Protective Effect of Polyethylene Glycol against Prolonged Cold Ischemia and Reperfusion Injury: Study in the Isolated Perfused Rat Kidney
- 1Unité de Transplantation Expérimentale, Département de Génétique Animale, Institut National de Recherche Agronomique, Domaine du Magneraud, Surgères (M.C.), and 2Faculté de Médecine, Poitiers and Centre Hospitalier et Universitaire, Poitiers, France (T.H., D.M., J.-M.G., M.E.)
Abstract
The purpose of this study was to evaluate an intracellular solution with polyethylene glycol (PEG, molecular weight 20,000) as an impermeant, compared with University of Wisconsin (UW) and Euro-Collins (EC) solutions, after a 48-h cold storage (CS). The normothermic isolated perfused rat kidney (IPK) technique was used to assess renal function after CS. Five groups were studied: a control group (immediately reperfused, n = 10); one that received EC (n = 16); one that received UW (n = 16); and two that each received an intracellular (IC) solution, one with PEG (ICPEG, n= 16) and one without PEG (IC, n = 16). The perfusion flow rate was significantly greater in the PEG group and correlated with less significant cellular and interstitial edema and lower renal vascular resistance than in the IC, EC, and UW groups. Glomerular filtration rate was significantly higher in the PEG group during reperfusion than in the IC, EC, and UW groups. Proximal tubular functions were more efficient with PEG: fractional sodium reabsorption and total sodium reabsorption were significantly greater during reperfusion in the PEG group than in the IC, EC, and UW groups. Of greater interest is the protective effect of PEG on lipid peroxidation, which reflects ischemia/reperfusion damage. The second major effect is the dramatic ATP restoration during reperfusion, which outlines the preservation of oxidative phosphorylation after preservation by ICPEG. These results are supported by histological studies, particularly concerning brush border and mitochondrial preservation. Our results indicate that PEG is promising for cold ischemia and reperfusion injury protection.
Footnotes
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Send reprint requests to: Dr. Thierry Hauet, INRA, Laboratoire de Transplantation Experimentale, Domaine du Magneraud, BP 52, 17700 Surgeres, France. E-mail:hauet{at}magneraud.inra.fr
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This work was supported in part by the Ministère de la Recherche and the Conseil Régional Poitou Charente.
- Abbreviations:
- EC
- Euro-Collins solution
- ATN
- acute tubular necrosis
- CS
- cold storage
- FRNa+
- fractional sodium reabsorption
- GFR
- glomerular filtration rate
- IC
- intracellular solution without PEG
- ICPEG
- intracellular solution with PEG
- IPK
- isolated perfused rat kidney
- MDA
- malondialdehyde
- PEG
- polyethylene glycol
- pHi
- intracellular pH
- PFR
- perfusate flow rate
- PP
- perfusion pressure
- UW
- University of Wisconsin solution
- TNa+
- total sodium reabsorption
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- Received August 21, 2000.
- Accepted October 24, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
