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Eur J Cardiothorac Surg 2007;32:225-230. doi:10.1016/j.ejcts.2007.03.048
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Beta-blockade at low doses restoring the physiological balance in myocytic antagonism

^a Klinik und Poliklinik für Thorax, Herz und Gefäßchirurgie, Universität Münster, Germany
^b Institut für Numerische Mathematik, Universität Münster, Germany
^c Department of Cardio-Thoracic Surgery, Hospital Geral de Roraima, Universidade Estadural de Roraima, Boa Vista, Brazil
^d Department of Cardiothoracic Surgery, Pretoria Academic Hospital, Pretoria, South Africa
^e Institut für Biomedizinische Technik, ETH und Universität Zürich, Switzerland
^f Cardiac Unit, Institute of Child Health, University College, London, UK

Received 15 September 2006; received in revised form 5 February 2007; accepted 30 March 2007.

^_* Corresponding author. Address: Klinik und Poliklinik für Thorax, Herz und Gefäßchirurgie, Domagkstr. 11, 48129 Münster, Germany. Tel.: +49 251 8356256; fax: +49 251 8356257. (Email: redmann{at}uni-muenster.de).

Objective: The ventricular mass is organized in the form of meshwork, with populations of myocytes aggregated in a supporting matrix of fibrous tissue, with some myocytes aligned obliquely across the wall so as to work in an antagonistic fashion compared to the majority of myocytes, which are aggregated together in tangential alignment. Prompted by results from animal experiments, which showed a disparate response of the two populations of aggregated myocytes to negative inotropic medication, we sought to establish whether those myocytes that aggregated so as to extend obliquely across the thickness of the ventricular walls are more sensitive to beta-blockade than the prevailing population in which the myocytes are aggregated together with tangential alignment. If the two populations respond in similar differing fashion in the clinical situation, we hypothesize that this might help to explain why drugs blocking the beta-receptors improve function of the ventricular pump in the setting of congestive cardiac failure. Methods: We implanted needle probes in 13 patients studied during open heart surgery, measuring the forces generated in the ventricular wall and seeking to couple the probes either to myocytes aggregated together with tangential alignment or to those aggregated in oblique fashion across the ventricular walls. In a first series of patients, we injected probatory doses intravenously, amounting to a total bolus of 40–100 mg Esmolol, while in a second series, we gave fixed yet rising doses of 5, 10, and 20 mg Esmolol in three separate boluses. Results: Forces recorded in the aggregated myocytes with tangential alignment decreased insignificantly upon administration of low doses (57.1 ± 12.4 mN 56.6 ± 7.6 mN), while forces recorded in the myocytes aggregated obliquely across the ventricular wall showed a significant decrease in the mean (59.3 ± 11.6 mN 47.4 ± 6.4 mN). Conclusions: The markedly disparate action of drugs blocking beta-receptors at low dosage seems to be related to the heterogeneous extent, and time course, of systolic loading of the myocytes. This, in turn, depends on whether the myocytes themselves are aggregated together with tangential or oblique alignments relative to the thickness of the ventricular walls.

Key Words: Beta-blockade • Intrinsic antagonism • Auxotonic forces • Unloading forces

This article has been cited by other articles:

				R. H. Anderson, D. Sanchez-Quintana, P. Niederer, and P. P. Lunkenheimer Structural-functional correlates of the 3-dimensional arrangement of the myocytes making up the ventricular walls J. Thorac. Cardiovasc. Surg., July 1, 2008; 136(1): 10 - 18. [Full Text] [PDF]