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Biomedical subjects

L Brasile

Publications and source records attributed to L Brasile.

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

The cadaveric kidney and the organ shortage--a perspective review.

Despite the technical and logistical hurdles that must be overcome with the reintroduction of non-heartbeating donor kidneys, the potential of these organs represents the only near-term solution for effectively alleviating the growing disparity between demand and supply. This review provides an argumentative overview of the history of cadaveric kidney transplantation. During the early years of transplantation retrieval of kidneys from non-heartbeating donors necessitated a prolonged period of warm ischemic exposure, with a corresponding minimal ex vivo period since organ preservation was in its infancy. Today we have the inverse situation where warm ischemic times are quite limited and hypothermic preservation times average 24 h because organs are shipped to remote centers due to mandated organ sharing algorithms. The recent experience with the reintroduction of non-heartbeating donors has necessitated combining the worst aspects from both eras: substantial warm ischemia with prolonged hypothermic preservation. Nevertheless, recent results from several transplant groups poignantly highlight the potential of this approach in expanding the organ donor pool.

Cadaver↗
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↗