Myocardial protective effects of nicorandil, an opener of potassium channels on senile rat heart.
The purpose of this study was to investigate the cardioprotective effects of nicorandil, an opener of potassium channels, on senile rat hearts from ischemic reperfusion injury. A modified working model of isolated perfused hearts of senile rats was used. After isolation, the hearts underwent 60 min of global hypothermic ischemia treatment, followed by 30 min of reperfusion. These hearts were distributed into three groups, each receiving different cardioplegic solutions: (1) St. Thomas' solution (Group S), (2) 100 micromol/L nicorandil (Group N), (3) St. Thomas' solution combined with 100 micromol/L nicorandil (Group S+N). The pre- and post-ischemic myocardial function were assessed by the percentage recovery of the heart rate (HR), +/- dp/dt(max) (maximal rate of change of left ventricular pressure) and cardiac output (CO). Upon reperfusion, the cardioplegic solution was collected from the coronary sinus and tested for lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity. During 30 min of reperfusion, the percentage recovery of HR, +dp/dt and left ventricular stroke work (LVSW) were significantly higher in Group S+N than in Group S and Group N (p < 0.05). The percentage of recovery in CO was higher in Group N and Group S+N than in Group S. The electrical activities arresting time (EAT) and mechanical activities arresting time (MAT) were longer in Group N than in Group S and Group N+S (p < 0.01). There were no statistical significance between Group S and Group N+S (p > 0.05). There were no significant differences in the levels of LDH and CK-MB. Electron microscopic examination revealed better preservation of the ultrastructures of the myocardial tissue in Group N+S than the other two groups. These results indicate that nicorandil combined with St. Thomas' solution can improve the left ventricular function of the post-ischemic senile rat and offer a better myocardial protective effect on the ischemic senile myocardium.
Liu
Jinping
J
Departament of Cardiopulmonary Bypass, Cardiovascular Institute and Fuwai Hospital, Beijing, China. jinpingfw@hotmail.com
Long
Cun
C
Ji
Bingyang
B
Zhang
Hongjia
H
Wen
Fuxing
F
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects*; D003402:Creatine Kinase / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005334:Fever / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006836:Hydro-Lyases / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020108:Nicorandil / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010477:Perfusion; D015221:Potassium Channels / Q000819:agonists; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D020108:Nicorandil; D003402:Creatine Kinase; D006836:Hydro-Lyases; C045581:lactate dehydratase