| It has been shown that the reperfusion itself can induce a further injury on myocardium after ischemia,this phenomenon was named ischemia-reperfusion injury(IRI).If the ischemia-reperfusion injury could be treated and eliminated,the outcome for patients with myocardial infarct might further improve.So IRI is one of the most important phenomenon in the cardiovascular disease,understanding the mechanism and the influential factors will be helpful to the development of the cardiovascular interventional therapy,thrombolytic therapy and vascular surgery.Recent animal experiments has suggested that prenatal hypoxia can induce low birth weight,increase the cross-sectional area of the left ventricular myocytes in adult life,decrease the responsibility to angiotensinⅡ,and increase the susceptibility of adult heart to IRI。As one of the most important substances which relax the vascular in vivo,Nitric Oxide(NO) plays an important role in ischemia-reperfusion injury process.Nitric oxide synthase catalysis L-Arg to form Endogenous NO.There are three isomerides,among them inducible nitric oxide synthase and endothelial nitric oxide synthase involved in ischemia-reperfusion,the disproportion of the two isomerides lead to the metabolic disorder of nitric oxide.Our research will study if prenatal hypoxia increases heart susceptibility to ischemia-reperfusion injury in adult rat,and the effect of nitric oxide sythase in this phenomenon.Part One:Establishment of a rat model of prenatal hypoxia.Experimental animals and hypoxic exposure:Time-dated pregnant Sprague-Dawley rats were randomly divided into the control group and the continuous hypoxic exposure group.The hypoxic exposure group was placed in the air of 10.5%oxygen from day 15 to day 21 of gestation.Foods and water were provided as desired just as the control group.At 3 months of age,the male progeny were picked up as experimental animals.Part Two:Effect of prenatal hypoxia on susceptibility to ischemia-reperfusion injury in isolated adult rat heart.Pick up randomly 8 male progeny from the continuous hypoxic exposure group,do the same from the control group.Hearts of the progeny were isolated rapidly and were perfused in a Langendorff apparatus.The left ventricular function was assessed by measuring the LV systolic pressure(LYSP),LV end-diastolic pressure(LYEDP),coronary flow(CF),first derivatives of LV pressure(dp/dt),heart rate(HR).After basal recording,the hearts were subjected to the protocol of I-R: 30-minute ischemia with 60-minute reperfusion.LV functional parameters were recorded at the time of reperfusion.At the end of experiment,the left ventricles were collected,and the areas of myocardial infarction were expressed as a percentage of the total LV weight.The results showed there was no significantly difference in the basal LV function and coronary flow between two groups.Compared with the control group,the postischemic recovery of the LV function was significantly decreased and the area of myocardial infarction was significantly increased in hypoxic exposure group.It suggested that prenatal hypoxia can increase the heart susceptibility to ischemia-reperfusion injury in isolated adult rat heart.Part Three:The effect of prenatal hypoxia on nitric oxide synthase in perfusion flow of adult isolated heart.The activity of nitric oxide synthase and endothelial nitric oxide synthase in perfusion flow of adult isolated heart was measured.The study showed that compared with the control group the activity of endothelial nitric oxide synthase in perfusion flow of the hypoxic exposure group was significantly decreased.It suggested the decreased activity of endothelial nitric oxide synthase was one of the mechanisms which were involved in increased susceptibility to ischemia-reperfusion injury caused by hypoxic exposure.
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