Background Recent studies have revealed that pretreatment with statin is effective in preventing arrhythmia, but its electrophysiological mechanism is unclear. This study was conducted to investigate the cardioprotect...Background Recent studies have revealed that pretreatment with statin is effective in preventing arrhythmia, but its electrophysiological mechanism is unclear. This study was conducted to investigate the cardioprotective effects of simvastatin on reversing electrical remodeling in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the ionic mechanism responsible for the anti-arrhythmic effect of statin. Methods Forty-five rabbits were randomly divided into three groups： ischemic-reperfusion group （I-R）, simvastatin intervention group （Statin） and sham-operated control group （CON）. Anesthetized rabbits were subjected to 30-minute ischemia by ligation of the left anterior descending coronary artery and a 60-minute reperfusion after a 3-day administration of oral simvastatin of 5 mg-kg^-1.d^-1 in the Statin group or a placebo in the I-R group. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region dedved from the hearts in the I-R and Statin group and the same anatomical region in the CON animals. The whole cell patch-clamp technique was used to record membrane ionic currents, including sodium current （IRa）, L-type calcium current （Ica-L） and transient outward potassium current （Ito）. Simultaneously, the level of serum cholesterol was examined. Results There was no significant difference in the serum cholesterol concentration among the three groups. The peak IRa current density （at -30 mV） was significantly decreased in I-R （（22.46±5.32） pA/pF, n=12） compared with CON （（42.78±5.48） pA/pF, n=16, P〈0.01） and Statin （（40.66±5.89） pA/pF, n=15, P〈0.01）, while the peak IRa current density in the Statin group was not different from CON （P〉0.05）. The peak ICa-L current density （at 0 mV） was significantly increased in I-R （（4.34±0.92） pA/pF, n=15） compared with CON （（3.13±1.22） pA/pF, n=13, P〈0.05） and Statin （（3.46±0.85） pNpF, n=16, P〈0展开更多
基金This work was supported by the National Natural Science Foundation of China (No. 39370270)the Natural Science Foundation of Educational Department of Sichuan Province (No. 2003A058).
基金This project was supported by a grant from the Natural Science Foundation of Hebei Province （No. C2004000615）.
文摘Background Recent studies have revealed that pretreatment with statin is effective in preventing arrhythmia, but its electrophysiological mechanism is unclear. This study was conducted to investigate the cardioprotective effects of simvastatin on reversing electrical remodeling in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the ionic mechanism responsible for the anti-arrhythmic effect of statin. Methods Forty-five rabbits were randomly divided into three groups： ischemic-reperfusion group （I-R）, simvastatin intervention group （Statin） and sham-operated control group （CON）. Anesthetized rabbits were subjected to 30-minute ischemia by ligation of the left anterior descending coronary artery and a 60-minute reperfusion after a 3-day administration of oral simvastatin of 5 mg-kg^-1.d^-1 in the Statin group or a placebo in the I-R group. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region dedved from the hearts in the I-R and Statin group and the same anatomical region in the CON animals. The whole cell patch-clamp technique was used to record membrane ionic currents, including sodium current （IRa）, L-type calcium current （Ica-L） and transient outward potassium current （Ito）. Simultaneously, the level of serum cholesterol was examined. Results There was no significant difference in the serum cholesterol concentration among the three groups. The peak IRa current density （at -30 mV） was significantly decreased in I-R （（22.46±5.32） pA/pF, n=12） compared with CON （（42.78±5.48） pA/pF, n=16, P〈0.01） and Statin （（40.66±5.89） pA/pF, n=15, P〈0.01）, while the peak IRa current density in the Statin group was not different from CON （P〉0.05）. The peak ICa-L current density （at 0 mV） was significantly increased in I-R （（4.34±0.92） pA/pF, n=15） compared with CON （（3.13±1.22） pA/pF, n=13, P〈0.05） and Statin （（3.46±0.85） pNpF, n=16, P〈0
