ABSTRACT
OBJECTIVE: To determine whether the caidioprotection of acetylcholine (ACh) against ischeniia/reperftision (I/R) injury is re-kited to mitochondrial permeability transition pore (MEW) and mitochondrial AW-sensitive potassium channel (mitoK(ATP)). METHODS: Male Sprague-Dawley rats were used for Langendorif isolated bean perkision. The hearts were subjected to global ischemia for 30 mm followed by 120 rein of reperfusion and the left ventricular hemodynaniic parameters were measured. Formazan, a product of 2,3, 5-triphenyl-tetrazolium chloride (TTC), which is proportional to myocardial viability, was measured at 490 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was measured to evaluate the cardiac injury. RESULTS: The pretreatment with ACh (0.1 mol/L, 5 mm) before I/R markedly increased myocardial formazan content, reduced LDH release, improved the recovery of the left veritficular developed pressure, +/- dP/dtmax, and rate pressure product (left ventricular developed pressure multiplied by hean rate) and attenuated the decrease of coronary flow during reperfusion. The opener of MPTP, atiractyloside (20 mmoL/L) or the inhibitor of mitoK(ATP), 5-hydroxydecanoate (100 micromol/L) abolisbed the beneficial effect of ACh. CONCLUSION: In the isolated rat bean, ACh protects myocardium against ischemia/reperfusion injury via inhibiting the opening of MPTP and increasing the opening of mitoKATP in heart.
Subject(s)
Acetylcholine/pharmacology , Ischemic Preconditioning/methods , Mitochondrial Membrane Transport Proteins/drug effects , Myocardial Reperfusion Injury/prevention & control , Animals , Cardiotonic Agents/pharmacology , In Vitro Techniques , Male , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Permeability Transition Pore , Myocardial Ischemia/physiopathology , Potassium Channels/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To investigate the effect of ethyl acetate extract from Chrysanthemum Morifolium Ramat (CME) on experimental arrhythmia induced by ischemia/reperfusion or aconitine in rats and to explore its underlying mechanisms. METHODS: Arrhythmia model in intact rat was induced by aconitine (30 microg/kg body weight, i.v.). In isolated Langendorff perfused rat hearts, regional ischemia and reperfusion was induced by ligation and release of left anterior descending artery. The ventricular fibrillation threshold (VFT), effective refractory period (ERP), and diastolic excitation threshold (DET) in the isolated heart were measured. The action potentials of papillary muscle in rat right ventricle were recorded by conventional glass microelectrode technique. RESULTS: Compared with control group CME significantly decreased the number and duration of ventricular tachycardia (VT); delayed the occurrence of ventricular premature beats (VPB) and VT induced by aconitine. Arrhythmia score of the CME group was lower than that in aconitine-treated group. CME markedly prolonged the ERP and increased the VFT in the isolated perfused rat hearts during ischemia and reperfusion. CME prolonged action potential duration at 50% and 90% repolarization of the right ventricular papillary muscles and decreased the maximal rate of rise of the action potential upstroke, but did not affect the resting potential, amplitude of action potential. CONCLUSION: CME can reduce myocardial vulnerability and exerts its antiarrhythmic effects induced by aconitine or ischemia/reperfusion, which may be related to its prolongation of action potential duration and effective refractory period that enhance the electrophysiological stability of myocardiaium.
