allopurinol and Constriction--Pathologic

Topics: Adenosine; Adult; Allopurinol; Cholestasis; Constriction, Pathologic; Glutathione; Humans; Insulin; Liver Transplantation; Male; Middle Aged; Organ Preservation Solutions; Postoperative Complications; Raffinose; Retrospective Studies; Risk Factors

This study compares biliary complication rates associated with use of two different preservative solutions, Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW), utilized in orthotopic liver transplantation (LT) with donations after cardiac death (DCDs).. Between 1997-2010, we retrospectively studied 35 LTs performed utilizing DCD donors, preserved either with HTK (n=17) or UW(n=18). Biliary complications were defined by the presence of anastomotic strictures, non-anastomotic strictures, and/or biliary leak on endoscopic retrograde cholangiopancreatography.. HTK and UW cohorts were similar in terms of demographics as well as pre- and post-operative biochemical profile. Donor age was significantly higher among HTK compared to UW recipients (41.5 ± 11.9 vs. 26.2 ± 8.8 years, p<0.001). The incidence of post-LT biliary complications was higher in the HTK group (76% vs. 39% in UW group, p=0.041). Hepatic arterial thrombosis (HAT) was observed among 3 HTK patients (17.7%) and 1 UW patient (5.6%), p=0.33. No patients underwent retransplantation in UW group, five recipients in HTK group underwent retransplantation (29%), p=0.019; 4 due to biliary complications and 1 due to HAT.. This single-center study reveals that the use of HTK preservative among DCD donors is associated with an increased risk of biliary complications. Multicenter retrospective studies are suggested to further verify this observation.

Topics: Adenosine; Adult; Allopurinol; Anastomosis, Surgical; Anastomotic Leak; Biliary Tract; Constriction, Pathologic; Female; Glucose; Glutathione; Hepatic Artery; Humans; Insulin; Liver Transplantation; Male; Mannitol; Middle Aged; Organ Preservation Solutions; Postoperative Complications; Potassium Chloride; Procaine; Raffinose; Reoperation; Retrospective Studies; Thrombosis; Tissue Donors

The nonpurine selective xanthine oxidase (XO) inhibitor febuxostat attenuates development of left ventricular (LV) hypertrophy and dysfunction in mice when treatment is initiated within 1 hour of transverse aortic constriction (TAC). This study investigated whether a 7-day delay of treatment with the XO inhibitors febuxostat or allopurinol would reverse TAC-induced changes after onset of heart failure (HF). Neither treatment significantly affected TAC-induced LV hypertrophy; only febuxostat caused a modest improvement in LV function ( approximately 10% increase in LV ejection fraction). However, the purine analog allopurinol tended to increase mortality compared with vehicle or febuxostat in HF mice.

Topics: Allopurinol; Animals; Constriction, Pathologic; Enzyme Inhibitors; Febuxostat; Hypertrophy, Left Ventricular; Male; Mice; Mice, Inbred C57BL; Thiazoles; Xanthine Oxidase

Topics: Aged; Allopurinol; Constriction, Pathologic; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Magnetic Resonance Imaging; Male; Spinal Cord Diseases; Thoracic Vertebrae

The development of biliary strictures (BSs) after liver transplantation (LT) continues to affect 10% to 30% of patients, causing substantial morbidity. The cause of BSs is multifactorial, including technical, immune, and, in particular, ischemic factors. The importance of adequate flushing of the peribiliary arterial tree has been stressed. We hypothesized that high-viscosity (HV) preservation solutions in the donor do not completely flush the small donor peribiliary plexus, leading to inadequate preservation of the bile ducts and posttransplant BSs. To test this hypothesis, we retrospectively compared the incidence of BSs in 2 groups of adults undergoing LT using different types of aortic preservation solution in the donor: group 1 (n = 24), low-viscosity (LV) Marshall solution; and group 2 (n = 27), HV University of Wisconsin (UW) solution. All donors in both groups received additional portal flushes with UW. All LTs were performed between November 1995 and August 1998 at 2 centers by the same surgeon, eliminating a technical bias. Terminal duct-to-duct anastomosis was performed in all recipients except 1 patient in group 1, who underwent a bile duct-to-jejunum anastomosis. BSs were first suspected on clinical and biochemical grounds and then confirmed by endoscopic retrograde cholangiopancreatography. Identical medical protocols were used in all patients. One-year patient survival rates in groups 1 and 2 were 92% and 100%, respectively (P =.9). One-year graft survival was identical to patient survival. The incidence of BSs in group 1 was 4.1% (1 of 24 patients), compared to 29.7% in group 2 (8 of 27 patients; P =.02). The BS in group 1 occurred 4 months post-LT and was anastomotic. BSs in group 2 occurred between 1 and 12 months post-LT and were anastomotic, extrahepatic, intrahepatic, or combined intrahepatic and extrahepatic. There were no significant differences in the following factors between groups 1 and 2: donor age, local versus imported liver, split-liver or full-liver transplantation, incidence of multiple vessels in the donor liver, indications for LT, recipient age, T-tube versus no T-tube, post-LT peak aspartate aminotransferase level, and treatment for rejection. There was no hepatic artery thrombosis or primary nonfunction in either group. Interestingly, cold ischemia time (CIT) was longer in group 1, which had the least incidence of BSs (692 +/- 190 v 535 +/- 129 minutes in group 2; P =.001). Follow-up was longer in group 1 (28.9 +/- 8.

Topics: Adenosine; Adult; Allopurinol; Aorta; Biliary Tract; Cold Temperature; Constriction, Pathologic; Glutathione; Graft Survival; Humans; Hypertonic Solutions; Insulin; Ischemia; Liver Transplantation; Middle Aged; Organ Preservation; Organ Preservation Solutions; Raffinose; Retrospective Studies; Survival Rate; Time Factors; Tissue Donors; Viscosity

Using a reversible chronic constriction injury (CCI) model of neuropathic pain, we previously demonstrated that changes in thermal hyperalgesia correlate with the changes in peripheral microvascular blood flow in the affected paw, and that recovery can be assessed by normalization of both behavioral and vascular responses. Using the same model, this study examined age-related changes in recovery after nerve injury and the involvement of free radicals and nitric oxide (NO) in these changes. Four loose, nonconstrictive ligatures were applied to the sciatic nerve in the right, mid-thigh region of young and old (3 and 24 months) Sprague Dawley rats. All rats were monitored weekly (for 8-10 weeks) for their thermal threshold using a 46 degrees C water bath and some groups were used to examine endothelial and smooth muscle-dependent microvascular responses to substance P (SP) and sodium nitroprusside (SNP), respectively. These substances were perfused over the base of blisters raised on the footpad innervated by the injured nerve. Free radical activity in the sciatic nerve was assessed by measuring the activity of xanthine oxidase (XO) and lipid hydroperoxides (LPO). Young rats showed signs of recovery (reduction in thermal hyperalgesia and improvement of peripheral microvascular blood flow) from the fifth week. No signs of recovery were observed in old rats for 8 weeks, with some reduction in thermal hyperalgesia observed by weeks 9 and 10. XO activity was significantly higher in young injured nerves compared to sham (400%) and was even significantly greater in old injured nerves (680%). Similarly, old injured nerves showed 300% increase in LPO levels compared to sham. The role of reactive oxygen species (ROS) in delayed recovery in old rats was examined using the antioxidant tirilazad mesylate. Tirilazad (20 mg/kg) was injected intramuscularly (im) in the mid-thigh region starting on day 1 post CCI, (early treatment) or day 7 (late treatment). Levels of LPO in the injured sciatic nerves were significantly reduced using either early or late treatment, however tirilazad had opposing effects on recovery, prolonging or alleviating thermal hyperalgesia, respectively. The role of neuronal nitric oxide (nNO) was then examined using the specific neuronal nitric oxide synthase (nNOS) inhibitor, 3-bromo-7-nitroindazole (3Br-7NI) (10 mg/kg). 3Br-7NI resulted in a significant alleviation of thermal hyperalgesia with improvement in the vascular responses from weeks 5 and

Topics: Aging; Animals; Antioxidants; Chronic Disease; Constriction, Pathologic; Free Radicals; Hot Temperature; Hyperalgesia; Lipid Peroxides; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Pain; Pregnatrienes; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sciatic Nerve; Xanthine Oxidase

Reactive oxygens are considered to be one of the mediators involved in inflammation. We investigated the constrictive effects of reactive oxygens generated by aerosolized xanthine/xanthine oxidase (XOD) on the airways of anesthetized guinea pigs. Airway resistance was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO). Inhalation of xanthine (1.0 M)/XOD (10, 15 U/ml) caused a significant increase in VO. This airway constriction tended to be enhanced by pretreatment with inhaled superoxide dismutase, but was suppressed by inhaled catalase. Inhalation of hydrogen peroxide caused an airway constriction in a concentration-dependent manner (0.1-2.0 M). Xanthine/XOD significantly enhanced the maximal change in VO after inducing airway inflammation by SO2 exposure. The pretreatment with inhalation of xanthine/XOD did not affect the airway constriction induced by inhaled histamine. However, in SO2-exposed guinea pigs, the inhalation of xanthine/XOD significantly increased the sensitivity to histamine. These results indicate that hydrogen peroxide and other reactive oxygen intermediates produced by xanthine/XOD may cause an airway constriction and airway hyperresponsiveness.

Topics: Administration, Inhalation; Aerosols; Airway Obstruction; Airway Resistance; Animals; Bronchoconstriction; Catalase; Constriction, Pathologic; Dose-Response Relationship, Drug; Drug Interactions; Guinea Pigs; Histamine; Hydrogen Peroxide; Male; Respiratory System; Sulfur Dioxide; Superoxide Dismutase; Xanthine; Xanthine Oxidase; Xanthines

Using 30 anesthetized cats, we examined whether oxygen radicals produce airway constriction or hyperresponsiveness. In one group, we administered aerosolized xanthine (0.1%) for 3 min followed by aerosolized xanthine oxidase (XO) (1 U/ml) for 5 min in order to generate oxygen radicals enzymatically in the airways. Pulmonary resistance (RL) instantaneously increased from 14.8 +/- 0.9 to 30.8 +/- 1.4 cm H2O/L/s (p less than 0.01). The increase in RL was significantly depressed by prior administration of polyethylene glycol-superoxide dismutase (PEG-SOD) or polyethylene glycolcatalase (PEG-CAT). In a second group, in order to examine changes in airway responsiveness, we studied acetylcholine (ACh) challenge before and 30, 60, and 120 min after inhalations of xanthine and XO. After xanthine-XO, the airways were hyperresponsive to ACh at 30 and at 60 min (p less than 0.05) but not at 120 min. The geometric means of ACh provocative concentrations that caused an increase in RL of 10 cm H2O/L/s above the baseline value before and 30, 60, and 120 min after xanthine-XO were 0.25, 0.045, 0.073, and 0.15%, respectively. The increase in responsiveness to ACh was significantly correlated with the increase in RL after xanthine-XO inhalation (r = 0.88, p less than 0.05). These data support the concept that oxygen radicals generated by xanthine-XO inhalation may induce bronchoconstriction and airway hyperresponsiveness.

Topics: Acetylcholine; Aerosols; Animals; Bronchi; Catalase; Cats; Constriction, Pathologic; Dose-Response Relationship, Drug; Free Radicals; Polyethylene Glycols; Superoxide Dismutase; Xanthine Oxidase; Xanthines