Ischemic shortening of action potential duration as a result of KATP channel opening attenuates myocardial stunning by reducing calcium influx.
Action potential duration (APD) shortening due to opening of sarcolemmal ATP-dependent potassium (KATP) channels has been postulated to protect the myocardium against postischemic damage by reducing Ca2+ influx. This hypothesis was assessed, assuming that increased postischemic stunning due to KATP channel inhibition with glibenclamide could be reverted by the addition of the Ca2+ channel blocker diltiazem. Percent wall thickening fraction (%WTh, conscious sheep) and APD (open-chest sheep) were obtained from the following groups: control: 12 min ischemia by anterior descending coronary artery occlusion followed by 2 h reperfusion; glibenclamide: same as control, with glibenclamide (0.4 mg/kg) infused 30 min before ischemia; diltiazem: same as control, with diltiazem (100 microg/kg) administered prior to ischemia; glibenclamide+diltiazem: both drugs infused as in glibenclamide and diltiazem groups. APD was reduced in control ischemia. Conversely, KATP-channel blockade by glibenclamide lengthened APD and increased postischemic stunning (p < 0.01 vs. control); glibenclamide+diltiazem did not shorten APD but enhanced functional recovery (p < 0.01 vs. glibenclamide). Ca2+ channel blockade improvement of increased stunning provoked by KATP channel inhibition supports the hypothesis that APD shortening due to opening of KATP channels protects against postischemic stunning by limiting Ca2+ influx.
Department of Physiology, Pharmacology and Biochemistry, Favaloro University, Buenos Aires, Argentina. lascano@favaloro.edu.ar
Elena C
EC
Lascano
Jorge A
JA
Negroni
Héctor F
HF
del Valle
D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003331:Coronary Vessels / Q000473:pathology; D004110:Diltiazem / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007511:Ischemia; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017682:Myocardial Stunning; D010496:Pericardium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy; D012756:Sheep; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D004110:Diltiazem; D005905:Glyburide; D002118:Calcium