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Protective effects of hyperpolarizing cardioplegia with pinacidil on myocardium in rats
Zhiwei Hu1, Kailun Zhang, Wendong Wang
1Department of Cardiovascular Surgery, Xiehe Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022.
Insights
Pinacidil, an ATP-sensitive potassium channel opener, demonstrated significant myocardial protection in prolonged global ischemic rat hearts. This hyperpolarized arrest method improved cardiac function and coronary blood flow post-ischemia.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Myocardial ischemia during cardiac surgery poses significant risks.
- Developing effective myocardial protection strategies is crucial for improving patient outcomes.
- The role of ATP-sensitive potassium channels in myocardial protection requires further investigation.
Purpose of the Study:
- To investigate the myocardial protective effects of pinacidil, an ATP-sensitive potassium channel opener.
- To evaluate the efficacy of hyperpolarized arrest using pinacidil compared to depolarized arrest during prolonged global ischemia in a rat heart model.
Main Methods:
- Utilized a modified isolated working rat heart model.
- Hearts were subjected to prolonged hypothermic global ischemia (60 or 120 minutes) followed by reperfusion.
- Compared hyperpolarized arrest solution with pinacidil against depolarized arrest solution (St. Thomas' solution).
Main Results:
- Hyperpolarized arrest with pinacidil significantly improved recovery of cardiac function compared to depolarized arrest.
- Post-ischemic coronary blood flow and myocardial ATP content were higher in the pinacidil group.
- Electromechanical arrest duration was longer with hyperpolarized arrest, without affecting myocardial water content.
Conclusions:
- Hyperpolarized arrest solution containing pinacidil confers marked myocardial protection during prolonged hypothermic global ischemia.
- Pinacidil shows promise as a therapeutic agent for myocardial protection in ischemic conditions.
- This study supports the use of ATP-sensitive potassium channel openers in cardiac preservation strategies.
Abstract:
Whether the ATP-sensitive potassium channel opener pinacidil can provide myocardial protective effects in prolonged isolated global ischemic rat heart was investigated. On modified isolated rat working heart model, 40 hearts were divided into four groups randomly: Hyperpolarized arrest H-K solution containing pinacidil (50 mumol/L) (P1 and P2) and depolarized arrest St. Thomas' solution (S1 and S2) subjected to 15 degrees C hypothermia, 60 min (P1 and S1) or 120 min (P1 and S2) of ischemia and 30 min reperfusion. The experimental indices included cardioplegic efficiency, cardiac function, coronary blood flow, myocardial enzyme release, myocardial water and ATP content. Hyperpolarized arrest provided significantly better recovery of cardiac function than depolarized arrest. Postischemic coronary flow and myocardial ATP content were higher. The arrest time of electro-mechanical activities were longer than depolarized arrest. There were no differences among the groups in myocardial water contents. The hyperpolarized arrest solution containing pinacidil can provide a marked myocardial protective effect during prolonged hypothermic myocardial ischemia.
