The cardioprotective effect of isosteviol on rats with heart ischemia-reperfusion injury.
This study was designed to assess the cardioprotective effect of isosteviol on rats with heart ischemia-reperfusion (IR) injury and to explore the mechanism of action of the compound. Sprague Dawley rats were divided into 8 groups (n=10-12): a sham-operated control and 7 ischemia-reperfusion groups (IR control, 3 isosteviol pre-treated (0.5, 1.0 and 2.0 mg kg(-1)), ligustrazine pre-treated, 5-hydroxydecanoate (5-HD) pre-treated and 5-HD+ isosteviol pre-treated groups). IR was produced by occluding the left coronary artery for 30 min followed by re-opening the artery for 90 min. The compounds under investigation were administered intravenously 10 min prior to occluding the artery. Hemodynamic parameters (+/-dp/dt(max), LVSP, LVDevP, MAP), heart rate, ventricular tachycardia (VT) and ventricular fibrillation (VF) were determined during the IR period. The myocardial infarct size, activities of serum lactate dehydrogenase and creatine kinase were determined at the end of the experiment. In the isosteviol pre-treated groups, the hemodynamic parameters were improved and the myocardial infarct size, the activities of serum enzymes, and the incidences of VT and VF were all decreased when compared to the control group. These effects of isosteviol were similar to that of a traditional cardioprotective agent, ligustrazine. The 5-HD+ isosteviol group displayed parameters that were between those in the equivalent isosteviol pre-treated group and the IR control group. In conclusion, damage due to a standard rat heart IR injury was reduced by pretreatment with intravenous isosteviol, and this effect was partly attenuated by a mitochondrial ATP-sensitive potassium channel blocker, 5-HD.
Xu
Deyi
D
Department of Pharmacology, School of Basic Medicine, South East University, Nanjing 210009, China.
Li
Yongfang
Y
Wang
Jiping
J
Davey
Andrew K
AK
Zhang
Shuangjie
S
Evans
Allan M
AM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003652:Decanoic Acids / Q000627:therapeutic use; D004195:Disease Models, Animal; D045786:Diterpenes, Kaurane / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects; D006880:Hydroxy Acids / Q000627:therapeutic use; D007275:Injections, Intravenous; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011719:Pyrazines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D003652:Decanoic Acids; D045786:Diterpenes, Kaurane; D006880:Hydroxy Acids; D011719:Pyrazines; C515747:isosteviol; C052853:5-hydroxydecanoic acid; C017953:tetramethylpyrazine