Previous studies indicated aging results in the significant cardiac function decreasing and myocardial apoptosis increasing in normal humans or rats. Additionally, animal experiments demonstrated aging increased myocardial ischemia / reperfusion (MI/R)-induced apoptosis. However, whether more myocardial apoptosis happen in the old acute myocardial infarction (AMI) patients is unclear. Reperfusion injury-induced apoptosis is an important cause of heart failure. This study determined the effect of aging upon myocardial apoptosis and cardiac function in patients suffering AMI. All enrolled AMI patients received percutaneous coronary intervention therapy. Volunteers and AMI patients were assigned to four groups: adult (age <65, n=24) volunteers, elderly (age ≥65, n=21) volunteers, adult (age <65, n=29) AMI patients, and elderly (age ≥65, n=36) AMI patients. Blood samples were obtained from all study participants. Plasma apoptotic markers (soluble form of Fas, tumor necrosis factor alpha, and interleukin 6) levels were determined. Cardiac function was evaluated with echocardiogram and Killip class. Due to lack of a direct apoptotic assay method in live human subjects, an additional animal experiment was performed. Both young (2 months) and old (24 months) rats were subjected to 30-min myocardial ischemia and 3 (for TUNEL/caspase activity apoptotic assay) or 24-h (for cardiac function determination) reperfusion. Compared to adult patients, the elderly patients manifested decreased cardiac function and increased plasma apoptotic marker levels significantly. The animal experiment results (cardiac function and plasma apoptotic markers assays) were consistent with the human result data. Animal TUNEL staining and caspase activity measurement revealed a higher myocardial apoptotic ratio in the older rat group. Aging exacerbated MI/R injury in humans and rats. Differential myocardial apoptosis may play a vital role in mediating the observed effects.

Previous studies indicate aging results in significantly decreased cardiac function and increased myocardial apoptosis after myocardial ischemia/reperfusion (MI/R) in humans or rats. The underlying mechanisms of aging-exacerbated effects remain unknown. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are known to play vital roles in aging-related MI/R injury. Heretofore, the effects of aging upon ROS and RNS formation were not investigated in humans, which is the focus of the current study. Due to experimental limitations with clinical trials, an additional animal experiment was performed. All enrolled acute myocardial infarction (AMI) patients received percutaneous coronary intervention (PCI) therapy. AMI patients were assigned into two groups: adult (age <65, n034) and elderly (age ≥65, n045) AMI patients. Blood samples were obtained from all study participants at 24 h and 3 days post-PCI. Plasma/white blood cell (WBC) ROS and RNS markers (malondialdehyde (MDA), myeloperoxidase (MPO), reduced glutathione (GSH), inducible nitric oxide synthase (iNOS) activity, NOx, and nitrotyrosine) were determined. The same markers were determined in rat cardiac tissue after 24 h MI/R. Compared to the adult group, elderly patients manifested increased plasma MDA and MPO and decreased plasma GSH concentrations. No significant differences in plasma NOx or nitrotyrosine concentration existed between adult and elderly patients. Furthermore, WBC iNOS activity in elderly patients was significantly decreased compared to the adult group. The measurement of ROS markers in the rat experiments was consistent and supported human study data. Surprisingly, RNS markers (NOx and nitrotyrosine) in blood and heart tissue increased from young to middle-aged rats but decreased from middle age to old age. Aging augments ROS, which might exacerbate MI/R injury. Additionally, our data

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