Myocardial oxygenation and high-energy phosphate levels during K _ATPchannel blockade

Inhibition of ATP-sensitive K⁺ (K_ATP) 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 K_ATP channel blockade can be ascribed to oxygen insufficiency. Myocardial blood flow and oxygen extraction were measured in open-chest dogs during K_ATP channel blockade with intracoronary glibenclamide, whereas high-energy phosphates were examined with ³¹P magnetic resonance spectroscopy (MRS), and myocardial deoxymyoglobin (Mb-δ) 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-δ 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 K_ATP channel blockade.