HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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 Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Walter H. Merrill Jeffrey M. Pearl Shahab A. Akhter Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pandalai, P. K. Articles by Akhter, S. A. Search for Related Content PubMed Articles by Pandalai, P. K. Articles by Akhter, S. A. Related Collections Cardiac - pharmacology Cardiac - physiology Molecular biology Transplantation - heart

J Thorac Cardiovasc Surg 2008;135:792-798
© 2008 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Acute β-blockade prevents myocardial β-adrenergic receptor desensitization and preserves early ventricular function after brain death

^a Department of Surgery, Section of Cardiothoracic Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio
^b Department of Pediatric Cardiothoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

Received for publication May 31, 2007; accepted for publication September 6, 2007.

^_* Address for reprints: Shahab A. Akhter, Assistant Professor of Surgery, Section of Cardiac & Thoracic Surgery, The University of Chicago, 5841 S. Maryland Avenue, MC 5040, Chicago, IL 60637. (Email: sakhter{at}surgery.bsd.uchicago.edu).

Objective: β-Adrenergic receptor desensitization through activation of the G protein–coupled receptor kinase 2 is an important mechanism of early cardiac dysfunction after brain death. We hypothesized that acute β-blockade can prevent myocardial β-adrenergic receptor desensitization after brain death through attenuation of G protein–coupled receptor kinase 2 activity, resulting in improved cardiac function.

Methods: Adult pigs underwent either sham operation, induction of brain death, or treatment with esmolol (β-blockade) for 30 minutes before and 45 minutes after brain death (n = 8 per group). Cardiac function was assessed at baseline and for 6 hours after the operation. Myocardial β-adrenergic receptor signaling was assessed 6 hours after operation by measuring sarcolemmal membrane adenylate cyclase activity, β-adrenergic receptor density, and G protein–coupled receptor kinase 2 expression and activity.

Results: Baseline left ventricular preload recruitable stroke work was similar among sham, brain death, and β-blockade groups. Preload recruitable stroke work was significantly decreased 6 hours after brain death versus sham, and β-blockade resulted in maintenance of baseline preload recruitable stroke work relative to brain death and not different from sham. Basal and isoproterenol-stimulated adenylate cyclase activities were preserved in the β-blockade group relative to the brain death group and were not different from the sham group. Left ventricular G protein–coupled receptor kinase 2 expression and activity in the β-blockade group were markedly decreased relative to the brain death group and similar to the sham group. β-Adrenergic receptor density was not different among groups.

Conclusion: Acute β-blockade before brain death attenuates β-adrenergic receptor desensitization mediated by G protein–coupled receptor kinase 2 and preserves early cardiac function after brain death. These data support the hypothesis that acute β-adrenergic receptor desensitization is an important mechanism in early ventricular dysfunction after brain death. Future studies with β-blocker therapy immediately after brain death appear warranted.

This article has been cited by other articles:

				K. M. Mikhova, C. W. Don, M. Laflamme, J. A. Kellum, M. S. Mulligan, E. D. Verrier, and D. G. Rabkin Effect of cytokine hemoadsorption on brain death-induced ventricular dysfunction in a porcine model J. Thorac. Cardiovasc. Surg., January 1, 2013; 145(1): 215 - 224. [Abstract] [Full Text] [PDF]