Activation of cardiac KATP channels: an endogenous protective mechanism during repetitive ischemia. Am J Physiol 1993 Feb;264(2 Pt 2):H495-504
Date
02/01/1993Pubmed ID
8447462DOI
10.1152/ajpheart.1993.264.2.H495Scopus ID
2-s2.0-0027548579 (requires institutional sign-in at Scopus site) 96 CitationsAbstract
The role of KATP channels in myocardial stunning produced by repetitive coronary occlusions was studied in barbital-anesthetized dogs. Regional percent segment function (%SS) was measured by sonomicrometry, and the monophasic action potential (MAP) in the ischemic region was measured by an epicardial probe. Under control conditions, six 5-min periods of coronary occlusion, interspersed with 10-min periods of reperfusion, and ultimately followed by 2 h of reperfusion produced regional segment dysfunction and a similar rate and amount of shortening of the MAP measured at 50% repolarization duration (MAPD50) during each successive ischemic period. Pretreatment with glibenclamide (0.3 mg/kg iv), a KATP channel antagonist, significantly prevented the reduction of MAPD50, particularly during the first occlusion period, and it worsened postischemic dysfunction. In contrast, pretreatment with aprikalim (10 micrograms/kg bolus +/- 0.1 microgram.kg-1.min-1 iv), a KATP channel opener, accelerated the rate and extent of shortening of MAPD50 during each occlusion and markedly improved %SS throughout reperfusion. Pretreatment with d-sotalol (2 mg/kg iv), an antagonist of voltage-dependent K+ channels, significantly prolonged MAPD50 of the ischemic region before coronary occlusion but did not alter the rate of shortening of MAPD50 during ischemia and did not affect the recovery of %SS. These results indicate that activation of KATP channels during ischemia with the resultant shortening of the MAPD50 is an endogenous adaptive mechanism that affords functional myocardial protection during repetitive, brief periods of coronary arterial occlusion.
Author List
Yao Z, Cavero I, Gross GJMESH terms used to index this publication - Major topics in bold
Action PotentialsAdenosine Triphosphate
Animals
Coronary Circulation
Dogs
Female
Glyburide
Hemodynamics
Male
Myocardial Ischemia
Myocardial Reperfusion
Myocardium
Picolines
Potassium Channels
Pyrans
Reaction Time
Sotalol
