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B M Stubenitsky

Publications and source records attributed to B M Stubenitsky.

23 records · Page 2Linked to original sources

University of Wisconsin solution is superior to histidine tryptophan ketoglutarate for preservation of ischemically damaged kidneys.

The current shortage of transplantable organs has renewed interest in kidneys obtained from non-heart-beating donors. Kidneys from these donors have suffered warm ischemia (WI). The effectiveness of two preservation solutions, i.e., the University of Wisconsin (UW) and the histidine tryptophan ketoglutarate (HTK) solutions, for preservation of kidneys that have been subjected to WI was tested in dogs. The left kidney was autotransplanted after 30 min of WI, and subsequent 24-hr cold storage (CS) in either UW (n = 6) or HTK (n = 6), with immediate contralateral nephrectomy. Surgical biopsies from the cortex were taken before WI, after 30 min of WI, after 24 hr of CS, and after 1 hr of reperfusion for electron microscopy and for analysis of energy metabolites. At 2 weeks after transplantation in the UW group, 4 out of 6 and, in the HTK group, 1 out of 6 dogs survived. As from day 2, serum creatinine was lower in the UW group as compared with the HTK group (P < 0.05). After 24 hr of CS, in the HTK group the luminal membranes of proximal tubular cells were partly denuded of microvilli. Moreover, the tubular lumen was filled with blebs and debris. In the UW group, the brush borders remained intact, although microvilli were swollen. Energy metabolites were analyzed with HPLC. Thirty minutes of WI resulted in a +/- 45% reduction of total adenine nucleotide (TAN) content. During CS, TAN levels further decreased in both groups; however, after 24 hr of CS, the levels of adenosine, inosine, hypoxanthine, and xanthine were significantly higher in the UW group as compared with the HTK group (P < 0.05, P < 0.01, P < 0.01, P < 0.01). At 1 hr of reperfusion, TAN levels were higher in the UW group as compared with the HTK group (4.66 +/- 0.16 vs. 4.02 +/- 0.28, P < 0.05). Our results show that UW is a superior solution compared with HTK in the preservation of ischemically damaged kidneys, demonstrating better survival, better recovery of kidney function, better protection against ischemia-induced ultrastructural damage, and better preservation of energy metabolism indicated by (a faster) regeneration of TAN levels after reperfusion.

Adenine Nucleotides↗

I: Negative effect of cold ischemia on initial renal function.

Correlation between post-transplant function and exposure to cold ischemia (CI) during preservation has been reported. We attempted to identify the effect of CI on renal function using exsanguinous metabolic support (EMS) technology, to eliminate effects of reperfusion complications. Small bovine kidneys were used to evaluate 4 vs. 24 hours of CI, after warm ischemic (WI) exposure of <15, 30 or 60 minutes. After CI, kidneys were warm perfused (30 degrees C to 32 degrees C) ex vivo using EMS technology. Restored renal metabolism and function were quantified by oxygen consumption, urine production, glomerular filtration rate (GFR), and hemodynamic characteristics. The results demonstrate a CI-associated lag phase in the restoration of metabolism, in which the longer cold-preserved kidneys exhibit a lower initial rate of oxygen consumption. However, after 3 hours of EMS perfusion there was no significant difference in the O2 consumed, urine flow, GFR, perfusion flow, or pressure between the kidneys stored for 4 or 24 hours. An initial reduction in metabolism after longer CI may influence the severity of actual reperfusion injury during transplantation. Therefore, these results provide preliminary evidence suggesting that an acellular warm temperature reperfusion ex vivo may enhance restoration of cellular metabolism and minimize damage from the cold seen upon actual reperfusion.

Animals↗

II: Ex vivo viability testing of kidneys after postmortem warm ischemia.

Future approaches to expand the organ donor pool with marginal and nonheartbeating donors, will be dependent upon prospective organ evaluation. Restoration of metabolism by preservation at warmer temperatures could potentially provide the window for such evaluation. Using a small bovine model, kidneys were subjected to either < 15, < 30 or < 60 minutes of warm ischemia (WI) followed by cold ischemia (CI) in ViaSpan. After WI and CI, kidneys were transitioned to a warm temperature perfusion (30 degrees C to 32 degrees C) using exsanguinous metabolic support (EMS) technology. Restored renal metabolism and function was assessed by oxygen consumption, glucose consumption, urine production, glomerular filtration rate, and hemodynamic characteristics. The results of this study suggest that it is feasible to distinguish viable from nonviable organs ex vivo by assessing renal metabolism and function during warm preservation using EMS technology.

Animals↗