Characterization of beta3-adrenoceptors in human internal mammary artery and putative involvement in coronary artery bypass management.

Bertrand Rozec MD, Sabrina Serpillon, PhD; Gilles Toumaniantz, PhD; Camille Sèze, MSc; Yohann Rautureau, PhD; Olivier Baron MD, Jacques Noireaud, PhD and Chantal Gauthier, PhD. Journal of the American College of Cardiology 2005; 46 (2): 351-9

Reviewer: Hong Liu, MD
UC Davis Health System
Sacramento, CA

Objectives and Background: The aim of the present study was to analyze whether beta3-adrenoceptors (β₃-ARs) were effectively pres-ent and functional in the human internal mammary artery (IMA). The beta1- and beta2-adrenoceptors classically mediate the relaxant effects of catecholamines in the vessels. In vitro and in vivo studies performed in various animal species described vasodilating effects due to activation of a third beta-ARs subtype (β₃).

Methods: Reverse transcription-polymerase chain reaction analysis, Western blot experiments, and pharmacological studies were carried out in human IMA samples harvested from 27 patients undergoing coronary bypass surgery(CABG).

Results: The β₃-ARs messenger ribonucleic acid and protein were detected in intact IMA, but were absent in endothelium-free samples. This finding was confirmed by immunohistochemical experiments. In organ baths, a β₃-AR agonist, SR 58611A, induced an endothelium-dependent relaxation of phenylephrine-precontracted IMA rings. This vasodilation was not modified by β₁/β₂-AR antagonists, but was greatly altered in the presence of L-748,337, a selective human β₃-AR antagonist. Moreover, the inhibition of nitric oxide (NO) synthases abolished β₃-adrenergic vasodilation, suggesting the involvement of a NO-signaling pathway.

Conclusions: Those results demonstrated the presence of β₃-ARs in the endothelial layer of human IMA. The present work highlights the role of β₃-ARs in vasomotor control of IMA and opens new fields of investigation in coronary bypass graft management, heart failure, and hypertension.

Comments: The development of IMA grafting is the most remarkable achievement in coronary artery surgery in the past two decades. It has a superior graft patency and increased long-term survival compared with saphenous vein grafts. However, the development of IMA malperfusion syndrome is a critical complication of CABG (1.9% and up to 20% after primary coronary bypass and reoperation, respectively) and can have devastating effects on the outcome of a cardiac operation leading to a perioperative increase in morbidity and mortality. The etiology of the syndrome is multifactorial, but a spasm of the graft has been frequently suggested. The vasoconstriction can be evoked by several stimuli such as mechanical trauma, nerve stimulation, and vasoconstrictor substances. Circulating sympathomimetic substances are considered as possible spasmogenic agents. It is, therefore, essential to treat and to prevent the vasospasm. The authors used complementary approaches of molecular biology, biochemistry, and pharmacology to show the presence of functional endothelial β₃-ARs to be responsible for a vasodilation involving the NO pathway in the human IMA. The development of a third genera-tion of beta-blockers with vasodilating properties resulting from a β₃-AR agonistic effect might constitute an interesting new method of investigation. Combined with other studies, the present findings highlighted the potential role of β₃-ARs in blood flow regulation, especially in the flow regulation in IMA. By opening the new field of concerning the involvement of β₃-ARs in human cardiovascular physiopathology, we expect to see a greater improvement in IMA malperfusion syndrome and better outcome of CABG operation.

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Table of Contents:

• President's Message
• Call for Nominations


• Literature Reviews
  • Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: Implications on operative outcome.
  • Increased prothrombotic state lasting as long as one month after on-pump and off-pump coronary surgery.
  • Characterization of beta3-adrenoceptors in human internal mammary artery and putative involvement in coronary artery bypass management.
  • Aprotinin reduces bleeding and blood product use in patients treated with clopidogrel before coronary artery bypass grafting.
  • Secondary tricuspid regurgitation or dilatation: Which should be the criteria for surgical repair?
  • Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function.
  • Overexpression of mitochondrial transcription factor A ameliorates mito­chondrial deficiencies and cardiac failure after myocardial infarction.
  • An essential role for mitochondrial aldehyde dehydrogenase in nitroglyc­erin bioactivation.


• Drug and Innovation Updates
  • Child-Pugh and MELD classifications and the mortality following cardiac surgery.
  • Anesthetic preconditioning and perioperative myocardial protection


• PRO/CON: Conscious Neuraxial Anesthesia is a Viable Alternative to General Anesthesia in Cardiac Surgery.
• Pro - Paul Kessler, MD
• Con - Peggy T. Y. Li, MBChB & Anthony M. H. Ho, MD, FRCPC, FCCP

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