Protective effect of polyethylene glycol against prolonged cold ischemia and reperfusion injury: study in the isolated perfused rat kidney.

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.

Trimetazidine reverses deleterious effects of ischemia-reperfusion in the isolated perfused pig kidney model.

BACKGROUND: Delayed graft function has remained an important complication after renal transplantation. METHODS: The purpose of this study was to evaluate Euro-Collins (EC) plus trimetazidine (TMZ) in comparison with standard EC solution after 24- or 48-hour cold storage. The normothermic isolated perfused pig kidney technique combined with proton nuclear magnetic spectroscopy was used. RESULTS: The study verified that TMZ plus EC had a beneficial preservation effect over EC in terms of better perfusate flow rate at both 24 and 48 h (p < 0.01 and p < 0.001, respectively). In addition, TMZ also was beneficial in terms of increased glomerular filtration rate, better proximal tubular functions, and less tubular injury markers. Lipid peroxidation, evaluated by malondialdehyde renal tissue levels, was decreased in kidney homogenates preserved with TMZ, particularly after 48-hour cold storage. Citrate excretion which reflects a better intracellular pH regulation was detected in urine from kidneys preserved with TMZ. Histological data paralleled findings of the above when comparing cellular injury factors such as vacuolization, necrosis, tubular structure, and interstitial edema. CONCLUSION: These results indicate that, under the conditions of our experiments, the addition of TMZ to EC solution increased the preservation quality of kidneys particularly after prolonged cold ischemia.

Lipid peroxidation after cold storage and normothermic reperfusion: the effect of trimetazidine.

Ischemia reperfusion injury is still a leading cause of early graft dysfunction after transplantation. Trimetazidine (TMZ) has been postulated to be protective against renal damage from oxygen free radicals. The aim of this study was to assess the effect TMZ during cold storage (CS) and normothermic reperfusion in an isolated perfused pig kidney model. Three groups were studied: control group, immediately perfused (G0), 48 h CS in Euro-Collins solution (G1), and 48 h CS in Euro-Collins solution plus TMZ (G2). Glomerular filtration rate (GFR) and fractional sodium reabsorption (FRNa+) were calculated during reperfusion from urine and perfusate samples. Lipid peroxidation was determined by the renal tissue level of Schiff bases (SB) and malondialdehyde (MDA) after reperfusion. A histological evaluation was performed after reperfusion. Renal function was significantly improved and lipid peroxidation reduced after preservation in Euro-Collins solution plus TMZ. Functional data were closely related to histological damage. In conclusion, TMZ is a useful protective agent against renal damage induced by CS.

Trimetazidine prevents renal injury in the isolated perfused pig kidney exposed to prolonged cold ischemia.

BACKGROUND: Ischemia caused by cold storage (CS) and reperfusion of the kidney is often responsible for delayed graft function after transplantation. Significant attention has been focused on the cascade of events involved in ischemia-reperfusion injury, with the objective of identifying drugs to ameliorate the functional damage that occurs. METHODS: The purpose of this study was to evaluate the renal function of isolated perfused pig kidneys after 48 hr of CS with Euro-Collins (EC) solution plus trimetazidine (EC+TMZ), standard EC solution, or University of Wisconsin (UW) solution. Normothermic isolated perfused pig kidneys were randomized into five experimental groups: (A) control group (cold flush with cold heparinized saline and immediately reperfused; n=6); (B) cold flush with cold heparinized saline with TMZ (10(-6) M), n=6; (C) 48 hr of CS with EC and reperfusion (n=8); (D) 48 hr of CS with EC+TMZ alone and reperfusion (n=8); (E) 48 hr of CS with UW and reperfusion (n=8). Proton nuclear magnetic resonance spectroscopy and biochemical studies were performed for the functional evaluation during reperfusion. Lipid peroxidation was also determined. Histological examination (optical and electron microscopy) was performed after CS and reperfusion. RESULTS: Using TMZ, the renal perfusate flow rate as well as the glomerular filtration rate and proximal tubular function were significantly improved. This improvement of renal function during reperfusion was correlated with a less significant cellular and interstitial edema. In addition, tubular injury markers were significantly lower in the group preserved with EC+TMZ, and TMZ reduced lipid peroxidation dramatically during reperfusion. CONCLUSIONS: The addition of TMZ to the EC solution increased the preservation quality and renal tubular function, and gave protection from reperfusion injury better than EC alone or UW. These results strongly suggest that TMZ has a cytoprotective effect and may therefore be useful for kidney preservation.

Evaluation of normothermic ischemia and simple cold preservation injury in pig kidney by proton nuclear magnetic resonance spectroscopy.

The isolated perfused pig kidney (IPK) model was used to mimic the non-heart-beating donor situation. This model was performed to assess initial renal functions after normothermic ischemia, cold flush, and 24 hr cold-storage preservation (CSP) with Euro-Collins and to determine normothermic ischemia and reperfusion impairment by biochemical, histological, and proton nuclear magnetic resonance (NMR) spectroscopy analysis. Twenty-four pig kidneys were used. There were three experimental groups: Group 1 (G1), control kidneys flushed with cold heparinized saline and immediately perfused; Group 2 (G2), cold flush followed by 24 hr CSP and reperfusion; and Group 3 (G3), 30 min of normothermic ischemia followed by cold flush and 24 hr CSP and reperfusion. Kidneys were perfused for 2 hr at 37.5 degrees C for functional evaluation. Perfusate flow rate is significantly different for G3 (P < 0.01). Glomerular filtration rate is less in G3 (P < 0.05). Fractional reabsorptions of sodium (FRNa+) and glucose (Glc) excretion in urine are different in G3 (P < 0.01 and P < 0.05, respectively). Amino acid excretion in NMR spectroscopy was higher in G3 (P < 0.05). Elevated levels of trimethylamine-N-oxide (TMAO) and lactate (Lac) were detected by proton NMR spectroscopy in G2 and particularly G3. A peak is present in G3 and related with poor glomerular and tubular functions and worse histological data. Malondialdehyde tissue level was higher in G3. This study shows that the IPK with proton NMR spectroscopy may be a useful method in the evaluation of kidneys after cold ischemia and transplantation. This model might be suitable for a variety of experimental protocols, particularly to improve functional performance after ischemia and reperfusion.

Evaluation of injury preservation in pig kidney cold storage by proton nuclear magnetic resonance spectroscopy of urine.

The isolated perfused kidney (IPK) model from pig was used to assess initial renal functions after cold flush and a 24- and 48-hour cold storage preservation (CSP) with Euro-Collins (EC) and to determine ischemia reperfusion (IR) impairment by biochemical, histological and proton nuclear magnetic resonance (NMR) spectroscopy of urine analysis. Eighteen pig kidneys were used. There were three experimental groups: Group 1--control kidneys flushed with cold heparinized saline, Group 2--cold flush followed by 24-hour CSP and reperfusion, Group 3--cold flush followed by 48-hour CSP and reperfusion. Kidneys were perfused for 2-hour at 37.5C for the determination of exogenous creatinine clearance (CCr), perfusion flow rate (PFR) and tubular function. Functional parameters and histological data are very poor after prolonged cold ischemia. Levels of tubular injury markers determined by proton NMR spectroscopy analysis were significantly higher with a longer ischemic time correlating well with the increased degree of renal functional and anatomic impairment. A new peak detected only in the 48-hour ischemic group was identified. In this model, proton NMR spectroscopy may be a useful technique in the evaluation of both new preservation solutions or methods.

[Technique for protecting the liver graft less tolerant than the small bowel to heat-induced ischemia in experimental liver + small bowel transplantation in swine]. / Technique visant à protéger le greffon hépatique moins tolérant à l'ischémie chaude que le grêle dans une transplantation expérimentale foie + grêle chez le porc.

Multivisceral and orthotopic liver/small bowel transplantations have been performed to treat patients with intestinal failure associated with liver failure induced by parenteral nutrition. The aim of this experimental study was to determine the experimental liver-small bowel harvesting and transplantation technique that achieves the best compromise between liver and intestine ischemia times in pigs. Initial portal revascularization of the liver which reduces the hepatic warm ischemia time after cold ischemia preparation of the graft immersed in lactated ringer's solution at 4 degrees C, reduce the risk of primary non function of the graft.

[Ectopic ureteral orifice into the seminal duct with homolateral renal agenesis: contribution of ultrasonography]. / Abouchement ectopique de l'uretère dans le tractus séminal avec agénésie rénale homolatérale: apport de l'échographie.

Based on an incidental case of ectopic ureteric orifice in the seminal tract associated with homolateral renal agenesis, the authors demonstrate the value of ultrasonography, particular transrectal, both for diagnosis and follow-up. Digital rectal examination is the key to the diagnosis, combined with ultrasonography and urography. The indications for surgery depend on the clinical symptoms and signs.