| Myocardial reperfusion injury is a paradox by which reperfusion, ultimately needed for long-term tissue survival after prolonged ischemia (myocardial infarction), may potentiate injury to the heart. Characteristics of reperfusion injury after myocardial ischemia involve: myocardial stunning, (reperfusion) arrhythmias, the no-reflow phenomenon (microvascular damage), and/or accelerated cell death. Of importance, reperfusion injury may account for as much as 25–60% of the total infarct volume following ischemia and reperfusion. Recently, apoptosis has been implicated in the death of myocardialcytes in animal models of myocardial ischemia and in humans with acute myocardial infarction. Caspases are a conserved family of cysteine proteases that are universal effectors of apoptosis. Although caspases have been shown to mediate cell death in a number of disease processes including ischemia brain injury, their potential role in myocardial infarction is largely unknown. Here we demonstrate that multiple caspases are activated in a rat model of myocardial ischemia and reperfusion, and studied the effect of Fosinopril on Caspase-3mRNA in cardiac myocytes.Materials and MethodsWistar rats were randomly divided into three groups: (1) Sham surgical group (n=8); (2) Ischemia-Reperfusion group (n=8) the left anterior descending was occluded for 30 min followed by 24 hours reperfusion; (3) Fosinopril (20mg/kg) group (n=8). Fosinopril was fed 24 hours before the coronary artery was occluded and was fed in the morning of the next day. Sham surgical group and Ischemia-Reperfusion group was fed of 0.9% Saline at the same time. Establish myocardial ischemia and reperfusion model as follows:After anesthetized with ether, rat were faced upward fixed on the operating table. Open the chest between the left third and fourth rib. The heart was exposed. A 0 nylon suture attached to a fine needle was placed under the left anterior descending coronary artery and ligated coronary artery immediately. Return heart into the chest, Squeeze the blood and water out and swiftly close the chest. The time opening the chest is no more than 30 seconds. Sham surgical group placed the suture only but not ligate coronary artery. After 30 min, the ischemia cardialmyocates was reperfused for 24 hours. After that , Left ventricular systolic pressure(LVSP) and peak and end–diastolic LVP and the first derivative of LVP (+dp/dt) were measured by a 2F catheter-tip manometer inserted via the right carotid artery.rats were anesthetized. Blood pressure and heart rate were recorded through femoral arterial cannulatio. Blood was collected through groin aorta. Assay serum AST, LDH, and CK-MB with 7150 automatic biochemical analyzer. The hearts were taken out and perfused with NS through aorta. Crosscut myocardium of left ventricle into four or five slices. Some slices were observed by light microscope and electron microscope. RNA was extracted from myocardial tissue. Use these RNA to RT-PCR, observed the expression of caspase-3 mRNA.ResultFosinpril group significant decreased serum CK-MB, LDH, AST activity. This demonstrate that the model of ischemia and reperfusion was good.; Fosinpril significant improved cardiac function of rats after ischemia and reperfusion. The tissues of myocardium after HE Staining were observed. I/R group: cardiac myocyte plasm was pigmenting deeply, nucleus was concentration, but Fosinpril group didn't observed that. Myofilament and myotome of Fosinpril group were normal on the whole under the electron microscope, but myofilament and myotome of Ischemia-Reperfusion group were broken, intercalated disc structure were not clear. The expression of Caspase-3mRNA of Fosinpril group were less than that of Ischemia-Reperfusion group.ConclusionFosinpril may significant decreased serum CK-MB, LDH, AST activity. This illustrate that death of cardiac myocytes is less than I/R group. Fosinpril can protect cardiac myocytes after ischemia and reperfusion; Fosinpril may decrease the expression Caspase-3 mRNA. activating Caspa...
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