thiourea and Cadaver

Terminal sterilization of bone allografts by gamma radiation is often essential prior to their clinical use to minimize the risk of infection and disease transmission. While gamma radiation has efficacy superior to other sterilization methods it also impairs the material properties of bone allografts, which may result in premature clinical failure of the allograft. The mechanisms by which gamma radiation sterilization damages bone tissue are not well known although there is evidence that the damage is induced via free radical attack on the collagen. In the light of the existing literature, it was hypothesized that gamma radiation induced biochemical damage to bone's collagen that can be reduced by scavenging for the free radicals generated during the ionizing radiation. It was also hypothesized that this lessening of the extent of biochemical degradation of collagen will be accompanied by alleviation in the extent of biomechanical impairment secondary to gamma radiation sterilization. Standardized tensile test specimens machined from human femoral cortical bone and specimens were assigned to four treatment groups: control, scavenger treated-control, irradiated and scavenger treated-irradiated. Thiourea was selected as the free radical scavenger and it was applied in aqueous form at the concentration of 1.5 M. Monotonic and cyclic mechanical tests were conducted to evaluate the mechanical performance of the treatment groups and the biochemical integrity of collagen molecules were assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native mechanical properties of bone tissue did not change by thiourea treatment only. The effect of thiourea treatment on mechanical properties of irradiated specimens were such that the post-yield energy, the fracture energy and the fatigue life of thiourea treated-irradiated treatment group were 1.9-fold, 3.3-fold and 4.7-fold greater than those of the irradiated treatment group, respectively. However, the mechanical function of thiourea treated and irradiated specimens was not to the level of unirradiated controls. The damage occurred through the cleavage of the collagen backbone as revealed by SDS PAGE analysis. Irradiated specimens did not exhibit a noteworthy amount of intact alpha-chains whereas those irradiated in the presence of thiourea demonstrated intact alpha-chains. Results demonstrated that free radical damage is an important pathway of damage, caused by cleaving the collagen backbone. Block

Topics: Adult; Bone Transplantation; Cadaver; Collagen; Femur; Free Radical Scavengers; Gamma Rays; Humans; In Vitro Techniques; Male; Microscopy, Electron, Scanning; Radiation-Protective Agents; Sterilization; Tensile Strength; Thiourea; Transplantation, Homologous

The shortage of donors for lung transplantation may be alleviated with the use of lungs retrieved from cadavers. The purpose of this study was to determine whether a free radical scavenger, dimethylthiourea, would improve the function of lungs retrieved from ventilated cadavers.. Left lung transplantation was performed in 21 dogs. Donors were sacrificed then ventilated with 100% oxygen. After 2 hours, donor lungs were flushed in a blinded fashion with 2 L of modified Euro-Collins solution, with either dimethylthiourea (n = 10) or saline solution (n = 11) added, then harvested. A donor right lung lobe was perfused with trypan blue vital dye to assess cell viability at harvest and after the transplantation. Percentage of nonviability was similar in the dimethylthiourea and control groups (13 versus 20 at retrieval and 38 versus 41 at graft reperfusion). After transplantation, the right pulmonary artery and bronchus were occluded, rendering the recipient on the pulmonary graft. The recipient's lungs were ventilated for 8 hours, with the inspired oxygen fraction maintained at 0.4.. Seven of ten dogs in the dimethylthiourea group survived the 8-hour period, compared with 4 of 11 dogs in the control group. Compared with the control survivors (n = 4) at 8 hours after the operation, the dimethylthiourea survivors (n = 7) had a higher mean arterial oxygen pressure (144 +/- 21 versus 98+/- 12 mm Hg) and cardiac output (2.2 +/- 0.2 versus 1.6 +/- 0.2 L/min) and a lower mean pulmonary vascular resistance (946 +/- 96 versus 1414 +/- 128 dynes.sec-1.cm5, p < 0.05) and extravascular lung water (10.6 +/- 1.2 versus 12.3 +/- 3.2 ml/kg). Differences between groups during the 8-hour period were usually insignificant.. This model imposes a rigorous challenge to the single transplanted lung, and yet cadaver lungs still supported life in half of the recipients. Dimethylthiourea may confer a benefit to recipients of cadaver lungs.

Topics: Animals; Cadaver; Cardiac Output; Dogs; Extravascular Lung Water; Free Radical Scavengers; Lung; Lung Transplantation; Organ Preservation; Oxygen; Oxygen Inhalation Therapy; Reactive Oxygen Species; Thiourea; Tissue Survival; Vascular Resistance

The pulmonary donor pool would increase substantially if lungs could be safely transplanted after cessation of circulation. To determine whether the addition of the free radical scavenger dimethylthiourea to the perfusate of cadaver lungs could improve graft function, canine donors were sacrificed, and lungs retrieved 2 hours after death. In a blinded fashion, dimethylthiourea was added to the modified Euro-Collins solution and infused into recipients (n = 9) perioperatively; a placebo was included in the perfusate of control animals (n = 9). Donor animals were ventilated with 100% oxygen only during flush and harvest. Recipients were rendered dependent upon the single left transplanted lung by occlusion of the right pulmonary artery and bronchus 1 hour after transplantation. Ventilation was maintained at a constant inspiratory oxygen fraction of 0.4. Recipients were followed up for 8 hours or until death. Three of 9 control animals survived the 8-hour observation period, whereas 6 of 9 recipients of cadaver lungs harvested with dimethylthiourea survived the observation period. Two deaths in the dimethylthiourea group occurred after 7 hours, implying that the effects of the ischemia and reperfusion injury were ameliorated by the use of this agent in this model. This study supports the notion that perfusate modification may improve the yield of cadaver lung retrieval and may allow for transplantation of lungs harvested from cadavers after cessation of circulation.

Topics: Animals; Cadaver; Dogs; Free Radical Scavengers; Hypertonic Solutions; Lung Transplantation; Organ Preservation; Reperfusion Injury; Thiourea; Time Factors