The Ib Phase of Ventricular Arrhythmias in Ischemic In Situ Porcine Heart Is Related to Changes in Cell-to-Cell Electrical Coupling

Smith, William T.; Fleet, William F.; Johnson, Timothy A.; Engle, Connie L.; Cascio, Wayne E.

doi:10.1161/01.cir.92.10.3051

Cited by 218 publications

(161 citation statements)

References 49 publications

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“…One other possibility is a direct electrophysiological eect of NO generated from NCX4016, although the evidence surrounding this property of NO remains controversial (Pabla & Curtis, 1995;Barnes & Coker, 1995). Furthermore, the observation that both phase 1a and 1b arrhythmias were attenuated by NCX4016 would argue against this, since there is some evidence that dierent electrophysiological mechanisms underlie these two phases of arrhythmias in the porcine heart (Smith et al, 1995).…”

Section: +4* 187+13{mentioning

confidence: 99%

NCX4016 (NO‐aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs

Wainwright

Miller

Work

et al. 2002

British J Pharmacology

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1 The eect of the nitro-derivative of aspirin, NCX4016, was assessed on ischaemic ventricular arrhythmias and myocardial infarct size in anaesthetized pigs in comparison to native aspirin. 2 Pigs were given aspirin (10 mg kg 71; n=6), low dose NCX4016 (18.4 mg kg 71; n=6) or high dose NCX4016 (60 mg kg 71 ; n=7) orally for 5 days prior to coronary occlusion and reperfusion. None of the interventions had any eect on baseline haemodynamics prior to coronary occlusion in comparison to control pigs (n=9). Aspirin and high dose NCX4016 both prevented the generation of thromboxane A 2 from platelets activated ex vivo with A23187 (30 mM), whereas all three interventions markedly attenuated platelet aggregation in response to collagen in whole blood in comparison to controls. 3 None of the drug interventions had any eect on the incidence of ventricular ®brillation (VF) during myocardial ischaemia (100% in all groups). However, 60 mg kg 71 NCX4016 signi®cantly attenuated the total number of premature ventricular beats (PVB's) (62+16 vs 273+40 in control pigs; P50.05) during the ®rst 30 min of occlusion. The higher dose of NCX4016 also signi®cantly reduced myocardial infarct size (22.6+3.7% of area at risk vs 53.0+2.8% of area at risk in control pigs; P50.05). 4 These results suggest that the nitro-derivative of aspirin, NCX4016, is an eective antiplatelet agent, which unlike aspirin also reduces the extent of myocardial injury following ischaemia and reperfusion.

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Section: +4* 187+13{mentioning

confidence: 99%

NCX4016 (NO‐aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs

Wainwright

Miller

Work

et al. 2002

British J Pharmacology

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“…Experiments have shown that ischemia 1B ventricular fibrillation is based on reentry around fixed lines of block, which are thought to arise from heterogeneous subepicardial electrical uncoupling in the central ischemic zone (CIZ). 2,10 We hypothesize that heterogeneous uncoupling between depressed depolarized midmyocardium and the surviving subepicardium in ischemia phase 1B results in heterogeneous refractoriness in the subepicardium and that this dispersion in effective refractory period (ERP) contributes to the substrate for reentrant arrhythmias in ischemia phase 1B. Furthermore, we investigate how vulnerability to reentrant arrhythmias is affected by the degree of heterogeneous uncoupling between subepicardial and midmyocardial layers as well as by the degree of depolarization in the inactive midmyocardial layer.…”

Section: Introductionmentioning

confidence: 99%

Reentry in survived subepicardium coupled to depolarized and inexcitable midmyocardium: Insights into arrhythmogenesis in ischemia phase 1B

et al. 2008

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“…Previous studies have demonstrated that reduced expression of Cx43 results in a significant reduction in conduction velocity during acute MI and accelerates the onset and increases the incidence of ischemia-induced ventricular arrhythmias (2,3,(8)(9)(10). These results suggest that the changes in Cx43 expression may play a significant role in the genesis of ventricular arrhythmias during acute MI.…”

Section: Discussionmentioning

confidence: 72%

Increased susceptibility to ischemia-induced ventricular tachyarrhythmias in depressed rats: Involvement of reduction of connexin 43

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Connexin 43 (Cx43) has been reported to contribute to the occurrence of ventricular arrhythmias during myocardial ischemia (MI). In this study, we investigated the expression of Cx43 and the incidences of ventricular tachyarrhythmias [i.e., ventricular tachycardia (VT) and ventricular fibrillation (VF)] during acute MI in chronic mild stress (CMS) in rats. Male Sprague-Dawley (SD) control and CMS rats were assigned into a sham operation (SO) group and a MI group. Ventricular tachyarrhythmias were assessed and Cx43 protein expression was measured by Western blotting. During 30-min ischemia, the incidences of VT (7/12, 58.3%) and VF (5/12, 41.7%) in the CMS-MI group were significantly decreased compared with those in the control-MI group (12/12, 100.0% and 11/12, 91.7%; P<0.05). The amount of total Cx43 of the CMS-SO group was significantly decreased to approximately 50% compared with that of the control-SO group (P<0.05). The 30-min ischemia did not result in a significant change in the amount of total Cx43 (total Cx43 is defined as the non-phosphorylated Cx43 and phosphorylated Cx43) compared to that of the SO group in CMS rats (P>0.05). The amount of non-phosphorylated Cx43 in the CMS-MI group was markedly increased compared to that of the CMS-SO group (P<0.05), suggesting that the relative amount of phosphorylated Cx43 was significantly decreased in CMS rats. The gap junctional permeability in the CMS-MI group (50.4±4.9%) was significantly decreased compared with the normal non-ischemic value in the CMS-SO group (100%). The present study suggested that the incidence of ischemia-induced ventricular tachyarrhythmias was markedly increased in depressed rats, which may be associated with the reduction of Cx43 protein expression in the ventricle of depressed rats.

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The Ib Phase of Ventricular Arrhythmias in Ischemic In Situ Porcine Heart Is Related to Changes in Cell-to-Cell Electrical Coupling

Cited by 218 publications

References 49 publications

NCX4016 (NO‐aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs

NCX4016 (NO‐aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs

Reentry in survived subepicardium coupled to depolarized and inexcitable midmyocardium: Insights into arrhythmogenesis in ischemia phase 1B

Increased susceptibility to ischemia-induced ventricular tachyarrhythmias in depressed rats: Involvement of reduction of connexin 43

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