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Autonomic dysfunction and phase 2 ventricular fibrillation 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 ventricular fibrillation (VF) are poorly characterised .However, if VF is phase dependant like it is in animal models, then phase 2 VF accounts for 87 % of 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 ischaemia. In animal models the timing of susceptibility to VF is well characterised. 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 ischeamia 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. By reviewing a range of different types of data we have outlined the likely mechanisms of phase 2 VF and have evaluated some of the evidence available that suggests that the autonomic nervous system dysfunction is the mechanism underlying phase 2 VF post myocardial infarction. We have also extensively reviewed the current models that have been used for the study of phase 2 VF. We conclude by evaluating possible future directions to help evolve a strategy for the suppression of phase 2 VF by drugs.

Mostra/Nascondi contenuto.
Dr Charles Murimi Mugera MSc Pharmacology Introduction The majority of the approximately 100,000 sudden cardiac deaths each year in the UK are caused by ventricular fibrillation related to ischaemia and infarction (Clements- Jewery et al., 2005; Wannamethee et al., 1995). Despite rapid advancements in the diagnosis and management of acute myocardial infarction (MI), an estimated 50% of patients die suddenly in the first hours before receiving medical attention (Lowel et al., 1993). Clinical studies indicate that the risk of sudden cardiac death is highest during the first 24 hours after an MI and diminishes thereafter (Zehender et al., 1991).The majority of these early deaths are caused by VF. Surprisingly little is known, however, about the exact time course of VF and even less about their underlying mechanisms in man. Ventricular arrhythmias post myocardial ischaemia and infarction have been extensively evaluated using animal models, and have been shown to occur in 2 distinct phases, phase 1 and phase 2 (Ravingerova et al., 1995; Clements-Jewery et al., 2005; Johnston et al., nd 1983). Animal studies have shown the 2 phase to be the more malignant arrhythmogenic period accounting for 87% of the arrhythmic deaths (Opitz et al., 1995). The relative importance of the phases of VF have not been elucidated in man and the spatial and temporal patterns of VF in man are difficult to acertain .However, the phases of VF in animal models have shown incredible similarity that cuts across all species from rodents to primates with little species variation (Curtis et al., 1987) . This evidence puts forward the elegant hypothesis that man exhibits the same biphasic susceptibility to VF (Clements-Jewery et al., 2005). 1 Cardiovascular Division King's College London the Rayne Institute St. Thomas' Hospital

International thesis/dissertation

Autore: Charles Mugera Contatta »

Composta da 98 pagine.


Questa tesi ha raggiunto 23 click dal 30/08/2010.


Consultata integralmente una volta.

Disponibile in PDF, la consultazione è esclusivamente in formato digitale.