| Diabetes has a significantly greater incidence and severity of angina, acute myocardial infarction, congestive heart failure and ventricular arrhythmias than non-diabetic population. Ischemic heart accident accounts for more than 50% of all deaths in patients with diabetes mellitus. Diabetes is also one of the main causes for increased incidence of complication during perioperative period. Clinically, Diabetes represents an important risk factor for cardiovascular accident and poor outcomes after coronary revascularization. Diabetes is thought as an independent predictor of low output syndrome after coronary artery bypass graft (CABG) surgery. So, a strict blood glucose control is performed in diabetic patients during perioprative period. However, there exist controversies as to the sensitivity of diabetic heart to ischemic injury and its mechanism. In this work, we studied the alteration in sensitivity of diabetic heart to ischemia/reperfusion injury and whether hyperglycemia affects this alteration in Langendorff-perfused isolated diabetic hearts. 1.Establishment of the model of diabetic rat and isolated rat hearts perfusionDiabetes was induced in 12-week-old male Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin, (prepared in ice-cold 0.1M citrate buffer, pH 4.3) at a dose of 60 mg/kg after fasted for 24?h. Non-diabetic animals(control) were injected with the buffer only(1ml/kg body weight).The diabetic state was confirmed by the presence of glucosuria as determined by using glucose test strips (Glukotest; Boehringer, Mannheim, Germany)on the third day after STZ injection. All animals were housed in an air/humidity-controlled room with a 12-h dark/light cycle, and allowed food and water freely. Four weeks after STZ injection, Isolated heart perfusion was performed as published with modifications. Rats were anesthetized with sodium pentobarbital (60 mg/kg, ip) and hearts were excised and connected rapidly to the aortic cannula of a Langendorff apparatus. The retrograde perfusion was instantly started with Krebs-Henseleit buffer kept at 37 ℃ and bubbled constantly with 95% O2 and 5% CO2 (pH 7.4) throughout the perfusion period. The left atrium was connected to a cannula and perfused for filling of left ventricle. Perfusion pressure in the aorta and left atrium was set at 90 cmH2O and 10 cmH2O, respectively. An epicardial electrogram (EG) was registered by means of three silver electrodes attached to the apex and right atrium of the heart and the aortic annula and continuously recorded. Heart rate was calculated from the EG. Arrhythmias were analyzed in accordance with The Lambeth Conventions. Heart function was observed through a catheter inserted into the left ventricular cavity. Left ventricular developing pressures (LVDP), left ventricular end diastolic pressure (LVEDP) were monitored throughout the perfusion. Rate-pressure production (RPP) was used as index of cardiac performance.2.Alteration of resistance to ischemia-reperfusion injury in diabetic heartsThe resistance of heart to ischemia-reperfusion injury was assessed in Langendorff-perfused isolated diabetic hearts (n=16) and non-diabetic hearts (n=10). After 20min equilibration, all hearts were subjected to normothermic global ischemia by clamping both atrial inflow and aortic outflow for 30min. The ischemia was then followed by 40min reperfusion. The diabetic heart showed an impaired cardiac function before ischemia-reperfusion injury, including reduced heart rate, LVP, RPP and ±dp/dt. However, the resistance to ischemia-reperfusion injury was increased significantly in diabetic heart. The duration between ischemia to arrest increased significantly in diabetic hearts compared with non-diabetic hearts. LVP, RPP, CF and ±dp/dt recovered better after reperfusion in diabetic hearts than in non-diabetic hearts.3. Effect of hyperglycemia on resistance to ischemia-reperfusion injury in diabetic heartsAfter 20min equilibration, the diabetic hearts were divided into two groups randomly, one continuing KHB perfusion... |
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