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

Abstract

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.

Loss of preconditioning in rabbits with vascular tolerance to nitroglycerin

“…Discussion These results confirm previous findings that the global myocardial ischaemia induced by VOP is markedlŷ attenuated by a preceding ischaemic challenge provoked by VOP (Szilvassy et al, 1994). The results also indicate that this protection is lost when tolerance to the vasodilator effect of NG develops.…”

“…Introduction The intracellular messenger, cyclic guanosine 3': 5'-monophosphate (cyclic GMP) has been suggested to play a crucial role in the mechanism of the anti-ischaemic effect of preconditioning induced by ventricular overdrive pacing (VOP) in conscious rabbits (Szilvassy et al, 1994). Results obtained with anaesthetized dogs (Vegh et al, 1992) also suggest that nitric oxide (NO), a stimulator of soluble guanylate cyclase, contributes to the antiarrhythmic effect of preconditioning produced by brief coronary artery occlusions.…”

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

“…Soon, however, a variety of preconditioning stimuli were uncovered including hypoxia , rapid cardiac pacing (Szilvassy et al, 1994;Verdouw et al, 1996), thermal stress, and various pharmacological receptor-dependent and -independent agents (pharmacological preconditioning) Schulz et al, 2001;Yellon and Downey, 2003). For pharmacological preconditioning, the endogenous pathways of cardioprotection serve as the contemporary templates for therapeutic cardioprotection.…”

Pacing-Induced Dys-Synchrony Preconditions Rabbit Myocardium Against Ischemia/Reperfusion Injury

“…2,3,18 Except by 1 group of investigators, 18 protection by rapid ventricular pacing has been attributed to concomitant myocardial ischemia. Interestingly, rapid atrial pacing does not induce preconditioning, 19 even though coronary flow, hemodynamics, and electrophysiological variables were affected to a similar degree as during rapid ventricular pacing.…”

“…This so-called preconditioning (PC) has been achieved by, among others, brief ischemia, 1 rapid pacing 2,3 and increased cardiac preload, 4,5 and afterload. 6 Dys-synchronous ventricular activation, as elicited by ventricular pacing (VP), induces regional differences in myocardial mechanical work within the left ventricular (LV) wall.…”