Cardiac preconditioning with 4-h, 17 degrees C ischemia reduces [Ca(2+)](i) load and damage in part via K(ATP) channel opening.
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.
Chen
Qun
Q
Department of Anesthesiology, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Camara
Amadou K S
AK
An
Jianzhong
J
Riess
Matthias L
ML
Novalija
Enis
E
Stowe
David F
DF
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*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D002118:Calcium