raffinose and Edema

Intestinal transplantation has become the therapy of choice for patients with intestinal failure and life-threatening complications from total parenteral nutrition. Results, however, remain inferior as compared with other transplant types with the quality of the organ graft as the most important factor of outcome after transplantation. The intestine is extremely sensitive to ischemia. Unfortunately, a relatively long ischemic preservation period is inevitable. The current standard in organ preservation [cold storage (CS) with University of Wisconsin solution] was developed for kidney/liver preservation and is suboptimal for the intestinal graft despite good results for other organs. This review aimed at appraising the results from the use of previously applied and recently developed preservation solutions and techniques to identify key areas for improvement. As the studies available do not reveal the most effective method for intestinal preservation, an optimal strategy will result from a synergistic effect of different vital elements identified from a review of published material from the literature. A key factor is the composition of the solution using a low-viscosity solution to facilitate washout of blood, including amino acids to improve viability, impermeants and colloids to prevent edema, and buffer for pH-homeostasis. Optimizing conditions include a vascular flush before CS and luminal preservation. The most effective composition of the luminal solution and a practical, clinically applicable optimal technique are yet to reach finality. Short-duration oxygenated arterial and/or luminal perfusion have to be considered. Thus, a tailor-made approach to luminal preservation solution and technique need further investigation in transplant models and the human setting to develop the ultimate technique meeting the physiologic demands of the intestinal graft during preservation.

Topics: Adenosine; Allopurinol; Amino Acids; Animals; Antioxidants; Buffers; Colloids; Disaccharides; Edema; Electrolytes; Glutamates; Glutathione; Histidine; Humans; Insulin; Intestine, Small; Mannitol; Organ Preservation; Organ Preservation Solutions; Raffinose; Viscosity

The impact of different preservation solutions for washout of kidney grafts was evaluated regarding temperature, kidney weight, remaining red blood cells (RBCs) and histological evaluation after ex vivo washout using 500 mL cold preservation solution at 4 degrees C followed by 24 hours cold storage (CS).. Kidneys retrieved from Landrace pigs (20-30 kg) were immediately washed (warm ischemic time 0 min [WIT 0]), using 500 mL cold University of Wisconsin solution (UW), histidine-tryptophan-ketoglutarate (HTK), or Polysol (PS) followed by 24 hours, CS. Also, kidneys were retrieved after a WIT of 30 minutes followed by washout using HTK or PS.. After washout, the weight of kidneys washed out with HTK had increased, whereas that of organs in the UW or PS group had decreased. After washout with UW, the core temperature of WIT 0 kidneys was lower than that with HTK. The time needed for washout using 500 mL solution was shorter using PS compared with HTK for both WIT 0 and WIT 30 groups. The amount of remaining RBCs was similar between all WIT 0 groups; whereas in the WIT 30 groups the amount was higher in kidneys washed out using HTK compared with PS. Histological evaluation showed less tissue injury among PS-washed kidneys compared with UW or HTK.. Overall, kidneys washed-out with PS showed better preservation of structural integrity after 24 hours, CS compared with either UW or HTK. Washout of warm ischemically damaged kidneys was more effective using PS compared with HTK.

Topics: Adenosine; Allopurinol; Animals; Edema; Erythrocyte Count; Glucose; Glutathione; Insulin; Kidney; Kidney Glomerulus; Kidney Transplantation; Kidney Tubules; Mannitol; Organ Preservation; Organ Preservation Solutions; Potassium Chloride; Procaine; Raffinose; Swine; Tissue Donors

Although hypothermic machine perfusion (HMP) preservation has been shown to improve organ function and to expand the organ donor pool, problems still exist with the current HMP technology for liver preservation. The present study was conducted to investigate endothelial and hepatocellular functions following extended HMP (> r =24 hr) in rat liver model.. Following 24-hour hypothermic HMP with University of Wisconsin (UW) solution or 24-hour simple cold storage (SCS), livers were reperfused with Krebs-Henseleit buffer solution at 37 degree C for 30 minutes. Hepatocyte damage and function were assessed by measuring lactate dehydrogenase (LDH) activity, bile production, and indocyanine green (ICG) extraction. Sinusoidal endothelial cell (SEC) function and permeability were determined by hyaluronic acid (HA) uptake and multiple indicator dilution (MID) method, respectively.. After 24-hour hypothermic preservation, HMP livers showed lower released LDH levels, higher bile flow rate, and greater hepatic ICG uptake compared with SCS livers. However, LDH levels became significantly higher in HMP than in SCS after 30 minutes of warm perfusion. The increased enzyme levels were accompanied by a significant increase in endothelial permeability to albumin and a decrease in hyaluronic acid uptake in HMP compared to SCS. Liver wet/dry weight ratio confirmed a greater edema in HMP livers than SCS livers.. These results suggest that 24-hour hypothermic HMP may help preservation of hepatocyte function, but endothelial cell dysfunction during the cold preservation may play a key role in hepatocyte dysfunction and parenchymal cell death upon reperfusion.

Topics: Adenosine; Albumins; Allopurinol; Animals; Bile; Cryopreservation; Edema; Endothelium; Glucose; Glutathione; Hepatocytes; Hyaluronic Acid; Insulin; L-Lactate Dehydrogenase; Liver; Liver Diseases; Male; Organ Preservation; Organ Preservation Solutions; Perfusion; Permeability; Raffinose; Rats; Rats, Sprague-Dawley; Time Factors; Tromethamine

University of Wisconsin (UW) solution (Viaspan) is currently used to preserve organs from nonheartbeating donors. Histidine-tryptophan-ketoglutarate (HTK) solution (Custodiol) is of proven efficacy in experimental pancreas preservation, but its efficacy in combined warm ischemia (WI) and cold ischemia (CI) is unknown. The viability of HTK-preserved porcine pancreatic grafts was assessed after various periods of WI and compared with grafts flushed and preserved with UW solution.. A total of 14 pigs were used: G1 (n=4, UW) and G2 (n=4, HTK) with 15-min WI and 16-hr cold storage; G3 (n=3, UW) and G4 (n=3, HTK) with 30-min WI and 16-hr cold storage.. All animals in G1 and G2 were normoglycemic, whereas only 66% of pancreases were functioning in G3 and G4. HTK perfusion was associated with increased wet weight. Transient hyperinsulinemia was noted in all the groups on postoperative day 1 (mean range: 8.9-12.4 microU/L). Postoperative serum amylase and lipase were more pronounced in G3 and G4. However, HTK-stored grafts exhibited less evidence of biochemical pancreatitis as compared with UW-stored grafts on the first postoperative day in the group with 15-min WI. Mean K values of intravenous glucose tolerance tests on postoperative day 14 were similar in both groups. Vascular congestion was uniformly observed and was considered a typical feature of WI.. Porcine pancreatic grafts are viable after 16-hr CI following 15-min WI in this experimental nonheartbeating donor model. HTK solution seems to provide reliable graft function in this setting and to be equivalent to UW.

Topics: Adenosine; Allopurinol; Amylases; Animals; Cold Temperature; Edema; Glutathione; Graft Survival; Hot Temperature; Hyperinsulinism; Hypoglycemia; Insulin; Lipase; Models, Animal; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Raffinose; Reperfusion Injury; Swine

Topics: Adenosine; Allopurinol; Amylases; Animals; Disaccharides; Edema; Electrolytes; Endothelin-1; Female; Glutamates; Glutathione; Histidine; Insulin; Lipase; Mannitol; Organ Preservation; Organ Preservation Solutions; Oxygen Consumption; Pancreas; Pancreas Transplantation; Raffinose; Swine; Swine, Miniature

Topics: Adenosine; Allopurinol; Cold Temperature; Edema; Follow-Up Studies; Glutathione; Graft Rejection; Humans; Insulin; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Postoperative Complications; Raffinose; Safety; Time Factors; Treatment Failure; Treatment Outcome

Studies of myocardial edema and diastolic dysfunction in rat heart transplantation have been flawed by ischemic injury. This study uses improved methods to prevent ischemic contracture.. Hearts of 30 ACI rats were transplanted into the abdomen of Lewis rats by use of cold University of Wisconsin solution for improved preservation. Left ventricular diastolic properties were expressed as volume at standardized pressure intervals.. On posttransplantation day 3, mean left ventricular volume at 15 mm Hg in allografts (290 +/- 9 microl, SEM) was not significantly different vs isografts (299 +/- 32 microl), allografts on day 0 (337 +/- 28 ml) or day 1 (324 +/- 20 microl), or native hearts (334 +/- 19 microl). However, volume was reduced to 173 +/- 17 microl on day 4 and to 70 +/- 23 microl on day 5 (p < 0.05). Similar findings were obtained for volume at 5 and 10 mm Hg. Allograft myocardial water content on day 3, 76.3% +/- 5%, similar to allografts on day 0 and 1 and to isografts on day 3, increased to 77.6% +/- 8% on day 4 (NS) and 79.4% +/- 6% on day 5 (p < 0.05 vs day 0). Histologically, rejection in allografts was mild on day 3, moderate on day 4, and severe on day 5.. Reduced left ventricular filling volume during rejection is only partially explained by edema. Abnormalities of diastolic properties previously attributed to the unloaded state of nonworking heart models may actually reflect inadequate peritransplantation myocardial protection.

Topics: Adenosine; Allopurinol; Animals; Cardiomyopathies; Cardioplegic Solutions; Diastole; Edema; Glutathione; Graft Rejection; Heart Transplantation; Insulin; Male; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred ACI; Rats, Inbred Lew; Transplantation, Heterotopic; Ventricular Dysfunction, Left

The University of Wisconsin solution has been proven to be effective for prolonged heart preservation. However, 24-hour heart preservation by simple cold immersion in University of Wisconsin solution has been disappointing. We have performed hypothermic low-pressure continuous coronary perfusion with oxygenated University of Wisconsin solution for experimental prolonged heart preservation. However, the high potassium concentration of University of Wisconsin solution combined with prolonged ischemia has detrimental effects on endothelial function, which increases coronary tone during preservation and after reperfusion. The severe vasoconstriction and tissue edema result in damage to the coronary microcirculation. The purpose of this study was to determine whether hypothermic low-pressure continuous coronary perfusion technique with oxygenated University of Wisconsin solution containing a selective endothelin-A receptor antagonist (FR139317) would increase the effectiveness of the perfusion technique and improve postischemic cardiac function, both minimizing tissue edema and suppressing vasoconstriction.. Preischemic and postischemic cardiac function of isolated rabbit hearts was evaluated with a Langendorff apparatus. The hearts were divided into three groups (n = 7 each): group I (hypothermic low-pressure continuous coronary perfusion with University of Wisconsin solution), group II (hypothermic low-pressure continuous coronary perfusion with oxygenated University of Wisconsin solution), and group III (hypothermic low-pressure continuous coronary perfusion with oxygenated University of Wisconsin solution containing 10 mg/L of FR139317). Preservation was performed for 24 hours. The initial perfusion pressure for continuous coronary perfusion was set at 5 mm Hg. Measurement of percentage of tissue water content and ultrastructural examination of the myocardium was then performed. In groups I, II, and III, the perfusion pressures at the end of the 24-hour preservation period increased from 5 mm Hg to 12.2 +/- 2.5, 8.1 +/- 1.3, and 5.4 +/- 0.8 mm Hg (p < 0.05), respectively. Percent recovery rate of cardiac output was 56.6 +/- 2.8, 82.3 +/- 8.2, and 93.3 +/- 6.0 (p < 0.05), respectively. And percent recovery rate of coronary flow was 55.5 +/- 8.1, 80.0 +/- 8.0, and 94.3 +/- 9.4 (p < 0.05), respectively. A significant inverse correlation was found between continuous coronary perfusion pressure at the end of preservation and the recovery rate of cardiac output (r = 0.85, p < 0.05). Tissue water content was significantly higher in group I than in groups II and III. These effects were inhibited by oxygenation of the University of Wisconsin solution (group II) and by the addition of the selective endothelin-A receptor antagonist (FR139317) (group III). Damage to coronary circulation was reduced by oxygenation and the addition of endothelin-A receptor antagonist during prolonged heart preservation.. We concluded that hypothermic low-pressure continuous coronary perfusion technique with oxygenated UW solution containing endothelin-A receptor antagonist (FR139317) maintained coronary circulation by suppressing tissue edema and vasoconstriction during preservation, which improved postischemic functional recovery.

Topics: Adenosine; Allopurinol; Animals; Azepines; Blood Pressure; Body Water; Cardiac Output; Cardioplegic Solutions; Coronary Circulation; Cryopreservation; Edema; Endothelin Receptor Antagonists; Glutathione; Heart Transplantation; Hypothermia, Induced; Indoles; Insulin; Ischemia; Microcirculation; Myocardial Contraction; Myocardium; Organ Preservation; Organ Preservation Solutions; Oxygen; Rabbits; Raffinose; Reperfusion; Time Factors; Vasoconstriction

The effectiveness of University of Wisconsin (UW) and University of Pittsburgh (UP) solutions for the preservation of rat hearts was compared. Lewis rat hearts were preserved with UW (group A, n = 45) or UP (group B, n = 45) solution for 0 or 24 h and then transplanted heterotopically into the recipients' abdomen. Ten recipients in each group were observed to obtain 1-week graft survival rates. Tissue water content and tissue content of adenine nucleotides were measured 2 h after transplantation in six grafts from each group. Six hearts preserved for 0 h and seven hearts preserved for 24 h were taken from each group 24 h after grafting for histopathology. The 1-week graft survival rates of groups A24 and B24 were 60% and 10%, respectively. In the 24-h preserved grafts, adenosine triphosphate (ATP) and energy charge [(ATP + adenosine diphosphate/2)/(ATP + adenosine diphosphate + adenosine monophosphate)] of groups A and B were 0.972 +/- 0.165 and 0.200 +/- 0.123 mg/g wet tissue (P < 0.05) and 74.4% and 61.1% (P < 0.05), respectively. The tissue water content of group A24 was 71.7%, whereas that of group B24 was 74.1% (P < 0.05). Histopathology revealed more severe muscle edema and necrosis and infiltration of polymorphonuclear cells in group B24 than in group A24. We conclude that UW solution is more appropriate for rat heart preservation than UP solution.

Topics: Abdomen; Adenine Nucleotides; Adenosine; Allopurinol; Animals; Body Water; Cardioplegic Solutions; Edema; Energy Metabolism; Glutathione; Graft Survival; Heart; Heart Transplantation; Insulin; Male; Myocardium; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred Lew; Transplantation, Heterotopic

Topics: Adenosine; Allopurinol; Analysis of Variance; Animals; Cardioplegic Solutions; Coronary Vessels; Edema; Glutathione; Heart; Heart Arrest, Induced; Insulin; Magnetic Resonance Spectroscopy; Male; Organ Preservation; Organ Preservation Solutions; Perfusion; Polyethylene Glycols; Raffinose; Rats; Rats, Wistar; Time Factors; Ventricular Function, Left

Topics: Adenosine; Adolescent; Adult; Allopurinol; Amylases; Edema; Female; Glutathione; Humans; Insulin; Magnetic Resonance Imaging; Male; Middle Aged; Organ Preservation; Organ Preservation Solutions; Pancreas Transplantation; Pancreatic Diseases; Raffinose; Time Factors; Tissue Donors

The role of eicosanoid metabolism and its relationship with nitric oxide production in the ischemia-reperfusion associated with pancreas transplantation in the rat is explored in this study. Twenty-six male Sprague-Dawley rats were randomized into 3 groups, as follows: group 1, control animals not surgically manipulated; group 2, pancreas transplantation, after 12 hr of organ preservation in University of Wisconsin solution; group 3, same as group 2 but with administration of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) (10 mg/kg) before organ revascularization. The results show posttransplantation increases in edema and in 6-keto-prostaglandin F1 alpha (x1.9), thromboxane B2 (x4), and prostaglandin E2 (x5) levels in pancreatic tissue. Nitric oxide synthase inhibition reversed the increases in edema and eicosanoid production, which suggests that eicosanoid generation in the recipient rat would be mediated, in part, through a nitric oxide-dependent mechanism.

Topics: Adenosine; Allopurinol; Animals; Arginine; Dinoprostone; Edema; Glutathione; Insulin; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Organ Preservation; Organ Preservation Solutions; Pancreas Transplantation; Prostaglandins F; Raffinose; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Thromboxane B2

Topics: Adenosine; Adolescent; Adult; Allopurinol; Edema; Glutathione; Humans; In Vitro Techniques; Insulin; Magnetic Resonance Imaging; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Pancreatic Diseases; Raffinose; Time Factors; Tissue Donors; Water