reflecting left ventricular systolic function after reperfusion was improved more significantly (1204.31±77.26 Kpa/s vs 849.74±92.16 Kpa/s, P=0.000); the cardiac perfusion volumes of ischemic regions after reperfusion were larger (A'·β,0.12±0.02 vs 0.05±0.01, P=0.000); the concentrations of cardiac troponin were lower after perfusion (1.50±0.47 ng/L vs 3.94±0.76ng/L, P=0.000); the myocardial areas of infarction was smaller (23.26±1.88% vs 48.90±2.66%, P=0.000), the expressions of superoxide dismutase (SOD) of myocardial tissues were higher(37.94±3.62 U/mg pro vs 10.14±0.73 U/mg pro, P=0.000) and the expressions of the malondialdehyde (MDA) of myocardial tissues were lower (0.84±0.06nmol/mg pro vs 2.40±0.19nmol/mg pro, P=0.000) in the treatment group I. In contrast with the control groupⅡ, the incidence of reperfusion VT,VF and mortality rate were lower (χ2=11.221, P=0.015;χ2= 0.183, P=0.669;χ2= 0.183, P=0.669), parameter+dp/dtmax reflecting left ventricular systolic function after reperfusion was improved more significantly (941.40±85.14 Kpa/s vs 821.78±59.61 Kpa/s, P=0.000). the cardiac perfusion volumes of ischemic regions after reperfusion were larger (A'·β,0.13±0.03 vs 0.06±0.02, P=0.000); the concentrations of cardiac troponin were lower after perfusion (2.59±0.77 ng/L vs 3.85±0.78 ng/L,P=0.000); the myocardial areas of infarction was smaller (31.64±1.54% vs 51.25±2.60%, P=0.000); the expressions of SOD of myocardial tissues were higher(23.68±2.49 U/mg pro vs 10.64±0.75 U/mg pro; P=0.000); the expressions of the MDA was lower (1.17±0.1 Onmol/mg pro vs 2.28±0.07nmol/mg pro, P=0.000) in the treatment groupⅡ. Comparing to the treatment groupⅡ, the incidence of reperfusion VT,VF and mortality rate were lower(χ2=4.571, P=0.033;χ2=4.571, P=0.033;χ2=4.571, P=0.033). left ventricular systolic function after reperfusion was improved more significantly (1204.31±77.26 Kpa/s vs 941.40±85.14 Kpa/s, P=0.000); the cardiac perfusion volumes of ischemic regions after reperfusion were no significant difference between these two treatment groups (A'·β,O.12±0.02vs0.13±0.03, P=0.280); there are more advantages in terms of improving cardiac ischemia-reperfusion injury, decreasing the concentrations of cardiac troponin (1.50±0.47 ng/L vs 2.59±0.77 ng/L, P=0.004); increasing expressions of SOD of myocardial tissues (37.94±3.62 U/mg pro vs 23.68±2.49 U/mg pro, P=0.000); decreasing the expressions of the MD A (0.84±0.06nmol/mg pro vs 1.17±0.1 Onmol/mg pro, P=0.000) and reducing the infarction areas of cardiac muscle (23.26±1.88% vs 31.64±1.54%, P=0.000) in the treatment group I.[Conclusions] PEO could offer protection by increasing myocardium perfusion of ischemic areas, improving the markers of myocardial ischemical reperfusion injury of rats and decreasing the incidence of arrhythmia. If given before reperfusion, PEO could still significantly improve the systolic function of the left ventricular, lower the concentrations of plasma cardiac troponin, and reducing the infarction areas of myocardium, so these results suggest that PEO has protective effects on myocardial ischemical reperfusion injury, especially given before reperfusion, PEO could significantly improve ischemic myocardial infarction and cardiac function.
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