In conscious rabbits equipped with right ventricular electrode and left ventricular polyethylene catheters, zaprinast and cicletanine, inhibitors of phosphodiesterase (PDE) V and PDEs I and V, respectively, as well as verapamil, a Ca2+ channel blocker, decreased intracavital ST-segment elevation induced by ventricular overdrive pacing (VOP). Zaprinast and cicletanine attenuated VOP-induced QT reduction and increase in left ventricular end-diastolic pressure (LVEDP), whereas verapamil increased LVEDP. These results suggest that inhibition of cGMP-PDEs can protect heart against ischemia.