TY - JOUR
T1 - Lipopolysaccharide Pretreatment Prevents Medullary Vascular Congestion following Renal Ischemia by Limiting Early Reperfusion of the Medullary Circulation
AU - McLarnon, Sarah R.
AU - Wilson, Katie
AU - Patel, Bansari
AU - Sun, Jingping
AU - Sartain, Christina L.
AU - Mejias, Christopher D.
AU - Musall, Jacqueline B.
AU - Sullivan, Jennifer C.
AU - Wei, Qingqing
AU - Chen, Jian Kang
AU - Hyndman, Kelly A.
AU - Marshall, Brendan
AU - Yang, Haichun
AU - Fogo, Agnes B.
AU - O’Connor, Paul M.
N1 - Copyright © 2022 by the American Society of Nephrology.
PY - 2022/4
Y1 - 2022/4
N2 - Background Vascular congestion of the renal medulla—trapped red blood cells in the medullary microvasculature—is a hallmark finding at autopsy in patients with ischemic acute tubular necrosis. Despite this, the pathogenesis of vascular congestion is not well defined. Methods In this study, to investigate the pathogenesis of vascular congestion and its role in promoting renal injury, we assessed renal vascular congestion and tubular injury after ischemia reperfusion in rats pretreated with low-dose LPS or saline (control). We used laser Doppler flowmetry to determine whether pretreatment with low-dose LPS prevented vascular congestion by altering renal hemodynamics during reperfusion. Results We found that vascular congestion originated during the ischemic period in the renal venous circulation. In control animals, the return of blood flow was followed by the development of congestion in the capillary plexus of the outer medulla and severe tubular injury early in reperfusion. Laser Doppler flowmetry indicated that blood flow returned rapidly to the medulla, several minutes before recovery of full cortical perfusion. In contrast, LPS pretreatment prevented both the formation of medullary congestion and its associated tubular injury. Laser Doppler flowmetry in LPS-pretreated rats suggested that limiting early reperfusion of the medulla facilitated this protective effect, because it allowed cortical perfusion to recover and clear congestion from the large cortical veins, which also drain the medulla. Conclusions Blockage of the renal venous vessels and a mismatch in the timing of cortical and medullary reperfusion results in congestion of the outer medulla’s capillary plexus and promotes early tubular injury after renal ischemia. These findings indicate that hemodynamics during reperfusion contribute to the renal medulla’s susceptibility to ischemic injury.
AB - Background Vascular congestion of the renal medulla—trapped red blood cells in the medullary microvasculature—is a hallmark finding at autopsy in patients with ischemic acute tubular necrosis. Despite this, the pathogenesis of vascular congestion is not well defined. Methods In this study, to investigate the pathogenesis of vascular congestion and its role in promoting renal injury, we assessed renal vascular congestion and tubular injury after ischemia reperfusion in rats pretreated with low-dose LPS or saline (control). We used laser Doppler flowmetry to determine whether pretreatment with low-dose LPS prevented vascular congestion by altering renal hemodynamics during reperfusion. Results We found that vascular congestion originated during the ischemic period in the renal venous circulation. In control animals, the return of blood flow was followed by the development of congestion in the capillary plexus of the outer medulla and severe tubular injury early in reperfusion. Laser Doppler flowmetry indicated that blood flow returned rapidly to the medulla, several minutes before recovery of full cortical perfusion. In contrast, LPS pretreatment prevented both the formation of medullary congestion and its associated tubular injury. Laser Doppler flowmetry in LPS-pretreated rats suggested that limiting early reperfusion of the medulla facilitated this protective effect, because it allowed cortical perfusion to recover and clear congestion from the large cortical veins, which also drain the medulla. Conclusions Blockage of the renal venous vessels and a mismatch in the timing of cortical and medullary reperfusion results in congestion of the outer medulla’s capillary plexus and promotes early tubular injury after renal ischemia. These findings indicate that hemodynamics during reperfusion contribute to the renal medulla’s susceptibility to ischemic injury.
KW - Acute Kidney Injury/etiology
KW - Animals
KW - Humans
KW - Ischemia/complications
KW - Kidney Medulla/blood supply
KW - Kidney/pathology
KW - Lipopolysaccharides
KW - Rats
KW - Renal Circulation/physiology
KW - Reperfusion Injury/complications
KW - Reperfusion/adverse effects
UR - http://www.scopus.com/inward/record.url?scp=85128001015&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85128001015&partnerID=8YFLogxK
U2 - 10.1681/ASN.2021081089
DO - 10.1681/ASN.2021081089
M3 - Article
C2 - 35115326
AN - SCOPUS:85128001015
SN - 1046-6673
VL - 33
SP - 769
EP - 785
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 4
ER -