Superior Anti-Arrhythmogenic Effect of Combined Conditioning with Nicotinamide Mononucleotide and Ubiquinol in Myocardial Ischemia/Reperfusion Injury in Aged Rats

Purpose: Lethal ventricular arrhythmias are a significant clinical concern following reperfusion therapies in elderly patients with myocardial infarction. The combination of multi-target therapies to achieve optimal anti-arrhythmogenesis and improve the chances of successful translation for patient benefit has prompted considerable interest. This study examined the anti-arrhythmic effect of nicotinamide mononucleotide (NMN)/ubiquinol combination treatment following myocardial ischemia/reperfusion (IR) injury in aged rats, with an emphasis on the role of oxidative stress and nitric oxide (NO). Methods: Male Wistar rats (n=30, 22-24 months old, 400-450g) were randomized into five groups with or without IR and/or NMN and ubiquinol, either alone or in combination. NMN (100mg/kg/48hours) was administered intraperitoneally for 28 days before IR, and ubiquinol (30mg/kg) was injected intravenously at early reperfusion. Electrocardiographic signals were recorded during the ischemia and the first 30 minutes of reperfusion. Two hours after reperfusion, myocardial hemodynamic and LDH release were measured, and the left ventricle samples were obtained to evaluate oxidative stress markers and NO levels. Results: NMN/ubiquinol combination treatment significantly minimized the occurrence and severity of IR-induced arrhythmias, improved myocardial function, and reduced LDH release (P<.05). It also decreased MDA content, increased SOD, GPx, and CAT activities, and enhanced NO formation (P<.05). This combined treatment showed greater efficacy than the single treatments. Conclusion: This study revealed the anti-arrhythmic effect of NMN/ubiquinol combination treatment in IR-treated aged rats, which may be associated with reduced oxidative stress and increased NO formation. This combinational approach deserves more investigation due to its potential to confer better anti-arrhythmic effect during aging.