Ventricular overdrive pacing-induced anti-ischemic effect: a conscious rabbit model of preconditioning

To study whether ventricular overdrive pacing (VOP) induces preconditioning, rabbits were equipped with right ventricular electrode catheters for pacing and intracavital recording and polyethylene cannulas in the left ventricle and right carotid artery to measure intraventricular pressure and blood pressure. One week after surgery in conscious animals, VOP at 500 beats/min over 2, 5, or 10 min resulted in an intracavital S-T segment elevation, shortening of ventricular effective refractory period, decrease in maximum rate of pressure development and blood pressure, and increase in left ventricular end-diastolic pressure proportional to the duration of stimulation. A 5-min preconditioning VOP applied 5 or 30 min before a 10-min VOP markedly attenuated ischemic changes, whereas a 2-min VOP had no effect. In anesthetized rabbits, a 5-min VOP slightly increased guanosine 3',5'-cyclic monophosphate (cGMP) and profoundly elevated adenosine 3',5'-cyclic monophosphate (cAMP) content in left ventricular samples. When this VOP was preceded (5 or 30 min) by a preconditioning VOP, the cAMP increase was significantly attenuated, whereas the cGMP increase was amplified. We conclude that a single 5-min VOP induces preconditioning in association with alterations in cardiac cyclic nucleotide contents.