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. 1995 Jun;73(6):540–543. doi: 10.1136/hrt.73.6.540

Beta adrenoceptor density in the donor heart: a guide to prognosis?

M R Chester 1, A A Amadi 1, D B Barnett 1
PMCID: PMC483916  PMID: 7626353

Abstract

BACKGROUND--Failure of the donor (graft) heart is the main cause of mortality in the first month after orthotopic cardiac transplantation. In a preliminary study marked downregulation of cardiac beta adrenoceptor density was found in apparently normal donor hearts of recipients who developed severe cardiac failure soon after implantation. Cardiac beta adrenoceptors are an important factor in the development of cardiac failure in the human heart. The aim of this study therefore was to determine whether fatal graft failure in the first month after transplantation is associated with downregulation of beta adrenoceptor density in the donor heart. PATIENTS AND METHODS--Right ventricular endomyocardial biopsy specimens were taken from consecutive adult donor patients immediately before implantation. A previously described radioligand binding method was used to determine beta adrenoceptor density in consecutive patients who developed fatal graft failure and died within 1 month of transplantation and in a group of control donors transplanted during the same period. RESULTS--Perioperative fatal graft failure developed in 13 patients. Forty one specimens from donor hearts that were transplanted into recipients who did not develop fatal graft heart failure formed the control group. There were no systematic differences in donor or recipient characteristics between the graft heart failure and control groups. In particular donor catecholamine requirement and recipient pulmonary vascular resistance did not differ between groups. Total beta adrenoceptor density was reduced in the fatal graft heart failure group compared with that in the controls (13.4 (7) fmol/mg v 21 (7) fmol/mg; P < 0.01). There was a positive correlation between beta adrenoceptor density in the donor heart and time to death in the graft heart failure group (r2 = 0.3, P < 0.05). The beta adrenoceptor binding affinity (Kd) did not differ between the graft failure group and the controls (47 (6) pM v 44 (7) pM). CONCLUSION--The development of perioperative fatal cardiac failure after orthotopic cardiac transplantation is associated with downregulation of beta adrenoceptors in the donor heart before implantation.

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Selected References

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  1. Barovsky K., Brooker G. (-)-[125I]-iodopindolol, a new highly selective radioiodinated beta-adrenergic receptor antagonist: measurement of beta-receptors on intact rat astrocytoma cells. J Cyclic Nucleotide Res. 1980;6(4):297–307. [PubMed] [Google Scholar]
  2. Bristow M. R., Ginsburg R., Minobe W., Cubicciotti R. S., Sageman W. S., Lurie K., Billingham M. E., Harrison D. C., Stinson E. B. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med. 1982 Jul 22;307(4):205–211. doi: 10.1056/NEJM198207223070401. [DOI] [PubMed] [Google Scholar]
  3. Bristow M. R., Hershberger R. E., Port J. D., Minobe W., Rasmussen R. Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol. 1989 Mar;35(3):295–303. [PubMed] [Google Scholar]
  4. Chester M. R., Madden B., Barnett D., Yacoub M. The effect of orthotopic transplantation on total, beta 1- and beta 2-adrenoceptors in the human heart. Br J Clin Pharmacol. 1992 Apr;33(4):417–422. doi: 10.1111/j.1365-2125.1992.tb04061.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Connor R. C. Heart damage associated with intracranial lesions. Br Med J. 1968 Jul 6;3(5609):29–31. doi: 10.1136/bmj.3.5609.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Costard-Jäckle A., Hill I., Schroeder J. S., Fowler M. B. The influence of preoperative patient characteristics on early and late survival following cardiac transplantation. Circulation. 1991 Nov;84(5 Suppl):III329–III337. [PubMed] [Google Scholar]
  7. Darracott-Cankovic S., Stovin P. G., Wheeldon D., Wallwork J., Wells F., English T. A. Effect of donor heart damage on survival after transplantation. Eur J Cardiothorac Surg. 1989;3(6):525–532. doi: 10.1016/1010-7940(89)90113-9. [DOI] [PubMed] [Google Scholar]
  8. Darracott-Cankovíc S., Wheeldon D., Cory-Pearce R., Wallwork J., English T. A. Biopsy assessment of fifty hearts during transplantation. J Thorac Cardiovasc Surg. 1987 Jan;93(1):95–102. [PubMed] [Google Scholar]
  9. Denniss A. R., Marsh J. D., Quigg R. J., Gordon J. B., Colucci W. S. Beta-adrenergic receptor number and adenylate cyclase function in denervated transplanted and cardiomyopathic human hearts. Circulation. 1989 May;79(5):1028–1034. doi: 10.1161/01.cir.79.5.1028. [DOI] [PubMed] [Google Scholar]
  10. Fowler M. B., Laser J. A., Hopkins G. L., Minobe W., Bristow M. R. Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response. Circulation. 1986 Dec;74(6):1290–1302. doi: 10.1161/01.cir.74.6.1290. [DOI] [PubMed] [Google Scholar]
  11. Ginsburg R., Bristow M. R., Billingham M. E., Stinson E. B., Schroeder J. S., Harrison D. C. Study of the normal and failing isolated human heart: decreased response of failing heart to isoproterenol. Am Heart J. 1983 Sep;106(3):535–540. doi: 10.1016/0002-8703(83)90698-1. [DOI] [PubMed] [Google Scholar]
  12. Kolin A., Brezina A., Lewis A. J., Norris J. W. Quantitative evaluation of myocardial injury induced by acute cerebral ischaemia and its prevention by beta 1-adrenergic blockade. An ultrastructural morphometry study. Br J Exp Pathol. 1989 Dec;70(6):659–667. [PMC free article] [PubMed] [Google Scholar]
  13. Kriett J. M., Kaye M. P. The Registry of the International Society for Heart Transplantation: seventh official report--1990. J Heart Transplant. 1990 Jul-Aug;9(4):323–330. [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Myers M. G., Norris J. W., Hachniski V. C., Sole M. J. Plasma norepinephrine in stroke. Stroke. 1981 Mar-Apr;12(2):200–204. doi: 10.1161/01.str.12.2.200. [DOI] [PubMed] [Google Scholar]
  16. SMITH R. P., TOMLINSON B. E. Subendocardial haemorrhages associated with intracranial lesions. J Pathol Bacteriol. 1954 Oct;68(2):327–334. doi: 10.1002/path.1700680204. [DOI] [PubMed] [Google Scholar]
  17. Yamour B. J., Sridharan M. R., Rice J. F., Flowers N. C. Electrocardiographic changes in cerebrovascular hemorrhage. Am Heart J. 1980 Mar;99(3):294–300. doi: 10.1016/0002-8703(80)90343-9. [DOI] [PubMed] [Google Scholar]

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