Effects of KATP channel modulation on myocardial glycogen content, lactate, and amino acids in nonischemic and ischemic rat hearts.
ATP-sensitive potassium (KATP) channels are involved in the mechanisms underlying ischemic preconditioning. KATP channels open during ischemia, presumably secondary to intracellular metabolic alterations. The direct effects of KATP channel modulation on myocardial metabolism have not been studied. The aim of the present study was to investigate whether a KATP opener (diazoxide) and blocker (glibenclamide) modulates myocardial glycogen, lactate, and amino acid content before, during, and after ischemia. In isolated perfused rat hearts, we investigated the effect of diazoxide (30 microM) and glibenclamide (10 microM) administered 15 minutes before ischemia on myocardial glycogen, lactate, and amino acid content before, during, and after ischemia. Diazoxide increased left-ventricular developed pressure during reperfusion (P < 0.05) and decreased myocardial glycogen depletion (P < 0.05) and lactate accumulation (P < 0.05) during ischemia compared with the control group. Glibenclamide decreased myocardial glycogen content (P < 0.05) and increased myocardial lactate (P < 0.05) and alanine (P < 0.05) content before ischemia and reduced myocardial glycogen content after ischemia (P < 0.05) compared with control. KATP channel activation by diazoxide modulates myocardial metabolism. These findings suggest that activation of KATP channels protects against ischemia-reperfusion injury by a mechanism that involves decreased energy depletion.
Kristiansen
Steen B
SB
Department of Cardiology, Skejby Sygehus, Aarhus University Hospital, Aarhus, Denmark. sbk@iekf.au.dk
Nielsen-Kudsk
Jens Erik
JE
Bøtker
Hans Erik
HE
Nielsen
Torsten Toftegaard
TT
D000409:Alanine / Q000032:analysis; D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D004347:Drug Interactions; D018698:Glutamic Acid / Q000032:analysis; D005905:Glyburide / Q000494:pharmacology; D006003:Glycogen / Q000032:analysis*; D019344:Lactic Acid / Q000032:analysis*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019344:Lactic Acid; D018698:Glutamic Acid; D006003:Glycogen; D003981:Diazoxide; D000409:Alanine; D005905:Glyburide