Nonphysiologic blood flow triggers endothelial and arterial remodeling in vivo

Implications for novel left ventricular assist devices with a peripheral anastomosis

Carlo R. Bartoli, Paul A. Spence, Thorsten Siess, Daniel H. Raess, Steven C. Koenig, Robert Dowling

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objectives Less invasive circulatory support devices have been developed that require anastomosis to a peripheral artery. The Symphony Heart Assist System (Abiomed, Inc, Danvers, Mass) is a volume-displacement pump sewn to the subclavian artery to provide partial circulatory support. The surgical configuration produces nonphysiologic blood pressure and bidirectional flow in the subclavian artery. Our objective was to identify effects of altered hemodynamics on arterial structure and function. Methods In calves (n = 23; 80-100 kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely, carotid blood pressure and flow were recorded to evaluate hemodynamic changes. After medium-term support (1-4 weeks), carotid artery was studied. Histologic and molecular assays evaluated architectural changes. Quantitative real-time polymerase chain reaction evaluated gene expression of matrix metalloproteinase (MMP)-2, MMP-9, and connective tissue growth factor. In vitro carotid arterial-ring studies evaluated physiologic responses. Results During Symphony support, carotid arterial pressure was 200/15 mm Hg. Antegrade flow increased significantly (P <.05) from 1.40 ± 0.32 to 4.29 ± 0.33 L/min. Flow during native cardiac diastole reversed completely from 0.25 ± 0.05 to -4.15 ± 0.38 L/min in carotid artery proximal to the anastomosis. After medium-term support, the carotid artery was significantly dilated with significantly thinner tunica media and thicker tunica adventitia than in control carotid arteries. MMP-9 gene expression decreased significantly, connective tissue growth factor gene expression increased significantly, and collagen, elastin, and total extracellular matrix increased significantly. Endothelial cells were significantly hypertrophied and produced significantly more von Willebrand factor. Endothelial apoptosis increased significantly. Platelet-endothelial interactions decreased significantly. Endothelial- independent contraction decreased significantly, whereas endothelial-dependent relaxation increased modestly. Conclusions Assisted circulation with a left ventricular assist device triggered arterial remodeling that allowed a peripheral artery to accommodate the altered hemodynamics of a novel partial-support pump. Further delineation of remodeling pathways may be of significance for the emerging field of partial circulatory support.

Original languageEnglish (US)
Pages (from-to)311-321
Number of pages11
JournalJournal of Thoracic and Cardiovascular Surgery
Volume148
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

Heart-Assist Devices
Carotid Arteries
Connective Tissue Growth Factor
Subclavian Artery
Hemodynamics
Matrix Metalloproteinase 9
Gene Expression
Assisted Circulation
Arteries
Blood Pressure
Tunica Media
Adventitia
Diastole
Elastin
Matrix Metalloproteinase 2
von Willebrand Factor
Extracellular Matrix
Real-Time Polymerase Chain Reaction
Arterial Pressure
Collagen

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

@article{f595f7cf2346483883bc104789d0ba22,
title = "Nonphysiologic blood flow triggers endothelial and arterial remodeling in vivo: Implications for novel left ventricular assist devices with a peripheral anastomosis",
abstract = "Objectives Less invasive circulatory support devices have been developed that require anastomosis to a peripheral artery. The Symphony Heart Assist System (Abiomed, Inc, Danvers, Mass) is a volume-displacement pump sewn to the subclavian artery to provide partial circulatory support. The surgical configuration produces nonphysiologic blood pressure and bidirectional flow in the subclavian artery. Our objective was to identify effects of altered hemodynamics on arterial structure and function. Methods In calves (n = 23; 80-100 kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely, carotid blood pressure and flow were recorded to evaluate hemodynamic changes. After medium-term support (1-4 weeks), carotid artery was studied. Histologic and molecular assays evaluated architectural changes. Quantitative real-time polymerase chain reaction evaluated gene expression of matrix metalloproteinase (MMP)-2, MMP-9, and connective tissue growth factor. In vitro carotid arterial-ring studies evaluated physiologic responses. Results During Symphony support, carotid arterial pressure was 200/15 mm Hg. Antegrade flow increased significantly (P <.05) from 1.40 ± 0.32 to 4.29 ± 0.33 L/min. Flow during native cardiac diastole reversed completely from 0.25 ± 0.05 to -4.15 ± 0.38 L/min in carotid artery proximal to the anastomosis. After medium-term support, the carotid artery was significantly dilated with significantly thinner tunica media and thicker tunica adventitia than in control carotid arteries. MMP-9 gene expression decreased significantly, connective tissue growth factor gene expression increased significantly, and collagen, elastin, and total extracellular matrix increased significantly. Endothelial cells were significantly hypertrophied and produced significantly more von Willebrand factor. Endothelial apoptosis increased significantly. Platelet-endothelial interactions decreased significantly. Endothelial- independent contraction decreased significantly, whereas endothelial-dependent relaxation increased modestly. Conclusions Assisted circulation with a left ventricular assist device triggered arterial remodeling that allowed a peripheral artery to accommodate the altered hemodynamics of a novel partial-support pump. Further delineation of remodeling pathways may be of significance for the emerging field of partial circulatory support.",
author = "Bartoli, {Carlo R.} and Spence, {Paul A.} and Thorsten Siess and Raess, {Daniel H.} and Koenig, {Steven C.} and Robert Dowling",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.jtcvs.2013.10.027",
language = "English (US)",
volume = "148",
pages = "311--321",
journal = "Journal of Thoracic and Cardiovascular Surgery",
issn = "0022-5223",
publisher = "Mosby Inc.",
number = "1",

}

Nonphysiologic blood flow triggers endothelial and arterial remodeling in vivo : Implications for novel left ventricular assist devices with a peripheral anastomosis. / Bartoli, Carlo R.; Spence, Paul A.; Siess, Thorsten; Raess, Daniel H.; Koenig, Steven C.; Dowling, Robert.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 148, No. 1, 01.01.2014, p. 311-321.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nonphysiologic blood flow triggers endothelial and arterial remodeling in vivo

T2 - Implications for novel left ventricular assist devices with a peripheral anastomosis

AU - Bartoli, Carlo R.

AU - Spence, Paul A.

AU - Siess, Thorsten

AU - Raess, Daniel H.

AU - Koenig, Steven C.

AU - Dowling, Robert

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objectives Less invasive circulatory support devices have been developed that require anastomosis to a peripheral artery. The Symphony Heart Assist System (Abiomed, Inc, Danvers, Mass) is a volume-displacement pump sewn to the subclavian artery to provide partial circulatory support. The surgical configuration produces nonphysiologic blood pressure and bidirectional flow in the subclavian artery. Our objective was to identify effects of altered hemodynamics on arterial structure and function. Methods In calves (n = 23; 80-100 kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely, carotid blood pressure and flow were recorded to evaluate hemodynamic changes. After medium-term support (1-4 weeks), carotid artery was studied. Histologic and molecular assays evaluated architectural changes. Quantitative real-time polymerase chain reaction evaluated gene expression of matrix metalloproteinase (MMP)-2, MMP-9, and connective tissue growth factor. In vitro carotid arterial-ring studies evaluated physiologic responses. Results During Symphony support, carotid arterial pressure was 200/15 mm Hg. Antegrade flow increased significantly (P <.05) from 1.40 ± 0.32 to 4.29 ± 0.33 L/min. Flow during native cardiac diastole reversed completely from 0.25 ± 0.05 to -4.15 ± 0.38 L/min in carotid artery proximal to the anastomosis. After medium-term support, the carotid artery was significantly dilated with significantly thinner tunica media and thicker tunica adventitia than in control carotid arteries. MMP-9 gene expression decreased significantly, connective tissue growth factor gene expression increased significantly, and collagen, elastin, and total extracellular matrix increased significantly. Endothelial cells were significantly hypertrophied and produced significantly more von Willebrand factor. Endothelial apoptosis increased significantly. Platelet-endothelial interactions decreased significantly. Endothelial- independent contraction decreased significantly, whereas endothelial-dependent relaxation increased modestly. Conclusions Assisted circulation with a left ventricular assist device triggered arterial remodeling that allowed a peripheral artery to accommodate the altered hemodynamics of a novel partial-support pump. Further delineation of remodeling pathways may be of significance for the emerging field of partial circulatory support.

AB - Objectives Less invasive circulatory support devices have been developed that require anastomosis to a peripheral artery. The Symphony Heart Assist System (Abiomed, Inc, Danvers, Mass) is a volume-displacement pump sewn to the subclavian artery to provide partial circulatory support. The surgical configuration produces nonphysiologic blood pressure and bidirectional flow in the subclavian artery. Our objective was to identify effects of altered hemodynamics on arterial structure and function. Methods In calves (n = 23; 80-100 kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely, carotid blood pressure and flow were recorded to evaluate hemodynamic changes. After medium-term support (1-4 weeks), carotid artery was studied. Histologic and molecular assays evaluated architectural changes. Quantitative real-time polymerase chain reaction evaluated gene expression of matrix metalloproteinase (MMP)-2, MMP-9, and connective tissue growth factor. In vitro carotid arterial-ring studies evaluated physiologic responses. Results During Symphony support, carotid arterial pressure was 200/15 mm Hg. Antegrade flow increased significantly (P <.05) from 1.40 ± 0.32 to 4.29 ± 0.33 L/min. Flow during native cardiac diastole reversed completely from 0.25 ± 0.05 to -4.15 ± 0.38 L/min in carotid artery proximal to the anastomosis. After medium-term support, the carotid artery was significantly dilated with significantly thinner tunica media and thicker tunica adventitia than in control carotid arteries. MMP-9 gene expression decreased significantly, connective tissue growth factor gene expression increased significantly, and collagen, elastin, and total extracellular matrix increased significantly. Endothelial cells were significantly hypertrophied and produced significantly more von Willebrand factor. Endothelial apoptosis increased significantly. Platelet-endothelial interactions decreased significantly. Endothelial- independent contraction decreased significantly, whereas endothelial-dependent relaxation increased modestly. Conclusions Assisted circulation with a left ventricular assist device triggered arterial remodeling that allowed a peripheral artery to accommodate the altered hemodynamics of a novel partial-support pump. Further delineation of remodeling pathways may be of significance for the emerging field of partial circulatory support.

UR - http://www.scopus.com/inward/record.url?scp=84902547941&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902547941&partnerID=8YFLogxK

U2 - 10.1016/j.jtcvs.2013.10.027

DO - 10.1016/j.jtcvs.2013.10.027

M3 - Article

VL - 148

SP - 311

EP - 321

JO - Journal of Thoracic and Cardiovascular Surgery

JF - Journal of Thoracic and Cardiovascular Surgery

SN - 0022-5223

IS - 1

ER -