title: Myocardial susceptibility to ischaemia/reperfusion in obesity: a re-evaluation of the effects of age.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Four 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.
  
  
  RESULTS
  Age 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: I
authors.initials: I
authors.lastname: Webster
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Salie
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: E
authors.initials: E
authors.lastname: Marais
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: W-J
authors.initials: WJ
authors.lastname: Fan
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: G
authors.initials: G
authors.lastname: Maarman
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Stellenbosch, South Africa.|Biotechnology and Innovation Platform of the SA Medical Research Council, Cape Town, South Africa.
authors.forename: B
authors.initials: B
authors.lastname: Huisamen
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Stellenbosch, South Africa. alo@sun.ac.za.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-6847-5091
authors.initials: A
authors.lastname: Lochner
mesh_terms: D000375:Aging; D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D017208:Rats, Wistar
keywords: Age; Diet-induced obesity; Infarct size; Ischaemic preconditioning; Myocardial function