Introduction.

We have previously shown in the embryonic chick heart model that chronic ventricular pacing leads to structural, hemodynamic, and metabolic remodeling. We also aimed at determining to what extent the L-type Ca²⁺ channel, the sarcolemmal (sarcK_ATP), and the mitochondrial KATP (mitoK_ATP) channels are involved in the pacing-induced protection against anoxia-reoxygenation.

Methods and results.

Hearts of 4-day-old chick embryos were paced in ovo during 12-48 hours using asynchronous intermittent ventricular stimulation at 110% of the intrinsic rate. Sham operated and paced hearts were then submitted in vitro to anoxia (30 minutes) and reoxygenation (60 minutes). ECG disturbances and alterations of atrial and ventricular electromechanical delay (EMD) reflecting excitation-contraction (E-C) coupling were systematically investigated. Baseline functional parameters were stable during at least 2 hours. Anoxia induced tachycardia, followed by bradycardia, atrial ectopy, first-, second-, and third-degree atrio-ventricular blocks and, finally, transient electromechanical arrest. Reoxygenation triggered also Wenckebach phenomenon and ventricular escape beats. At the onset of reoxygenation QT, PR, and ventricular EMD increased by 68%, 70%, and 250%, respectively, whereas atrial EMD was not altered. These hearts were exposed to L-type Ca²⁺ channel agonist Bay-K-8644 (BAY-K) or blocker verapamil, nonselective K_ATP channel antagonist glibenclamide (GLIB), mitoK_ATP channel agonist diazoxide (DIAZO), or antagonist 5-hydroxydecanoate. Under normoxia, heart rate, QT duration, conduction, EMD, and ventricular shortening were similar in sham and paced hearts. During reoxygenation, arrhythmias ceased earlier and ventricular EMD recovered faster in paced hearts than in sham hearts. In sham hearts, BAY-K (but not verapamil), DIAZO (but not 5-hydroxydecanoate) or GLIB accelerated recovery of ventricular EMD, reproducing the pacing-induced protection. In contrast, none of these agents further ameliorated recovery of the paced hearts.

Conclusion.

The protective effect of chronic asynchronous pacing at near physiological rate on ventricular E-C coupling appears to be associated with subtle activation of L-type Ca²⁺ channel, inhibition of sarcK_ATP channel, and/or opening of mitoK_ATP channel.