Original article| Volume 108, ISSUE 1, P53-59, July 1986

Alterations of intravascular volume: Influence on renal susceptibility to ischemic injury

  • R.A. Zager
    Reprint requests: R. A. Zager, M.D., Department of Medicine, ZA-67, Harborview Medical Center, 325 Ninth Ave., Seattle, WA 98104.
    From the Department of Medicine, University of Washington Seattle, Washington, U.S.A.
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      The purpose of this investigation was to test whether alterations of intravascular volume change renal susceptibility to ischemic injury. Acute volume depletion (2% body weight; by furosemide injection or by hemorrhage) or volume expansion (10% body weight; by saline infusion) was induced in Sprague-Dawley rats. The effects of these interventions on renal blood flow (RBF), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), and renal adenine nucleotide content were assessed by comparison with values observed in euvolemic control rats. Volume-depleted, volume-expanded, and euvolemic control rats were also subjected to 25 minutes of bilateral renal artery occlusion (RAO). The severity of ischemic injury was assessed 24 hours later (by determination of GFR, blood urea nitrogen, creatinine, and histology). Before RAO, the volume-depleted rats had significant reductions in GFR (33%), MAP (20% to 45%), and RBF (52% to 72%), but renal adenosine triphosphate (ATP) content was totally preserved. Both groups of volume-depleted rats had normal susceptibility to RAO, compared with the euvolemic controls. Before RAO, volume expansion had no significant effect on GFR, MAP, or RBF, but it decreased renal ATP content by 21%. In addition, volume expansion significantly exacerbated the ATP depletion that occurred both during and after RAO. Nevertheless, the volume-expanded rats were almost totally protected against ischemia. It is concluded that the kidney can tolerate severe volume depletion without apparent deterioration in tubular cell energetics or a change in renal susceptibility to superimposed ischemic injury. Acute volume expansion can protect against ischemic injury, despite lowering renal ATP content.


      ADP (adenosine diphosphate), AMP (adenosine monophosphate), ATP (adenosine triphosphate), BUN (blood urea nitrogen), Cioth (clearance of iothalamate sodium I 125), D5W (5% dextrose in water), GFR (glomerular filtration rate), MAP (mean arterial pressure), RAO (renal artery occlusion), RBF (renal blood flow), TAN (total adenine nucleotides)
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