Effect of remodelling, stretch and ischaemia on ventricular fibrillation frequency and dynamics in a heart failure model

Abstract

The dynamics of ventricular fibrillation (VF) in the presence of heart failure (HF) are different from those in the normal heart. This has been attributed solely to HF-induced electrophysiologic remodelling. We hypothesized that acute stretch and ischaemia, which are normally present during VF, might contribute significantly to the altered VF dynamics in HF. HF was induced in eight sheep by rapid ventricular pacing for 4-6 weeks. Eight sheep served as controls. Optical mapping of isolated hearts was performed during VF at low intraventricular pressure (0-5 mm Hg), high pressure (25-30 mm Hg, in six HF and six controls), and at low pressure after 5 min of global ischaemia (six HF, five controls). Maximum dominant frequency (DF(max)), singularity point (SP) density and number of SP lasting more than one revolution (rotors) were analyzed. Possible statistical interactions between HF and ischaemia (HF x ischaemia) or stretch (HF x stretch) were evaluated. At low pressure, VF in HF was slower (13% reduction in DF(max)) and more organized than in control: 33% less SPs and 74% less rotors with 20% longer life spans. Acute stretch did not affect DF(max) but increased SP and rotors density similarly in both groups (no interaction HF x stretch). In controls, ischaemia caused a marked decrease in DF(max), SP density and incidence of rotors. However, in HF animals, the ischaemia-induced decrease in SP density was virtually abolished, indicating a significant interaction HF x ischaemia (p<0.005). HF remodelling decreases VF rate and increases VF organization. Acute stretch partially reverses these effects by a mechanism that is independent of remodelling. The effects of acute ischaemia on VF dynamics are significantly attenuated in HF compared to normal hearts.