Surgical implantation and evaluation of heart rate transmitters in captive bighorn sheep.

A surgical approach was developed for implantation of transmitters to monitor heart rate of bighorn sheep (Ovis canadensis) with an objective of discrete long-term, long-range data collection. We surgically implanted Telonics model HR400 transmitters on the dorsolateral thorax of 15 captive adult bighorn sheep ewes in April-May and October-November 1995. No complications or marked impairment of function were associated with the surgery; however, a transmitter was passively expelled from one ewe 19.5 mo post-implantation. Twelve of 15 transmitters remained functional > or = 1 yr, while three failed 3.5 to 4.5 mo following implantation. Heart rate data collected from the transmitters using a Lotek SRX_400 telemetry receiver/datalogger equipped with W9 EVENT_LOG accurately reflected heart rate as measured with electrocardiogram tracings. Line of sight signal range was at least 800 m in 95% (37/39) of collections made from standing ewes, while data could be collected reliably (74%; 29/39) to 600 m from bedded ewes. When a reliable long-lasting inconspicuous telemetry system is required, we believe that this approach holds promise for success in free-ranging as well as captive ungulates.

Hypoxia regulates xanthine dehydrogenase activity at pre- and posttranslational levels.

Hypoxia increases the activity of xanthine oxidase (XO) and its precursor, xanthine dehydrogenase (XDH), but the mechanism of regulation is unclear. In hypoxic Swiss 3T3 cells, an early (0-24 h) cycloheximide-insensitive increase in XO-XDH activity, coupled with a lack of increase in de novo XO-XDH synthesis (immunoprecipitation) or mRNA levels (quantitative RT-PCR), demonstrated a posttranslational effect of hypoxia. Similarly, hyperoxia decreased XO-XDH activity faster than could be accounted for by cessation of XO-XDH protein synthesis. In further support of a posttranslational effect, cells transfected with a constitutively driven XDH construct displayed an exaggerated increase in activity in hypoxia but no increase in activity in hyperoxia. However, more prolonged exposure to hypoxia (24-48 h) induced an increase in XO-XDH mRNA levels and de novo XO-XDH protein synthesis, suggesting an additional pretranslational effect. Finally, hypoxic induction of XO-XDH activity was found to be cell-type-restricted. We conclude that control of XO-XDH levels by oxygen tension is a complex process which involves several points of regulation.

XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism.

Circulating xanthine oxidase (XO) can modify adhesive interactions between neutrophils and the vascular endothelium, although the mechanism underlying this effect are not clear. We found that treatment with XO of bovine pulmonary artery endothelial cells (EC), but not neutrophils or plasma, increased adherence, suggesting that XO had its primary effect on EC. The mechanism by which XO increased neutrophil adherence to EC involved binding of XO to EC and production of H2O2. XO also increased platelet-activating factor production by EC by a H2O2-dependent mechanism. Similarly, the platelet-activating factor-receptor antagonist WEB-2086 completely blocked XO-mediated neutrophil EC adherence. In addition, neutrophil adherence was dependent on the beta 2-integrin Mac-1 (CD11b/CD18) but not on leukocyte functional antigen-1 (CD11a/CD18). Treatment of EC with XO for 30 min did not alter intercellular adhesion molecule-1 surface expression but increased expression of P-selectin and release of von Willibrand factor. Antibodies against P-selectin (CD62) did not affect XO-mediated neutrophil adherence under static conditions but decreased both rolling and firm adhesive interactions under conditions of shear. We conclude that extracellular XO associates with the endothelium and promotes neutrophil-endothelial cell interactions through dual intercellular adhesion molecule-1 and P-selectin ligation, by a mechanism that involves platelet-activating factor and H2O2 as intermediates.

Endogenous nitric oxide decreases xanthine oxidase-mediated neutrophil adherence: role of P-selectin.

The oxygen radical-producing enzyme xanthine oxidase (XO) can promote neutrophil adherence to endothelium. Recognizing that a balance often exists in inflammatory processes, we sought to determine whether XO initiates antiadherent pathways. We found that bovine pulmonary arterial endothelial cells (EC) exposed to XO released increased amounts of nitrite into the media, reflecting an increased production of nitric oxide (NO). When EC were subjected to shear stress, treatment with XO and/or the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA) increased neutrophil rolling behavior and firm neutrophil adherence to EC in an additive fashion. Both rolling and adherent interactions were abolished by monoclonal antibodies directed against P-selectin. In addition, treatment of EC with XO and/or L-NNA increased both surface expression of P-selectin and release of von Willebrand factor into media. Finally, treatment of EC with the NO donor sodium nitroprusside decreased XO-mediated neutrophil rolling and adherence. We conclude that XO stimulates EC to produce NO and that NO decreases the P-selectin-dependent neutrophil adhesion initiated by XO. Such increases in endogenous NO may constitute an important negative-feedback response to the acute proadhesive effects of XO.

Femoral head and neck excision in a dog that had previously undergone contralateral hind limb amputation.

A German Shepherd Dog that underwent left hind limb amputation at 6 weeks of age because of quadriceps contracture developed arthritis of the remaining coxofemoral joint when it was 6 months old. The dog subsequently underwent femoral head and neck excision, and following rehabilitation that included intensive physical therapy, the dog was able to walk and run without signs of pain or disability. Strength and agility were maintained during a 4.5-year follow-up period. This case demonstrates the importance of postoperative management in the successful outcome of femoral head and neck excision in a large dog with only 1 hind limb.

Ex vivo biomechanics of Kirschner-Ehmer external skeletal fixation applied to canine tibiae.

The purpose of this study was to determine the respective contribution of each of the following parameters to the compressive, bending, and torsional rigidity of the Kirschner-Ehmer (KE) external fixation splint as applied to canine tibiae with an osteotomy gap: bilateral versus unilateral splints; increasing the number of fixation pins; altering the diameter of fixation pins and side bars; decreasing side bar distances from the bone; increasing pin separation distances in each pin group; decreasing distances between pin groups; altering pin clamp orientation; and altering side bar conformation. Bilateral splints were 100% (mean) stiffer than unilateral splints, with stiffness enhanced to the greatest extent in mediolateral bending and torsion. Increasing pin numbers stiffened both bilateral (mean, 41%; 8 versus 4) and unilateral splints (mean, 14%; 8 versus 4). Medium KE splints were 85% (mean) stiffer than small KE splints. Decreasing side bar distances to the bone from 1.5 cm to 1.0 cm to 0.5 cm increased stiffness of both bilateral and unilateral splints by a mean of 13% to 35%. Widening pin spacing from 1.67 cm to 2.5 cm increased stiffness in craniocaudal bending only (56% increase, bilateral splints; 73% increase, unilateral splints). Decreasing the distance between pin groups from 5.84 cm to 2.5 cm increased stiffness in torsion between 23% (unilateral splints) and 45% (bilateral splints) and decreased stiffness of unilateral splints by 29% in craniocaudal bending. Altering pin clamp configuration so that the bolts of the clamp were inside the side bar rather than outside the side bar increased stiffness in axial compression only (73% increase, bilateral splints; 54% increase, unilateral splints). Conforming the lateral side bar to the tibiae increased only axial compressive stiffness by 77% but was no different than placing the clamps inside the side bars of an unconformed bilateral splint. These results quantify the relative importance of specific parameters affecting KE splint rigidity as applied to unstable fractures in the dog.

Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity.

Exposure to decreasing oxygen tensions progressively increased xanthine dehydrogenase (XD) and xanthine oxidase (XO) activities over 48 hr in cultured pulmonary artery endothelial cells (EC) without altering XD/XO ratios. Increases in XD and XO activity in EC induced by hypoxia were associated upon reoxygenation with increased (P less than 0.05) extracellular superoxide anion (O2-.) levels that were inhibited by treatment with XO inhibitors (tungsten, allopurinol) or an anion-channel blocker (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid). EC monolayers subjected to hypoxia/reoxygenation also leaked more preloaded 51Cr, were more adherent to neutrophils, and permitted greater albumin transit than control monolayers. Treatment with tungsten, allopurinol, and/or superoxide dismutase decreased (P less than 0.05) 51Cr release, neutrophil adherence, and albumin transit in EC monolayers exposed to hypoxia/reoxygenation. We conclude that prolonged hypoxia increases both XO and XD activity in EC and may predispose the endothelium to oxidative and inflammatory damage.

A comparison of surgical training with live anesthetized dogs and cadavers.

Cadavers were compared with live anesthetized dogs for their effectiveness as models for surgical training of veterinary medical students. One group of students was trained using cadavers, and a peer group was trained using live anesthetized dogs. Both groups then performed an intestinal anastomosis using a live subject. The time to completion of the procedure was recorded. The anastomoses and celiotomy closures were evaluated. Each anastomosis was isolated and pressure tested. Reviewers blindly scored each surgical team's performance based on actual inspection of the surgical site and on viewing videotapes of the procedure. The participants' attitudes toward the use of live animals in teaching and research were documented before and after training. No statistically significant differences could be detected between the two groups. The results suggest that some substitution of cadavers for live dogs in surgical training might be feasible.

Partial carpal arthrodesis for third degree carpal sprains. A review of 45 carpi.

The efficacy of partial carpal arthrodesis was evaluated retrospectively in 39 dogs (45 carpi) with severe sprains of the middle carpal joints, the carpometacarpal joints, or both. The carpometacarpal joint was the most frequently injured joint. Jumping or falling from heights was the cause of injury in 49% of these animals. Of the 25 owners who responded to a mailed questionnaire (mean follow-up, 32 months), all stated their animal had improved or greatly improved after partial carpal arthrodesis and all were pleased or very pleased with the final surgical result. Hyperextension persisted in 11% of the cases and degenerative joint disease of the antebrachiocarpal joint was present in 15.5% of the cases. No dogs with partial carpal arthrodesis required panarthrodesis at a later date.

Screw fixation of accessory carpal bone fractures in racing Greyhounds: 12 cases (1981-1986).

Fractures of the accessory carpal bone in 12 racing Greyhounds were repaired by use of internal fixation with screws. All dogs had a sprain-avulsion fracture of the distal margin of the articular surface of the accessory carpal bone, where the accessorioulnar ligament inserts (type I). Two dogs had a second avulsion fracture at the proximal margin of the articular surface, where the palmar ulnocarpal ligament inserts (type II), and 2 dogs had a second fracture at the caudal end of the bone at the insertion of the accessoriometacarpal ligaments (type III). Fractures were exposed surgically, using a palmarolateral approach between the fourth and fifth accessoriometacarpal ligaments, and were repaired using 1.5-mm or 2-mm cortical screws. Eight dogs were evaluated radiographically to monitor fracture healing. Union of fractures, with bridging of the fracture gap, usually developed by 5 to 8 weeks after surgery. Follow-up evaluation after surgical repair was possible in 11 dogs; 10 (91%) returned to training or racing, and 5 (45%) of those won 1 or more races.

Treatment of humeroulnar subluxation with a dynamic proximal ulnar osteotomy. A review of 13 cases.

Humeroulnar subluxation was treated surgically in 13 dogs with 18 affected elbows using a proximal osteotomy of the ulna that allowed the ulna to elongate dynamically. Distal humeroulnar subluxation was secondary to premature closure of the distal ulnar physis in 16 elbows. One distal subluxation was secondary to a radioulnar synostosis, and one proximal subluxation developed after premature closure of the distal radial physis. The mean follow-up time was 22 months. Twenty-eight percent of the elbows were judged to have excellent results, 22% good results, 50% fair results, and none was judged to have a poor outcome. The presenting lameness grade and the severity of preoperative and postoperative humeroulnar subluxation had significant correlations with the prognosis. Associated orthopedic abnormalities and complications of concurrent surgical procedures affected the outcome in several dogs. Overall, the dynamic proximal ulnar osteotomy was a simple and effective technique for the treatment of uncomplicated humeroulnar subluxation.

Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains.

The contribution of toxic O2 metabolites to cerebral ischemia reperfusion injury has not been determined. We found that gerbils subjected to temporary unilateral carotid artery occlusion (ischemia) consistently developed neurologic deficits during ischemia with severities that correlated with increasing degrees of brain edema and brain H2O2 levels after reperfusion. In contrast, gerbils treated just before reperfusion (after ischemia) with dimethylthiourea (DMTU), but not urea, had decreased brain edema and brain H2O2 levels. In addition, gerbils fed a tungsten-rich diet for 4, 5, or 6 wk developed progressive decreases in brain xanthine oxidase (XO) and brain XO + xanthine dehydrogenase (XD) activities, brain edema, and brain H2O2 levels after temporary unilateral carotid artery occlusion and reperfusion. In contrast to tungsten-treated gerbils, allopurinol-treated gerbils did not have statistically significant decreases in brain XO or XO + XD levels, and reduced brain edema and brain H2O2 levels occurred only in gerbils developing mild but not severe neurologic deficits during ischemia. Finally, gerbils treated with DMTU or tungsten all survived, while greater than 60% of gerbils treated with urea, allopurinol, or saline died by 48 h after temporary unilateral carotid artery occlusion and reperfusion. Our findings indicate that H2O2 from XO contributes to reperfusion-induced edema in brains subjected to temporary ischemia.

Xanthine oxidase mediates elastase-induced injury to isolated lungs and endothelium.

Xanthine oxidase (XO)-generated toxic O2 metabolites appear to contribute to reperfusion injury, but the possibility that XO is involved in hyperoxic or neutrophil elastase-mediated injury has not been investigated. We found that lungs isolated from rats fed a tungsten-rich diet had negligible XO activities and after exposure to hyperoxia developed less acute edematous injury during perfusion with buffer or purified neutrophil elastase than XO-replete lungs from control rats which had been exposed to hyperoxia. In parallel, tungsten-treated XO-depleted cultured bovine pulmonary arterial endothelial cells made less superoxide anion and as monolayers leaked less 125I-labeled albumin after exposure to neutrophil elastase than XO-replete endothelial cell monolayers. Our findings suggest that XO-derived O2 metabolites contribute to acute edematous lung injury from hyperoxia directly and by enhancing susceptibility to neutrophil elastase.