Delayed ischemic preconditioning is mediated by opening of ATP-sensitive potassium channels in the rabbit heart.
Cardioprotection from preconditioning reappears 24 h after the initial stimulus. This phenomenon is called the second window of protection (SWOP). We hypothesized that opening of the ATP-sensitive potassium (KATP) channel mediates the protective effect of SWOP. Rabbits were preconditioned (PC) with four cycles of 5-min regional ischemia each followed by 10 min of reperfusion. Twenty-four hours later, the animals were subjected to sustained ischemia for 30 min followed by 180 min of reperfusion (I/R). Glibenclamide (Glib, 0.3 mg/kg ip) or 5-hydroxydecanoate (5-HD, 5 mg/kg iv) was used to block the KATP channel function. Infarct size was reduced from 41.2 +/- 2. 6% in sham-operated rabbits to 11.6 +/- 1.0% in PC rabbits, a 71% reduction (n = 11, P < 0.01). Treatment with Glib or 5-HD before I/R increased the infarct size to 43.4 +/- 2.6 and 37.8 +/- 1.9%, respectively (P < 0.01 vs. PC group, n = 12/group). Sham animals treated with either Glib or 5-HD had an infarct size of 39.0 +/- 3.4 and 37.8 +/- 1.5%, respectively, which was not different from control (40.0 +/- 3.8%) or sham (41.2 +/- 2.6%) I/R hearts. Monophasic action potential duration (APD) at 50% repolarization significantly shortened by 28.7, 26.6, and 23.3% in sham animals during 10, 20, and 30 min of ischemia. However, no further augmentation in the shortening of APD was observed in PC hearts. Glib and 5-HD significantly suppressed ischemia-induced epicardial APD shortening, suggesting that 5-HD may not be a selective blocker of the mitochondrial KATP channel in vivo. We conclude that SWOP is mediated by a KATP channel-sensitive mechanism that may have occurred because of the opening of the sarcolemmal KATP channel in vivo.
Bernardo
N L
NL
Division of Cardiology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
D'Angelo
M
M
Okubo
S
S
Joy
A
A
Kukreja
R C
RC
D000200:Action Potentials / Q000502:physiology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001790:Blood Physiological Phenomena; D005740:Gases / Q000097:blood; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D011930:Reaction Time / Q000502:physiology; D013997:Time Factors
D005740:Gases; D015221:Potassium Channels; D000255:Adenosine Triphosphate