title: Protection afforded by preconditioning to the diabetic heart against ischaemic injury.
abstract: OBJECTIVE
  The aim of this study was to assess whether the cardioprotective effect of ischaemic preconditioning (IPC) on endothelial function in coronary arteries and myocardial function is affected in the streptozotocin-induced diabetic rat heart.
  
  
  METHODS
  Isolated hearts, perfused under constant flow conditions, were exposed to 30 min of partial ischaemia (flow rate 1 ml min-1) followed by 20 min of reperfusion.
  
  
  RESULTS
  In the diabetic group (without ischaemia or IPC), infusion of 10 microM serotonin (5-HT), an endothelium-dependent, and 3 microM sodium nitroprusside (SNP), an endothelium-independent vasodilator, in the coronary bed preconstricted with 0.1 microM U-46619 induced a marked vasodilation. Ischaemia, either without or with preconditioning with a single 5 min ischaemia and 10 min reperfusion (IPC1) before ischaemia, was accompanied by a reduced 5-HT-induced vasodilation in diabetic hearts. In contrast, IPC1 preserved the response to 5-HT in non-diabetic hearts. A more extensive IPC with 3 periods of 5 min ischaemia followed by 5 min reperfusion (IPC3) preserved the vasodilation produced by 5-HT in both diabetic and non-diabetic hearts. IPC3 increased the recovery of d P/dtmax and d P/dtmin during the 30 min ischaemic period and during reperfusion in all hearts. In contrast, IPC1 had no effect on myocardial recovery in either groups. Adenosine pre-treatment started 30 min before ischaemia mimicked IPC3, preserving the vasodilation to 5-HT and improving myocardium recovery in both groups. When adenosine was started 15 min before ischaemia, vasodilation to 5-HT was preserved in non-diabetic hearts only.
  
  
  CONCLUSIONS
  These results suggest that IPC affords protection to endothelial function in resistance coronary arteries of diabetic hearts. To achieve this protection, a more extensive IPC is needed, which may be related to a longer exposure to adenosine.
authors.affiliation: Faculty of Pharmacy, University of Montreal, Québec, Canada.
authors.forename: J F
authors.initials: JF
authors.lastname: Bouchard
authors.forename: D
authors.initials: D
authors.lastname: Lamontagne
mesh_terms: D000241:Adenosine / Q000627:therapeutic use; D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000150:complications / Q000517:prevention & control*; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002317:Cardiovascular Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D000241:Adenosine