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 - 2014/7
Y1 - 2014/7
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.
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U2 - 10.1016/j.jtcvs.2013.10.027
DO - 10.1016/j.jtcvs.2013.10.027
M3 - Article
C2 - 24332190
AN - SCOPUS:84902547941
SN - 0022-5223
VL - 148
SP - 311
EP - 321
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 1
ER -