Skeletal muscle microvasculature response to β-adrenergic stimuli is diminished with cardiac surgery.


Journal

Surgery
ISSN: 1532-7361
Titre abrégé: Surgery
Pays: United States
ID NLM: 0417347

Informations de publication

Date de publication:
02 2020
Historique:
received: 21 01 2019
revised: 08 07 2019
accepted: 24 07 2019
pubmed: 9 9 2019
medline: 10 5 2020
entrez: 9 9 2019
Statut: ppublish

Résumé

Cardiac surgery and cardiopulmonary bypass are associated with alterations in blood pressure in the perioperative period, which, if uncontrolled, can result in end organ damage or dysfunction. Microvessels, significant contributors to blood pressure, both in the myocardium and peripheral skeletal muscle, have diminished responsiveness to major mediators of vascular tone, including thromboxane and serotonin after cardiopulmonary bypass. Responsiveness of these vessels to β-adrenergic stimulation, a major mediator of vascular tone, has not yet been studied. In this report, we investigated the role of β-adrenergic receptors in vascular tone regulation in human skeletal muscle microvessels before and after β-adrenergic stimulation. Skeletal muscle microvessels were isolated from patients undergoing cardiac surgery before and after cardiopulmonary bypass. Vessels were exposed in an ex vivo model to the β-adrenergic agonist isoproterenol, or the direct adenylyl cyclase activator, forskolin, and the selective β-receptor antagonist ICI18.551 hydrochloride plus isoproterenol. Immunofluorescence of β receptors and Western blotting were also performed. Microvessels showed diminished responsiveness to isoproterenol (10 Microvessels isolated from human skeletal muscle show diminished responsiveness to isoproterenol and its downstream activator forskolin after cardiopulmonary bypass, suggesting there is an alteration in β-adrenergic receptor responsive in adenylate cyclase. The relaxation response to isoproterenol was via activation β-2 receptors without changes in β-adrenergic receptor abundance.

Sections du résumé

BACKGROUND
Cardiac surgery and cardiopulmonary bypass are associated with alterations in blood pressure in the perioperative period, which, if uncontrolled, can result in end organ damage or dysfunction. Microvessels, significant contributors to blood pressure, both in the myocardium and peripheral skeletal muscle, have diminished responsiveness to major mediators of vascular tone, including thromboxane and serotonin after cardiopulmonary bypass. Responsiveness of these vessels to β-adrenergic stimulation, a major mediator of vascular tone, has not yet been studied. In this report, we investigated the role of β-adrenergic receptors in vascular tone regulation in human skeletal muscle microvessels before and after β-adrenergic stimulation.
METHODS
Skeletal muscle microvessels were isolated from patients undergoing cardiac surgery before and after cardiopulmonary bypass. Vessels were exposed in an ex vivo model to the β-adrenergic agonist isoproterenol, or the direct adenylyl cyclase activator, forskolin, and the selective β-receptor antagonist ICI18.551 hydrochloride plus isoproterenol. Immunofluorescence of β receptors and Western blotting were also performed.
RESULTS
Microvessels showed diminished responsiveness to isoproterenol (10
CONCLUSION
Microvessels isolated from human skeletal muscle show diminished responsiveness to isoproterenol and its downstream activator forskolin after cardiopulmonary bypass, suggesting there is an alteration in β-adrenergic receptor responsive in adenylate cyclase. The relaxation response to isoproterenol was via activation β-2 receptors without changes in β-adrenergic receptor abundance.

Identifiants

pubmed: 31493902
pii: S0039-6060(19)30524-0
doi: 10.1016/j.surg.2019.07.018
pmc: PMC7002023
mid: NIHMS1536414
pii:
doi:

Substances chimiques

Adrenergic beta-Agonists 0
Adrenergic beta-Antagonists 0
Receptors, Adrenergic, beta 0
Colforsin 1F7A44V6OU
Isoproterenol L628TT009W

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

493-498

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL046716
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103652
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128831
Pays : United States
Organisme : NHLBI NIH HHS
ID : T35 HL094308
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136347
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127072
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Olivia Ziegler (O)

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.

Kelsey Anderson (K)

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.

Yuhong Liu (Y)

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.

Afshin Ehsan (A)

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.

James Fingleton (J)

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.

Neel Sodha (N)

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.

Jun Feng (J)

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.

Frank W Sellke (FW)

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI. Electronic address: fsellke@lifespan.org.

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Classifications MeSH