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Published on: April 16, 2018
Melatonin enhanced the cardioprotective effects of HTK solution on Langendorff-perfused mouse hearts subjected to
Mingchu Sun1, Zihui Zhang1, Yue Yin2
1Institute of Medical Research, Northwestern Polytechnical University, Xi'an Shaanxi, 710072 China.
Insights
Melatonin enhances the protective effects of Histidine-tryptophan-ketoglutarate (HTK) solution against cardiac ischemia/reperfusion injury. This combination reduces mitochondrial damage, improves energy metabolism, and inhibits apoptosis, offering improved perioperative cardioprotection.
Area of Science:
- Cardiology
- Biochemistry
- Cell Biology
Background:
- Cardiac surgery often involves inducing cardiac arrest, leading to ischemia/reperfusion (I/R) injury.
- Histidine-tryptophan-ketoglutarate (HTK) solution is a standard organ protection fluid, but its efficacy can be improved.
Purpose of the Study:
- To evaluate the cardioprotective effects of HTK solution combined with melatonin during cardiac I/R.
- To investigate the underlying mechanisms, including the role of AMP-activated protein kinase α2 (AMPKα2).
Main Methods:
- Isolated Langendorff-perfused mouse heart model.
- Comparison of four groups: control, I/R, HTK+I/R, and HTK+M+I/R.
- Measurement of cardiac function, myocardial injury markers, and ER stress.
Main Results:
- Melatonin significantly enhanced HTK solution's cardioprotective effects.
- Melatonin reduced mitochondrial damage, improved energy metabolism, inhibited apoptosis, and decreased infarct size.
- Melatonin alleviated ER stress and carbonyl stress, with effects dependent on AMPKα2.
Conclusions:
- Melatonin improves HTK solution's efficacy in protecting the heart against I/R injury.
- The findings support the development of novel perioperative cardioprotective strategies using melatonin.
Objectives:
Cardiac arrest is a crucial procedure in various cardiac surgeries, during which the heart is subjected to an ischemic state. The occurrence of ischemia/reperfusion (I/R) injury is inevitable due to aortic blockage and opening. The Histidine-tryptophan-ketoglutarate (HTK) solution is commonly used as an organ protection liquid to mitigate cardiac injury during cardiac surgery. Despite its widespread use, there is significant potential for improving its protective efficacy.
Materials And Methods:
The cardioprotective effect of HTK solution with and without melatonin was evaluated using the isolated Langendorff-perfused mouse heart model. The isolated C57bL/6 mouse hearts were randomly divided into four groups: control, I/R, HTK solution treatment before reperfusion (HTK+I/R), and HTK solution combined with melatonin before reperfusion (HTK+M+I/R). Cardiac function and myocardial injury markers were then measured. AMP-activated protein kinase α2 (AMPKα2) KO mice were used to investigate the underlying mechanism.
Results:
In our study, we found that melatonin significantly improved the protective effects of HTK solution in an isolated Langendorff-perfused mouse model, mechanistically by reducing mitochondrial damage, improving energy metabolism, inhibiting cardiomyocyte apoptosis, and reducing myocardial infarction size. We also observed that the HTK solution alone was ineffective in inhibiting ER stress, but when melatonin was added, there was a significant reduction in ER stress. Furthermore, melatonin was found to alleviate carbonyl stress during cardiac I/R. Interestingly, our results showed that the cardioprotective properties of melatonin were dependent on AMPKα2.
Conclusion:
The findings presented in this study offer a valuable empirical foundation for the development of perioperative cardioprotective strategies.
