CICLETANINE ATTENUATES OVERDRIVE PACING-INDUCED GLOBAL MYOCARDIAL-ISCHEMIA IN RABBITS - POSSIBLE ROLE OF CARDIAC CYCLIC-NUCLEOTIDES

Background: This study examined whether cicletanine, an antihypertensi ve drug with cGMP phosphodiesterase inhibitory effect, could alleviate ventricular overdrive pacing-induced myocardial ischemia in chronical ly instrumented rabbits.Methods: An electrode-catheter implanted into the right ventricle was used for pacing (500 bpm over 5 min) and for m easuring intracavital ST-segment elevation and ventricular effective r efractory period (VERP). PQ and QT intervals were measured in the ches t-lead ECG, and dP/dt(max) as well as left ventricular end-diastolic p ressure (LVEDP) were recorded through a left intraventricular catheter . In separate groups, mean arterial blood pressure (MABP) was monitore d from the right carotid artery. Experiments were performed on conscio us rabbits after a week of convalescence. In anesthetized, open-chest rabbits, samples were taken from the left ventricle before and after d rug treatment and/or overdrive pacing for determination of cGMP and cA MP contents by radioimmunoassay. Results: Intravenous cicletanine, 30 mg/kg body weight, did not change resting MABP, dP/dt(max), and LVEDP, but it did reduce heart rate and prolonged PQ and QT intervals and VE RP. Overdrive pacing produced intracavital ST-segment elevation, incre ased LVEDP, and decreased dP/dt(max) and MABP. Cicletanine administere d 15 minutes before pacing significantly attenuated ST-segment elevati on, increased LVEDP, and decreased dP/dt(max) and MABP. In anesthetize d animals, cicletanine itself slightly increased cardiac cGMP and cAMP contents. Overdrive pacing moderately increased cGMP and profoundly e levated cAMP, and in overpaced rabbits, cicletanine further increased cGMO and markedly attenuated cAMP content increased by overdrive pacin g. Conclusions: These results suggest that in correlation with alterat ions of cardiac cycle nucleotide contents, cicletanine protects the he art against pacing-induced myocardial ischemia.