Blockade of ATP-sensitive K+ channels attenuates preconditioning effect on myocardial metabolism in swine: myocardial metabolism and ATP-sensitive K+ channels.
OBJECTIVE
We investigated if blockade of ATP-sensitive K+ channels (KATP) abolishes the protective effect of ischemic preconditioning (IP) on myocardial metabolism and ischemia-induced reactive hyperemia (RH) in pigs.


METHODS
IP was elicited by a single cycle of 5 min occlusion and 5 min reperfusion of coronary artery, followed by 15 min of test ischemia and 120 min of reperfusion. Vehicle or the ATP-sensitive K+ channels (KATP) blocker, glibenclamide (3 or 6 mg/kg; G3 or G6) was administered before IP (groups; IP, G3+IP, G6+IP). As respective controls, the same treatment was performed in groups without IP (groups; C, G3, G6). Tissue levels of ATP, creatine phosphate (CP) and intracellular pH (pHi) in the area at risk were measured by 31P-nuclear magnetic resonance spectroscopy. RH after 5 min of preconditioning ischemia was assessed by regional myocardial blood flow.


RESULTS
ATP and pHi were preserved after 15 min of ischemia in the IP group [C/IP; ATP=57+/-4/76+/-10% of baseline, pHi=6.18+/-0.08/6.66+/-0.03, P<0.05, C vs. IP]. Both doses of glibenclamide completely abolished the ATP sparing effect of IP. The high dose completely abolished pHi preservation (G6+IP=6.33+/-0.06), while the low dose showed only a partial effect (G3+IP=6.48+/-0.03). Glibenclamide did not adversely affect myocardial metabolism in groups without IP. Glibenclamide attenuated RH after 5 min of ischemia by 30% in both subendocardium and subepicardium.


CONCLUSIONS
Blockade of KATP abolished the preconditioning effect on myocardial metabolism, and partially attenuated post-ischemic reactive hyperemia in pigs. These results indicate that KATP activation might be involved in the mechanisms of these phenomena, reactive hyperemia is not sufficient to induce IP protection.
Yokota
R
R
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Tanaka
M
M
Yamasaki
K
K
Araki
M
M
Miyamae
M
M
Maeda
T
T
Koga
K
K
Yabuuchi
Y
Y
Sasayama
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003331:Coronary Vessels / Q000503:physiopathology; D005905:Glyburide / Q000008:administration & dosage; D006439:Hemodynamics; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D019157:Ischemic Preconditioning, Myocardial; D009682:Magnetic Resonance Spectroscopy; D017202:Myocardial Ischemia / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D026902:Potassium Channel Blockers; D012039:Regional Blood Flow; D013552:Swine; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D026902:Potassium Channel Blockers; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D005905:Glyburide