title: Cardiac preconditioning with 4-h, 17 degrees C ischemia reduces [Ca(2+)](i) load and damage in part via K(ATP) channel opening.
abstract: Brief ischemia before normothermic ischemia protects hearts against reperfusion injury (ischemic preconditioning, IPC), but it is unclear whether it protects against long-term moderate hypothermic ischemia. We explored in isolated guinea pig hearts 1) the influence of two 2-min periods of normothermic ischemia before 4 h, 17 degrees C hypothermic ischemia on cardiac cytosolic [Ca(2+)], mechanical and metabolic function, and infarct size, and 2) the potential role of K(ATP) channels in eliciting cardioprotection. We found that IPC before 4 h moderate hypothermia improved myocardial perfusion, contractility, and relaxation during normothermic reperfusion. Protection was associated with markedly reduced diastolic [Ca(2+)] loading throughout both hypothermic storage and reperfusion. Global infarct size was markedly reduced from 36 +/- 2 (SE)% to 15 +/- 1% with IPC. Bracketing ischemic pulses with 200 microM 5-hydroxydecanoic acid or 10 microM glibenclamide increased infarct size to 28 +/- 3% and 26 +/- 4%, respectively. These results suggest that brief ischemia before long-term hypothermic storage adds to the cardioprotective effects of hypothermia and that this is associated with decreased cytosolic [Ca(2+)] loading and enhanced ATP-sensitive K channel opening.
authors: Department of Anesthesiology, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors: Qun
authors: Q
authors: Chen
authors: Amadou K S
authors: AK
authors: Camara
authors: Jianzhong
authors: J
authors: An
authors: Matthias L
authors: ML
authors: Riess
authors: Enis
authors: E
authors: Novalija
authors: David F
authors: DF
authors: Stowe
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003080:Cold Temperature; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D007036:Hypothermia, Induced; D015640:Ion Channel Gating; D019157:Ischemic Preconditioning, Myocardial; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D015221:Potassium Channels / Q000502:physiology*
chemical_list: D015221:Potassium Channels; D000255:Adenosine Triphosphate; D002118:Calcium