A combination of melatonin and nicotinamide mononucleotide alleviates inflammation and enhances isolated heart function in aged rats following ischemia-reperfusion injury

Aging markedly increases vulnerability to cardiovascular disorders, including acute coronary syndrome and coronary artery disease. Although melatonin (M) and nicotinamide mono-nucleotide (N) have each shown cardioprotective properties, their combined effects on ischemia-reperfusion (IR) injury in the aged heart remain unclear. This study investigated co-administration of M and N enhances cardiac functional recovery and reduces inflammatory responses following myocardial IR injury in aged rats. Forty adult male Wistar rats (n = ۸/group) were randomly assigned to five groups: Sham, IR, M (IR + M), N (IR + N), and N + M (IR + N + M). Cardiac function was evaluated after IR by measuring coronary flow, heart rate, left ventricular end-diastolic pressure, and left ventricular developed pressure. Melatonin was administered at ۵۰.۰۰ µM in the reperfusion solution for ۱۵ min after ۳۰ min of ischemia, N was administered intraperitoneally at ۱۰۰ mg kg-۱ every other day for ۲۸ days. Creatine kinase and inflammatory markers, including interleukin IL-۱β, IL-۶, tumor necrosis factor-alpha, and nuclear factor kappa B, were also assessed. IR significantly impaired coronary flow and heart rate, both of which were improved by M and N treatment. These agents also reduced left ventricular end-diastolic pressure and improved left ventricular developed pressure recovery, with the combined therapy producing the greatest effect. Likewise, creatine kinase and inflammatory marker levels were significantly elevated in the IR group but markedly reduced by treatment, especially by combined administration. These findings suggest that M and N exert additive cardioprotective effects against IR injury in aged rats.

کلیدواژه ها:

Hemodynamic Parameters ، Inflammation ، Melatonin ، Nicotinamide Mononucleotide