Spatial heterogeneity of the restitution portrait in rabbit epicardium

Abstract

Spatial heterogeneity of repolarization can provide a substrate for reentry to occur in myocardium. This heterogeneity may result from spatial differences in APD restitution. The restitution portrait (RP) measures many aspects of rate-dependent restitution: the dynamic restitution curve (RC), S1-S2 RC, and short-term memory response. We used the RP to characterize epicardial patterns of spatial heterogeneity of restitution that were repeatable across animals. NZW rabbit ventricles were paced from either the epicardial apex, mid-ventricle, or base, and optical action potentials were recorded from the same three regions. A perturbed downsweep pacing protocol was applied that measured the RP over a range of cycle lengths from 1000-140 ms. The time constant of short-term memory measured close to the stimulus was dependent on location. In the mid-ventricle the mean time constant was 19.1±1.1 sec, but it was 39% longer at the apex (p<0.01) and 23% longer at the base (p=0.03). The S1-S2 RC slope was dependent on pacing site (p=0.015), with steeper slope when pacing from the apex than from the base. There were no significant repeatable spatial patterns in steady-state APD at all cycle lengths or in dynamic RC slope. These results indicate that transient patterns of epicardial heterogeneity of APD may occur following a change in pacing rate. Thus, it may affect cardiac electrical stability at the onset of a tachycardia or during a series of ectopic beats. Differences in restitution with respect to pacing site suggest that vulnerability may be affected by the location of reentry or ectopic foci.

Uncoupling the mitochondria facilitates alternans formation in the isolated rabbit heart

“…The amplitudes of APD and CaD alternans were calculated at each pixel as a difference between odd and even beats, as previously described (17,47): ⌬X ϭ |X even Ϫ Xodd| Ն 5 ms, where X is APD or CaD. All variations smaller than the temporal threshold of alternans (5 ms) were defined as 1:1 responses.…”

Variability of action potential duration in pharmacologically induced long QT syndrome type 1

“…The tissue was then submerged in a heated bath and perfused with warm, normal Tyrode solution, and allowed to equilibrate for 90 minutes. The excitation-contraction uncoupler blebbistatin was added to the perfusate at 5–10 µM concentration and the perfusate was recirculated [9, 10]. …”

“…We used a downsweep pacing protocol developed by our group [9, 12]. Briefly, the protocol begins with constant pacing at an initial basic cycle length (BCL), BCL0 (typically 1000 ms).…”

Cardiac repolarization instability during normal postnatal development

“…The hearts of six 2-week old (infant) and six 7-week old (adolescent) New Zealand White rabbits were isolated and arterially-perfused (20). Briefly, the rabbits were pre-medicated with intramuscular ketamine (35 mg/kg) and xylazine (5 mg/kg) and then given a bolus of intravenous heparin (800 U/kg), followed by thiopental sodium (20 mg/kg).…”