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. 1972 Jan;51(1):118–126. doi: 10.1172/JCI106781

The Role of Cell Swelling in Ischemic Renal Damage and the Protective Effect of Hypertonic Solute

Jorge Flores 1, Donald R DiBona 1, Clyde H Beck 1, Alexander Leaf 1
PMCID: PMC332936  PMID: 5007042

Abstract

The failure of blood flow to return to the kidney following a transient period of ischemia has long been recognized. The cause of this “no-reflow” has been investigated in the rat after a transient period of total obstruction of the renal arteries. The vascular pattern of the kidneys as visualized with silicone rubber injection shows a diffuse patchy ischemia throughout the kidney, which persists after release of the obstructed renal artery. Electron microscopic studies of ischemic kidneys showed that all cellular elements were swollen and limiting the available vascular space. Functional studies revealed an increase in plasma urea nitrogen and creatinine after 1 hr or longer ischemic periods. The ischemia, cell swelling, “no-reflow,” and subsequent renal dysfunction occurring after obstruction to the renal arteries were corrected by the administration of hypertonic mannitol, but were unaffected by an equivalent expansion of the extracellular fluid volume either with isotonic saline or isotonic mannitol, showing that the osmotic effect was primary. The hypothesis is presented that ischemic swelling of cells may occlude small blood vessels so that recirculation does not resume even after the initial cause of the ischemia is no longer present; solutes which do not penetrate cell membranes are able to shrink swollen cells, increase the available vascular space and thus permit reflow of blood to the ischemic organ.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames A., 3rd, Wright R. L., Kowada M., Thurston J. M., Majno G. Cerebral ischemia. II. The no-reflow phenomenon. Am J Pathol. 1968 Feb;52(2):437–453. [PMC free article] [PubMed] [Google Scholar]
  2. BARRY K. G., COHEN A., KNOCHEL J. P., WHELAN T. J., Jr, BEISEL W. R., VARGAS C. A., LEBLANC P. C., Jr Mannitol infusion. II. The prevention of acute functional renal failure during resection of an aneurysm of the abdominal aorta. N Engl J Med. 1961 May 11;264:967–971. doi: 10.1056/NEJM196105112641902. [DOI] [PubMed] [Google Scholar]
  3. BLOCK M. A., WAKIM K. G., MANN F. C. Certain features of the vascular beds of the corticomedullary and medullary regions of the kidney. AMA Arch Pathol. 1952 May;53(5):437–443. [PubMed] [Google Scholar]
  4. Cantu R. C., Ames A., 3rd Experimental prevention of cerebral vasculature obstruction produced by ischemia. J Neurosurg. 1969 Jan;30(1):50–54. doi: 10.3171/jns.1969.30.1.0050. [DOI] [PubMed] [Google Scholar]
  5. Chiang J., Kowada M., Ames A., 3rd, Wright R. L., Majno G. Cerebral ischemia. III. Vascular changes. Am J Pathol. 1968 Feb;52(2):455–476. [PMC free article] [PubMed] [Google Scholar]
  6. GOLDBERG A. H., LILIENFIELD L. S. EFFECTS OF HYPERTONIC MANNITOL ON RENAL VASCULAR RESISTANCE. Proc Soc Exp Biol Med. 1965 Jul;119:635–642. doi: 10.3181/00379727-119-30259. [DOI] [PubMed] [Google Scholar]
  7. Gazitùa S., Scott J. B., Swindall B., Haddy F. J. Resistance responses to local changes in plasma osmolality in three vascular beds. Am J Physiol. 1971 Feb;220(2):384–391. doi: 10.1152/ajplegacy.1971.220.2.384. [DOI] [PubMed] [Google Scholar]
  8. Gazitúa S., Scott J. B., Chou C. C., Haddy F. J. Effect of osmolarity on canine renal vascular resistance. Am J Physiol. 1969 Oct;217(4):1216–1223. doi: 10.1152/ajplegacy.1969.217.4.1216. [DOI] [PubMed] [Google Scholar]
  9. HARVEY R. B. Vascular resistance changes produced by hyperosmotic solutions. Am J Physiol. 1960 Jul;199:31–34. doi: 10.1152/ajplegacy.1960.199.1.31. [DOI] [PubMed] [Google Scholar]
  10. Kowada M., Ames A., 3rd, Majno G., Wright R. L. Cerebral ischemia. I. An improved experimental method for study; cardiovascular effects and demonstration of an early vascular lesion in the rabbit. J Neurosurg. 1968 Feb;28(2):150–157. doi: 10.3171/jns.1968.28.2.0150. [DOI] [PubMed] [Google Scholar]
  11. LEAF A. Maintenance of concentration gradients and regulation of cell volume. Ann N Y Acad Sci. 1959 Feb 6;72(12):396–404. doi: 10.1111/j.1749-6632.1959.tb44168.x. [DOI] [PubMed] [Google Scholar]
  12. LEAF A. On the mechanism of fluid exchange of tissues in vitro. Biochem J. 1956 Feb;62(2):241–248. doi: 10.1042/bj0620241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lauson H. D., Bradley S. E., Cournand A., Andrews V. V. THE RENAL CIRCULATION IN SHOCK. J Clin Invest. 1944 May;23(3):381–402. doi: 10.1172/JCI101506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Leaf A. Regulation of intracellular fluid volume and disease. Am J Med. 1970 Sep;49(3):291–295. doi: 10.1016/s0002-9343(70)80019-5. [DOI] [PubMed] [Google Scholar]
  15. MARSH W. H., FINGERHUT B., MILLER H. AUTOMATED AND MANUAL DIRECT METHODS FOR THE DETERMINATION OF BLOOD UREA. Clin Chem. 1965 Jun;11:624–627. [PubMed] [Google Scholar]
  16. MUDGE G. H. Electrolyte and water metabolism of rabbit kidney slices; effect of metabolic inhibitors. Am J Physiol. 1951 Oct;167(1):206–223. doi: 10.1152/ajplegacy.1951.167.1.206. [DOI] [PubMed] [Google Scholar]
  17. SELKURT E. E., ELPERS M. J. Influence of hemorrhagic shock on renal hemodynamics and osmolar clearance in the dog. Am J Physiol. 1963 Jul;205:147–152. doi: 10.1152/ajplegacy.1963.205.1.147. [DOI] [PubMed] [Google Scholar]
  18. SHEEHAN H. L., DAVIS J. C. Renal ischaemia with failed reflow. J Pathol Bacteriol. 1959 Jul;78:105–120. [PubMed] [Google Scholar]
  19. Stern J. R., Eggleston L. V., Hems R., Krebs H. A. Accumulation of glutamic acid in isolated brain tissue. Biochem J. 1949;44(4):410–418. [PMC free article] [PubMed] [Google Scholar]
  20. WILSON T. H. Ionic permeability and osmotic swelling of cells. Science. 1954 Jul 16;120(3107):104–105. doi: 10.1126/science.120.3107.104. [DOI] [PubMed] [Google Scholar]
  21. Wendling M. G., Eckstein J. W., Abboud F. M. Effects of mannitol on the renal circulation. J Lab Clin Med. 1969 Oct;74(4):541–547. [PubMed] [Google Scholar]

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