Cardioprotection by multiple preconditioning cycles does not require mitochondrial K(ATP) channels in pigs.
To test whether cardioprotection induced by ischemic preconditioning depends on the opening of mitochondrial ATP-sensitive K(+) (K(ATP)) channels, the effect of channel blockade was studied in barbital-anesthetized open-chest pigs subjected to 30 min of complete occlusion of the left anterior descending coronary artery and 3 h of reflow. Preconditioning was elicited by two cycles of 5-min occlusion plus 10-min reperfusion before the 30-min occlusion period. 5-Hydroxydecanoate (5 mg/kg iv) was injected 15 min before preconditioning or pharmacological preconditioning induced by diazoxide (3.5 mg/kg, 1 ml/min iv). Infarct size (percentage of the area at risk) after 30 min of ischemia was 35.1 +/- 9.9% (n = 7). Preconditioning markedly limited myocardial infarct size (2.7 +/- 1.6%, n = 7), and 5-hydroxydecanoate did not abolish protection (2.4 +/- 0.9%, n = 8). Diazoxide infusion also significantly limited infarct size (14.6 +/- 7.4%, n = 7), and 5-hydroxydecanoate blocked this effect (30.8 +/- 8.0%, n = 7). Thus the opening of mitochondrial K(ATP) channels is cardioprotective in pigs, but these data do not support the hypothesis that opening of mitochondrial K(ATP) channels is required for the endogenous protection afforded by preconditioning.
Schwartz
Lisa M
LM
Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA. lschwartz@usuhs.mil
Welch
Timothy S
TS
Crago
Mark S
MS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001794:Blood Pressure; D002316:Cardiotonic Agents / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D006339:Heart Rate; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008928:Mitochondria / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015221:Potassium Channels / Q000378:metabolism*; D011237:Predictive Value of Tests; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; D014665:Vasodilator Agents; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D003981:Diazoxide