Increased Ischemia Time Research Articles

#1270 Exploring the shift in gut microbiota due to renal ischemia/reperfusion injury in rats

Abstract Background and Aims Acute kidney injury (AKI) due to renal ischemia/reperfusion (I/R) is a major clinical problem in renal transplantation and partial nephrectomy, which is associated with morbidity and mortality and substantial healthcare expenditures, but there is no effective and specific treatment. Recently, the clinical impact of the interaction between gut bacteria and the kidney function has become increasingly clear. Experimental evidence has highlighted a bidirectional relationship between gut microbiota and kidney disease. Therefore, we investigated the possibility that I/R can ameliorate AKI by studying gut-renal interactions and gut microbiota in AKI. Method We induced varying degrees of renal I/R injury in adult male Wistar rats by clamping the left renal pelvis for 30 and 45 minutes, simulating mild and severe conditions, respectively. These samples were subjected to extensive histologic examination using standard techniques such as hematoxylin and eosin (HE), Sirius Red, and F4/80 staining. In addition, we performed a quantitative analysis of the mRNA expression levels of fibrotic and inflammatory markers in both kidney and colon tissues using real-time PCR. Gut microbiota genomic DNA was extracted from rat feces and microbial 16S ribosomal RNA (rRNA) gene sequencing was performed. Results Renal function deteriorated with increasing ischemia time and fibrosis progressed, as confirmed by Sirius Red staining and qPCR of fibrosis genes such as TGFB. The expression of inflammatory genes such as IL-1B and IL-6 was also increased. The expression of inflammatory genes such as Toll-like receptor, C3, and IL-1B in the intestine also increased with ischemia time. In the fecal microbiota, the total read percentage of Bacteroides acidifaciens at the species level increased with increasing ischemia time. Conclusion The observed shifts in gut microbiota composition may serve as a critical indicator of chronic kidney disease (CKD)-induced gut dysbiosis secondary to AKI. This finding highlights the need for further research into the identification and migration patterns of the gut microbiota, which represents a promising avenue for early detection, prevention, and therapeutic intervention in AKI. Future investigations elucidating the mechanisms by which the microbiota influence IRI-induced AKI and the development of practical therapeutic strategies have the potential to significantly improve clinical outcomes in patients suffering from IRI-induced AKI.

Determinants of Success in Single- and Multi-Digit Replant.

Purpose: Understanding the variables that influence success in digital replant surgery is essential to guide clinical decision-making and to counsel patients. The purpose of this study was to determine the replant success rate and identify predictors of success at our tertiary care centre. Methods: This was a single centre, retrospective cohort study of consecutive patients who underwent digital replantation from January 2000 to September 2018. Adult patients with flexor zone I to III amputations were included. Patient demographics, comorbidities, injury pattern, operative data, and post-operative care were reviewed. The primary outcome was survival of the replanted digit at discharge. Results: A total of 146 patients met inclusion criteria. Of these, 100 had single-digit replants and 46 underwent multi-digit replants for a total of 220 digits. The success rate was 71%. Predictors of success included sharp mechanism of injury (P < .01), incomplete amputation (P < .01), amputation proximal to zone I flexor level (P = .02), post-operative acetylsalicylic acid use (P < .01), absence of leech use (P = .05), and absence of operative re-exploration (P < .01). Daytime replants had similar outcome compared to nighttime replants despite having increased ischemia time (7.9 ± 3.9 hours vs 6.8 ± 2.6 hours, P = .02). However, daytime operative time (7.8 ± 3.7 hours) was significantly shorter than nighttime replant time (9.6 ± 5.9 hours, P = .01). Conclusion: Sharp amputation, intact venous drainage, proximal amputation, and acetylsalicylic acid use were associated with replant survival and are factors to consider when managing patients for digital replantation. Leech therapy and operative re-exploration were associated with poor outcome. Nighttime replants required significantly longer operative time than daytime replants despite similar survival outcome.

PD11-02 TO CLAMP OR NOT TO CLAMP: FOREGOING HILAR CLAMPING DURING PARTIAL NEPHRECTOMY DOES NOT CHANGE RENAL OUTCOMES

INTRODUCTION AND OBJECTIVE:Early retrospective data has shown that vascular clamping and increased ischemia time during partial nephrectomy (PN) has led to higher rates of both acute and chronic ki...

Ischemia time impacts on respiratory chain functions and Ca2+-handling of cardiac subsarcolemmal mitochondria subjected to ischemia reperfusion injury

BackgroundMitochondrial impairment can result from myocardial ischemia reperfusion injury (IR). Despite cardioplegic arrest, IR-associated cardiodepression is a major problem in heart surgery. We determined the effect of increasing ischemia time on the respiratory chain (RC) function, the inner membrane polarization and Ca2+ homeostasis of rat cardiac subsarcolemmal mitochondria (SSM).MethodsWistar rat hearts were divided into 4 groups of stop-flow induced warm global IR using a pressure-controlled Langendorff system: 0, 15, 30 and 40 min of ischemia with 30 min of reperfusion, respectively. Myocardial contractility was determined from left ventricular pressure records (dP/dt, dPmax) with an intraventricular balloon. Following reperfusion, SSM were isolated and analyzed regarding electron transport chain (ETC) coupling by polarography (Clark-Type electrode), membrane polarization (JC1 fluorescence) and Ca2+-handling in terms of Ca2+-induced swelling and Ca2+-uptake/release (Calcium Green-5 N® fluorescence).ResultsLV contractility and systolic pressure during reperfusion were impaired by increasing ischemic times. Ischemia reduced ETC oxygen consumption in IR40/30 compared to IR0/30 at complex I-V (8.1 ± 1.2 vs. 18.2 ± 2.0 nmol/min) and II-IV/V (16.4 ± 2.6/14.8 ± 2.3 vs. 2.3 ± 0.6 nmol/min) in state 3 respiration (p < 0.01). Relative membrane potential revealed a distinct hyperpolarization in IR30/30 and IR40/30 (171.5 ± 17.4% and 170.9 ± 13.5%) compared to IR0/30 (p < 0.01), wearing off swiftly after CCCP-induced uncoupling. Excess mitochondrial permeability transition pore (mPTP)-gated Ca2+-induced swelling was recorded in all groups and was most pronounced in IR40/30. Pyruvate addition for mPTP blocking strongly reduced SSM swelling in IR40/30 (relative AUC, ± pyruvate; IR0/30: 1.00 vs. 0.61, IR15/30: 1.68 vs. 1.00, IR30/30: 1.42 vs. 0.75, IR40/30: 1.97 vs. 0.85; p < 0.01). Ca2+-uptake remained unaffected by previous IR. Though Ca2+-release was delayed for ≥30 min of ischemia (p < 0.01), Ca2+ retention was highest in IR15/30 (RFU; IR0/30: 6.3 ± 3.6, IR 15/30 42.9 ± 5.0, IR30/30 15.9 ± 3.8, IR40/30 11.5 ± 6.6; p ≤ 0.01 for IR15/30 against all other groups).ConclusionsIschemia prolongation in IR injury gradually impaired SSM in terms of respiratory chain function and Ca2+-homeostasis. Membrane hyperpolarization appears to be responsible for impaired Ca2+-cycling and ETC function. Ischemia time should be considered an important factor influencing IR experimental data on subsarcolemmal mitochondria. Periods of warm global ischemia should be minimized during cardiac surgery to avoid excessive damage to SSMs.

Abstract 17: Increasing Ischemia Time Diminishes Chimerism After Vascularized Bone Marrow Allotransplantation

PURPOSE: Vascularized composite allotransplantation (VCA) can include vascularized bone marrow (VBM) to potentially generate chimerism and subsequent tolerance in the recipient. While increasing ischemia time is known to be detrimental to free flaps and solid organ transplants, it is unknown whether increasing VCA ischemia time may diminish VBM’s capacity to achieve chimerism and tolerance. This study determines whether increasing cold ischemia time results in decreased peripheral chimerism levels, increasing loss of the donor bone marrow compartment, and increased skin paddle rejection in a murine VCA model. METHODS: Twenty-three adult Lewis rats received osteomyocutaneous hind limb allografts from 3 groups of Brown-Norway rats. The groups underwent 0, 6, and 12 hours of cold ischemia at 4°C (n=8, 6, and 9 respectively). Immunosuppressive conditioning consisted of anti-lymphocyte serum 1cc 3 days pre-operatively and on post-op day (POD) 1, tacrolimus 2mg/kg/day for PODs 1–7, and then concluded with rapamycin 3mg/kg/day for PODs 8–28. Peripheral chimerism levels were drawn after POD 30. Skin paddle was observed for 30 days after immunosuppression cessation for rejection or tolerance. Allograft was collected at POD 60 for flow cytometry and histologic analysis. RESULTS: Peripheral chimerism levels in both myeloid and lymphoid lines were decreased in the 12 & 6 hours groups versus 0 hours (p<0.01). At POD 60, the amount of donor cells in the allograft bone marrow was significantly decreased at 12 & 6 hours versus the 0 hours group (p<0.05). At 12 hours, hematoxylin & eosin histology demonstrated significantly increased reactive lymphocytes, increased stroma, significantly decreased hematopoetic cells, and significant myelofibrosis. At 6 hours, moderate stromal increases, moderately decreased hematopoetic cells, and moderate myelofibrosis was observed. Trichrome staining revealed viable bone at all time points though with there were increasing amounts of collagen deposition with increasing ischemia and osteoslerosis was noted at 12 hours. Microvasculature was preserved at all time points. By POD 60, 0% of skin paddles survived in the 12 hours group, 17% at 6 hours, and 73% at 0 hours. CONCLUSION: With increasing ischemia time prior to VCA re-vascularization, there is decreased peripheral chimerism levels, increased loss of donor hematopoetic cells in the donor bone marrow, and increased skin paddle rejection. These findings indicate that ischemia time may significantly limit the capacity for VBM to facilitate chimerism and subsequent VCA tolerance and thus strategies using VBM to induce tolerance may need to consider the additional obstacle of time. Prolonged ischemia time may be a contributing factor to the absence of stable chimerism and tolerance in human VBM-bearing VCA recipients.

Surgical Outcomes of Three vs Four Arm Robotic Partial Nephrectomy: Is the Fourth Arm Necessary?

ObjectiveTo compare the cost, efficacy, and safety of 3-arm versus 4-arm technique in robotic partial nephrectomy (RPN). Surgeons may either elect to utilize three vs four robotic instruments depending on preference. The purpose of this study is to compare the outcomes between the two techniques. MethodsRPNs from June 2016 to August 2017 were retrospectively reviewed. Tumor features, surgical parameters, and operative outcomes were evaluated. The number of arms used was determined. Statistical analysis was performed with the Student's t test, chi-squared, and Mann-Whitney test. ResultsA total of 61 consecutive 3-arm RPNs and 59 consecutive 4-arm RPNs were evaluated. Mean tumor diameter and median nephrometry score were 3.4 cm (± 1.1 SD) and 7 (6-8 IQR) for the 3-arm group and 3.3 cm (±1.2 SD) and 6 (5-8 IQR) for the 4-arm group, respectively (size: p = 0.7, nephrometry: p = 0.07). Hospital length of stay, operative time, estimated blood loss, complication rate, blood transfusion rate, and readmission rate all demonstrated no statistically significant difference between 3-arm and 4-arm groups (p >0.05). Mean ischemia time was shorter by 5.1 minutes in the 4-arm group (p = 0.02). Rate of margin positivity was higher in the 4-arm group (0% vs 10%, p = 0.03). ConclusionRPN can be safely and effectively completed with 3-robotic arms. While there was increased ischemia time, the difference was small and likely not of clinical significance. The routine addition of the fourth robotic arm in RPN is not necessary.

Critical Ischemia Time, Perfusion, and Drainage Function of Vascularized Lymph Nodes.

Vascularized lymph node transfer is a promising surgical treatment for lymphedema. This study investigated the effect of ischemia on the lymphatic drainage efficiency of vascularized lymph node flaps and the critical ischemia time of lymph nodes. Twenty-four lymph nodes containing groin flaps in 12 Sprague-Dawley rats were dissected. Clamping of the vascular pedicle was performed for 0, 1, 3, 5, 6, or 7 hours; then, each was allowed to reperfuse by means of the vascular pedicle for 1 hour. Perfusion and ischemic changes were assessed using indocyanine green lymphography; laser Doppler flowmetry; and histologic studies with associated lymphatic vessel endothelial hyaluronan receptor-1, CD68, 4',6-diamidino-2-phenylindole, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, and glutathione assay stains. The mean latency period of the groin lymph node flaps was 247 ± 67, 83 ± 15, 72 ± 42, 30 ± 18, and 245 ± 85 seconds in the 0-, 1-, 3-, 5-, and 6-hour groups, respectively. Perfusion detected by laser Doppler was 85.2 ± 14.5, 87.2 ± 36.7, 129.8 ± 33.7, 140.4 ± 148.5, 156.1 ± 91.4, and 41.2 ± 34.8 perfusion units at ischemia times of 0, 1, 3, 5, 6, and 7 hours, respectively. Cell damage measured by glutathione was 46.8 ± 10.2, 67.7 ± 14.2, 62.8 ± 15.4, 126.6 ± 5.9, 259.0 ± 70.3, and 109.1 ± 27.5 at ischemia times of 0, 1, 3, 5, 6, and 7 hours, respectively. Histologically, as ischemia time increased, hemorrhage and congestion became more severe. The critical ischemia time of vascularized lymph nodes is 5 hours in the rodent animal model, verified by indocyanine green lymphatic fluid uptake, laser Doppler perfusion, and histologic assessments. Interestingly, lymphatic drainage and perfusion of vascularized lymph nodes were improved with an increased ischemia time before the critical 5 hours was reached.

Current approaches in retrieval and heart preservation.

Fifty years after the first successful heart transplantation, despite multiple advances in the treatment of advanced acute and chronic heart failure, there is still no equivalent to heart transplantation as a long-term treatment for end-stage heart failure. Transplantation is, however, limited by the scarcity and quality of heart allografts. Donors are nowadays significantly older, particularly in European countries, and traumatic head injury as the cause of death has been replaced by intracerebral hemorrhage or hypoxic brain damage in the majority of cases. In addition, many donors have undergone extensive resuscitation efforts. Recipient characteristics have progressively changed too within the last couple of decades; recipients are older, often with comorbidities and nearly half of them are bridged to transplant with a wide variety of mechanical circulatory support devices. These developments have resulted in heart transplant surgery becoming significantly more challenging with longer more complex surgery and increased ischemia times for organs that were previously considered to be borderline or non-transplantable in many cases. To address this, several options have been explored within the last years and as a result, novel strategies have been developed and tested in order to optimize graft preservation and potentially increase the donor pool. The two notable developments are the ability to procure hearts from donors after circulatory death and the advent of ex-vivo perfusion of hearts. This technology has made the transplantation of extended criteria organs, including those from circulatory determined death (DCD) donors possible, and allow for out of body time of more than 12 hours in heart transplantation. In this review, we set out the basis of the current practices in organ procurement, and the opportunities for the future as demands for organ transplantation continue to increase.

Utilization of high donor sequence number grafts in cardiac transplantation.

Donor sequence number (DSN) represents the number of candidates to whom a graft was offered and declined prior to acceptance for transplantation. We sought to investigate the outcomes of patients receiving high DSN grafts. Consecutive isolated adult cardiac transplantations performed at a single-center were reviewed. Recipients were grouped into standard (≤75th percentile) DSN and high (>75th percentile) DSN. A previously validated donor risk index was used to quantify the risk associated with donor grafts, and recipient outcomes were assessed. Overall, 254 patients were included: 194 standard DSN (range 1-79) and 60 high DSN (range 82-1723). High DSN grafts were harvested at greater distance (P<.001) with increased ischemia time (P<.001), resulting in a modest increase in donor risk index (1 point median difference, P=.014). High DSN recipients were less frequently listed as UNOS status 1A (P<.001). Despite a nonsignificant trend toward increased in-hospital/30-day mortality in high DSN recipients, there were no differences in primary graft dysfunction or 1-year survival (high DSN 89% vs standard DSN 88%, P=.82). After adjustment for risk factors, high DSN was not associated with increased 1-year mortality (hazard ratio 1.18, 95%-CI 0.54-2.58, P=.68).

3D printed renal cancer models derived from MRI data: application in pre-surgical planning.

To determine whether patient-specific 3D printed renal tumor models change pre-operative planning decisions made by urological surgeons in preparation for complex renal mass surgical procedures. From our ongoing IRB approved study on renal neoplasms, ten renal mass cases were retrospectively selected based on Nephrometry Score greater than 5 (range 6-10). A 3D post-contrast fat-suppressed gradient-echo T1-weighted sequence was used to generate 3D printed models. The cases were evaluated by three experienced urologic oncology surgeons in a randomized fashion using (1) imaging data on PACS alone and (2) 3D printed model in addition to the imaging data. A questionnaire regarding surgical approach and planning was administered. The presumed pre-operative approaches with and without the model were compared. Any change between the presumed approaches and the actual surgical intervention was recorded. There was a change in planned approach with the 3D printed model for all ten cases with the largest impact seen regarding decisions on transperitoneal or retroperitoneal approach and clamping, with changes seen in 30%-50% of cases. Mean parenchymal volume loss for the operated kidney was 21.4%. Volume losses>20% were associated with increased ischemia times and surgeons tended to report a different approach with the use of the 3D model compared to that with imaging alone in these cases. The 3D printed models helped increase confidence regarding the chosen operative procedure in all cases. Pre-operative physical 3D models created from MRI data may influence surgical planning for complex kidney cancer.

Alternans in Rabbit Heart During Acute Regional Ischemia: Optical Mapping and Microelectrode Recordings

T-wave alternans during acute ischemia have been determined as a precursor of ventricular arrhythmias usually resulting in sudden cardiac death. Optical mapping is often used to investigate the mechanisms of alternans in heart preparations. Several hypothesis exist that may explain the formation of optical alternans. One of them is that optical action potential amplitude (OAPA) alternans may indicate the formation of alternating conduction blocks. In our study by using optical mapping simultaneously with microelectrode recordings we aimed to investigate the occurrence of OAPA alternans during acute regional ischemia and to determine the electrical origin underlying the alternans formation. Experiments were performed in Langendorff-perfused rabbit hearts stained with near-infrared dye di-4-ANBDQBS. Optical signals were registered from left ventricle epicardium. The hearts were stimulated by applying 300 ms, and 200 ms pacing cycle. Results showed that OAP started alternate with high and low amplitudes at 200 ms pacing at early ischemia (4-6 minutes). The alternation zone migrated, shrank and finally disappeared with increasing ischemia time. In order to elucidate the mechanism of this phenomenon two glass microelectrodes were used to examine electrical activity by registering action potentials from subepicardial and deeper (3-5 mm) myocardial layers simultaneously. Microelectrode recordings revealed that OAPA alternans is the result of 2:1 conduction blocks in a certain layer whilst the regular response is held in the other layers. During later ischemia (10-15 minutes) deep myocardial layers lose their excitability remaining optical signals only with low amplitude. It explains the disappearing of OAPA alternans. Thus, our experimental data show that OAPA alternans which arise during the early acute ischemia can be caused by alternation of conduction blocks in a certain myocardial layers.Research is funded by the European Social Fund under the Global Grant measure.

A novel mouse model of pediatric cardiac arrest and cardiopulmonary resuscitation reveals age-dependent neuronal sensitivities to ischemic injury

BackgroundPediatric sudden cardiac arrest (CA) is an unfortunate and devastating condition, often leading to poor neurologic outcomes. However, little experimental data on the pathophysiology of pediatric CA is currently available due to the scarcity of animal models. New methodWe developed a novel experimental model of pediatric cardiac arrest and cardiopulmonary resuscitation (CA/CPR) using postnatal day 20–25 mice. Adult (8–12 weeks) and pediatric (P20-25) mice were subjected to 6min CA/CPR. Hippocampal CA1 and striatal neuronal injury were quantified 3 days after resuscitation by hematoxylin and eosin (H&E) and Fluoro-Jade B staining, respectively. ResultsPediatric mice exhibited less neuronal injury in both CA1 hippocampal and striatal neurons compared to adult mice. Increasing ischemia time to 8min CA/CPR resulted in an increase in hippocampal injury in pediatric mice, resulting in similar damage in adult and pediatric brains. In contrast, striatal injury in the pediatric brain following 6 or 8min CA/CPR remained extremely low. As observed in adult mice, cardiac arrest causes delayed neuronal death in pediatric mice, with hippocampal CA1 neuronal damage maturing at 72h after insult. Finally, mild therapeutic hypothermia reduced hippocampal CA1 neuronal injury after pediatric CA/CPR. Comparison with existing methodThis is the first report of a cardiac arrest and CPR model of global cerebral ischemia in mice. ConclusionsTherefore, the mouse pediatric CA/CPR model we developed is unique and will provide an important new tool to the research community for the study of pediatric brain injury.

Editorial Comment to Different methods of hilar clamping during partial nephrectomy: Impact on renal function

Partial nephrectomy (PN) has gained in popularity since current scientific evidence has suggested that renal function preservation should be increasingly prioritized.1-3 Renal ischemia related to hilar clamping is deleterious to the remaining renal parenchyma. Many studies have investigated ischemia time limits and altering factors in relation to subsequent renal function.4-6 Ischemia time is the strongest modifiable surgical risk factor for postoperative chronic kidney disease.7 However, the safe duration of ischemia remains controversial. The great merit of the study by Lee et al. is that it reported renal function data in a large and homogeneous series of 369 patients managed by open PN for a single localized unilateral pT1a renal tumor; 10.6% of whom had no vascular clamping, 54.4% had warm ischemia and 35.0% had cold ischemia.8 They concluded that the impact of warm and cold ischemia seems to be comparable with a significant decrease of estimated glomerular filtration rate (eGFR) in the early postoperative period, but without significant impact on 1-year eGFR. As expected, ultimate renal function decreases proportionally with increasing ischemia time, in both hilar clamping groups. The authors' conclusions underscore the importance of minimization of ischemia time whenever hilar clamping is required. As the vast majority of prior studies assessing the impact of ischemia, this series included patients with a normal contralateral kidney. It should be noted that, in this case, the effect on serum creatinine is blunted and, therefore, the effect on total GFR is minimized, although there might be a significant reduction in the GFR of the operated kidney. Renal reserve serves to protect the organism, maintaining a near normal GFR, and ischemic damage is potentially masked by the compensatory role of the normal contralateral kidney. Therefore, analysing renal function consequences of various technical scenarios during PN on a solitary kidney could be particularly informative. In a series of PN on solitary kidneys, Thompson et al. concluded that whenever pedicle clamping was expected, warm ischemia should be completed within 20 min, and cold ischemia within 35 min. They also showed that warm ischemia patients are significantly more likely to develop acute renal failure in the postoperative period and chronic kidney disease during follow up compared with patients managed without hilar clamping.9 Nguyen and Gill found a similar benefit in limiting warm ischemia to less than 20–25 min when renal function decreases at a faster rate with additional minutes of ischemia.10 This accumulated data should prompt us to preferentially choose PN with no clamping whenever technically feasible, especially in patients with a solitary kidney or preoperative renal function impairment. It is noteworthy that the absence of significant differences in eGFR decrease at 1 year in the present study could be due to the short ischemia time in this series, probably as a result of the small size of the tumors (<4 cm). These results are probably not transposable to patients with more complex tumors where vascular clamping is often necessary for allowing good hemostasis and obtaining a bloodless field, which is essential for successful tumor removal, with negative surgical margins and accurate surgical collecting system closure. Finally, it is obvious that a certain number of small renal tumors are indolent and not life-threatening. We should therefore integrate information, such as age, comorbidities, baseline renal function and technical difficulty of PN, in our decision algorithm. This is particularly true because increased alternative options exist for small renal tumor management, including active surveillance or ablative techniques, which are less deleterious options in regard to renal function. None declared.

Different methods of hilar clamping during partial nephrectomy: Impact on renal function

To evaluate the impact of different hilar clamping methods on changes in renal function after partial nephrectomy. We analyzed the clinical data of 369 patients who underwent partial nephrectomy for a single renal tumor of size ≤4.0 cm and a normal contralateral kidney. Patients were separated into three groups depending on hilar clamping method: non-clamping, cold ischemia and warm ischemia. Estimated glomerular filtration rate was examined at preoperative, nadir and 1 year postoperatively. Percent change in estimated glomerular filtration rate was used as the parameter to assess the renal functional outcome. Percent change in nadir estimated glomerular filtration rate in the non-clamping group was significantly less compared with the cold ischemia and warm ischemia groups (P < 0.001). However, no significant differences among the groups were noted in percent change of estimated glomerular filtration rate at 1 year (P = 0.348). The cold ischemia group had a similar serial change of postoperative renal function compared with the warm ischemia group. Percent change in 1-year estimated glomerular filtration rate increased with increasing ischemia time in the cold ischemia (P for trend = 0.073) and warm ischemia groups (P for trend = 0.010). On multivariate analysis, hilar clamping (both warm ischemia and cold ischemia) were significantly associated with percent change in nadir estimated glomerular filtration rate, but not in 1-year estimated glomerular filtration rate. Non-clamping partial nephrectomy results in a lower percent change in nadir estimated glomerular filtration rate, whereas it carries an estimated glomerular filtration rate change at 1 year that is similar to partial nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia provide a similar effect on renal function. Therefore, when hilar clamping is required, minimization of ischemia time is necessary.

137 PADUA score accurately predicts the risk and grade of complication and ischemic time in patients who are candidates for nephron sparing surgery

INTRODUCTION AND OBJECTIVES: to prospectively test the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification in a cohort of patients submitted to open nephron sparing surgery (NSS) and to correlate the PADUA score to ischemia time. METHODS: from December 2009 and September 2010, 112 consecutive patients were treated with open NSS with the technique of hilar arterial clamping. Tumor were reclassified according to the PADUA classification. Complication were graded according to the modified Clavien system. Univariable and multivariable logistic regression analyses tested the predictive value of PADUA score on overall complication rate and on the ischemic time. RESULTS: Sixty-one patients underwent extraperitoneal NSS through a flank incision, while 51 patients underwent transperitoneal approach. Mean patients age was 61.8 °A 13.3 years. The median tumor diameter was 3.4–1.5 cm. The median PADUA score was 8 (range 6–13). Mean ischemia time was 20–10 min. Overall complication rate was 18.7% (n 21). On univariable analysis, the PADUA score correlated with complication rate (p 0.027) and with increased ischemia time, considered as a continuous variable as well as categorical one (°U 25 min vs 25 min) (p 0.001 and p 0.03, respectively). On multivariable analysis PADUA score achieved the independent predictor status of complication rate, after adjusting for body mass index and surgical approach. Patients with PADUA score 8–9 had a 4-fold risk of complication, while patients with PADUA score 10 had a 15-fold risk compared to those with scores of 6–7 (p 0.013). Moreover. patients with PADUA score 10 had a 6-fold risk of ischemic time 25 minutes (p 0.002). CONCLUSIONS: our study confirms that PADUA score can reliably predict risk complication and ischemic time in patients treated with NSS, independently from the extra or transperitoneal approach. PADUA classification can help the selection of patients who may benefit from additional techniques such as hypothermic procedure.

536 PADUA SCORE ACCURATELY PREDICTS THE RISK OF COMPLICATION AND ISCHEMIC TIME IN PATIENTS WHO ARE CANDIDATES FOR NEPHRON SPARING SURGERY

You have accessJournal of UrologyKidney Cancer: Evaluation and Staging1 Apr 2011536 PADUA SCORE ACCURATELY PREDICTS THE RISK OF COMPLICATION AND ISCHEMIC TIME IN PATIENTS WHO ARE CANDIDATES FOR NEPHRON SPARING SURGERY Roscigno Marco, Rayan Matloob, Maria Nicolai, Elena Strada, Giovanni Petralia, Federico Deho, Francesco Sozzi, Gianfranco Deiana, Roberto Bertini, and Luigi Filippo da Pozzo Roscigno MarcoRoscigno Marco Bergamo, Italy More articles by this author , Rayan MatloobRayan Matloob Milan, Italy More articles by this author , Maria NicolaiMaria Nicolai Bergamo, Italy More articles by this author , Elena StradaElena Strada Milan, Italy More articles by this author , Giovanni PetraliaGiovanni Petralia Milan, Italy More articles by this author , Federico DehoFederico Deho Bergamo, Italy More articles by this author , Francesco SozziFrancesco Sozzi Milan, Italy More articles by this author , Gianfranco DeianaGianfranco Deiana Bergamo, Italy More articles by this author , Roberto BertiniRoberto Bertini Milan, Italy More articles by this author , and Luigi Filippo da PozzoLuigi Filippo da Pozzo Bergamo, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1260AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES to prospectively test the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification in a cohort of patients submitted to open nephron sparing surgery (NSS) and to correlate the PADUA score to ischemia time. METHODS from December 2009 and September 2010, 112 consecutive patients were treated with open NSS with the technique of hilar arterial clamping. Tumor were reclassified according to the PADUA classification. Complication were graded according to the modified Clavien system. Univariable and multivariable logistic regression analyses tested the predictive value of PADUA score on overall complication rate and on the ischemic time. RESULTS Sixty-one patients underwent extraperitoneal NSS through a flank incision, while 51 patients underwent transperitoneal approach. Mean patients age was 61.8 °À 13.3 years. The median tumor diameter was 3.4–1.5 cm. The median PADUA score was 8 (range 6–13). Mean ischemia time was 20–10 min. Overall complication rate was 18.7% (n=21). On univariable analysis, the PADUA score correlated with complication rate (p=0.027) and with increased ischemia time, considered as a continuous variable as well as categorical one (°Ü 25 min vs < 25 min) (p < 0.001 and p= 0.03, respectively). On multivariable analysis PADUA score achieved the independent predictor status of complication rate, after adjusting for body mass index and surgical approach. Patients with PADUA score 8–9 had a 4-fold risk of complication, while patients with PADUA score > 10 had a 15-fold risk compared to those with scores of 6–7 (p=0.013). Moreover. patients with PADUA score >10 had a 6-fold risk of ischemic time > 25 minutes (p=0.002). CONCLUSIONS our study confirms that PADUA score can reliably predict risk complication and ischemic time in patients treated with NSS, independently from the extra or transperitoneal approach. PADUA classification can help the selection of patients who may benefit from additional techniques such as hypothermic procedure. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e218 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Roscigno Marco Bergamo, Italy More articles by this author Rayan Matloob Milan, Italy More articles by this author Maria Nicolai Bergamo, Italy More articles by this author Elena Strada Milan, Italy More articles by this author Giovanni Petralia Milan, Italy More articles by this author Federico Deho Bergamo, Italy More articles by this author Francesco Sozzi Milan, Italy More articles by this author Gianfranco Deiana Bergamo, Italy More articles by this author Roberto Bertini Milan, Italy More articles by this author Luigi Filippo da Pozzo Bergamo, Italy More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Release of Danger Signals during Ischemic Storage of the Liver: A Potential Marker of Organ Damage?

Liver grafts suffer from unavoidable injury due to ischemia and manipulation before implantation. Danger signals such as high-mobility group box -1(HMGB1) and macrophage migration inhibitory factor (MIF) play a pivotal role in the immune response. We characterized the kinetics of their release into the effluent during cold/warm ischemia and additional manipulation-induced mechanical damage. Furthermore, we evaluated the relationship between HMGB1/MIF release and ischemic/mechanical damage. Liver enzymes and protein in the effluent increased with increasing ischemia time. HMGB1/MIF- release correlated with the extent of hepatocellular injury. With increasing ischemia time and damage, HMGB1 was translocated from the nucleus to the cytoplasma as indicated by weak nuclear and strong cytoplasmic staining. Enhancement of liver injury by mechanical damage was indicated by an earlier HMGB1 translocation into the cytoplasm and earlier release of danger signals into the effluent. Our results suggest that determination of HMGB1 and MIF reflects the extent of ischemic injury. Furthermore, HMGB1and MIF are more sensitive than liver enzymes to detect the additional mechanical damage inflicted on the organ graft during surgical manipulation.

Critical Evaluation of Perioperative Complications in Laparoscopic Partial Nephrectomy

To analyze our experience with laparoscopic partial nephrectomy (LPN) to detail postoperative adverse events and identify factors that may contribute to adverse surgical outcomes. Complications from LPN result from a variety of factors, both technical and inherent. Single-center review of 144 consecutive LPN (4 surgeons) performed between November 2002 and January 2008 was conducted. Identified complications were graded using standard reporting criteria. Univariate and multivariate statistical analysis of variables and their association with complication event and blood loss was performed. A total of 39 complications occurred in 29 (20%) cases. Of these, 20 (51%) were urologic and 19 (49%) were nonurologic. Individual adverse events by grade were as follows: grade I, 6 (15.4%); grade II, 19 (48.7%), grade III, 11 (28.2%), and grade IV, 3 (7.7%). No grade V complications occurred. The median tumor size and ischemia time were 2.7 cm and 35 minutes, respectively. Univariate analysis identified increased American Society of Anesthesiologists risk score (odds ratio 2.99, 95% confidence interval [CI] 1.28, 6.94) and ischemia time (odds ratio 1.31; 95% CI 1.00, 1.71) as associated with complication risk. On multivariate analysis, longer ischemia time was associated with increased estimated blood loss (95% CI 3, 57; P = .03). Hospital readmission and reintervention was required in 15 (10.4%) and 9 (6.2%) patients, respectively. Complications from LPN occur in a meaningful proportion of procedures although the majority does not require reintervention and half are not urologic. Increasing ischemia time and American Society of Anesthesiologists score are associated with risk for unfavorable surgical outcomes.

Neurocognitive performance after cardiopulmonary resuscitation in pigs

To test the feasibility of a neurocognitive test based on operant conditioning in a porcine model of cardiac arrest and cardiopulmonary resuscitation. Furthermore, to characterize the influence of different durations of cardiac arrest on cognitive performance and the accompanying neurohistopathological changes. Randomized controlled laboratory animal study. Animal research facility of a university hospital. Seventeen male domestic pigs. Animals were anesthetized and mechanically ventilated before arterial and pulmonary artery catheters were inserted. Cardiac arrest was induced electrically after randomization of the animals into two groups (n = 7/group) left untreated for either 5 or 8 mins. Cardiopulmonary resuscitation was performed with 100% oxygen and cardiac compressions at 100/min for 5 mins before defibrillation was attempted. Three animals treated identically, with the exception that neither cardiac arrest was induced nor cardiopulmonary resuscitation was performed, served as controls. Hemodynamic variables as well as variables of gas exchange were measured at baseline and 10, 60, 120, 240, and 360 mins after cardiopulmonary resuscitation. Neurocognitive performance was evaluated using a test based on operant conditioning 5 days before and 4 days after cardiopulmonary resuscitation. On the fifth postoperative day, animals were killed and the brains removed for histopathological evaluation of vulnerable brain regions. No noteworthy differences in hemodynamics or gas exchange were observed at baseline or after cardiopulmonary resuscitation. Animals exposed to 8 mins of untreated cardiac arrest showed severe neurocognitive dysfunction, which was statistically significant on postoperative days 2 and 3 in comparison to animals exposed to 5 mins of cardiac arrest or controls. Neurohistopathological evaluation revealed a significantly greater proportion of ischemically damaged neurons in the caudate nucleus and putamen in pigs subjected to 8 mins of cardiac arrest. Neurocognitive testing is feasible in this setting. Performance worsens with increasing ischemia time and is structurally associated with alterations in the caudate nucleus and the putamen.

Assessment of renal ischemia by optical spectroscopy 1,2

No reliable method currently exists for quantifying the degree of warm ischemia in kidney grafts before transplantation. We describe a method for evaluating pretransplant warm ischemia time using optical spectroscopic methods. Lewis rat kidney vascular pedicles were clamped unilaterally in vivo for 0, 5, 10, 20, 30, 60, 90, or 120 min; eight animals were studied at each time point. Injured and contralateral control kidneys were then flushed with Euro-Collins solution, resected, and placed on ice. 335 nm excitation autofluorescence as well as cross-polarized light scattering images were then taken of each injured and control kidney using filters of various wavelengths. The intensity ratio of the injured to normal kidneys was compared to ischemia time. Autofluorescence intensity ratios through a 450-nm filter and light scattering intensity ratios through an 800-nm filter both decreased significantly with increasing ischemia time (P < 0.0001 for each method, one-way analysis of variance). All adjacent and nonadjacent time points between 0 and 90 min were distinguishable using one of these two modalities by Fisher's protected least significant difference. Optical spectroscopic methods correlate with warm ischemia time in kidneys that have been subsequently hypothermically preserved. Further studies are needed to correlate results with physiological damage and posttransplant performance.