Preconditioning Attenuates the Shortening of Recovery During Coronary Occlusion in Isolated Rabbit Hearts With d-Sotalol-Induced Long QT Intervals

Abstract

The effects of 20-min ligations of the anterior branch of the left coronary artery were studied in Langendorff-perfused rabbit hearts with 92 microM D-sotalol added to the perfusate to induce long QT intervals and triggered arrhythmias. Epicardial electrograms, a left ventricular endocardial monophasic action potential, and simulated X and Y lead electrocardiograms were used to characterize ventricular conduction and recovery. In contrast to previous work showing that global ischemia eliminated triggered activity, coronary occlusion did not alter its mean incidence. Although the anatomic distribution of earliest sites of epicardial activation by triggered beats was altered, triggered beats still appeared on the epicardial surface in the nonperfused regions. Coronary occlusion had a small and variable effect on epicardial conduction velocity but caused a significantly greater percent shortening of epicardial activation-recovery intervals in the nonperfused region of hearts given D-sotalol than in control hearts. In hearts given D-sotalol, preconditioning significantly attenuated the shortening of epicardial activation-recovery intervals in response to coronary occlusion. However, preconditioning had no effect on the mean incidence of triggered activity during coronary occlusion. Thus, the persistence of triggered activity and the shortened myocardial recovery time associated with coronary occlusion could contribute to increasing the likelihood of occurrence of malignant ventricular arrhythmias. Preconditioning by attenuating the shortening of recovery would be anti-arrhythmic.

β1-Adrenoreceptor activation contributes to ischemia-reperfusion damage as well as playing a role in ischemic preconditioning

“…After sedation the rabbits were heparinized (500 U iv) and euthanized with propofol (100 mg iv). Our preparation was published previously (46). The hearts were removed via a midsternal thoracotomy and rinsed in cool, oxygenated Tyrode solution.…”

“…Ten additional hearts underwent classic ischemic preconditioning (Precon). Hearts were preconditioned by two global ischemic episodes of 5 min in duration at a perfusion rate of 2.5 ml/min and separated by 10 min (46). Ten minutes after the second preconditioning episode, coronary occlusion was performed for 30 min, followed by 2 h of reperfusion.…”

Mitochondrial LON protease-dependent degradation of cytochrome c oxidase subunits under hypoxia and myocardial ischemia

“…More recently Lu et al (44) showed phosphorylation of Tfam not only alters its DNA binding ability, but also its sensitivity to Lon mediated degradation (54) under conditions when catalytic subunit of PKAα was forcibly expressed in mitochondria. Studies from our laboratory showed that PKA mediated phosphorylation of CcO subunits I, IVi1 and Vb during pathophysiological conditions of hypoxia and myocardial ischemia/reperfusion renders them more sensitive to degradation (4, 8–10, 26–28). In support, Hori et al showed that ER stress transmitted to mitochondria also induce degradation of CcO II, IVi1 and Vb in a Lon dependent manner (52).…”

“…Hearts from New Zealand male white rabbits (2–2.5 kg) were removed after euthanasia and perfused using a Langendorff perfusion apparatus as described before (4;28). The aorta was cannulated and the heart suspended on a Langendorff perfusion apparatus in which the coronary arteries were perfused from a reservoir with oxygenated temperature-controlled Tyrode’s solution at a constant pressure of 80 mmHg.…”

Cardioprotection by PI3K-mediated signaling is required for anti-arrhythmia and myocardial repair in response to ischemic preconditioning in infarcted pig hearts

“…It is generally thought that IP is able to limit the mass of myocardium at risk that ultimately becomes infarcted and results in reducing lethal arrhythmia. 2,3 However, lack of IP enhanced inflammatory response, and subsequent left ventricle (LV) dysfunction, are related to VT/VF development after AMI. 4 It has also been reported that cardioprotection with IP is related to the enhanced expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factors (bFGF) after MI.…”