title: Myocardial oxygenation and high-energy phosphate levels during KATP channel blockade.
abstract: Inhibition of ATP-sensitive K+ (KATP) channel activity has previously been demonstrated to result in coronary vasoconstriction with decreased myocardial blood flow and loss of phosphocreatine (PCr). This study was performed to determine whether the high-energy phosphate abnormality during KATP channel blockade can be ascribed to oxygen insufficiency. Myocardial blood flow and oxygen extraction were measured in open-chest dogs during KATP channel blockade with intracoronary glibenclamide, whereas high-energy phosphates were examined with 31P magnetic resonance spectroscopy (MRS), and myocardial deoxymyoglobin (Mb-delta) was determined with 1H MRS. Glibenclamide resulted in a 20 +/- 8% decrease of myocardial blood flow that was associated with a loss of phosphocreatine (PCr) and accumulation of inorganic phosphate. Mb-delta was undetectable during basal conditions but increased to 58 +/- 5% of total myoglobin during glibenclamide administration. This degree of myoglobin desaturation during glibenclamide was far greater than we previously observed during a similar reduction of blood flow produced by a coronary stenosis (22% of myoglobin deoxygenated during stenosis). The findings suggest that reduction of coronary blood flow with an arterial stenosis was associated with a decrease of myocardial energy demands and that this response to hypoperfusion was inhibited by KATP channel blockade.
authors.affiliation: Department of Medicine and Center for Megnetic Resonance Research, University of Minnesota Health Science Center, Mayo Mail Code 508, 420 Delaware St. SE, Minneapolis, MN 55455, USA. zhang047@umn.edu
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
authors.forename: Arthur H L
authors.initials: AH
authors.lastname: From
authors.forename: Kamil
authors.initials: K
authors.lastname: Ugurbil
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bache
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000031:analogs & derivatives* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010710:Phosphates / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*
chemical_list: D009211:Myoglobin; D010710:Phosphates; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C055547:deoxymyoglobin; D000255:Adenosine Triphosphate; D005905:Glyburide