Myocardial protective effects of nicorandil, an opener of potassium channels on senile rat heart

Abstract

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.

Exercise training improves functional post-ischemic recovery in senescent heart

“…Indeed, additional investigations are clearly required to make an inventory of the multiples mechanisms whereby endurance training can first protect aging of the heart and second limit its vulnerability to IR and especially: ionichomeostasis (Tani et al, 1999;Besse et al, 2004;Liu et al, 2006b), endothelin production (Besse et al, 2001), Bax/Bcl-2 ratio and apoptosis (Liu et al, 2002) or mitochondrial defects (Lesnefsky et al, 2006). Active tension 6.9 ± 0.3 7.4 ± 0.5 (g.g -1 heart weight)…”

Low-flow Perfusion of Guinea Pig Isolated Hearts With 26°C Air-saturated Lifor Solution for 20 Hours Preserves Function and Metabolism

“…Many of the heart studies have compared one preservation solution with another,26,29–33,35,39–44 and with or without additives, such as channel activators or blockers,1,11,45–49 exchange inhibitors,50–52 anesthetics,2,9,49 nitric oxide (NO) donors,53 perfluorocarbons54 or BDM 1,30,55. For example, Celsior solution preserved function better than ViaSpan in several studies,44,56 whereas others found that ViaSpan was better than Celsior 29,30.…”

Novel cardioprotection strategies for the aged heart: evidence from pre‐clinical studies

“…Based on these observations, K + channel openers have been added to cardioplegic solutions to determine whether this enhances cardioprotection in experimental models (Table ). The addition of K ATP channel openers (pinacidil, diazoxide, nicorandil) to crystalloid cardioplegia enhances the recovery of contractile function in reperfusion in Langendorff‐perfused rabbit and rat hearts . K ATP channel openers also reduce infarct size, ultrastructural damage and mitochondrial damage, although whether they reduce release of cardiac enzymes is controversial .…”

“…The addition of K ATP channel openers (pinacidil, diazoxide, nicorandil) to crystalloid cardioplegia enhances the recovery of contractile function in reperfusion in Langendorff‐perfused rabbit and rat hearts . K ATP channel openers also reduce infarct size, ultrastructural damage and mitochondrial damage, although whether they reduce release of cardiac enzymes is controversial . Diazoxide cardioplegia also improves contractile function and reduces infarct size in a rabbit cardiopulmonary bypass model .…”

“…11,43,44 K ATP channel openers also reduce infarct size, ultrastructural damage and mitochondrial damage, although whether they reduce release of cardiac enzymes is controversial. 11,43,44 Diazoxide cardioplegia also improves contractile function and reduces infarct size in a rabbit cardiopulmonary bypass model. 19 The role of mPTP opening in mediating damage associated with cardioplegia also has been explored ( Table 3).…”