We investigated whether the
adenosine triphosphate (
ATP)-sensitive K+ (K(
ATP)) channel activation by
bimakalim, at concentrations devoid of both negative inotropic and action-potential duration (APD) shortening effects, might exhibit myocardial protection after
hypoxia and reoxygenation in human atrial myocardium by using 112 preparations. The recovery of contractility of human atrial trabeculae, subjected either to short-duration (5 min) or to long-duration (60 min) and severe (high pacing rate)
hypoxia followed by reoxygenation, was assessed by challenging with
dobutamine. Treated preparations were exposed to 10 or 100 nM
bimakalim, 1 microM
glibenclamide, or both before
hypoxia. Variations of isometric developed tension (%DT) or APD90 were studied. At concentrations <100 nM,
bimakalim showed no negative inotropic effects and did not modify significantly APD90 either in normoxia or in hypoxic conditions. In the short-duration
hypoxia protocol, preparations treated with
bimakalim showed a
dobutamine-induced %DT increase significantly higher (p < 0.001) than in controls and similar to that observed in the absence of
hypoxia. This
bimakalim effect was blocked by
glibenclamide. In the long-duration
hypoxia protocol, %DT after
dobutamine was 50% of that observed in normoxic preparations. Preparations treated with
bimakalim showed after
dobutamine %DT more than twofold above controls (p < 0.001), whereas in the
glibenclamide group, recovery of DT with
dobutamine remained 50% of what observed in normoxia (p < 0.001). In conclusion, exposure to
hypoxia (either short- or long-lasting) and reoxygenation affects contractility of human atrial myocardium with pronounced reduction of the positive inotropic action of
dobutamine. Pretreatment with
bimakalim restores the response expected in the absence of
hypoxia, and
glibenclamide blocks the effect of
bimakalim or further impairs the response to
dobutamine when used alone before long-duration
hypoxia. Evidence is provided for protective effects of the K(
ATP) opener
bimakalim on the human myocardial contractile function in conditions of
hypoxia/reoxygenation, at concentrations at which negative inotropism and APD90 shortening are not contributory.