title: Angiotensin-converting enzyme inhibition and food restriction restore delayed preconditioning in diabetic mice.
abstract: BACKGROUND
  Classical and delayed preconditioning are powerful endogenous protection mechanisms against ischemia-reperfusion damage. However, it is still uncertain whether delayed preconditioning can effectively salvage myocardium in patients with co-morbidities, such as diabetes and the metabolic syndrome. We investigated delayed preconditioning in mice models of type II diabetes and the metabolic syndrome and investigated interventions to optimize the preconditioning potential.
  
  
  METHODS
  Hypoxic preconditioning was induced in C57Bl6-mice (WT), leptin deficient ob/ob (model for type II diabetes) and double knock-out (DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome). Twenty-four hours later, 30 min of regional ischemia was followed by 60 min reperfusion. Left ventricular contractility and infarct size were studied. The effect of 12 weeks food restriction or angiotensin-converting enzyme inhibition (ACE-I) on this was investigated. Differences between groups were analyzed for statistical significance by student's t-test or one-way ANOVA followed by a Fisher's LSD post hoc test. Factorial ANOVA was used to determine the interaction term between preconditioning and treatments, followed by a Fisher's LSD post hoc test. Two-way ANOVA was used to determine the relationship between infarct size and contractility (PRSW). A value of p<0.05 was considered significant.
  
  
  RESULTS
  Left ventricular contractility is reduced in ob/ob compared with WT and even further reduced in DKO. ACE-I improved contractility in ob/ob and DKO mice. After ischemia/reperfusion without preconditioning, infarct size was larger in DKO and ob/ob versus WT. Hypoxic preconditioning induced a strong protection in WT and a partial protection in ob/ob mice. The preconditioning potential was lost in DKO. Twelve weeks of food restriction or ACE-I restored the preconditioning potential in DKO and improved it in ob/ob.
  
  
  CONCLUSIONS
  Delayed preconditioning is restored by food restriction and ACE-I in case of type II diabetes and the metabolic syndrome.
authors: Department of Cardiovascular Sciences, Research Unit Experimental Cardiac Surgery, K.U. Leuven, Herestraat 49, Leuven, Belgium.
authors: Gerry
authors: G
authors: Van der Mieren
authors: Ines
authors: I
authors: Nevelsteen
authors: Annelies
authors: A
authors: Vanderper
authors: Wouter
authors: W
authors: Oosterlinck
authors: Willem
authors: W
authors: Flameng
authors: Paul
authors: P
authors: Herijgers
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000628:therapy*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors