This Article Full Text Full Text (PDF) 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 Owen, V. J. Articles by Harding, S. E. Search for Related Content PubMed PubMed Citation Articles by Owen, V. J. Articles by Harding, S. E. Related Collections Contractile function CV surgery: transplantation, ventricular assistance, cardiomyopathy

(Circulation. 1999;99:2565-2570.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

Myocardial Dysfunction in Donor Hearts

A Possible Etiology

Virginia J. Owen, PhD; Paul B. J. Burton, BSc, MBBS; Martin C. Michel, MD; Oliver Zolk, MD; Michael Böhm, MD; John R. Pepper, FRCS; Paul J. R. Barton, PhD; Magdi H. Yacoub, FRCS, DSc; Sian E. Harding, PhD

From Cardiothoracic Surgery (V.J.O., P.B.J.B., J.R.P., P.J.R.B., M.H.Y.) and Cardiac Medicine (S.E.H.), National Heart and Lung Institute at Imperial College School of Medicine, London, UK; Nephrology Laboratory (M.C.M.), Klinikum Essen, Essen, Germany; and Klinik III fur Innere Medizin (O.Z., M.B.), Universitat zu Köln, Germany.

Background—Potential cardiac donors show various degrees of myocardial dysfunction, and the most severely affected hearts are unsuitable for transplantation. The cause of this acute heart failure is poorly understood. We investigated whether alterations in calcium-handling proteins, ß-adrenoceptor density, or the inhibitory G protein G_i could account for this phenomenon in unused donor hearts (n=4 to 8). We compared these with end-stage failing hearts (n=14 to 16) and nonfailing hearts (n=3 to 12).

Methods and Results—Myocardial samples were obtained from unused donor hearts displaying ejection fractions <30%. Both trabeculae and isolated myocytes responded as poorly as those from the group of failing hearts to increasing stimulation frequency with regard to inotropic function in vitro. Immunodetectable abundance of sarcoplasmic reticulum calcium-ATPase and sodium calcium exchanger were greater (177%; P<0.01) and smaller (29%; P<0.01), respectively, in the unused donor hearts relative to the failing group, which suggests that alterations of these proteins are not a common cause of contractile dysfunction in the 2 groups. Myocytes from the unused donor group were desensitized to isoprenaline to a similar degree as those from the failing heart group. However, ß-adrenoceptor density was reduced in the failing (P<0.001) but not in the unused donor heart group (P=0.37) relative to the nonfailing heart group (n=5). G_i activity was increased in samples from unused donor and failing hearts relative to nonfailing hearts (P<0.05).

Conclusions—Increased activity of the inhibitory G protein G_i is a significant contributory factor for impaired contractility in these acutely failing donor hearts.

Key Words: transplantation • heart failure • proteins • receptors, adrenergic, beta • contractility

This article has been cited by other articles:

				R. J. Belin, M. P. Sumandea, T. Kobayashi, L. A. Walker, V. L. Rundell, D. Urboniene, M. Yuzhakova, S. H. Ruch, D. L. Geenen, R. J. Solaro, et al. Left ventricular myofilament dysfunction in rat experimental hypertrophy and congestive heart failure Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2344 - H2353. [Abstract] [Full Text] [PDF]

				R. S. Warraich, E. Griffiths, A. Falconar, V. Pabbathi, C. Bell, G. Angelini, M.-S. Suleiman, and M. H. Yacoub Human cardiac myosin autoantibodies impair myocyte contractility: a cause-and-effect relationship FASEB J, April 1, 2006; 20(6): 651 - 660. [Abstract] [Full Text] [PDF]

				N. M. Banki, A. Kopelnik, M. W. Dae, J. Miss, P. Tung, M. T. Lawton, B. J. Drew, E. Foster, W. Smith, W. W. Parmley, et al. Acute Neurocardiogenic Injury After Subarachnoid Hemorrhage Circulation, November 22, 2005; 112(21): 3314 - 3319. [Abstract] [Full Text] [PDF]

				C. M.N Terracciano, S. E Harding, D. Adamson, M. Koban, P. Tansley, E. J Birks, P. J.R Barton, and M. H Yacoub Changes in sarcolemmal Ca entry and sarcoplasmic reticulum Ca content in ventricular myocytes from patients with end-stage heart failure following myocardial recovery after combined pharmacological and ventricular assist device therapy Eur. Heart J., July 2, 2003; 24(14): 1329 - 1339. [Abstract] [Full Text] [PDF]

				V.J Owen, P.B.J Burton, A.J Mullen, E.J Birks, P Barton, and M.H Yacoub Expression of RGS3, RGS4 and Gi alpha 2 in acutely failing donor hearts and end-stage heart failure Eur. Heart J., June 2, 2001; 22(12): 1015 - 1020. [Abstract] [PDF]

				M.H. Yacoub A novel strategy to maximize the efficacy of left ventricular assist devices as a bridge to recovery Eur. Heart J., April 1, 2001; 22(7): 534 - 540. [PDF]

				C. M.N. Terracciano, K. D. Philipson, and K. T. MacLeod Overexpression of the Na+/Ca2+ exchanger and inhibition of the sarcoplasmic reticulum Ca2+-ATPase in ventricular myocytes from transgenic mice Cardiovasc Res, January 1, 2001; 49(1): 38 - 47. [Abstract] [Full Text] [PDF]

				H. Yokoyama, S. Gunasegaram, S. E. Harding, and M. Avkiran Sarcolemmal Na+/H+ exchanger activity and expression in human ventricular myocardium J. Am. Coll. Cardiol., August 1, 2000; 36(2): 534 - 540. [Abstract] [Full Text] [PDF]

				E. J. Birks, V. J. Owen, P. B. J. Burton, A. E. Bishop, N. R. Banner, A. Khaghani, J. M. Polak, and M. H. Yacoub Tumor Necrosis Factor-{alpha} Is Expressed in Donor Heart and Predicts Right Ventricular Failure After Human Heart Transplantation Circulation, July 18, 2000; 102(3): 326 - 331. [Abstract] [Full Text] [PDF]