Experimental Simulation of Sudden Cardiac Death in Humans: Electrophysiological Mechanisms and Role of Adrenergic Influences

Scherlag, B J; Patterson, Eugene; Berbari, Edward J.; Lazzara, Ralph

doi:10.1007/978-3-642-74317-7_24

Cited by 2 publications

(1 citation statement)

References 21 publications

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“…Moreover, it is possible to evoke VF in dogs with myocardial infarction by activating sympathetic drive to the heart (e.g., Schwartz et al ., 1984). Unfortunately, although there are many studies that have focused on catecholamines and phase 1 VF (Bolli et al ., 1984) or have utilised the Harris 2‐stage ligation model with its inherent limitations to undertake equivalent studies (Scherlag et al ., 1989), there are few studies that specifically address the role of locally released catecholamines in the initiation of phase 2 VF. If there is a role for catecholamines, their action is presumably mediated in the uninvolved or border zone region of the infarcting myocardium since, although catecholamine accumulation in the involved region increases during the first hour of ischaemia (Lameris et al ., 2000), it has been shown that 1 h after coronary ligation β 1 ‐adrenoceptors (the likely molecular target of arrhythmogenic catecholamines) become uncoupled from adenylyl cyclase (Vatner et al ., 1988a, 1988b).…”

Section: Future Directionsmentioning

confidence: 99%

Phase 2 ventricular arrhythmias in acute myocardial infarction: a neglected target for therapeutic antiarrhythmic drug development and for safety pharmacology evaluation

Clements‐Jewery

Hearse

Curtis

2005

British J Pharmacology

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Ventricular fibrillation (VF), a cause of sudden cardiac death (SCD) in the setting of acute myocardial infarction (MI), remains a major therapeutic challenge. In humans, VF may occur within minutes or hours after the onset of chest pain, so its precise timing in relation to the onset of ischaemia is variable. Moreover, because VF usually occurs unobserved, out of hospital, and is usually lethal in the absence of intervention, its precise timing of onset is actually unknown in most patients. In animal models, the timing of susceptibility to VF is much better characterised. It occurs in two distinct phases. Early VF (defined as phase 1 VF, with possible subphases 1a and 1b in some animal species) occurs during the first 30 min of ischaemia when most myocardial injury is still reversible. Late VF, defined as phase 2 VF, occurs when myocardial necrosis is becoming established (after more than 90 min of ischaemia). Although much is known about the mechanisms and pharmacology of phase 1 VF, little is known about phase 2 VF. By reviewing a range of different types of data we have outlined the likely mechanisms and clinical relevance of phase 2 VF, and have evaluated possible future directions to help evolve a strategy for its suppression by drugs. The possibility that a proarrhythmic effect on phase 2 VF contributes to the adverse cardiac effects of certain cardiac and noncardiac drugs is also discussed in relation to the emerging field of safety pharmacology. It is concluded that suppression of phase 2 as well as phase 1 VF will almost certainly be necessary if drugs of the future are to achieve what drugs of the past and present have failed to achieve: full protection against SCD. Likewise, safety will require avoidance of exacerbation of phase 2 as well as phase 1 VF.

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Section: Future Directionsmentioning

confidence: 99%

Phase 2 ventricular arrhythmias in acute myocardial infarction: a neglected target for therapeutic antiarrhythmic drug development and for safety pharmacology evaluation

Clements‐Jewery

Hearse

Curtis

2005

British J Pharmacology

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Ventricular Arrhythmias Following Thermal Damage of Epicardial Tissue: Possible Causes and Clinical Implications

Ware¹,

Boor

Yang

et al. 2000

Pacing Clinical Electrophis

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Epicardial heating may be used for ventricular tachycardia (VT) ablation and transmyocardial revascularization. However, the potential risks of thermal epicardial injury, including arrhythmia, have not been fully explored. This study relates the pathologic and arrhythmic sequellae of epicardial heating when applied with a diode laser at varying doses. Acute pathology and dosimetry were determined in a group of normal dogs using 2-3 W over 30-90 seconds. Another group received a similar dose range before undergoing 24-hour monitoring, and electrophysiological testing was done at 4 weeks. In this group, four dogs each received 12 lesions (90-180 J) according to a randomized block design. Another dog received nine lower dose lesions (30-120 J). Acute lesions measured 2.5-8.0-mm wide by 4-8.5-mm deep. Charring and vaporization were common when 3 W were applied over 45 seconds. Within 24 hours, VT with features of abnormal automaticity occurred in all dogs receiving this dose. The dog in whom lower doses induced coagulation only had no VT. Four weeks later, electrophysiological study induced no VT. At this time fibrosis and granulation tissue were organizing the contraction band necrosis seen acutely, and some lesion borders were becoming calcified. No major vessels had been damaged. Abnormal automaticity and VT may occur if thermal damage of the epicardium exceeds coagulation. This could be related to tissue injury caused by sudden water vaporization, and may have clinical relevance given the growing indications for myocardial heating.

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Experimental Simulation of Sudden Cardiac Death in Humans: Electrophysiological Mechanisms and Role of Adrenergic Influences

Cited by 2 publications

References 21 publications

Phase 2 ventricular arrhythmias in acute myocardial infarction: a neglected target for therapeutic antiarrhythmic drug development and for safety pharmacology evaluation

Phase 2 ventricular arrhythmias in acute myocardial infarction: a neglected target for therapeutic antiarrhythmic drug development and for safety pharmacology evaluation

Ventricular Arrhythmias Following Thermal Damage of Epicardial Tissue: Possible Causes and Clinical Implications

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