| Acute myocardial infarction is a serious disease to threaten the extensive people's lives. Utilizing coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) or thrombolysis to restore coronary artery flow as early as possible is the best effective treatment method. Reperfusion of the ischemic myocardium, however, can trigger the onset of various cardiac arrhythmias especially ventricular fibrillation. And it is found that many of the antiarrhythmic agents that are effective against ischemia-induced arrhythmias may not be effective against reperfusion-induced arrhythmias. Both experimental and clinical studies have demonstrated a large amount of release of endogenous catecholamines during the early stages of reperfusion in the ischemic myocardium. Catecholamines combine adrenoceptors on ischemic myocytes, potentially resulting in arrhythmias, calcium overloading, and membrane injury. Reducing myocardial catecholamine reserves, with 6-hydroxydopamine or reserpine pretreatment, has been shown to decrease reperfusion-induced arrhythmias. Our and others observations might suggest that stimulation of adrenoceptors may be involved in the genesis of reperfusion-induced arrhythmias. Thus, μ -receptor antagonists would be expected to be effective anti-arrhythmic agents during reperfusion. The aim of the present study is to compare the effect of carvedilol and μ i-selective adrenoceptors blockers on endogenousnorepinephrine release and reperfusion-induced ventricular fibrillation, to investigate the mechanism of action of carvedilol against reperfusion-induced ventricular fibrillation, which will provide new theoretical basis for the therapy of ischemic heart disease.Methods:1. Ninety male guinea pigs (weighing 200~300g) were randomized to eleven groups: the control group; metoprolol, bisoprolol and carvedilol at the concentrations of 0.1,1.0 and 10.0μmol/L were marked as the MET0.l group, the MET1.0 group, the MET10.0 group, the BIS.0.l group, the BIS 1.0 group, the BISl0.0group, the CAR0.lgroup, the CAR1.0 group and the CAR10.0 group, respectively; as well as the carvedilol-vehicle group.2. Experiments were performed on a isolated, perfused, denervated heart model. Anesthesia was induced with pentobarbitone sodium intraperitoneally (45mg/kg). The thorax was opened, and 500U heparin was injected into the inferior vena cava. The hearts were rapidly removed. For coronary perfusion, the aorta was cannulated and retrogradely perfused in a classical Langendorff apparatus. All hearts were perfused at a constant flow of 6ml/min with a modified Krebs-Hensenleit solution gassed with 95%O2 and 5%CO2. The gas flow was adjusted to achieve a pH of 7.30-7.40, and the temperature of the perfusion solution was kept at 37.0+0.3 Hearts were initially subjected to 20min of aerobic perfusion. During the first l0min of perfusion, standard drug-free perfusion fluid was used; however, during the second lOmin period, perfusion was switched to a fluid containing various concentrations of # -receptor blockers, then hearts were treated with 20min of global stop-flow ischemia, each followed by 5min of reperfusion with drug-free perfusion fluid. The results were then compared with hearts receiving drug-free perfusion fluid throughout the experimental time course. Samples for determination of norepinephrine were collected from the heart effluent during the first minute of reperfusion period. Endogenous norepinephrine was quantified by high-performance liquid chromatography and electrochemical detection (HPLC-EC). The onset of ventricular arrhythmias wascontinuously monitored and recorded using ECG from the start of the experiment to after 5-min of reperfusion.3. Statistical evaluation of the data was performed using SPSS 10.0. P<0.05 was regarded as statistically significant. Results:1. In hearts treated with 10.0μmol/L metoprolol, with 10.0μmol/L bisoprolol, with l.0μmol/L carvedilol and with 10.0μmol/L carvedilol, the amounts of no...
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