Reduced Pulsatility Induces Periarteritis in Kidney: Role of the Local Renin–Angiotensin System Chiyo Ootaki, MD, Michifumi Yamashita, MD, PhD, Yoshio.

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Reduced Pulsatility Induces Periarteritis in Kidney: Role of the Local Renin–Angiotensin System Chiyo Ootaki, MD, Michifumi Yamashita, MD, PhD, Yoshio Ootaki, MD, PhD, Keiji Kamohara, MD, Stephan Weber, Dipl Ing, Ryan S. Klatte, BSBME, William A. Smith, DEng, PE, Alex L. Massiello, MEBME, Steven N. Emancipator, MD, Leonard A.R. Golding, MD, Kiyotaka Fukamachi, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 136, Issue 1, Pages 150-158 (July 2008) DOI: 10.1016/j.jtcvs.2007.12.023 Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Hematoxylin and eosin staining of renal arteries in the corticomedullary junction area (magnification ×40). A, Calf with continuous flow left ventricular assist device (LVAD). Extensive hyperplasia of the intima, media, and adventitia of the arteries is evident, along with mononuclear inflammatory cell infiltrates. B, Calf with continuous flow right ventricular assist device (RVAD). C, Calf with pulsatile total artificial heart (TAH). D, Control normal calf. There are no morphologic changes, suggesting that periarteritis exists in the other groups (B, C, and D). The Journal of Thoracic and Cardiovascular Surgery 2008 136, 150-158DOI: (10.1016/j.jtcvs.2007.12.023) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Hematoxylin and eosin staining of kidney in calf with continuous flow LVAD. A, The corticomedullary junction area (magnification ×40). The medium-sized arteries, such as the arcuate artery and interlobular arteries, showed wall thickening and the presence of inflammatory cells. B, The arcuate artery: expanded view of area encircled with yellow line in A (magnification ×100), showing abundant mononuclear cells accumulating in the periarterial area. The artery structure is relatively conserved and has few inflammatory cells in the vascular wall. There is extensive hyperplasia of the smooth muscle layer of the media of the vessels. For abbreviations, see Figure 1. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 150-158DOI: (10.1016/j.jtcvs.2007.12.023) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Histopathology and immunohistochemistry of serial sections of renal arteries from a calf with a continuous flow LVAD (magnification ×200). Hematoxylin and eosin staining of the interlobular artery (A) and cortical interstitial area (B). Immunohistochemical staining for angiotensin II type 1 receptor (AT1R) (C and D) and angiotensin-converting enzyme (ACE) (E and F). AT1R is observed in the endothelial cells and inflammatory cells that infiltrated the periarterial area (C) and cortical interstitial area (D). ACE is observed in renal tubuli, endothelial cells, the smooth muscle layer, and in inflammatory cells that had infiltrated the periarterial area (E) and cortical interstitial area (F). For abbreviations, see Figure 1. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 150-158DOI: (10.1016/j.jtcvs.2007.12.023) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 The number of inflammatory cells in periarterial areas from the continuous flow LVAD group was significantly higher than in the other groups. †P < .01. For abbreviations, see Figure 1. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 150-158DOI: (10.1016/j.jtcvs.2007.12.023) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 The number of AT1R-positive cells in periarterial areas from the continuous flow LVAD group was significantly higher than in the other groups. ∗P < .001. For abbreviations, see Figure 1. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 150-158DOI: (10.1016/j.jtcvs.2007.12.023) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 The number of ACE-positive cells in periarterial areas from the continuous flow LVAD group was significantly higher than in the other groups. ∗P < .001. For abbreviations, see Figure 1. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 150-158DOI: (10.1016/j.jtcvs.2007.12.023) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

Figure 7 Immunohistochemical staining for endothelial nitric oxide synthase (eNOS) (magnification ×200). A, Calf with continuous flow LVAD. The immunohistochemical study showed a prominent expression of eNOS in the endothelium of renal arteries that appeared more prominent in LVAD group than other group. B, Calf with continuous flow RVAD. C, Calf with pulsatile-TAH. D, Control normal calf. For abbreviations, see Figure 1. The Journal of Thoracic and Cardiovascular Surgery 2008 136, 150-158DOI: (10.1016/j.jtcvs.2007.12.023) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions