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Cardiopulmonary bypass (CPB) causes acute lung injury. Reactive oxygen species (ROS) from NADPH oxidase may contribute to this injury. To determine the role of NADPH oxidase, we pretreated pigs with structurally dissimilar NADPH oxidase inhibitors. Low-dose apocynin (4-hydroxy-3-methoxy-acetophenone; 200 mg/kg, n = 6), high-dose apocynin (400 mg/kg, n = 6), or diphenyleneiodonium (DPI; 8 mg/kg) was compared with diluent (n = 8). An additional group was treated with indomethacin (10 mg/kg, n = 3). CPB was performed for 2 h with deflated lungs, complete pulmonary artery occlusion, and bronchial artery ligation to maximize lung injury. Parameters of pulmonary function were evaluated for 25 min following CPB. Blood chemiluminescence indicated neutrophil ROS production. Electron paramagnetic resonance determined the effect of apocynin and DPI on in vitro pulmonary endothelial ROS production following hypoxia-reoxygenation. Both apocynin and DPI attenuated blood chemiluminescence and post-CPB hypoxemia. At 25 min post-CPB with Fi(O(2)) = 1, arterial Po(2) (Pa(o(2))) averaged 52 +/- 5, 162 +/- 54, 335 +/- 88, and 329 +/- 119 mmHg in control, low-dose apocynin, high-dose apocynin, and DPI-treated groups, respectively (P0.01). Indomethacin had no effect. Pa(O(2)) correlated with blood chemiluminescence measured after drug administration before CPB (R = -0.60, P0.005). Neither apocynin nor DPI prevented the increased tracheal pressure, plasma cytokine concentrations (tumor necrosis factor-alpha and IL-6), extravascular lung water, and pulmonary vascular protein permeability observed in control pigs. NADPH oxidase inhibition, but not xanthine oxidase inhibition, significantly blocked endothelial ROS generation following hypoxia-reoxygenation (P0.05). NADPH oxidase-derived ROS contribute to the severe hypoxemia but not to the increased cytokine generation and pulmonary vascular protein permeability, which occur following CPB.

Background . Ischemic preconditioning is an endogenous mechanism whereby brief periods of ischemia render neurons resistant to subsequent lethal insults. This protection appears to alter cellular apoptosis and can be induced by potassium channel openers acting on the inner membrane of the mitochondria (mitoK ATP ). To test the hypothesis that pharmacologic preconditioning could provide neuroprotection, the mitoK ATP opener diazoxide was used in a canine model of brain injury induced by hypothermic circulatory arrest (HCA). Methods . Seventeen dogs were placed on cardiopulmonary bypass (CPB) and cooled to 18°C. After 2 hours of HCA, animals were rewarmed and weaned from CPB. Six dogs received intravenous diazoxide (2.5 mg/kg bolus 15 minutes prior to CPB, then 0.5 mg/min until circulatory arrest, then restarted for the first hour of rewarming). Six animals received vehicle only. Five received diazoxide and the mitoK ATP blocker 5-hydroxydecanoate (5-HD). Using a modified Pittsburgh Canine Neurological Scoring System (0 = normal, 500=brain death), animals were evaluated every 24 hours for 3 days. The brains were removed and histologic sections of four regions characteristically injured in this model were scored (0 = no injury, 4=infarction) by a neuropathologist in a blinded fashion. Results . Clinical scoring showed marked improvement in the diazoxide group at 48 hours (101 ± 10.5 vs 165 ± 14.8, p p p Conclusions . Pretreatment with diazoxide resulted in significant improvement in both clinical neurologic scores and histopathology in our model of HCA. This suggests that pharmacologic preconditioning with the mitoK ATP channel opener diazoxide may offer effective neuroprotection during HCA.

A seven-year-old, castrated male domestic shorthair was presented with lethargy, fever, and sneezing. In spite of intensive therapy, the cat's condition progressively worsened to severe dyspnea and death. At necropsy, a single, second instar larval stage of Cuterebra sp. was found in the trachea. This represents an unusual site for Cuterebra migration in an aberrant host. The cause of death was attributed to a combination of local tissue damage and anaphylaxis. Veterinarians should include Cuterebra migration in their differential diagnosis list for dyspnea.

ObjectiveThe transfer of tacit and codified knowledge on a surgical technique is studied in a consecutive cohort of teams participating in interactive multimodal continuing medical education (CME) retraining in off-pump coronary artery bypass (OPCAB).MethodsFifty teams of 1.3 ± 0.5 surgeons and 1.1 ± 1.9 anesthetists visited 2.2 ± 0.7 days. Variables describe the pre-visit cardiac activity and OPCAB attitude, complexity score (10 frequently cited complexity criteria), application, and conversion rate. The multimodal approach to knowledge transfer included interactive discussions (commitment; resistances; levers and process of change; methods; outcome; resource optimization), active participation in 3.8 ± 1.3 unselected cases (anchor-stitch, enucleation techniques), low-fidelity bench model (shunt placement, anastomotic technique), and CD-ROM. Exit end points included OPCAB attitude and complexity score. Late end points (3 months) included OPCAB attitude, complexity score, and application rate.ResultsOPCAB was considered, upon exit, beneficial for all patients by 90% of the teams (versus 29 % pre-visit), but by only 62 % of the teams at 3 months. The complexity score downgraded at exit from 3.6 ± 2 (pre-visit) to 1.2 ± 1 (P

Cardiovascular surgery requiring cardiopulmonary bypass (CPB) is frequently complicated by postoperative lung injury. Bronchial artery (BA) blood flow has been hypothesized to attenuate this injury. The purpose of the present study was to determine the effect of BA blood flow on CPB-induced lung injury in anesthetized pigs. In eight pigs (BA ligated) the BA was ligated, whereas in six pigs (BA patent) the BA was identified but left intact. Warm (37°C) CPB was then performed in all pigs with complete occlusion of the pulmonary artery and deflated lungs to maximize lung injury. BA ligation significantly exacerbated nearly all aspects of pulmonary function beginning at 5 min post-CPB. At 25 min, BA-ligated pigs had a lower arterial Po2at a fraction of inspired oxygen of 1.0 (52 ± 5 vs. 312 ± 58 mmHg) and greater peak tracheal pressure (39 ± 6 vs. 15 ± 4 mmHg), pulmonary vascular resistance (11 ± 1 vs. 6 ± 1 mmHg·l–1·min), plasma TNF-α (1.2 ± 0.60 vs. 0.59 ± 0.092 ng/ml), extravascular lung water (11.7 ± 1.2 vs. 7.7 ± 0.5 ml/g blood-free dry weight), and pulmonary vascular protein permeability, as assessed by a decreased reflection coefficient for albumin (σalb; 0.53 ± 0.1 vs. 0.82 ± 0.05). There was a negative correlation ( R = 0.95, P < 0.001) between σalband the 25-min plasma TNF-α concentration. These results suggest that a severe decrease in BA blood flow during and after warm CPB causes increased pulmonary vascular permeability, edema formation, cytokine production, and severe arterial hypoxemia secondary to intrapulmonary shunt.

Thrombosis is the major cause of early vein graft failure. Our aim was to determine whether alterations in the expression of the anticoagulant proteins, thrombomodulin (TM) and the endothelial cell protein C receptor (EPCR), impair endothelial thromboresistance that may contribute to vein graft failure. Immunohistochemical staining of autologous rabbit vein graft sections revealed that the expression of TM, but not EPCR, was reduced significantly early after graft implantation. Western blot analysis revealed that TM expression was reduced by >95% during the first 2 weeks after implantation, with gradual but incomplete recovery by 42 days. This resulted in up to a 95% reduction in the capacity of the grafts to activate protein C and was associated with an increase in bound thrombin activity, which peaked on day 7 at 28.7±3.8 mU/cm 2 and remained elevated for more than 14 days. Restoration of TM expression using adenovirus vector-mediated gene transfer significantly enhanced the capacity of grafts to activate protein C and reduced bound thrombin activity on day 7 to levels comparable to that of normal veins (5.7±0.4 versus 5.2±1.1 mU/cm 2 , respectively, P =0.74). Surprisingly, neointima formation was not affected by this inhibition of local thrombin activity. These data suggest that the early loss of TM expression significantly impairs vein graft thromboresistance and results in enhanced local thrombin generation. Although enhanced local thrombin generation may predispose to early vein graft failure due to thrombosis, it does not seem to contribute significantly to late vein graft failure due to neointimal hyperplasia.