Letter to the editor: “The role of short QT interval and elevated LV end-diastolic pressure in the genesis of ventricular tachycardia and fibrillation”
2013; American Physical Society; Volume: 305; Issue: 9 Linguagem: Inglês
10.1152/ajpheart.00581.2013
ISSN1522-1539
Autores Tópico(s)Cardiac Arrhythmias and Treatments
ResumoLetters to the EditorLetter to the editor: “The role of short QT interval and elevated LV end-diastolic pressure in the genesis of ventricular tachycardia and fibrillation”Hrayr S. KaragueuzianHrayr S. KaragueuzianDavid Geffen School of Medicine, University of California, Los Angeles, CaliforniaPublished Online:01 Nov 2013https://doi.org/10.1152/ajpheart.00581.2013MoreSectionsPDF (30 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations to the editor: We read with great interest the article by Pizzuto and associates (4) in the American Journal of Physiology-Heart and Circulatory Physiology, entitled: “Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and sudden cardiac death.” The authors demonstrate that the transiently elevated left ventricular (LV) end-diastolic pressure (EDP) and QT shortening in a pig model of chronic myocardial ischemia precede the ventricular tachycardia (VT)/ventricular fibrillation (VF) episode. These authors suggested that the trigger for the VT/VF could result from stretch due to transiently elevated LV EDP preceding the VT/VF (4).We would like to propose an alternative mechanism by which short QT in association with elevated LV EDP may promote VT and then VF. We have shown in the aged fibrotic rat hearts that glycolytic inhibition (GI) induced by replacing glucose with pyruvate in the arterial perfusate promotes early afterdepolariztions (EADs) and triggered activity causing VT and then VF. GI causes a cytosolic depletion of ATP, causing shortening of the action potential duration (APD) because of the activation of the ATP-sensitive K+ channel. Simultaneous with this effect, GI also decreases the ATP supply to the sarco(endo)plasmic reticulum Ca2+-activated ATPase 2a. This would result in the slowing of cytosolic Ca2+ uptake by the sarcoplasmic reticulum and a persistent diastolic elevation of the free cytosolic Ca2+, an effect that maintains a contractile tone because of the prevention of relaxation. To the extent that these two effects (short APD and elevated Ca2+) reflect short QT interval and elevated LV EDP, respectively (ample experimental data support this contention), then in addition to possible stretch, the following mechanism for the initiation and VT/VF may be operative in the pig model described by Puzitto and associates. Elevated cytosolic Ca2+ is extruded via the Na+/Ca2+ exchanger that produces a net inward depolarizing current carried by sodium ions (3). This NCX-induced depolarizing current in the face of the shortened APD facilitates and promotes the reactivation of the L-type Ca2+ channels causing EADs and EAD-mediated triggered activity (3). The triggered activity causes VT, which then progresses to VF because of combined intrinsic and dynamic heterogeneities in repolarization that emerge during rapid rates of activation (1). The arrhythmogenic potential of simultaneous formation of short APD, and persistently elevated diastolic Ca2+ is also demonstrated in a rabbit heart failure model (2). It is shown that short APD (immediately after the termination of the VF) in association with persistently elevated diastolic Ca2+ during the late phase 3 of the shortened APD results in EAD-mediated triggered activity, leading to the reemergence of VT/VF (2). This potential mechanism may also be operative in patients with short QT syndrome when coupled with maintained elevation of diastolic Ca2+, but this needs to be proved. Clearly, as the authors indicate more work is needed in this field to identify the dynamic precursors of VT/VF under diverse cardiac conditions, the study by Pizzuto and associates is a step in that direction.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the author(s).AUTHOR CONTRIBUTIONSH.S.K. edited, revised, and approved final version of manuscript.REFERENCES1. Morita N, Lee JH, Bapat A, Fishbein MC, Mandel WJ, Chen PS, Weiss JN, Karagueuzian HS. Glycolytic inhibition causes spontaneous ventricular fibrillation in aged hearts. Am J Physiol Heart Circ Physiol 301: H180–H191, 2011.Link | ISI | Google Scholar2. Ogawa M, Morita N, Tang L, Karagueuzian HS, Weiss JN, Lin SF, Chen PS. Mechanisms of recurrent ventricular fibrillation in a rabbit model of pacing-induced heart failure. Heart Rhythm 6: 784–792, 2009.Crossref | PubMed | ISI | Google Scholar3. Patterson E, Lazzara R, Szabo B, Liu H, Tang D, Li YH, Scherlag BJ, Po SS. Sodium-calcium exchange initiated by the Ca2+ transient: an arrhythmia trigger within pulmonary veins 1. J Am Coll Cardiol 47: 1196–1206, 2006.Crossref | PubMed | ISI | Google Scholar4. Pizzuto MF, Suzuki G, Banas MD, Heavey B, Fallavollita JA, Canty JM. Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and sudden cardiac death. Am J Physiol Heart Circ Physiol 304: H1697–H1707, 2013.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: H. S. Karagueuzian, UCLA David Geffen School of Medicine, 675 Charles E. Young Dr. S., MRL Bldg. Rm. 1630, Los Angeles, CA 90095 (e-mail: [email protected]ucla.edu). Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Related ArticlesReply to “Letter to the editor: ‘The role of short QT interval and elevated LV end-diastolic pressure in the genesis of ventricular tachycardia and fibrillation’” 01 Nov 2013American Journal of Physiology-Heart and Circulatory PhysiologyCited ByReply to “Letter to the editor: ‘The role of short QT interval and elevated LV end-diastolic pressure in the genesis of ventricular tachycardia and fibrillation’”Matthew F. Pizzuto, Gen Suzuki, Michael D. Banas, Brendan Heavey, James A. Fallavollita, and John M. Canty1 November 2013 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 305, No. 9 More from this issue > Volume 305Issue 9November 2013Pages H1405-H1405 Copyright & PermissionsCopyright © 2013 the American Physiological Societyhttps://doi.org/10.1152/ajpheart.00581.2013PubMed24186859History Published online 1 November 2013 Published in print 1 November 2013 Metrics
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