title: Hydrodynamic Isotonic Fluid Delivery Ameliorates Moderate-to-Severe Ischemia-Reperfusion Injury in Rat Kidneys.
abstract: Highly aerobic organs like the kidney are innately susceptible to ischemia-reperfusion (I/R) injury, which can originate from sources including myocardial infarction, renal trauma, and transplant. Therapy is mainly supportive and depends on the cause(s) of damage. In the absence of hypervolemia, intravenous fluid delivery is frequently the first course of treatment but does not reverse established AKI. Evidence suggests that disrupting leukocyte adhesion may prevent the impairment of renal microvascular perfusion and the heightened inflammatory response that exacerbate ischemic renal injury. We investigated the therapeutic potential of hydrodynamic isotonic fluid delivery (HIFD) to the left renal vein 24 hours after inducing moderate-to-severe unilateral IRI in rats. HIFD significantly increased hydrostatic pressure within the renal vein. When conducted after established AKI, 24 hours after I/R injury, HIFD produced substantial and statistically significant decreases in serum creatinine levels compared with levels in animals given an equivalent volume of salineviaperipheral infusion (P<0.05). Intravital confocal microscopy performed immediately after HIFD showed improved microvascular perfusion. Notably, HIFD also resulted in immediate enhancement of parenchymal labeling with the fluorescent dye Hoechst 33342. HIFD also associated with a significant reduction in the accumulation of renal leukocytes, including proinflammatory T cells. Additionally, HIFD significantly reduced peritubular capillary erythrocyte congestion and improved histologic scores of tubular injury 4 days after IRI. Taken together, these results indicate that HIFD performed after establishment of AKI rapidly restores microvascular perfusion and small molecule accessibility, with improvement in overall renal function.
authors.affiliation: Department of Cellular and Integrative Physiology.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Collett
authors.affiliation: Department of Craniofacial Biology, University of Colorado Denver, Anschutz Campus, Aurora, Colorado.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Corridon
authors.affiliation: Department of Cellular and Integrative Physiology.
authors.forename: Purvi
authors.initials: P
authors.lastname: Mehrotra
authors.affiliation: Department of Biology, Indiana University-Purdue University, Indianapolis, Indiana; and.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Kolb
authors.affiliation: Division of Nephrology, Department of Medicine.
authors.forename: George J
authors.initials: GJ
authors.lastname: Rhodes
authors.affiliation: Department of Anatomy and Cell Biology, and.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Miller
authors.affiliation: Division of Nephrology, Department of Medicine.|Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
authors.affiliation: Department of Anatomy and Cell Biology, and.
authors.forename: Janice G
authors.initials: JG
authors.lastname: Pennington
authors.affiliation: Division of Nephrology, Department of Medicine.
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Sandoval
authors.affiliation: Department of Biology, Indiana University-Purdue University, Indianapolis, Indiana; and.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Atkinson
authors.affiliation: Division of Nephrology, Department of Medicine.
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Campos-Bilderback
authors.affiliation: Department of Cellular and Integrative Physiology.|Division of Nephrology, Department of Medicine.
authors.forename: David P
authors.initials: DP
authors.lastname: Basile
authors.affiliation: Division of Nephrology, Department of Medicine, rbacalla@iu.edu.|Department of Medicine, Division of Nephrology, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Bacallao
mesh_terms: D000818:Animals; D005440:Fluid Therapy / Q000379:methods*; D057446:Hydrodynamics; D007552:Isotonic Solutions / Q000008:administration & dosage*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000628:therapy*; D012720:Severity of Illness Index
chemical_list: D007552:Isotonic Solutions
keywords: acute renal failure; peritubular capillaries; retrograde saline delivery