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Biomedical subjects

B M Stubenitsky

Publications and source records attributed to B M Stubenitsky.

At least 19 recordsLinked to original sources
PubMed2001

Pretransplantation prognostic testing on damaged kidneys during ex vivo warm perfusion.

BACKGROUND: Further expansion of the donor pool with ischemically damaged kidneys will be predicated on the ability to develop prognostic testing. Using a well-established canine autotransplantation injury model, we assessed whether actual restoration of renal metabolism by ex vivo warm perfusion could be used to predict the status of an organ before transplantation. METHODS: Kidneys were subjected to 30 min of warm ischemia followed by 24 hr of static storage in ViaSpan at 4 degrees C. After warm ischemia and static storage the kidneys were transitioned to 3 hr of warm perfusion using Exsanguinous Metabolic Support technology. During this period, parameters indicative of renal metabolism and vascular function were used to predict outcomes prospectively. Parameters included measures of oxidative metabolism, perfusion characteristics, and vascular condition. A Viability Score (VS) was calculated as the sum of the three parameters mentioned above. Results were grouped by a VS>2 and a VS<2. RESULTS: A clear association between the severity and duration of graft dysfunction and the VS was observed. Organs with a VS>2 had a significantly milder period of acute tubular necrosis, with both a less severe rise in serum creatinine (mean of 4.4 vs. 11 mg/dl) and a shorter recovery period (mean of 8 vs. 18 days) than those with a VS<2. CONCLUSIONS: Results indicate the possibility of utilizing warm perfusion to evaluate kidneys before transplantation. The VS developed demonstrated efficacy in classifying the severity of the acute tubular necrosis and the occurrence of primary nonfunction, offering a sensitive assay for prospective organ testing.

Animals↗
PubMed2001

Deletrious effect of prolonged cold ischemia on renal function.

The detrimental effect of prolonged cold ischemia (CI) on posttransplant renal function has long been recognized. However, the cellular consequences of CI have not been clearly defined. This study describes a model for the identification of CI-induced injury by evaluating ex-vivo renal metabolism and function prior to reperfusion. Small bovine kidneys were cold stored in Viaspan for 24-, 48-, 72-, and 96 h. Kidneys were then warm perfused (32 degrees C) using Exsangiunous Metabolic Support (EMS) technology and evaluated for oxidative metabolism, vascular dynamics and function. Oxygen consumption, vascular resistance, and diuresis were stable in kidneys with CI up to 48 h. After 72- and 96 h of CI, vascular resistance was increased while oxygen consumption and diuresis were reduced (P < 0.05). Glomerular filtration rate was diminished at CI greater than 24 h (P < 0.05). Results show that function was compromised with CI greater than 24 h and preceded the loss of cell viability following 48 h of CI.

Animals↗
PubMed2001

Hypothermia--a limiting factor in using warm ischemically damaged kidneys.

A study was performed to determine the limiting factors to expanding the donor pool with warm ischemically (WI) damaged kidneys. Canine kidneys were damaged by 30 min of WI, and then either cold stored (CS) in ViaSpan (4 degrees C) for 18 h, or warm perfused with exsanguineous metabolic support (EMS) technology (32 degrees C) for 18h, or subjected to combinations of both techniques. The kidneys were autotransplanted with contralateral nephrectomy. In kidneys with WI and CS alone, the mean peak serum creatinine value was 6.3mg/dL and took 14 days to normalize. In contrast, kidneys where renal metabolism was resuscitated ex vivo during 18 h of warm perfusion demonstrated mild elevations in the serum chemistries (2.6mg/dL). The damage in kidneys CS for 18h was ameliorated with 3 h of subsequent warm perfusion and eliminated by 18 h of warm perfusion. In contrast, reversing the order with CS following WI and 18h of warm perfusion resulted in a time-dependent increase in damage. These results identify hypothermia as a major limiting factor to expanding indications for kidney donation. While hypothermia represents the foundation of preservation in the heart-beating donor, its use in WI damaged organs appears to represent a limiting factor.

Animals↗
PubMed2000

Exsanguinous metabolic support perfusion--a new strategy to improve graft function after kidney transplantation.

BACKGROUND: The compounding damage of warm ischemia (WI) followed by cold preservation is a major barrier in renal transplantation. Although the relative effect of WI is not yet well understood, therapeutic strategies have mostly focused on minimizing the pathology seen upon reperfusion from the cold. Our study was designed to examine the effect of restoration of renal metabolism by warm perfusion on graft survival and to investigate the compounding damage of WI. METHODS: Using a known critical canine autotransplantation model (1), kidneys were exposed to 30 min WI followed by 24 hr cold storage in Viaspan. They were then either reimplanted directly or first transitioned to 3 hr of warm perfusion with an acellular perfusate before reimplantation. Contralateral kidneys were subjected to 0, 30, or 60 min WI; 24 hr cold storage, and 3 hr warm perfusion. RESULTS: Transplanted kidneys that were warm perfused before reimplantation had both lower 24 hr posttransplant serum creatinine (median of 3.2 vs. 4.1 mg/dl) and lower peak serum creatinine (median of 4.95 vs. 7.1 mg/dl). Survival rate for warm perfused kidneys was 90% (9/10) vs. 73% (8/11). In the contralateral kidneys, metabolism was affected by the compounding damage of WI. Renal oxygen and glucose consumption diminished significantly, whereas vascular resistance and lactate dehydrogenase-release rose significantly with increasing WI. CONCLUSIONS: The results demonstrate a reduction of reperfusion damage by an acellular ex vivo restoration of renal metabolism. Furthermore, data from the contralateral kidneys substantiates the relative role of WI on metabolism in renal transplantation.

Animals↗
PubMed2000

Horseshoe kidney transplantation: an overview.

The horseshoe kidney is the most common anatomical renal variation. It represents a fusion anomaly, mainly at the lower poles, occurring between the 4th and 6th week of gestation. Horseshoe kidneys display a great variation in origin, number and size of the vasculature. Transplantation of these deviant kidneys can be done en bloc or they can be split into two halves and transplanted into two recipients, depending on the number of vessels and the anatomy of the urinary collecting system. A literature review reveals 31 case histories, published between 1975 and 1998. Of these 21 were transplanted into 38 recipients after division and ten were implanted en bloc. Nineteen grafts (41%) showed immediate function and 21 grafts (46%) showed delayed function. Thrombosis and acute rejection, leading to non-function was seen in six grafts (13%). The overall success rate was 87%) with a mean follow-up of 22 months. The results of horseshoe kidney transplantation are good. provided that attention is paid to certain technical details. Because of donor scarcity, horseshoe kidneys should be used for transplantation.

Graft Survival↗
PubMed1999

Kidney preservation in the next millenium.

For the past decades, severe hypothermia has represented the foundation of organ preservation in clinical transplantation. Beneficial as hypothermia has proven to be in preserving grafts from heart-beating donors, hypothermia does not seem to provide the window necessary for the prospective evaluation of organ function. With the increasing use of non-heart-beating donors, it is logical to propose that if organs are to be evaluated prospectively, it will be necessary to preserve them at warmer temperatures. Since both glomerular and tubular functions are inhibited at temperatures below 18 degrees C, such a goal will necessitate organ preservation at a temperature above 20 degrees C. The principle of preservation at warmer temperatures is not new, but with future developments and approaches, successful realization appears within reach. In this overview, a brief history of previous attempts at warm preservation, in the context of the current status of kidney preservation, is presented. Future developments and approaches, with the potential for prospective testing of the function and enhanced resistance to ischemic damage, will be discussed.

Animals↗
PubMed1999

The value of dextran 12,000 in ischemically damaged canine kidneys during machine perfusion.

The use of non-heartbeating (NHB) donor kidneys has led to the search for new methods of viability-testing. We investigated, in a canine model, the relationship between the filtration of dextran 12, 000 into urine and a certain period of warm ischemic time (WIT) during machine perfusion. Twenty-four canine kidneys were divided into three groups, sustaining 0 min, 30 min or 60 min of WIT. After cooling and flushing, the kidneys were perfused on a perfusion machine for 8 h. Three hundred milligrams of dextran 12,000 was added to the perfusate. In the perfusate, dextran and lactate dehydrogenase (LDH) concentrations were measured. Dextran concentrations were also analysed in urine. Intrarenal vascular resistance (IRR) was calculated from pressure and flow characteristics. The 30WIT group showed a higher dextran excretion rate than the other two groups. IRR and LDH measurements showed lower levels in the ischemic groups compared with the control group. Dextran 12,000 is not suitable as a viability test but does show interesting results regarding the low LDH and IRR levels in the ischemic groups.

Animals↗
PubMed1998

Non-heartbeating donors: are they worth the effort?

This review on non-heartbeating donation focusses on three issues: the number of kidneys procured from a non-heartbeating donor programme, the transplant results and the influence of a non-heartbeating programme on public opinion regarding transplantation.

Cadaver↗
PubMed1995

Outcome of transplantation of non-heart-beating donor kidneys.

To reduce the shortage of kidneys for transplantation, we started a non-heart-beating (NHB) donor programme, and compared the short-term and long-term outcomes of kidneys from NHB donors with those of a matched group of kidneys from heart-beating (HB) donors. 57 NHB kidneys were procured at the University Hospital in Maastricht and at three regional hospitals in the Netherlands, and were transplanted in 21 transplant centres within the Eurotransplant exchange organisation. 114 matched controls from HB donors were selected from Eurotransplant files. Mean follow-up was 85 months. At 5 years, graft survival was 54% for NHB kidneys and 55% for HB kidneys; patient survival was 75% and 77%. Kidneys from NHB donors had a significantly higher rate of delayed graft function (60% vs 35%), resulting in a longer hospital stay. Primary non-function of the graft was seen as frequently in the NHB donor-kidney group as in the HB group (14% vs 8%, p = 0.3). We conclude that NHB donors are a valuable source of kidneys for transplantation.

Death↗
PubMed1995

Protection of canine renal grafts by renin-angiotensin inhibition through nucleoside transport blockade.

The aims of this study were (1) to investigate the effect of R 75231, a nucleoside transport inhibitor, on renin-angiotensin release after renal ischemia-reperfusion and (2) to establish a possible protective effect of this drug on renal function. We used a canine model for auto- transplantation of kidneys that had been subjected to 30 min of warm ischemia and subsequently to 24h of cold storage in HTK preservation solution, with immediate contralateral nephrectomy. R 75231 was injected intravenously into six dogs in two equal portions of 0.05 mg/kg both 30 min and 10 min before reanastomosis was established. Another six dogs were used as a control group. At 2 weeks post-transplantation, five out of six dogs in the R 75231 group and one out of six in the control group were still alive. Starting on day 4, serum creatinine was lower in the R 75231 group than in the control group (p < 0.005). In contrast to the control group, an inversion of the median preischemia adenosine/inosine ratio was observed in the R 75231 group after reperfusion (0.4 preischemia vs 4.0 after 60 min of reperfusion). Reperfusion of the graft resulted in an immediate increase in renin, angiotensin I, and angiotensin II venous blood levels in the control group. In the R 75231 group, renin, angiotension I, and angiotensin II levels were significantly lower. We conclude that administration of R 75231 before reperfusion has a protective effect on post-transplant function of kidneys that have been subjected to prolonged warm ischemia. This effect may, at least in part, be ascribed to inhibition of the breakdown and disposal of endogenous adenosine which, in turn, inhibits the excessive stimulation of the renin-angiotensin system in the early phase of reperfusion.

Animals↗
PubMed1995

Inhibition of CD18-dependent leukocyte adherence by mAb 6.5 E does not prevent ischemia-reperfusion injury as seen in grafted kidneys.

The present study was designed to determine whether beta-2 integrin-mediated leukocyte adherence to the endothelium is involved in renal ischemia-reperfusion damage and to evaluate the therapeutic intervention potency of monoclonal antibody (mAb) 6.5 E, directed against the leukocyte CD18 adhesion molecule. To answer these questions, we used a clinically relevant canine model for the autotransplantation of kidneys that had been subjected to 30 min of normothermic ischemia, followed by 24 h of cold storage preservation. Intravital fluorescence microscopy of capsular microvessels showed that substantial leukocyte adherence occurred after renal ischemia and reperfusion. Leukocyte adherence was observed in both arterioles and venules, but predominantly in the latter. Reperfusion of the graft resulted in a statistically significant reduction of the venular red blood cell velocity (RBCV). Moreover, the venular diameter increased. No significant changes in the arteriolar RBCV or in the arteriolar diameter were observed. Administration of mAb 6.5 E, 1 h before reperfusion, inhibited leukocyte adherence to the renal microvascular endothelium, resulting in an improved venular flow 2 h after reperfusion. However, we observed no beneficial effect of mAb 6.5 E pretreatment on post-transplant graft function and survival. We conclude that leukocyte adherence does not play a critical role in the development of renal injury following reperfusion of kidneys that have been subjected to prolonged warm and cold ischemia.

Animals↗
PubMed1995

Regeneration of ATP in kidney slices after warm ischemia and hypothermic preservation.

The current shortage of cadaveric kidneys may be alleviated to some degree by increasing our capabilities to use less than ideal donor kidneys, such as those from non-heart-beating donors. These kidneys are often exposed to no flow (ischemia) for varying lengths of time. Full utilization of these kidneys may require better methods of organ preservation that could reverse existing ischemic injury. This may conceivably require that, during preservation, energy stores (ATP) lost during warm ischemia be recharged. This would required continuous perfusion. Using a kidney slice model, we investigated the effects of simulated hypothermic machine perfusion with the UW gluconate perfusate on the capability of rabbit kidneys exposed to warm ischemia to regenerate ATP. After 30 min of warm ischemia, ATP content was low (0.2 mumol/g wet weight) but increased to 0.7-0.9 mumol/g wet weight after 24 h of simulated machine perfusion at 4 degrees C. After an additional 2 h of rewarming (37 degrees C in oxygenated Krebs Henseleit buffer), the slice ATP content increased to about 1.0 mumol/g wet weight (similar to kidneys not exposed to warm ischemia) when the antioxidants desferrioxamine and N-2-(mercaptopropionyl) glycine were included in the preservation media. Significantly less ATP was present without the antioxidants. After 60 min of warm ischemia, less ATP was regenerated after 24 h of simulated machine perfusion (about 0.4 mumol/g wet weight) than after 30 min of warm ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗