The effects of isosteviol against myocardium injury induced by ischaemia-reperfusion in the isolated guinea pig heart.
1. This study aimed to investigate the protective effects of isosteviol against myocardial ischaemia-reperfusion (IR) injury and its effects on mitochondrial adenosine triphosphate (ATP)-sensitive potassium channel (mitoK(ATP)) activity in vitro. 2. Groups of eight guinea pigs were treated as follows: constant perfusion control (PC), IR control, ischaemic preconditioning (IPC) + IR, isosteviol (50, 250 or 500 nmol) + IR, 5-hydroxydecanoate acid (5-HD) (5 micromol) + isosteviol (500 nmol) + IR. The guinea pig heart was isolated and perfused in Langendorff mode with modified Tyrode solution at a flow rate of 10 mL/min. Ischaemia was introduced for 30 min followed by reperfusion for 20 min. Cardiac function, coronary arterial flow rate, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the perfusate were measured prior to ischaemia and at the end of reperfusion. 3. There were no significant (P > 0.05) changes in cardiac function or markers of cell damage (i.e. activities of LDH and CK) in the PC group. In contrast, cardiac function was adversely affected in the IR group, with significant (P < 0.05) decreases in left ventricular developing pressure (LVDevP), dP/dt(max) and dP/dt(min) compared with baseline and the PC group. In addition, there were increases in activity of LDH (20%) and CK (67%) compared with baseline and the PC group. 4. Ischaemic preconditioning and pretreatment with isosteviol, at all dose levels, resulted in a significant (P < 0.05) attenuation of IR injury. Lactate dehydrogenase and CK activities were not significantly (P < 0.05) different compared with baseline. Isosteviol did not increase coronary flow, suggesting that the protective effect of isosteviol on the myocardium was not mediated by dilation of the coronary blood vessels. 5. Pretreatment with the mitoK(ATP) blocker 5-HD partially antagonized the effects of 500 nmol isosteviol, with a statistically significant attenuation of its protective effects on HR, LVDevP, dP/dt(max) and dP/dt(min) compared with isosteviol alone pretreatment. 6. The IR injury on the Langendorff perfused guinea pig heart was alleviated by isosteviol, which appears to mediate its effects through mitoK(ATP) channels. Future research might aim to investigate the interaction of isosteviol with mitoK(ATP) channels in order to clarify its mechanism of action.
Xu
Deyi
D
Department of Pharmacology, Southeast University, Nanjing, China.
Zhang
Shuangjie
S
Foster
David J R
DJ
Wang
Jiping
J
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology / Q000627:therapeutic use; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010477:Perfusion / Q000379:methods; D015221:Potassium Channels / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D045786:Diterpenes, Kaurane; D006880:Hydroxy Acids; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C515747:isosteviol; C052853:5-hydroxydecanoic acid; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase