Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart

Abstract

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF (n=18) and control (n=17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs)>1,000 ms but significantly shorter at BCLs<400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17-81%), and conduction velocity was significantly decreased in CHF (by 6-20%). In both groups, high-frequency stimulation (BCLs<150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs<150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

Early Referral for Ablation of Scar-Related Ventricular Tachycardia Is Associated With Improved Acute and Long-Term Outcomes

“…5,6 A recurrent VT itself may change the electrophysiological properties of the myocardium, predisposing the occurrence and stabilization of new VT re-entry circuits in nonhomogeneous tissue. 7 …”

Attenuated Ventricular β-Adrenergic Response and Reduced Repolarization Reserve in a Rabbit Model of Chronic Heart Failure

“…2B), the effect at shorter CLs of impaired I Ks on APD is not visible in the dynamic restitution curve, probably because increased extracellular potassium reduces I Ks and simultaneously decreases the ionic driving force for the I Ks channel, which further exacerbates the impairment of I Ks in 10 mM potassium compared with 5 mM. In the study of Harada et al, 8 an APDprolonging effect of tachypacing-induced HF was found only at CL above 800 ms and a shortening effect was found on CLs below 400 ms. Furthermore, an altered dynamic restitution curve was also seen in the paced HF rabbits compared with controls.…”

“…[6][7][8]10,11 Common for these is that they show decreased current densities of one or more of I Ca,L , I to , and I Ks , whereas an effect on I Kr or I K1 was seldom observed. Furthermore, Tsuji et al 6 demonstrate that tachycardia-induced HF introduces QT prolongation after only 3 weeks of pacing at 350-370 bpm and showed signs of HF similar to the present findings, that is, pleural effusion, cardiac hypertrophy, and impaired contractility.…”

“…One of these animal models uses long-term tachypacing, which over time will lead to HF due to the increased persistent workload on the heart. 4,5 These studies have been done in several species, among which rabbits have been extensively used [6][7][8][9][10][11] and have shown that besides structural remodeling, electrical remodeling is a common consequence of HF. Most of the tachypacinginduced HF studies have utilized a high-frequency and short-duration pacing protocol.…”

Exogenous midkine administration prevents cardiac remodeling in pacing-induced congestive heart failure of rabbits

“…Ventricular tachypacing-induced cHF was created by a similar procedure as previously described [11]. In brief, after open-chest procedure (right third intercostal space), a unipolar pacing lead was fixed to the anterior wall of the right ventricle and the lead was connected to a pacemaker (Medtronic, USa: 5985), which was implanted subcutaneously in the back.…”