Ventricular fibrillation: novel insights into pharmacology and mechanisms: Autonomic dysfunction and arrhythmogenesis post myocardial infarction

Sudden cardiac death (SCD) claims 100,000 lives in the UK and over 400,000 in the USA. In humans the spatial and temporal patterns of VF are poorly characterised. However,if VF is phase dependant like it is in animal models,then phase 2 VF would account for 87 % of VF related sudden cardiac deaths in humans. This would explain why most deaths (50-80 %) in the clinical setting occur within the first hours of the onset of myocardial ischemia. In every animal model examined to date ventricular fibrillation exhibits 2 phases. The acute phase of VF, Phase 1 VF, occurs early in the first 30 minutes of ischaemia and the late phase of VF, defined as phase 2 VF, occurs when irreversible myocardial necrosis sets in after more than 90 min of ischaemia. In animal models the second phase is by far the most lethal phase. Ironically,the pathophysiological mechanisms underlying phase 2 VF are poorly understood and it remains a neglected therapeutic target. There is an ever-growing body of evidence suggesting that heightened sympathetic activity combined with diminished parasympathetic activity may be the pathophysiological mechanism underlying the onset of phase 2 VF.