Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine epicardium exposed to simulated ischemia

Lukas, Anton

doi:10.1016/0008-6363(96)00115-0

Cited by 113 publications

(71 citation statements)

References 42 publications

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“…Studies performed in our laboratory involving isolated canine ventricular Epi and Endo tissues point to intrinsic cellular electrophysiological differences as the basis for their differential sensitivity to ischemic conditions [9][10][11][12][13]. The presence of a prominent I to -mediated spike and dome morphology (notch) in the epicardium [14] was shown to be, in large part, responsible for the differential response.…”

Section: Introductionmentioning

confidence: 92%

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Brugada syndrome and ischemia-induced ST-segment elevation. Similarities and differences

Diego

Fish

Antzelevitch

2005

Journal of Electrocardiology

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Introduction-ST-Segment elevation is a common electrocardiogram (ECG) manifestation of acute transmural myocardial ischemia in leads facing the injury. Acute myocardial ischemia involving the right-ventricular (RV) outflow tract is known to induce a Brugada-like ECG. In this paper, we examined the electrophysiological bases for the similarities between the ECG characteristics of the Brugada syndrome model induced by terfenadine (5 μmol/L) and the ECG manifestations of the acute transmural no-flow ischemia model.Methods-For both experimental simulations, we used isolated arterially perfused canine RV wedge preparations to record transmembrane action potentials (AP) from endocardium and epicardium together with a transmural pseudo-ECG (ECG); basic cycle length = 400 to 2000 ms.Results-In the presence of a prominent I to -mediated AP notch, no-flow ischemia causes true STsegment elevation because of selective depression and loss of the AP dome at some epicardial sites. In the absence of a prominent AP notch, ischemia ultimately produces an apparent ST-segment elevation, which is secondary to a prolongation of the R wave caused by marked transmural conduction delays. Similarly, in the Brugada syndrome model generated in preparations displaying a large epicardial I to , ST-segment elevation was due to loss of the epicardial AP dome at some sites but not at others. Transmural conduction delay giving the appearance of ST-segment elevation is also observed in the Brugada model in preparations exhibiting smaller AP notch. In both models, propagation of the dome from the site at which it is maintained to a site at which it is lost may result in closely coupled phase 2 reentrant extrasystoles.Conclusion-Our results suggest that I to can modulate the electrocardiographic manifestation of acute ischemia as well as that of the Brugada syndrome, and that both clinical entities are the result of a similar electrophysiological substrate.

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Section: Introductionmentioning

confidence: 92%

“…Phase 2 reentry-induced extrasystoles leading to polymorphic VT or VF was also anticipated [9,20,21], In addition, the presence of a much greater I to in right-vs left ventricular epicardium has also been proposed to account, at least in part, for the RV nature of this disease [15].…”

Section: Introductionmentioning

confidence: 97%

Brugada syndrome and ischemia-induced ST-segment elevation. Similarities and differences

Diego

Fish

Antzelevitch

2005

Journal of Electrocardiology

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“…S2B). This, in turn, may lead to the occurrence of a closely coupled complex that can capture the vulnerable window across the whole right ventricular wall, triggering a circular VT/VF reentry [Lukas and Antzelevitch, 1996;Yan and Antzelevitch, 1999]. The effect of quinidine in BrS is attributed to an inhibitory effect on I to , and thus to a reduction of the electrical heterogeneity and reduced phase 2 reentrant activity [Antzelevitch, 1998;Yan and Antzelevitch, 1999].…”

Section: Pathogenetic Mechanism-in Overviewmentioning

confidence: 99%

The genetic basis of Brugada syndrome: A mutation update

et al. 2009

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Brugada syndrome (BrS) is a condition characterized by a distinct ST-segment elevation in the right precordial leads of the electrocardiogram and, clinically, by an increased risk of cardiac arrhythmia and sudden death. The condition predominantly exhibits an autosomal dominant pattern of inheritance with an average prevalence of 5:10,000 worldwide. Currently, more than 100 mutations in seven genes have been associated with BrS. Loss-of-function mutations in SCN5A, which encodes the a-subunit of the Na v 1.5 sodium ion channel conducting the depolarizing I Na current, causes 15-20% of BrS cases. A few mutations have been described in GPD1L, which encodes glycerol-3-phosphate dehydrogenase-1 like protein; CACNA1C, which encodes the a-subunit of the Ca v 1.2 ion channel conducting the depolarizing I L,Ca current; CACNB2, which encodes the stimulating b2-subunit of the Ca v 1.2 ion channel; SCN1B and SCN3B, which, in the heart, encodes b-subunits of the Na v 1.5 sodium ion channel, and KCNE3, which encodes the ancillary inhibitory b-subunit of several potassium channels including the Kv4.3 ion channel conducting the repolarizing potassium I to current. BrS exhibits variable expressivity, reduced penetrance, and ''mixed phenotypes,'' where families contain members with BrS as well as long QT syndrome, atrial fibrillation, short QT syndrome, conduction disease, or structural heart disease, have also been described.

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“…7,[13][14][15] The proposed mechanism involves a rebalancing of the currents available at the end of phase 1 of the epicardial action potential. Diminution of inward currents (I Na and I Ca ) or enhancement of outward currents (I to , I K-ATP , I Kr , I Ks , I Cl(Ca) ) can result in an accentuation of the epicardial action potential notch as well as all-or-none repolarization at the end of phase 1.…”

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confidence: 99%

Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males

et al. 2002

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Background-The Brugada syndrome displays an autosomal dominant mode of transmission with low penetrance. Despite equal genetic transmission of the disease, the clinical phenotype is 8 to 10 times more prevalent in males than in females. The basis for this intriguing sex-related distinction is unknown. The present study tests the hypothesis that the disparity in expression of the Brugada phenotype is a result of a more prominent I to -mediated action potential notch in the right ventricular (RV) epicardium of males versus females. Methods and Results-We studied epicardial tissue slices, arterially perfused wedge preparations, and dissociated epicardial myocytes isolated from male and female canine hearts. RV epicardium action potential phase 1 amplitude was 64.8Ϯ2.0% of that of phase 2 in males compared with 73.8Ϯ4.4% in females (PϽ0.05) at a cycle length of 2000 ms. I to density was 26% smaller and time constant for inactivation 17% smaller at ϩ40 mV in female versus male RV epicardial cells (PϽ0.05). The other functional characteristics of I to , including the voltage dependence of inactivation and time course of reactivation, were no different between the sexes. Pinacidil caused loss of action potential dome in male, but not female, RV epicardial tissue slices. Terfenadine (5 mol/L) induced phase 2 reentry in 6 of 7 male but only 2 of 7 female arterially perfused wedge preparations. Two of 6 male and 1 of 2 female preparations developed polymorphic ventricular tachycardia/ventricular fibrillation. Conclusions-Our results suggest that the predominance of the Brugada phenotype in males is a result of the presence of a more prominent I to in males versus females.

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Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine epicardium exposed to simulated ischemia

Cited by 113 publications

References 42 publications

Brugada syndrome and ischemia-induced ST-segment elevation. Similarities and differences

Brugada syndrome and ischemia-induced ST-segment elevation. Similarities and differences

The genetic basis of Brugada syndrome: A mutation update

Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males

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