Reply 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’”
2013; American Physical Society; Volume: 305; Issue: 9 Linguagem: Inglês
10.1152/ajpheart.00659.2013
ISSN1522-1539
AutoresMatthew Pizzuto, Gen Suzuki, Michael D. Banas, Brendan M. Heavey, James A. Fallavollita, John M. Canty,
Tópico(s)Cardiac pacing and defibrillation studies
ResumoLetters to the EditorReply 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. Canty Jr.Matthew F. PizzutoCenter for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; , Gen SuzukiCenter for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; Department of Medicine, University at Buffalo, Buffalo, New York; , Michael D. BanasCenter for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; Department of Medicine, University at Buffalo, Buffalo, New York; , Brendan HeaveyCenter for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; , James A. FallavollitaVeterans Affairs Western New York Health Care System, Buffalo, New York; Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; Department of Medicine, University at Buffalo, Buffalo, New York; , and John M. Canty Jr.Veterans Affairs Western New York Health Care System, Buffalo, New York; Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York; Department of Medicine, University at Buffalo, Buffalo, New York; Department of Physiology and Biophysics, University at Buffalo, Buffalo, New York; and Department of Biomedical Engineering, University at Buffalo, Buffalo, New YorkPublished Online:01 Nov 2013https://doi.org/10.1152/ajpheart.00659.2013MoreSectionsPDF (32 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat reply: We appreciate Dr. Karagueuzian's (3) insight regarding the potential role of reduced cytosolic ATP (derived from glucose and glycogen) in explaining shortening of the QT interval (through activation of the ATP-sensitive K+ channel) as well as elevations in end-diastolic pressure (through reduced sarcoplasmic reticulum Ca2+ uptake and increased cytosolic Ca2+ during diastole) immediately before the development of ventricular tachycardia (VT)/ventricular fibrillation (VF) in swine with hibernating myocardium (5). This is an extremely interesting alternative interpretation of our results, but there are some observations that, at the same time, are somewhat difficult to completely reconcile with this hypothesis. These all center upon whether cytosolic ATP levels, which would initially be maintained by anaerobic glycolysis during ischemia, could fall to the levels promoting arrhythmogenesis within the time frame that spontaneous VT/VF developed. In swine with hibernating myocardium, ventricular fibrillation developed fairly quickly after the onset of sympathetic activation (median, 200 s; and mean, 422 s). In contrast, after a complete switch from glucose to pyruvate in the study of Morita et al. (4), myocardial glycogen content was sufficient to continue glycolysis (and presumably generate cytosolic ATP) with QT shortening and VF developing after a mean of 1,320 s. In addition, hibernating myocardium is actually protected from the development of metabolic evidence of ischemia during increases in demand (1) with slowed ATP depletion during simulated zero flow ischemia ex vivo (2). This may partially reflect an increase in myocyte glycogen content in hibernating myocardium (6). Despite these considerations, it is entirely possible that the intrinsic metabolic adaptations to ischemia, along with ischemia-induced remodeling of ion channels and contractile proteins, could vary temporally and lead to a transient situation where cytosolic ATP levels could fall more rapidly than one would predict from animals with hibernating myocardium that survive. Understanding whether the cellular and molecular substrate in myocardial tissue differs in animals developing VT/VF will require further study using high throughput discovery-based approaches such as proteomics to identify the targets. Regardless of whether reductions in glycolytically derived ATP arise through the development of subendocardial ischemia or transient alterations in myocyte protein expression, pharmacologically manipulating the ATP-sensitive K+ channel to prevent QT shortening may prove to be an interesting intervention to prevent the clinical problem of sudden cardiac arrest from VT/VF in chronic ischemic heart disease.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the author(s).AUTHOR CONTRIBUTIONSM.F.P., G.S., M.D.B., B.M.H., J.A.F., and J.M.C. approved final version of manuscript; J.M.C. drafted manuscript; J.M.C. edited and revised manuscript.REFERENCES1. Fallavollita JA, Malm BJ, Canty JM. Hibernating myocardium retains metabolic and contractile reserve despite regional reductions in flow, function, and oxygen consumption at rest. Circ Res 92: 48–55, 2003.Crossref | PubMed | ISI | Google Scholar2. Hu Q, Suzuki G, Young RF, Page BJ, Fallavollita JA, Canty JM. Reductions in mitochondrial O2 consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium. Am J Physiol Heart Circ Physiol 297: H223–H232, 2009.Link | ISI | Google Scholar3. Karagueuzian HS. Letter to the editor: “The role of short QT interval and elevated LV end-diastolic pressure in the genesis of ventricular tachycardia and fibrillation.” doi:10.1152/ajpheart.00581.2013.Link | Google Scholar4. 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 Scholar5. 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 Scholar6. Thomas SA, Fallavollita JA, Borgers M, Canty JM. Dissociation of regional adaptations to ischemia and global myolysis in an accelerated swine model of chronic hibernating myocardium. Circ Res 91: 970–977, 2002.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESJ. M. Canty, Div. of Cardiovascular Medicine, Univ. at Buffalo Clinical and Translational Research Ctr., Ste. 7030, 875 Ellicott St., Buffalo, NY 14203-1034 (e-mail: [email protected]edu). Download PDF Previous Back to Top FiguresReferencesRelatedInformationRelated ArticlesLetter 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 Physiology More from this issue > Volume 305Issue 9November 2013Pages H1406-H1406 https://doi.org/10.1152/ajpheart.00659.2013PubMed24186860History Published online 1 November 2013 Published in print 1 November 2013 Metrics
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