Consequences of labetalol administration on myocardial beta adrenergic receptors in the brain dead pig.

C. Seguin*, Y. Devaux, N. Aubert, E. M. Siaghy, F. Zannad, C. Burlet, D. Ungureanu-Longrois, P. M. Mertes

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)


OBJECTIVES: Cardiac dysfunction following brain death is associated with highly increased myocardial norepinephrine, lactate and adenosine concentrations. Administration of labetalol, a mixed alpha-, beta-adrenergic receptor antagonist, attenuates metabolic disturbances and improves myocardial function. The purpose of this study was to investigate beta-adrenergic receptor (beta AR) density and affinity in the presence or absence of labetalol administration, as a possible mechanism of the protective effects of this drug. METHODS: Experimental animals were divided into three groups: sham-operated, brain-dead pigs, and brain-dead pigs treated with labetalol (10 +/- 3 mg/kg). The maximum number of binding sites (Bmax) and the dissociation constant (Kd) of beta AR were determined with (-)-[125I]cyanopindolol on myocardial samples harvested 3 hours after brain death. RESULTS: Left ventricular beta AR density and affinity were identical in brain-dead and sham-operated animals. Labetalol-treated pigs exhibited a significant decrease of Bmax and an increase of Kd as compared with brain-dead pigs. Bmax decrease was due to the persistence of labetalol in the membrane preparations. Increased Kd was too low to be biologically significant. Therefore, beta AR number and affinity can be considered as unchanged after adrenergic blockade with labetalol. CONCLUSIONS: The protective mechanism of labetalol on brain death-induced myocardial dysfunction cannot be explained by changes in beta AR density and affinity but is probably related to a preservation of the oxygen consumption/oxygen delivery balance during the autonomic storm.

Original languageEnglish
Pages (from-to)54-60
Number of pages7
JournalAnnals of Transplantation
Issue number4
Publication statusPublished - 2000
Externally publishedYes


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