AIM To determine whether IHC-66 <3, 6-di (dimethylamino )-dibenzopyriodonium of ferric EDTA> may exert beneficial effects on the transmembrane action potentials during hypoxia and reoxygenation in isolated right ventricular papillary muscles of the guinea pig. METHODS The effects of IHC-66 on transmembrane action potentials of guinea pig papillary muscles during hypoxia and reoxygenation were studied using conventional microelectrode techniques. Right ventricular papillary muscles of the guinea pig in which ATP level was also determined by the luciferase method. RESULTS Hypoxia conditions induced a decrease in action potential duration (APD) without significantly affecting other action potential parameters. IHC-66 inhibited this hypoxia-induced decrease in APD. Pinacidil-induced shortening of APD was antagonized by IHC-66. Hypoxia significantly decreased the myocardial adenosine triphosphate (ATP) level, which was also prevented partly by IHC-66. CONCLUSION These results suggested that IHC-66 may inhibit the hypoxia induced shortening of APD by some mechanism, which contribute to the blocking K+-ATP channels and decrease in Ca2+、 Na+ inward current.