Novel cardioprotection strategies for the aged heart: evidence from pre‐clinical studies

Abstract

The incidence of cardiovascular disease is rising as the population ages. This has led to an increase in the need to perform cardiac surgery in older patients. However, aged hearts are particularly susceptible to reperfusion injury following periods of myocardial ischaemia that occur during cardiac surgery. Indeed, older adults experience myocardial dysfunction and reduced survival post-surgery compared to younger people and certain groups, including older women and frail older adults, are at particular risk. This highlights the need to design cardioprotective strategies specifically for the ageing heart. Cardioprotection during surgery is often accomplished by perfusing the heart with chemical arresting agents, known as cardioplegic solutions. New protective strategies have been developed and tested in animal models, where cardioplegic solutions have been modified by changing their temperature, chemical components and/or the frequency of delivery. In addition, drugs designed to activate cardioprotective mechanisms or to inhibit mechanisms involved in injury have been added to improve the efficacy of these solutions. However, most experimental studies have developed and optimized cardioplegic solutions in hearts from younger male animals. This review discusses pre-clinical models used to optimize cardioplegic solutions, with an emphasis on the few studies that have used hearts from older animals. Pharmacologic agents that have been shown to enhance the benefits of cardioplegia in younger hearts and could, in theory, protect vulnerable older hearts are also considered. We emphasize the need to conduct studies in frail older animals of both sexes to facilitate translation of laboratory-based observations to the clinic.

Inhibition of programmed necrosis limits infarct size through altered mitochondrial and immune responses in the aged female rat heart

“…Interestingly, profound cytokine reduction was only achieved in the MO OVX group, highlighting a necessary area for future investigation to determine how basal inflammation levels and acute inflammatory responses are differentially integrated in adult and aged subjects in ways that lead to cardiac protection. Finally, that Nec-1 can modulate signaling in both cardiomyocytes and neutrophils distinguishes it as a powerful inflammatory regulator with implications for reduced injury and significant clinical potential (29).…”

Effects of resveratrol on tolerance to ischemia/reperfusion injury in aged male mice: Role of autophagy and apoptosis

“…Heart function deteriorates with age at a rate of 1% per year and the incidence of myocardial ischemia/reperfusion injury is rising as the population ages (Kane & Howlett, 2016 ). There are structural and functional differences between the aging heart and the younger heart, which may make the aging heart more susceptible to I/R injury (Boengler et al, 2009 ).…”