Ectopic pacing at physiological rate improves postanoxic recovery of the developing heart

Abstract

Recently, rapid and transient cardiac pacing was shown to induce preconditioning in animal models. Whether the electrical stimulation per se or the concomitant myocardial ischemia affords such a protection remains unknown. We tested the hypothesis that chronic pacing of a cardiac preparation maintained in a normoxic condition can induce protection. Hearts of 4-day-old chick embryos were electrically paced in ovo over a 12-h period using asynchronous and intermittent ventricular stimulation (5 min on-10 min off) at 110% of the intrinsic rate. Sham (n ϭ 6) and paced hearts (n ϭ 6) were then excised, mounted in vitro, and subjected successively to 30 min of normoxia (20% O2), 30 min of anoxia (0% O2), and 60 min of reoxygenation (20% O2). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout the experiment. Reoxygenation-induced chrono-, dromo-, and inotropic disturbances, incidence of arrhythmias, and changes in electromechanical delay (EMD) in atria and ventricle were systematically investigated in sham and paced hearts. Under normoxia, the isolated heart beat spontaneously and regularly, and all baseline functional parameters were similar in sham and paced groups (means Ϯ SD): heart rate (190 Ϯ 36 beats/min), P-R interval (104 Ϯ 25 ms), mechanical atrioventricular propagation (20 Ϯ 4 mm/s), ventricular shortening velocity (1.7 Ϯ 1 mm/s), atrial EMD (17 Ϯ 4 ms), and ventricular EMD (16 Ϯ 2 ms). Under anoxia, cardiac function progressively collapsed, and sinoatrial activity finally stopped after ϳ9 min in both groups. During reoxygenation, paced hearts showed 1) a lower incidence of arrhythmias than sham hearts, 2) an increased rate of recovery of ventricular contractility compared with sham hearts, and 3) a faster return of ventricular EMD to basal value than sham hearts. However, recovery of heart rate, atrioventricular conduction, and atrial EMD was not improved by pacing. Activity of all hearts was fully restored at the end of reoxygenation. These findings suggest that chronic electrical stimulation of the ventricle at a near-physiological rate selectively alters some cellular functions within the heart and constitutes a nonischemic means to increase myocardial tolerance to a subsequent hypoxia-reoxygenation. chick embryo; hypoxia-reoxygenation; preconditioning; arrhythmias; excitation-contraction coupling IN THE ADULT HEART, it is well established that the deleterious consequences of prolonged ischemia can be minimized if this condition is preceded by a short episode(s) of ischemia, the so-called classical preconditioning (30). Cardioprotection is measured in terms of a decrease in infarct size, a delay in ultrastructural damage, a reduction in myocardial stunning, and a diminution in incidence and severity of ischemia-reperfusion-induced arrhythmias. Preconditioning can also be induced by numerous nonischemic stimuli, such as exercise, heat stress, endotoxins or cytokines, catecholamines, pharmacological agents, adenosine, reactive oxygen species (ROS), and nitric ...

mitoKATP channel activation in the postanoxic developing heart protects E-C coupling via NO-, ROS-, and PKC-dependent pathways

“…In contrast to the chronotropic and dromotropic parameters, the ventricular shortening and maxi- mal shortening velocity displayed important interindividual variations, even after in vitro stabilization (Table 1). Such variability of contractile activity might be due to slight differences in the developmental stage, variations of cardiac three- dimensional structure, and/or degree of flattening of the hearts in the culture compartment, as discussed previously (29,30). Shortening determined just before anoxia (19 Ϯ 17 m, n ϭ 56) and at the end of reoxygenation (20 Ϯ 16 m, n ϭ 56), as well as the rate of contractile recovery, was similar in all experimental groups, indicating that contractile activity fully recovered.…”

“…The intact and spontaneously beating heart was carefully excised and placed in the culture compartment of an airtight chamber. The chamber was equipped with two windows for observation and measurements and maintained under controlled metabolic conditions on the thermostabilized stage (37°C) of an inverted microscope (model IMT2, Olympus, Tokyo, Japan) as previously described in detail (30,38). Briefly, the culture compartment (300 l) was separated from the gas compartment by a thin (15 m) transparent and gas-permeable silicone membrane (RTV 141, Rhône-Poulenc, Lyon, France).…”

“…Electrical and contractile activities were recorded simultaneously and continuously throughout in vitro experiments as previously described (30,34).…”

“…Although the embryonic/fetal heart normally grows and functions in a relatively hypoxic environment, it rapidly reacts to oxygen deprivation and reoxygenation, e.g., as in the case of transient uteroplacental ischemia. We previously characterized the chrono-, dromo-, and inotropic responses of the isolated embryonic chick heart (4 -5 days old) to anoxia-reoxygenation (30,34). We also found that this preparation is subjected to an oxidative stress during reoxygenation (28) similar to reperfused cardiac cells obtained from 10-day-old chick embryo (41,45).…”

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

“…Intermittent ventricular pacing for 12 hours reduced the incidence of arrhythmias after ischemia. 20 In the present study, we followed a "classical" preconditioning scheme in mammalian hearts and used infarct size as the principal end point.…”