Claudio Montiglio

Predicting Irreparable Renal Ischemic Injury Using a Real-Time Marker in the Porcine Model

PURPOSE We determined the maximal renal tolerance of warm ischemia using renal cortical interstitial metabolic changes to identify a potential real-time marker of irreparable renal function. MATERIALS AND METHODS Using a single kidney model 3 groups of 5 pigs each underwent 120, 150 and 180 minutes of warm ischemia, respectively. Microdialysis samples were collected before, during and after ischemia. Renal function assessments consisting of serum creatinine and GFR measurements were performed before ischemia and on post-ischemia days 1, 5, 9, 14 and 28. Kidneys exposed and not exposed to ischemia were collected for histological study. RESULTS Interstitial glucose and pyruvate concentrations decreased, while lactate concentrations increased to stable levels during ischemia. Glutamate spiked at 30 minutes of ischemia and subsequently tapered, while glycerol increased throughout warm ischemia time. At post-ischemia day 28 renal function returned to pre-ischemia baseline levels in the group with 120 minutes of ischemia but did not recover to baseline in the 150 and 180-minute ischemic groups. Functional data correlated with histological findings. The 120-minute maximal renal tolerance of warm ischemia correlated with a mean +/- SD glycerol concentration of 167 +/- 24 micromol/l. CONCLUSIONS Interstitial glycerol is a real-time, renal unit specific, minimally invasive marker of renal function deterioration. Exposure of porcine kidneys to ischemic insults resulting in renal cortical interstitial glycerol concentrations higher than 167 micromol/l is associated with irreparable functional damage in this model.

Real-Time Analysis of Renal Interstitial Metabolites During Induced Renal Ischemia

PURPOSE Microdialysis is an innovative technique used to monitor the chemistry of the interstitial fluid in living tissue. We documented changes in concentration of interstitial fluid metabolites before, during, and after induced renal ischemia. MATERIALS AND METHODS Under general anesthesia, a microdialysis probe was laparoscopically positioned into the renal cortex of six pigs. Isotonic sterile perfusion fluid was pumped through the probe at 2 microL/min. After collecting a baseline sample, the renal artery was occluded with a Satinsky clamp for 90 (n = 3) or 120 (n = 3) minutes. A dialysate sample was collected every 30 minutes during the ischemic and 3-hour postischemic period. The samples were analyzed for glucose, lactate, pyruvate, glutamate, urea, and glycerol concentrations with the CMA/600 Microdialysis Analyzer. Serum metabolic panels from peripheral venous samples drawn before ischemia, after ischemia, and 3 hours after ischemia were analyzed. RESULTS Glucose and pyruvate concentrations significantly declined (P = 0.01, P = 0.05, respectively) while lactate and glycerol concentrations significantly increased during ischemia (P = <0.01, P < 0.01, respectively). Glutamate increased to 2.5 times the baseline concentration (P < 0.01) at 1 hour of ischemia and subsequently declined during ischemia. The lactate/pyruvate ratio increased sharply during ischemia and returned to baseline within 1 hour postischemia. There were no changes noted in serum creatinine levels before and after ischemia. CONCLUSIONS Microdialysis can accurately measure minute real-time changes in the renal interstitial environment caused by ischemia not detected with serum studies. These local changes may be correlated with ischemic times to predict tissue preservation in future studies.

Lapra-Ty Holding Strength and Slippage with Various Suture Types and Sizes

OBJECTIVES To investigate the holding strength and slippage of Lapra-Ty clips on various suture types and sizes. METHODS Using an automated materials testing system with the Lapra-Ty in a fixed position, Lapra-Ty holding strength and displacement were determined with 0, 2-0, 3-0, and 4-0 Vicryl, Monocryl, and polydioxanone suture (PDS). To simulate clinical application, Lapra-Tys were also tested by applying a load to these sutures after being passed through a full-thickness layer of tautly suspended fresh porcine bladder tissue. Three trials were performed with each suture type and size. RESULTS The Lapra-Ty holding strength with Vicryl suture was significantly higher than with Monocryl or PDS of the same suture size in bladder tissue trials. Monocryl suture had a significantly higher displacement than Vicryl or PDS of the same suture size in bladder tissue trials (except for 4-0 Monocryl and PDS having insignificantly different displacements). Lapra-Tys slipped off Vicryl, Monocryl, and PDS in 25%, 67%, and 67% of their respective trials. Lapra-Tys did not slip during any of the trials with 2-0 suture of any type or 3-0 Vicryl. Lapra-Tys with holding strengths on suture less than approximately 8 Newtons (N) slipped and greater than 8 N pulled through the bladder tissue without slipping. CONCLUSIONS The optimal suture type and size to maximize Lapra-Ty holding strength and minimize slippage was determined to be 2-0 and 3-0 Vicryl, 2-0 Monocryl, and 2-0 PDS. Monocryl suture stretches more than Vicryl and PDS at higher loads.

The Effects of Ureteral Mobilization and Transection on Ureteral Oxygenation

OBJECTIVES To determine the impact of ureteral transection with and without prior ureteral mobilization on ureteral oxygen partial pressure (p(u)O(2)). METHODS Sixteen pigs underwent general anesthesia with laparoscopic transperitoneal access to the right ureter. With no dissection and minimal manipulation, a tissue oxygen probe (Licox, Kiel, Germany) was introduced via a trocar and inserted into the ureter. The probes were placed at the ureteropelvic junction (UPJ, n = 8) and ureterovesical junction (UVJ, n = 8). Baseline p(u)O(2) was measured. Subsequently, half of the animals at each level (n = 4) underwent complete ureteral transection proximal to UPJ probes and distal to UVJ probes with or without prior mobilization. p(u)O(2) levels were measured after ureteral mobilization and transection. RESULTS Of the ureters transected at the UPJ without mobilization, the mean p(u)O(2) level declined by 13 mm Hg relative to baseline (P = 0.07). The baseline UPJ p(u)O(2) level declined by 5 mm Hg after ureteral mobilization alone and subsequently by 31 mm Hg after transection (P <0.01). Of the ureters transected at the UVJ without mobilization, the p(u)O(2) level decreased by 4 mm Hg relative to baseline (P = 0.08). The baseline UVJ p(u)O(2) level decreased by 15 mm Hg after ureteral mobilization alone and subsequently by 39 mm Hg after transection (P <0.01). At both the UPJ and UVJ, the transected-only p(u)O(2) level was statistically higher than the mobilized and transected level (P = 0.03, respectively). CONCLUSIONS During ureteral surgery, mobilization alone exposes the distal ureter to more ischemia than the proximal ureter, and efforts to minimize ureteral mobilization when transection is necessary are crucial in maintaining tissue oxygenation.