title: Insulin addition after ischemia improves recovery of function equal to ischemic preconditioning in rat heart.
abstract: BACKGROUND
  Ischemic preconditioning (IPC) is considered the most potent mechanism to improve ischemia tolerance. We have demonstrated that insulin addition during reperfusion improves recovery of function in the isolated working rat heart. We herein compare the relative importance of these two mechanisms in improving recovery of postischemic function.
  
  
  METHODS
  Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing glucose (5 mmol/l) plus oleate (0.4 mmol/l) for 20 min and were then subjected to 15 min of ischemia followed by 35 min of reperfusion. IPC was achieved by an ischemic period of fi ve minutes followed by 10 minutes of reperfusion before ischemia. Insulin (1 mU/ml) was or was not added at the beginning of reperfusion. Wortmannin (WM, 3 micro mol/l), an inhibitor of phosphatidylinositol 3-kinase, was or was not present in the perfusate from the beginning of the experiments. We measured glucose uptake with [2-(3)H]glucose, cardiac power and tissue metabolite content at the end of the experiments.
  
  
  RESULTS
  Cardiac power before ischemia ranged from 7.17 to 10.4 mW. After ischemia, cardiac power recovered to 65.7 +/- 3.8% (Control). Insulin significantly improved recovery (96.3 +/- 10.8%, p < 0.05 vs. Control). This effect was also achieved by IPC (recovery 86.2 +/- 6.2%, p < 0.05). The effects of insulin and IPC were not additive (recovery 83.4 +/- 6.2%, p < 0.05). WM fully inhibited the effects of both insulin and IPC (69.5 +/- 3.3, 72.0 +/- 6.9, respectively). Basal glucose uptake ranged from 2.53 to 3.46 micro mol/gdry, and was significantly lower after ischemia in the presence of WM.
  
  
  CONCLUSIONS
  Insulin is a potent tool to improve postischemic contractile function. The improvement of recovery afforded by insulin added after ischemia may be mediated through a similar mechanism as ischemic preconditioning.
authors.affiliation: Department of Cardiovascular Surgery, Albert-Ludwigs-University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg i. Br., Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Fischer-Rasokat
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: Torsten
authors.initials: T
authors.lastname: Doenst
mesh_terms: D000730:Androstadienes / Q000009:adverse effects; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D012107:Research Design; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002316:Cardiotonic Agents; D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D005947:Glucose; D000077191:Wortmannin