{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T14:17:03Z","timestamp":1794320223229,"version":"4.9.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1999,11,26]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014Three-dimensional cardiac mapping in rabbits with nonischemic cardiomyopathy has shown that ventricular arrhythmias initiate by a nonreentrant mechanism that may be due to triggered activity from delayed afterdepolarizations. Delayed afterdepolarizations are thought to be due to spontaneous release of Ca<jats:sup>2+<\/jats:sup>from the sarcoplasmic reticulum (SR) and consequent activation of an inward Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup>exchange (NaCaX) current. The goal of this study was to determine whether there is enhanced NaCaX gene expression and functional activity that may contribute to nonreentrant activation. Heart failure (HF) was induced in rabbits by combined aortic insufficiency and aortic constriction. HF rabbits had left ventricular enlargement (left ventricular end-diastolic dimension increased from 1.43\u00b10.03 to 1.97\u00b10.05 cm) and severely depressed function (fractional shortening reduced from 37% to 26%,<jats:italic>P<\/jats:italic>&lt;0.02). Heart-to-body weight was increased by 79% in HF. Western blots showed a 93% increase in NaCaX protein in HF (<jats:italic>P<\/jats:italic>&lt;0.04). NaCaX mRNA (7-kb transcript) was increased by 104% relative to the 18S rRNA in HF. A 14-kb NaCaX transcript was also seen in the HF rabbits, raising total NaCaX mRNA to 2.7-fold compared with controls. The amplitude of caffeine-induced contractures, used to assess SR Ca<jats:sup>2+<\/jats:sup>load, was not significantly different in HF. Relaxation and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>decline during caffeine-induced contractures is attributable to Ca<jats:sup>2+<\/jats:sup>transport by NaCaX and was 61% and 45% faster in HF (<jats:italic>P<\/jats:italic>&lt;0.05), respectively. NaCaX current measured under controlled voltage clamp conditions was also 2-fold higher in HF cells. SR Ca<jats:sup>2+<\/jats:sup>-ATPase mRNA and protein levels and Ca<jats:sup>2+<\/jats:sup>current density were not significantly altered in HF. Twitch amplitudes from HF myocytes were 26% smaller compared with control (<jats:italic>P<\/jats:italic>&lt;0.02), but twitch relaxation and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>decline (due largely to SR Ca<jats:sup>2+<\/jats:sup>-ATPase) were not altered. Thus myocytes and myocardium from HF rabbits exhibit enhanced NaCaX expression and function. The enhanced NaCaX activity may contribute to depressed contractions, increased transient inward current (for a given SR Ca<jats:sup>2+<\/jats:sup>release), delayed afterdepolarizations, and nonreentrant initiation of ventricular tachycardia in this arrhythmogenic model of HF.<\/jats:p>","DOI":"10.1161\/01.res.85.11.1009","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"1009-1019","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":295,"title":["Upregulation of Na<sup>+<\/sup>\/Ca<sup>2+<\/sup>Exchanger Expression and Function in an Arrhythmogenic Rabbit Model of Heart Failure"],"prefix":"10.1161","volume":"85","author":[{"given":"Steven M.","family":"Pogwizd","sequence":"first","affiliation":[{"name":"From the University of Illinois at Chicago (S.M.P.), Section of Cardiology, Chicago, and Loyola University Chicago, Department of Physiology and Cardiovascular Institute (M.Q., W.Y., A.M.S., D.M.B.), Maywood, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Qi","sequence":"additional","affiliation":[{"name":"From the University of Illinois at Chicago (S.M.P.), Section of Cardiology, Chicago, and Loyola University Chicago, Department of Physiology and Cardiovascular Institute (M.Q., W.Y., A.M.S., D.M.B.), Maywood, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilong","family":"Yuan","sequence":"additional","affiliation":[{"name":"From the University of Illinois at Chicago (S.M.P.), Section of Cardiology, Chicago, and Loyola University Chicago, Department of Physiology and Cardiovascular Institute (M.Q., W.Y., A.M.S., D.M.B.), Maywood, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen M.","family":"Samarel","sequence":"additional","affiliation":[{"name":"From the University of Illinois at Chicago (S.M.P.), Section of Cardiology, Chicago, and Loyola University Chicago, Department of Physiology and Cardiovascular Institute (M.Q., W.Y., A.M.S., D.M.B.), Maywood, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald M.","family":"Bers","sequence":"additional","affiliation":[{"name":"From the University of Illinois at Chicago (S.M.P.), Section of Cardiology, Chicago, and Loyola University Chicago, Department of Physiology and Cardiovascular Institute (M.Q., W.Y., A.M.S., D.M.B.), Maywood, Ill."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.72.4.2863012"},{"key":"e_1_3_2_2_2","first-page":"145","volume":"15","year":"1994","unstructured":"Pogwizd SM, Corr PB. 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