This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saba, Z. Articles by Anderson, P. A.W. Search for Related Content PubMed PubMed Citation Articles by Saba, Z. Articles by Anderson, P. A.W.

(Circulation. 1996;94:472-476.)
© 1996 American Heart Association, Inc.

Articles

Cardiac Troponin T Isoform Expression Correlates With Pathophysiological Descriptors in Patients Who Underwent Corrective Surgery for Congenital Heart Disease

Ziad Saba, MD; Rashid Nassar, PhD; Ross M. Ungerleider, MD; Annette E. Oakeley; Page A.W. Anderson, MD

the Departments of Pediatrics, Division of Pediatric Cardiology (Z.S., R.N., A.E.O., P.A.W.A.) and Surgery (R.M.U.), Duke University, Durham, NC.

Correspondence to Page A.W. Anderson, MD, Professor of Pediatrics, Duke University Medical Center, Room 113, Research Park Bldg 2, Box 3218, Durham, NC 27710. E-mail ander005@mc.duke.edu.

Background This study examined cardiac troponin T (cTnT) isoform expression in patients who had undergone surgery at Duke University Medical Center (Durham, NC) between December 1, 1993, and January 31, 1995, to correct congenital heart defects. The human heart expresses four cTnT isoforms (cTnT₁ through cTnT₄) whose sequence differences result from combinatorial alternative splicing of two exons. We have previously shown that cTnT₄ is expressed at higher levels in severely failing hearts from transplant patients. In this study, we tested the hypothesis that congenital heart defects that have a more negative effect on myocardial function increase cTnT₄ expression. We used the presence or absence of drug treatment for heart failure or congested circulation before surgery and the duration of inotropic support after corrective surgery as indicators of the pathophysiological state of the heart just before surgery.

Methods and Results Right atrial appendage tissue was collected from 34 patients, 6 days to 35 years old (median age, 3.4 months). The amounts of the cTnT₁ through cTnT₄ isoforms, measured as a percentage of total cTnT, were determined from Western blots probed with MAb13-11, a cTnT-specific monoclonal antibody. We found that cTnT₄ expression correlated positively with the duration of inotropic support and was higher in patients who received drug treatment before surgery than in those who did not. Furthermore, we found that the percent of cTnT₄ was significantly higher in hearts with congenital defects that caused congestive failure than in hearts with tetralogy of Fallot.

Conclusions These findings suggest that in patients with congenital cardiac defects, cTnT₄ expression is modulated by heart failure and is increased in hearts that are more hemodynamically stressed.

Key Words: atrium • inotropic agents • heart failure • molecular biology • proteins

This article has been cited by other articles:

				E. E. Jweied, R. D. McKinney, L. A. Walker, I. Brodsky, A. S. Geha, M. G. Massad, P. M. Buttrick, and P. P. de Tombe Depressed cardiac myofilament function in human diabetes mellitus Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2478 - H2483. [Abstract] [Full Text] [PDF]

				R. Nassar, N. N. Malouf, L. Mao, H. A. Rockman, A. E. Oakeley, J. R. Frye, J. R. Herlong, S. P. Sanders, and P. A. W. Anderson cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1147 - H1156. [Abstract] [Full Text] [PDF]

				S. B. Marston and C. S. Redwood Modulation of Thin Filament Activation by Breakdown or Isoform Switching of Thin Filament Proteins: Physiological and Pathological Implications Circ. Res., December 12, 2003; 93(12): 1170 - 1178. [Abstract] [Full Text] [PDF]

				J.-P. Jin, A. Chen, O. Ogut, and Q.-Q. Huang Conformational modulation of slow skeletal muscle troponin T by an NH2-terminal metal-binding extension Am J Physiol Cell Physiol, October 1, 2000; 279(4): C1067 - C1077. [Abstract] [Full Text] [PDF]

				I. F Purcell, W. Bing, and S. B Marston Functional analysis of human cardiac troponin by the in vitro motility assay: comparison of adult, foetal and failing hearts Cardiovasc Res, September 1, 1999; 43(4): 884 - 891. [Abstract] [Full Text] [PDF]

				J van der Velden, L.J Klein, M van der Bijl, M.A.J.M Huybregts, W Stooker, J Witkop, L Eijsman, C.A Visser, F.C Visser, and G.J.M Stienen Isometric tension development and its calcium sensitivity in skinned myocyte-sized preparations from different regions of the human heart Cardiovasc Res, June 1, 1999; 42(3): 706 - 719. [Abstract] [Full Text] [PDF]

				G. Paternostro, D. Pagano, T. Gnecchi-Ruscone, R. S Bonser, and P. G Camici Insulin resistance in patients with cardiac hypertrophy Cardiovasc Res, April 1, 1999; 42(1): 246 - 253. [Abstract] [Full Text] [PDF]

				C. Haller, H. A. Katus, F. S. Apple, and S. W. Sharkey Expression of Cardiac Troponin T in Skeletal Muscle Clin. Chem., February 1, 1998; 44(2): 358 - 359. [Full Text] [PDF]

				M. D. McLaurin, F. S. Apple, E. M. Voss, C. A. Herzog, and S. W. Sharkey Cardiac troponin I, cardiac troponin T, and creatine kinase MB in dialysis patients without ischemic heart disease: evidence of cardiac troponin T expression in skeletal muscle Clin. Chem., June 1, 1997; 43(6): 976 - 982. [Abstract] [Full Text] [PDF]

				V. Ricchiuti, J. Zhang, and F. S. Apple Cardiac troponin I and T alterations in hearts with severe left ventricular remodeling Clin. Chem., June 1, 1997; 43(6): 990 - 995. [Abstract] [Full Text] [PDF]

				G. S. Bodor, L. Survant, E. M. Voss, S. Smith, D. Porterfield, and F. S. Apple Cardiac troponin T composition in normal and regenerating human skeletal muscle Clin. Chem., March 1, 1997; 43(3): 476 - 484. [Abstract] [Full Text] [PDF]