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Right arrow Cardiac - physiology
Right arrow Mechanical Circulatory Assistance

J Thorac Cardiovasc Surg 2008;136:150-158
© 2008 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Reduced Pulsatility Induces Periarteritis in Kidney: Role of the Local Renin–Angiotensin System

Chiyo Ootaki, MDa, Michifumi Yamashita, MD, PhDb, Yoshio Ootaki, MD, PhDa, Keiji Kamohara, MDa, Stephan Weber, Dipl Inga, Ryan S. Klatte, BSBMEa, William A. Smith, DEng, PEa, Alex L. Massiello, MEBMEa, Steven N. Emancipator, MDb, Leonard A.R. Golding, MDa, Kiyotaka Fukamachi, MD, PhDa,*

a Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
b Department of Pathology, Case Western Reserve University, Cleveland, Ohio

Received for publication July 9, 2007; revisions received November 11, 2007; accepted for publication December 6, 2007.

* Address for reprints: Kiyotaka Fukamachi, MD, PhD, Department of Biomedical Engineering/ND20, The Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195. (Email: fukamak{at}ccf.org).

Objective: The need for pulsatility in the circulation during long-term mechanical support has been a subject of debate. We compared histologic changes in calf renal arteries subjected to various degrees of pulsatile circulation in vivo. We addressed the hypothesis that the local renin–angiotensin system may be implicated in these histologic changes.

Methods and Results: Sixteen calves were implanted with devices giving differing degrees of pulsatile circulation: 6 had a continuous flow left ventricular assist device (LVAD); 6 had a continuous flow right ventricular assist device (RVAD); and 4 had a pulsatile total artificial heart (TAH). Six other calves were histologic and immunohistochemical controls. In the LVAD group, the pulsatility index was significantly lower (0.28 ± 0.07 LVAD vs 0.56 ± 0.08 RVAD, vs 0.53 ± 0.10 TAH; P < 0.01), and we observed severe periarteritis in all cases in the LVAD group. The number of angiotensin II type 1 receptor–positive cells and angiotensin converting enzyme–positive cells in periarterial areas was significantly higher in the LVAD group (angiotensin II type 1 receptor: 350 ± 139 LVAD vs 8 ± 6 RVAD, vs 3 ± 2 TAH, vs 3 ± 2 control; P < .001; angiotensin-converting enzyme: 325 ± 59 LVAD vs 6 ± 4 RVAD, vs 6 ± 5 TAH, vs 3 ± 1 control; P < .001).

Conclusions: The reduced pulsatility produced by a continuous flow LVAD implantation induced severe periarteritis in the kidneys. The local renin–angiotensin system was up-regulated in the inflammatory cells only in the continuous flow LVAD group.

Abbreviations and Acronyms ACE = angiotensin-converting enzyme; Ang II = angiotensin II; AT1R = angiotensin II type 1 receptor; eNOS = endothelial nitric oxide synthase; LVAD = left ventricular assist device; pa = periarterial areas; RAS = renin–angiotensin system; RVAD = right ventricular assist device; TAH = total artificial heart






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