Disease relevance of Cold Ischemia

• Immunotargeting of catalase to donor rats augments the antioxidant capacity of the pulmonary endothelium, reduces oxidative stress, ameliorates ischemia-reperfusion injury, prolongs the acceptable cold ischemia period of lung grafts, and improves the function of transplanted lung grafts [1].
• We compared the effects of two preservation solutions during cold ischemia (4 degrees C): normal saline with 2 mM CaCl2 (4 h and 8 h ischemia) and the University of Wisconsin solution (8 h and 24 h ischemia) [2].
• By univariate analysis, five factors were found to affect significantly the yield, purity, or overall success rate of islet isolation: organ cold ischemic time, donor age, donor plasma glucose levels, donor body weight, and cause of donor death [3].
• After adjustment for cold ischemia time, retransplantation, donor age, delayed graft function, and HLA mismatch, recipients of a class S allele transplant had serum creatinine levels 0.81 times (95% confidence interval: 0.70-0.95, P =0.01) those of recipients of a non-class S allele transplant [4].
• Also, human leukocyte antigen (HLA) identity or not, first and second warm and cold ischemia times, left or right kidney and fossa, donor kidney anatomy, donor serum creatinine and proteinuria, and transplantation year were included [5].

High impact information on Cold Ischemia

• Following cold ischemia/isotransplantation, HO-1 overexpression extended animal survival from 40% in untreated controls to about 80% after CoPP or Ad-HO-1 therapy [6].
• Concentrations of amino acids (alanine, cysteine, leucine, isoleucine, methionine, lysine, ornithine, and threonine) and transaminases (alanine aminotransferase and aspartate aminotransferase) in the preservation fluid correlated with the duration of cold ischemia [7].
• RESULTS: Compared with baseline values, similar alterations were found in both groups after cold ischemia for hepatocyte function (intrahepatic resistance, bile secretion, lactate dehydrogenase release, oxygen consumption, and taurocholate intrinsic clearance) and for sinusoidal endothelial cell function (hyaluronic acid intrinsic clearance) [8].
• Experiments were designed to evaluate (i) hepatic cytosolic calpain activity during different periods of cold ischemia (CI), rewarming, or reperfusion, and (ii) effects of inhibition of calpain on liver graft function using the isolated perfused rat liver and arterialized orthotopic liver transplantation models [9].
• Nitroglycerin improves functional recovery of neonatal lamb hearts after 2 hours of cold ischemia [10].

Chemical compound and disease context of Cold Ischemia

• No differences were seen for body weight, number of mismatches, cold ischemia time, immunosuppressive regimens, and other pharmacokinetic parameters of methylprednisolone (e.g. bioavailability, distribution volume, trough levels) [11].
• NADH and FAD fluorescence was measured in the left ventricular wall of guinea pig isolated hearts assigned to five groups of eight animals each: hypothermia alone, hypothermia with ischemia, IPC with cold ischemia, 5-hydroxydecanoic acid (5-HD) alone, and 5-HD with IPC and cold ischemia [12].
• Hyperkalemia at 1-min postrevascularization did not correlate with the extent of preservation injury of the graft liver (represented by the peak value of aspartate aminotransferase measured within the first 72 h after OLT) or the duration of cold ischemia [13].
• RESULTS: Adenosine triphosphate was 71% +/- 4%, 71% +/- 7%, and 38% +/- 5% of baseline at 30 minutes, and 71% +/- 4%, 48% +/- 5%, and 39% +/- 6% at 42 minutes of ischemia in the cold ischemia, warm ischemia, and normothermic ischemia without prior cardioplegia groups, respectively [14].
• Glycine has been shown to decrease membrane injury in isolated cells due to hypoxia or cold ischemia [15].

Biological context of Cold Ischemia

• In autotransplantation studies on protracted cold ischemia, verapamil produced a modest, although physiologically significant, increase in GFR during warm reperfusion but failed to alter graft survival [16].
• The results also showed that prolonged incubation (cold ischemic time) to 2 h and pretreatment with serotonin further enhanced gene expression [17].
• CONCLUSIONS: ET-A receptor activation mediates microvascular dysfunction through precapillary blockades and leukocyte-endothelial cell interactions after cold ischemia and reperfusion in the canine small bowel [18].
• Neither endothelial-dependent nor endothelial-independent cGMP-mediated vasorelaxation was dysfunctional after cold ischemia alone, but both were significantly impaired after reperfusion [19].
• This protective effect, reflected by decreased intestinal damage and bacterial translocation, was related to a decrease in adenosine triphosphate depletion during cold ischemia before intestinal transplantation, and to the reduced availability of xanthine oxidase substrates for free radical generation during reperfusion [20].

Anatomical context of Cold Ischemia

• Effect of antibody to leukocyte adhesion molecule CD18 on recovery of neonatal lamb hearts after 2 hours of cold ischemia [21].
• In living-donor transplants, erythrocyte velocity did not correlate with donor age, both warm (WIT) and cold ischemic time (CIT), time to the initial urination, and best creatine clearance [22].
• OBJECTIVE: To investigate whether tirilazad mesylate, a 21-aminosteroid, protects the small intestinal mucosa from injury following total warm or cold ischemia and reperfusion [23].
• The results indicate that increases in pancreas 6-keto PGF1 alpha occur as a consequence of cold ischemia while TXB2 remains unchanged [24].
• We investigated reimplantation-induced lung injury in isolated, reperfused rat lungs after preservation via the pulmonary artery with Celsior, Celsior + prostacyclin, and reduced-potassium (40 mmol) Euro-Collins solution (40 ml/kg/body wt each) followed by 2 h of cold ischemia [25].

Associations of Cold Ischemia with chemical compounds

• This endogenous protective mechanism is capable of blocking xanthine/XOD generation in liver grafts during cold ischemia [26].
• The addition of U74006F to University of Wisconsin preservation solution significantly prolonged endothelial cell viability after 48 and 72 hr of cold ischemia and reoxygenation (p < 0.01) [27].
• The following experimental groups were studied: I, cold ischemia; I+X, effect of xanthine; I+T, effect of adenosine (blocking its receptor by theophylline); I+A, effect of excess adenosine; I+T+X, effect of xanthine alone, and I+T+ spermine NONOate (NONOs), I+A+NONOs, I+X+NONOs, role of NO [28].
• The study objective was to assess hepatic utilization of exogenous adenosine or adenine to enhance ATP recovery in rat liver after cold ischemia [29].
• In a multivariate regression model, donor age and recipient creatinine were observed to be significant covariates in both groups, while donor race, cold ischemia time (CIT), female to male transplants, and recipient albumin were independent predictors of survival of HCV- recipients [30].

Gene context of Cold Ischemia

• Interleukin-10 plasma levels did not correlate either with cold ischemia time or with the occurrence of rejection episodes [31].
• CINC mRNA also increased as cold-ischemia time was prolonged [32].
• The W/D ratio and myeloperoxidase decreased in both 24- and 48-hour groups, with TGF-beta1-active compared with CAT, and 18-hour cold ischemia groups (W/D, p < 0.02 and p < 0.004, respectively; myeloperoxidase, p < 0.05 and p < 0.01, respectively) [33].
• Multiple regression revealed a significant correlation between cold ischemia time and posttransplant urinary FBPase excretion (multiple R = 0.65, p < 0.001) [34].
• In renal grafts with pretransplantation cold ischemia and subsequent ischemia-reperfusion injury, overactivation of PARP-1 may lead to a higher index of acute tubular necrosis, a delay in total recovery of the function of the transplanted organ, and an early progression to chronic graft nephropathy [35].

Analytical, diagnostic and therapeutic context of Cold Ischemia

• Ischemic preconditioning reduced xanthine accumulation and conversion of XDH to XOD in liver grafts during cold ischemia [26].
• Relative to control isografts, cold ischemia induced transiently enhanced endothelial expression of intercellular adhesion molecule-1 (ICAM-1) at 4 hours post-transplant [36].
• During cold ischemia, the adenosine triphosphate (ATP) level was not correlated with graft function, but two grafts with low total adenine nucleotides (TAN) levels showed poor function after transplantation [37].
• METHODS: Fischer 344 and Brown Norway rat heart allografts and Lewis isografts were treated with rapamycin or cyclosporine, exposed to 4 hr of cold ischemia, and observed for 100 to 300 days before the incidence and degree of TVP and perivascular infiltration were assessed [38].
• We postulate that this is caused by a combination of warm ischemia, cold ischemia, and hypertonic citrate during in situ preservation (ISP) rather than hypothermic machine preservation [39].

References