Abstract
BackgroundAlthough obesity is still considered a risk factor in the development of cardiovascular disorders, recent studies suggested that it may also be associated with reduced morbidity and mortality, the so-called “obesity paradox”. Experimental data on the impact of diabetes, obesity and insulin resistance on myocardial ischaemia/reperfusion injury are controversial. Similar conflicting data have been reported regarding the effects of ischaemic preconditioning on ischaemia/reperfusion injury in hearts from such animals. The aim of the present study was to evaluate the susceptibility to myocardial ischaemia/reperfusion damage in two models of diet-induced obesity as well as the effect of ischaemic and pharmacological preconditioning on such hearts.MethodsThree groups of rats were fed with: (i) normal rat chow (controls) (ii) a sucrose-supplemented diet (DIO) (iii) a high fat diet (HFD). After 16 weeks, rats were sacrificed and isolated hearts perfused in the working mode and subjected to 35 min regional ischaemia/60 min reperfusion. Endpoints were infarct size and functional recovery. Infarct size was determined, using tetrazolium staining. Activation of PKB/Akt and ERKp44/p42 (RISK pathway) during early reperfusion was determined using Western blot. Statistical evaluation was done using ANOVA and the Bonferroni correction.ResultsInfarct sizes of non-preconditioned hearts from the two obese groups were significantly smaller than those of the age-matched controls. Ischaemic as well as pharmacological (beta-adrenergic) preconditioning with a beta2-adrenergic receptor agonist, formoterol, caused a significant reduction in infarct size of the controls, but were without effect on infarct size of hearts from the obese groups. However, ischaemic as well as beta-preconditioning caused an improvement in functional performance during reperfusion in all three groups. A clear-cut correlation between the reduction in infarct size and activation of ERKp44/p42 and PKB/Akt was not observed: The reduction in infarct size observed in the non-preconditioned hearts from the obese groups was not associated with activation of the RISK pathway. However, beta-adrenergic preconditioning caused a significant activation of ERKp44/p42, but not PKB/Akt, in all three groups.ConclusionsRelatively long-term administration of the two obesity-inducing diets resulted in cardioprotection against ischaemia/reperfusion damage. Further protection by preconditioning was, however, without effect on infarct size, while an improvement in functional recovery was observed.
Highlights
Obesity is still considered a risk factor in the development of cardiovascular disorders, recent studies suggested that it may be associated with reduced morbidity and mortality, the so-called “obesity paradox”
ischaemic preconditioning (IPC) as well as Beta-adrenergic preconditioning (BPC) caused a significant lowering in infarct size of hearts from non-diet controls (NDC) (p < 0.01 respectively) (Figure 2), when compared to those of NPC hearts
A number of interesting observations were made: (i) relatively long-term administration of the two obesityinducing diets had no effect on the baseline mechanical performance of isolated working hearts, when compared with rats fed a control diet (NDC); (ii) the infarct sizes of NPC hearts subjected to 35 min regional ischaemia, were significantly lower in the Diet-induced obese rats (DIO) and high fat diet (HFD) groups than in hearts from rats receiving normal rat chow, suggesting diet-induced cardioprotection; (iii) in contrast
Summary
Obesity is still considered a risk factor in the development of cardiovascular disorders, recent studies suggested that it may be associated with reduced morbidity and mortality, the so-called “obesity paradox”. Experimental data on the impact of diabetes, obesity and insulin resistance on myocardial ischaemia/ reperfusion injury are controversial. The aim of the present study was to evaluate the susceptibility to myocardial ischaemia/reperfusion damage in two models of diet-induced obesity as well as the effect of ischaemic and pharmacological preconditioning on such hearts. Experimental data on the impact of diabetes, obesity and insulin resistance on myocardial ischaemia/ reperfusion injury (IRI) are controversial (for reviews see references [4,5]). Similar findings were reported in other animal models [9,23,24,25,26] These studies have shown that an increased infarct size is associated with concomitant poor functional recovery in hearts from obese animals compared to the controls. A possible explanation for the variation in susceptibility to ischaemia/reperfusion damage may be differences in the age of the animals and the duration of obesity
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