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Cardioprotective effects of simvastatin on reversing electrical remodeling induced by myocardial ischemia-reperfusion in normocholesterolemic rabbits.
Chin Med J (Engl). 2008 Mar 20; 121(6):551-6.CM

Abstract

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 x kg(-1) x 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 derived 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 (I(Na)), L-type calcium current (I(Ca-L)) and transient outward potassium current (I(to)). 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 I(Na) 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 I(Na) current density in the Statin group was not different from CON (P>0.05). The peak I(Ca-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) pA/pF, n=16, P<0.05), while the Peak I(Ca-L) current density in Statin was not different from CON (P>0.05). The I(to) current density (at +60 mV) was significantly decreased in I-R ((9.49+/-1.91) pA/pF, n=11) compared with CON ((17.41+/-3.13) pA/pF, n=15, P<0.01) and Statin ((14.54+/-2.41) pA/pF, n=11, P<0.01), although there was a slight reduction in the Statin group compared with CON (P<0.05).

CONCLUSIONS

It is implied that ischemia-reperfusion induces significant down-regulation of I(Na) and I(to) and up-regulation of I(Ca-L), which may underlie the altered electrical activity and long abnormal transmembrane action potential duration of the surviving ventricular myocytes, thus contributing to ventricular arrhythmias during acute ischemia-reperfusion period. Pretreatment with simvastatin could attenuate these changes and reverse this electrical remodeling without lowering the serum cholesterol level, contributing to the ionic mechanism of statin in treatment of arrhythmia independent of a decrease in cholesterol.

Authors+Show Affiliations

Department of Cardiology, Second Hospital of Hebei Medical University, Institute of Cardiocerebrovascular Disease of Hebei Province, Shijiazhuang, Hebei 050000, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18364145

Citation

Ding, Chao, et al. "Cardioprotective Effects of Simvastatin On Reversing Electrical Remodeling Induced By Myocardial Ischemia-reperfusion in Normocholesterolemic Rabbits." Chinese Medical Journal, vol. 121, no. 6, 2008, pp. 551-6.
Ding C, Fu XH, He ZS, et al. Cardioprotective effects of simvastatin on reversing electrical remodeling induced by myocardial ischemia-reperfusion in normocholesterolemic rabbits. Chin Med J (Engl). 2008;121(6):551-6.
Ding, C., Fu, X. H., He, Z. S., Chen, H. X., Xue, L., & Li, J. X. (2008). Cardioprotective effects of simvastatin on reversing electrical remodeling induced by myocardial ischemia-reperfusion in normocholesterolemic rabbits. Chinese Medical Journal, 121(6), 551-6.
Ding C, et al. Cardioprotective Effects of Simvastatin On Reversing Electrical Remodeling Induced By Myocardial Ischemia-reperfusion in Normocholesterolemic Rabbits. Chin Med J (Engl). 2008 Mar 20;121(6):551-6. PubMed PMID: 18364145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardioprotective effects of simvastatin on reversing electrical remodeling induced by myocardial ischemia-reperfusion in normocholesterolemic rabbits. AU - Ding,Chao, AU - Fu,Xiang-hua, AU - He,Zhen-shan, AU - Chen,Hui-xiao, AU - Xue,Ling, AU - Li,Jun-xia, PY - 2008/3/28/pubmed PY - 2008/6/6/medline PY - 2008/3/28/entrez SP - 551 EP - 6 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 121 IS - 6 N2 - 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 x kg(-1) x 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 derived 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 (I(Na)), L-type calcium current (I(Ca-L)) and transient outward potassium current (I(to)). 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 I(Na) 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 I(Na) current density in the Statin group was not different from CON (P>0.05). The peak I(Ca-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) pA/pF, n=16, P<0.05), while the Peak I(Ca-L) current density in Statin was not different from CON (P>0.05). The I(to) current density (at +60 mV) was significantly decreased in I-R ((9.49+/-1.91) pA/pF, n=11) compared with CON ((17.41+/-3.13) pA/pF, n=15, P<0.01) and Statin ((14.54+/-2.41) pA/pF, n=11, P<0.01), although there was a slight reduction in the Statin group compared with CON (P<0.05). CONCLUSIONS: It is implied that ischemia-reperfusion induces significant down-regulation of I(Na) and I(to) and up-regulation of I(Ca-L), which may underlie the altered electrical activity and long abnormal transmembrane action potential duration of the surviving ventricular myocytes, thus contributing to ventricular arrhythmias during acute ischemia-reperfusion period. Pretreatment with simvastatin could attenuate these changes and reverse this electrical remodeling without lowering the serum cholesterol level, contributing to the ionic mechanism of statin in treatment of arrhythmia independent of a decrease in cholesterol. SN - 0366-6999 UR - https://www.unboundmedicine.com/medline/citation/18364145/Cardioprotective_effects_of_simvastatin_on_reversing_electrical_remodeling_induced_by_myocardial_ischemia_reperfusion_in_normocholesterolemic_rabbits_ L2 - https://Insights.ovid.com/pubmed?pmid=18364145 DB - PRIME DP - Unbound Medicine ER -