Abstract
BackgroundReports on the effect of age and obesity on myocardial ischaemia/reperfusion (I/R) injury and ischaemic preconditioning are contradictory. The aim of this study was to re-evaluate the effects of age and diet-induced obesity (DIO) on myocardial I/R injury and preconditioning potential.MethodsFour groups of Wistar male rats were used: age-matched controls (AMC) receiving standard rat chow for (i) 16 weeks and (ii) 16 months respectively; DIO rats receiving a sucrose-supplemented diet for (iii) 16 weeks and (iv) 16 months respectively. The ages of groups (i) and (iii) were 22 weeks (“young”) and groups (ii) and (iv) 17 months (“middle-aged”) at time of experimentation. Isolated perfused working hearts were subjected to 35 min regional ischaemia/1 h reperfusion. Endpoints were infarct size (tetrazolium staining) and functional recovery. Hearts were preconditioned by 3 × 5 min ischaemia/5 min reperfusion. Results were processed using GraphPad Prism statistical software.ResultsAge did not affect baseline heart function before induction of ischaemia and I/R damage as indicated by infarct size and similar values were obtained in hearts from both age groups. Age also had no effect on functional recovery of hearts during reperfusion after regional ischaemia in AMC rats, but cardiac output during reperfusion was better in hearts from middle-aged than young DIO rats.The diet reduced infarct size in hearts from young rats (% of area at risk: AMC: 32.4 ± 3.6; DIO: 20.7 ± 2.9, p < 0.05), with no differences in hearts from middle-aged rats (AMC: 24.6 ± 4.6; DIO: 28.3 ± 13.5, p = NS). Compared to their respective AMC, diet-induced obesity had no significant effect on functional recovery of hearts from both age groups after exposure to regional ischaemia.When exposed to the more severe stress of global ischaemia, the functional recovery potential of middle-aged DIO rats appeared to be impeded compared to hearts of young DIO rats, while age had no effect on the functional recovery of AMC hearts.Preconditioning reduced infarct size in hearts from young control rats and both middle-aged groups, but not from young DIO rats. Age had a significant effect on functional recovery in preconditioning: it was improved in hearts from young control and DIO rats, but depressed in both middle-aged groups.ConclusionsThe data showed that middle-age and obesity had no effect on baseline myocardial function and did not increase susceptibility to I/R damage upon exposure to regional ischaemia. On the contrary, obesity reduced I/R damage in young rats. Preconditioned aging hearts showed a decreased infarct size, but a reduction in functional recovery.
Highlights
Reports on the effect of age and obesity on myocardial ischaemia/reperfusion (I/R) injury and ischaemic preconditioning are contradictory
Infarct size Age did not appear to affect the susceptibility of the heart to I/R damage: there was no significant difference in infarct size of hearts from young and middle-aged age-matched control rats when subjected to the same period of regional ischaemia (35 min) followed by 1 h reperfusion
There were no significant differences between infarct sizes of hearts from young and middle-aged diet-induced obesity (DIO) rats when exposed to a similar period of regional ischaemia and reperfusion (Fig. 1)
Summary
Reports on the effect of age and obesity on myocardial ischaemia/reperfusion (I/R) injury and ischaemic preconditioning are contradictory. The aim of this study was to re-evaluate the effects of age and diet-induced obesity (DIO) on myocardial I/R injury and preconditioning potential. The effect of ischaemia/reperfusion (I/R) on the myocardium as well as its response to cardioprotective interventions are influenced by several variables, amongst others, age and obesity. As cardiovascular diseases are the leading cause of death, in the elderly, cognizance should be taken of the role of age-induced changes in the response of the heart to pathophysiological conditions. Apart from the significant changes in βadrenergic signalling [8, 9], mitochondrial ROS production increases with age, which in turn, may cause mitochondrial damage [6]. The amounts of ROS generated are critical for the fate of the cell, since low amounts can function as signalling molecules and are important in cardioprotection, whereas high amounts are detrimental by opening the mitochondrial permeability transition pore, causing cell death [10]
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