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This article highlights the recommendations and considerations for maintaining a healthy canine lifestyle. A key component of a healthy lifestyle is the enhancement and optimization of mobility. Mobility is essential in maintaining a high quality of life and involves the interplay of a dog's structure, posture, body condition score, physical exercise, and a healthy human-animal bond throughout a dog's lifetime.

Research on working dogs is growing rapidly due to increasing global demand. Here we report genome scanning of the risk of puppies being eliminated for behavioral reasons prior to entering the training phase of the US Transportation Security Administration’s (TSA) canine olfactory detection breeding and training program through 2013. Elimination of dogs for behavioral rather than medical reasons was based on evaluations at three, six, nine and twelve months after birth. Throughout that period, the fostered dogs underwent standardized behavioral tests at TSA facilities, and, for a subset of tests, dogs were tested in four different environments. Using methods developed for family studies, we performed a case-control genome wide association study (GWAS) of elimination due to behavioral observation and testing results in a cohort of 528 Labrador Retrievers (2002–2013). We accounted for relatedness by including the pedigree as a covariate and maximized power by including individuals with phenotype, but not genotype, data (approximately half of this cohort). We determined genome wide significance based on Bonferroni adjustment of two quasi-likelihood score tests optimized for either small or nearly-fully penetrant effect sizes. Six loci were significant and five suggestive, with approximately equal numbers of loci for the two tests and frequencies of loci with single versus multiple mapped markers. Several loci implicate a single gene, including CHD2, NRG3 and PDE1A which have strong relevance to behavior in humans and other species. We briefly discuss how expanded studies of canine breeding programs could advance understanding of learning and performance in the mammalian life course. Although human interactions and other environmental conditions will remain critical, our findings suggest genomic breeding selection could help improve working dog populations.

The spread of SARS-CoV-2, which causes the disease COVID-19, is difficult to control as some positive individuals, capable of transmitting the disease, can be asymptomatic. Thus, it remains critical to generate noninvasive, inexpensive COVID-19 screening systems. Two such methods include detection canines and analytical instrumentation, both of which detect volatile organic compounds associated with SARS-CoV-2. In this study, the performance of trained detection dogs is compared to a noninvasive headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) approach to identifying COVID-19 positive individuals. Five dogs were trained to detect the odor signature associated with COVID-19. They varied in performance, with the two highest-performing dogs averaging 88% sensitivity and 95% specificity over five double-blind tests. The three lowest-performing dogs averaged 46% sensitivity and 87% specificity. The optimized linear discriminant analysis (LDA) model, developed using HS-SPME-GC-MS, displayed a 100% true positive rate and a 100% true negative rate using leave-one-out cross-validation. However, the non-optimized LDA model displayed difficulty in categorizing animal hair-contaminated samples, while animal hair did not impact the dogs’ performance. In conclusion, the HS-SPME-GC-MS approach for noninvasive COVID-19 detection more accurately discriminated between COVID-19 positive and COVID-19 negative samples; however, dogs performed better than the computational model when non-ideal samples were presented.

The guidelines are the first comprehensive consensus report on veterinary healthcare recommendations for working, assistance, and therapy dogs. This category of canine patients includes a broad assortment of animals, some with well-defined functions and others that provide a more generalized support role. The guidelines discuss recommendations for dogs trained for protection, odor/scent detection, service functions for people with diagnosed disabilities or physical limitations, emotional support, and therapeutic intervention. Although the term is often used to describe dogs providing animal-assisted activities, true therapy dogs provide goal-directed therapy, often under the supervision of a healthcare professional such as an occupational therapist or psychologist. Many working dogs undergo extensive training and have rigorous physical demands placed upon them. These factors make working, assistance, and therapy dogs inherently valuable and impose a need for a high level of primary veterinary care as described in the guidelines. Because working dogs have a particularly close relationship with their handlers, a trust relationship between the practice team and the working-dog client is imperative.

Canine sports medicine and rehabilitation recently have evolved to embody the optimization of performance, injury prevention, and mitigation of musculoskeletal degeneration. This article discusses the diverse factors and considerations of working dog wellness and injury prevention and the importance of recognizing normal and abnormal posture and anatomic structure for performance evaluation and early indication of musculoskeletal injury. The importance of a canine physical fitness program is highlighted and the need for a 4-phase recovery plan to determine if a working dog can safely return to work after injury discussed.

While the world awaits a widely available COVID-19 vaccine, availability of testing is limited in many regions and can be further compounded by shortages of reagents, prolonged processing time and delayed results. One approach to rapid testing is to leverage the volatile organic compound (VOC) signature of SARS-CoV-2 infection. Detection dogs, a biological sensor of VOCs, were utilized to investigate whether SARS-CoV-2 positive urine and saliva patient samples had a unique odor signature. The virus was inactivated in all training samples with either detergent or heat treatment. Using detergent-inactivated urine samples, dogs were initially trained to find samples collected from hospitalized patients confirmed with SARS-CoV-2 infection, while ignoring samples collected from controls. Dogs were then tested on their ability to spontaneously recognize heat-treated urine samples as well as heat-treated saliva from hospitalized SARS-CoV-2 positive patients. Dogs successfully discriminated between infected and uninfected urine samples, regardless of the inactivation protocol, as well as heat-treated saliva samples. Generalization to novel samples was limited, particularly after intensive training with a restricted sample set. A unique odor associated with SARS-CoV-2 infection present in human urine as well as saliva, provides impetus for the development of odor-based screening, either by electronic, chemical, or biological sensing methods. The use of dogs for screening in an operational setting will require training with a large number of novel SARS-CoV-2 positive and confirmed negative samples.

The spotted lanternfly (Lycorma delicatula) is an invasive species first detected in 2014. The insect feeds on plants causing severe damage in vineyards such as the occurrence of sooty mold fungus that impairs leaf photosynthesis. Currently, there is extensive research on how to track and ultimately prevent the spread of this species. It lays eggs that persist through the winter, while the adults die out, which presents a unique opportunity to enter infested or suspected infested areas to begin quarantine and management of the spread while the species is dormant. Detection dogs may be a tool that can be used to search out the spotted lanternfly egg masses during this overwintering period, however it is not known whether dogs can detect any specific odor from the spotted lanternfly eggs. Moreover, as the eggs are only available during certain times of the year, and hatch based on temperature, finding training aids for the dogs could prove difficult. In this study, we investigated whether three detection dogs could learn the odor from dead spotted lanternfly egg masses and if so, whether that would allow them to recognize live spotted lanternfly egg masses. We found that dogs could be trained to find dead spotted lanternfly egg masses, and could learn to ignore relevant controls, with high levels of sensitivity and specificity (up to 94.6% and 92.8%, respectively). Further, we found that after the training, dogs could find live spotted lanternfly egg masses without additional training and returned to previous levels of sensitivity and specificity within a few sessions. Coded videos of training and testing sessions showed that dogs spent more time at the egg masses than at controls, as expected from training. These results suggest that dead spotted lanternfly egg masses could be a useful training aid for spotted lanternfly detection dogs.

OBJECTIVE To compare the cause of death (COD; whether by natural death or euthanasia for poor quality of life caused by a primary pathological condition) between search-and-rescue (SAR) dogs deployed to the World Trade Center, Pentagon, or Fresh Kills Landfill on Staten Island following the 9/11 terrorist attacks and SAR dogs that were not deployed to these sites. ANIMALS 95 deployed SAR dogs (exposed dogs) and 55 nondeployed SAR dogs (unexposed dogs). PROCEDURES Following natural death or euthanasia, 63 dogs (44 exposed and 19 unexposed) underwent a necropsy examination. For the remaining 87 dogs, the COD was categorized on the basis of information obtained from medical records or personal communications. RESULTS The median age of death was 12.8 years for exposed dogs and 12.7 years for unexposed dogs. The COD was not impacted by deployment status. In the 150 exposed and unexposed dogs, degenerative conditions were the most common COD followed by neoplasia. Respiratory disease was infrequent (overall, 7 [4.7%] dogs); 4 of 5 cases of pulmonary neoplasia occurred in unexposed dogs. However, in dogs that underwent necropsy, pulmonary particulates were reported significantly more often in exposed dogs (42/44 [95%]), compared with unexposed dogs (12/19 [63.2%]). CONCLUSIONS AND CLINICAL RELEVANCE No difference was found in the COD on the basis of disease category and organ system involved between exposed and unexposed SAR dogs. The long life spans and frequency of death attributed to degenerative causes (ie, age-related causes) suggested that the risk of long-term adverse health effects in this population of SAR dogs was low.

To determine whether first responders delivering naloxone by either the IM or intranasal (IN) route were at risk of contamination with inert powder simulating canine opioid exposure.Prospective, crossover design.Research study (university setting).Ten clinically normal working dogs ranging from 9 to 44 months were enrolled based on training to detect odor and ability to be restrained with minimal stress. All enrolled dogs completed both arms of the study without adverse effects.Dogs were randomly assigned to fentanyl reversal with either IM or IN naloxone and then the alternate treatment after a 7-day washout period. Prior to reversal, dogs' heads were brushed with an inert glow-in-the-dark powder. First responders (the same 2 individuals for all dogs) performing the reversal were photographed under ultraviolet light prior to and 5 min after administering the medication. Digital photographs were scored by body region for presence of glowing powder by observers blinded to timing of photograph (pre- or postreversal) and route of reversal (IM vs IN).Compared to pretreatment, the inert powder scores were higher after treatment regardless of route of naloxone administration (P0.001). IN administration led to higher contamination than IM naloxone, particularly in the chest area (P = 0.012).Both IN and IM naloxone administration to dogs with clinical signs of opioid exposure result in a risk of first responders becoming contaminated with powder, which could include opioids. Awareness, proper personal protective equipment, and appropriate posttreatment decontamination are important to reduce risk of inadvertent exposure of mucous membranes to these contaminating powders.

OBJECTIVE To determine usefulness of skin turgor and capillary refill time (CRT) for predicting changes in hydration status of working dogs after a 15-minute exercise period. ANIMALS 9 exercise-conditioned working dogs between 8 and 108 months of age. PROCEDURES Skin tent time (SkTT; time for tented skin on the forehead to return to an anatomically normal position) and CRT (time for occluded mucous membrane capillary vessels to return to the color visible before occlusion) were measured on dogs in a field setting and by video review. Body weight (BW), SkTT, CRT, and core body temperature were measured before and after a 15-minute exercise period. Exercise challenge was performed on days 1 and 8. RESULTS Time (day 1 vs day 8) did not significantly affect results; therefore, data were pooled for the 2 trial days. Mean ± SE BW decreased (but not significantly) by 0.83 ± 0.27% after exercise. The SkTT increased significantly (both field setting and video review) after exercise. Correlation between SkTT results for the field setting and video review (r = 0.68) was significant. The CRT decreased (but not significantly) after exercise. CONCLUSIONS AND CLINICAL RELEVANCE Dogs became mildly dehydrated (mean BW loss, 0.83%) during a 15-minute exercise period, and the mild dehydration was evident as a visually detectable change in skin turgor. Monitoring the SkTT appeared to be a useful strategy for predicting small shifts in hydration status of dogs during exercise. The CRT decreased and was not a significant predictor of a change in hydration status.

OBJECTIVE To document the clinical and clinicopathological changes in cats presenting with vehicular trauma (VT) and to determine whether the calculated animal trauma triage (ATT) score was associated with any clinicopathological abnormalities. DESIGN Retrospective descriptive study conducted between 1998 and 2009. SETTING University veterinary teaching hospital. ANIMALS Seventy-five client-owned cats that presented for VT to an urban veterinary hospital. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Pertinent history, physical examination findings, results of biochemical testing, and outcome were extracted from medical records. ATT score was calculated based on physical examination. Patients were classified as having either a low (

OBJECTIVE: To document the clinical and clinicopathologic changes in cats presenting with trauma from bite wounds, identify common abnormalities associated with bite wounds, and to determine whether the calculated animal trauma triage (ATT) score is related to any clinicopathologic abnormalities. DESIGN: Retrospective descriptive study. SETTING: University veterinary teaching hospital. ANIMALS: Forty‐three client‐owned cats that presented for bite wounds to a large, urban, veterinary hospital between 1998 and 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pertinent history, physical examination findings, results of biochemical testing, and outcome were extracted from medical records. Animal triage trauma score was calculated based on the physical examination at presentation in cats with adequate available information. Patients were classified as having either a low (

Objective—To determine the safety and efficacy of an electrolyte solution for oral administration (OES) for the correction of mild to moderate dehydration associated with hemorrhagic diarrhea in dogs. Design—Nonrandomized, noncontrolled clinical trial. Animals—20 dogs that had hemorrhagic diarrhea with < 3 episodes of vomiting. Procedures—All dogs underwent testing for parvovirus infection, were given maropitant citrate to control emesis, and were offered an OES. Intravenous crystalloid fluid administration was performed when dogs refused the OES or had vomiting, a 5% increase in PCV, 5% decrease in body weight, serum creatinine or BUN concentration higher than at admission, or clinically important alterations in blood electrolyte or serum glucose concentrations. Results—13 (65%) dogs voluntarily consumed the OES; 7 (35%) dogs refused the OES and received a balanced electrolyte solution IV instead. All 13 dogs in the OES group consumed the solution ≤ 5 hours after hospital admission. Eight and 16 hours after admission, PCV and serum total protein and BUN concentrations were significantly lower than at hospital admission in the OES group, whereas no significant changes were identified in venous blood pH, base excess, and concentrations of sodium, potassium, chloride, ionized calcium, ionized magnesium, and lactate. The cost of treatment was significantly less for the OES group than for the IV treated group. Conclusions and Clinical Relevance—Rehydration therapy with an OES was effective and safe in dogs with mild to moderate dehydration associated with hemorrhagic diarrhea. Potential benefits of this treatment approach for gastroenteritis in dogs, compared with traditional IV fluid administration, include lower owner-related veterinary costs and decreased staff time associated with treatment. (J Am Vet Med Assoc 2013;243:851–857)

Objective—To characterize in vitro coagulation status in a cohort of dogs with extrahepatic biliary tract obstruction (EHBO) and to evaluate these patients for hypercoagulability by means of thromboelastography. Design—Prospective cohort study. Animals—10 dogs with EHBO and 19 healthy control dogs. Procedures—Partial or complete EHBO was confirmed via exploratory celiotomy. Venous blood samples were collected for evaluation of prothrombin time (PT) and activated partial thromboplastin time (APTT); fibrinogen and D-dimer concentrations; protein C and antithrombin activities; and factor VII, VIII, and XI coagulant activities in plasma as well as thromboelastography in whole blood. Thromboelastography variables were measured from the thromboelastography tracing, and a coagulation index was calculated. Thromboelastography results were compared with those of healthy control dogs previously evaluated by the same laboratory. Results—Hypercoagulability was diagnosed in all dogs with EHBO on the basis of a high coagulation index. Thromboelastography variables, including maximal amplitude, α-angle, and coagulation index, were significantly higher, and K (clot formation time) and R (reaction time) were significantly lower in these dogs than in control dogs. All dogs with EHBO had PT and APTT within respective reference ranges. Plasma D-dimer and fibrinogen concentrations were above reference ranges in 8 and 7 dogs, respectively, and protein C and antithrombin activities were below reference ranges in 3 and 1 dogs, respectively. Conclusions and Clinical Relevance—In vitro hypercoagulability was commonly detected in dogs with naturally occurring EHBO. The traditional view of EHBO as a disease that causes hypocoagulability may need to be reconsidered.

To determine the prevalence of rodenticide exposure in cats, describe the use of gastrointestinal decontamination (GID) after rodenticide exposure, and examine the efficacy of GID following exposure to anticoagulant rodenticides (ACR).Retrospective study from 2000-2010.Emergency service of an urban university teaching hospital.One hundred forty-six cats presented for rodenticide exposure.Annually, the number of cats that were presented for rodenticide exposure averaged 13 of 3,336 (0.39%) and totaled 146 cases over 11 years. Cats that had been exposed to rodenticide were significantly more likely to be young (P0.001), sexually intact (P0.001), and presented in the fall season (P = 0.002). The majority of cats lived indoors (67.6%). The type of rodenticide involved in the exposure was unknown in 50% (71/142) of cases. Of the known types, ACRs were most common (59/142, 41.5%) followed by cholecalciferol (7/142, 4.9%) and bromethalin (5/142, 3.5%). Gastrointestinal decontamination was attempted in 21/36 (58%) cats with exposure to a known ACR. Emesis was attempted in 17/21 (81%) and charcoal administered in 14/21 (67%) cats that underwent GID. This study did not detect an effect of GID efforts on prothrombin time (PT) prolongation 48 hours after exposure to a known ACR.Cats consume rodenticides. Due to the lack of evidence of altered outcome associated with GID in cats exposed to ACRs, a PT should be evaluated 48 hours after first exposure regardless of whether GID is performed. Treatment should be based on the results of the PT. Gastrointestinal decontamination should be performed at the clinician's discretion based on history, risks, calculated toxic dose, low prevalence of ACR toxicosis in cats, general resistance of cats to ACR toxicosis, and treatment options.

To examine available evidence on prehospital care in human and veterinary trauma and emergency medicine and develop best practice guidelines for use by both paramedical and nonparamedical personnel in the approach to the prehospital care of dogs and cats.Systematic evaluation of the literature gathered via medical databases searches of Medline, CAB abstracts, and Google Scholar.From a review and systematic evaluation of the available evidence, consensus guidelines on the approach to prehospital care of dogs and cats in 18 scenarios were developed.Due to the lack of current evidence in the veterinary prehospital arena, best practice guidelines were developed as an initial platform. Recommendations were based on a review of pertinent human and available veterinary literature as well as a consensus of the authors' professional opinions. It is anticipated that evidence-based additions will be made in the future.

Objective—To determine the seroprevalence of antibody against canine influenza virus H3N8 in a group of pet dogs that participate in flyball in Pennsylvania. Design—Serologic survey. Animals—Dogs attending a flyball tournament in Downingtown, Pa, from November 13 to 14, 2009. Procedures—Blood samples were collected from dogs following owner consent. Medical, travel, and activity history of the dogs for the previous 10.5 months was obtained from owners. Serum was harvested and submitted to Cornell University Diagnostic Laboratory for measurement of antibody against canine influenza virus H3N8 via hemagglutination inhibition testing. Results—Serum samples were obtained from 100 of 256 dogs participating in the flyball event. Although 3 of the 100 (3%) samples had positive results for antibody against canine influenza, none of the associated dogs had respiratory signs of infection (eg, coughing, sneezing, or nasal or ocular discharge) in the 10.5 months prior to testing. Eleven dogs had a history of respiratory signs, but none of those dogs had antibody against canine influenza H3N8. In addition, none of the study dogs had been vaccinated against canine influenza H3N8. Conclusions and Clinical Relevance—Although canine influenza is considered enzootic in certain areas of the country (eg, Pennsylvania or New York), this study identified a low seroprevalence in dogs considered at high risk for infection given their life conditions and geographic origins. More research is warranted to elucidate the prevalence of exposure to the H3N8 virus in competitive sporting dogs and determine whether vaccination is warranted in such dogs.

Stimulated macrophages produce nitric oxide (NO) via inducible nitric oxide synthase (iNOS) using molecular O(2), L-arginine, and NADPH. Exposure of macrophages to hypoxia decreases NO production within seconds, suggesting substrate limitation as the mechanism. Conflicting data exist regarding the effect of pO(2) on NADPH production via the oxidative pentose phosphate cycle (OPPC). Therefore, the present studies were developed to determine whether NADPH could be limiting for NO production under hypoxia. Production of NO metabolites (NOx) and OPPC activity by RAW 264.7 cells was significantly increased by stimulation with lipopolysaccharide (LPS) and interferon gamma (IFNgamma) at pO(2) ranging from 0.07 to 50%. OPPC activity correlated linearly with NOx production at pO(2)>0.13%. Increased OPPC activity by stimulated RAW 264.7 cells was significantly reduced by 1400 W, an iNOS inhibitor. OPPC activity was significantly increased by concomitant treatment of stimulated RAW 264.7 cells with chemical oxidants such as hydroxyethyldisulfide or pimonidazole, at 0.07 and 50% O(2), without decreasing NOx production. These results are the first to investigate the effect of pO(2) on the relationship between NO production and OPPC activity, and to rule out limitations in OPPC activity as a mechanism by which NO production is decreased under hypoxia.

Objective – To determine the relationship between plasma vascular endothelial growth factor (VEGF) levels, severity of illness, and edema formation in critically ill dogs. Design – Prospective, observational, descriptive, clinical study. Setting – University Teaching Hospital. Animals – Twenty-eight dogs. Interventions – None. Measurements and Main Results – Physical examination and multifrequency bioimpedance (MFBIA) measurements were performed daily on 28 critically ill dogs with evidence of severe inflammatory disease and compared with the corresponding plasma VEGF levels. The change in VEGF values and the relationship between MFBIA measurements and clinical evidence of edema were also examined. Eighteen dogs had a positive VEGF level, 12 dogs had clinical evidence of edema, and 7 dogs had both a positive VEGF level and clinical evidence of edema. There was no statistically significant correlation between VEGF levels and the presence of edema on physical examination (P=0.2). VEGF values were also evaluated with respect to WBC count, survival prediction index, presence of known sepsis, change in extracellular water, and outcome. No statistical relationship could be identified between VEGF levels in the blood of dogs with inflammatory disease and their survival prediction index (P=0.1), the WBC count (P=0.2), or presence of sepsis (P=0.2). Dogs with a VEGF level >70 pg/mL (n=3) were less likely to survive (P=0.04). Because of high variability within and between animals, conclusions regarding changes in MFBIA could not be made, suggesting that this technology requires further refinement and investigation in critically ill dogs. Conclusions – A relationship between VEGF and clinically evident increased vascular permeability was not found in this study. Dogs with markedly elevated VEGF levels may be more likely to die, but further studies are needed to determine the diagnostic and prognostic value of VEGF in critically ill dogs.

Objective—To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs. Animals—8 client-owned dogs with clinical signs of osteoarthritis. Procedures—Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E2, platelet thromboxane B2 (TXB2), and free serum TXB2 and 6-keto-prostaglandin F (PGF)-1α concentrations. Results—Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and α-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E2 decreased after treatment with carprofen or deracoxib, and platelet TXB2 production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1α did not change significantly after treatment with any of the drugs, although the ratio of free TXB2 to 6-keto-PGF-1α decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib. Conclusions and Clinical Relevance—At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.

In a surfactant-depletion model of lung injury, tidal recruitment of atelectasis and changes in shunt fraction lead to large Pao2 oscillations. We investigated the effect of these oscillations on conventional arterial blood gas (ABG) results using different sampling techniques in ventilated rabbits. In each rabbit, 5 different ventilator settings were studied, 2 before saline lavage injury and 3 after lavage injury. Ventilator settings were altered according to 5 different goals for the amplitude and mean value of brachiocephalic Pao2 oscillations, as guided by a fast responding intraarterial probe. ABG collection was timed to obtain the sample at the peak or trough of the Pao2 oscillations, or over several respiratory cycles. Before lung injury, oscillations were small and sample timing did not influence Pao2. After saline lavage, when Po2 fluctuations measured by the indwelling arterial Po2 probe confirmed tidal recruitment, Pao2 by ABG was significantly higher at peak (295 +/- 130 mm Hg) compared with trough (74 +/- 15 mm Hg) or mean (125 +/- 75 mm Hg). In early, mild lung injury after saline lavage, Pao2 can vary markedly during the respiratory cycle. When atelectasis is recruited with each breath, interpretation of changes in shunt fraction, based on conventional ABG analysis, should account for potentially large respiratory variations in arterial Po2.

Objective—To evaluate early medical and behavioral effects of deployment to the World Trade Center, Fresh Kills Landfill, or the Pentagon on responding search-and-rescue (SAR) dogs. Design—Prospective double cohort study. Animals—The first cohort included SAR dogs responding to the September 11, 2001, terrorist attacks (deployed), and the second cohort included SAR dogs trained in a similar manner but not deployed (controls). Enrollment occurred from October 2001 to June 2002. Procedure—Dogs were examined by their local veterinarians; thoracic radiographs and blood samples were shipped to the University of Pennsylvania for analysis. Handlers completed medical and training histories and a canine behavioral survey. Results—Deployed dogs were older and had more search experience than control dogs. Serum concentrations of globulin and bilirubin and activity of alkaline phosphatase were significantly higher in deployed dogs, independent of age and training. Despite significant differences in several blood parameters, values for both groups were within reference ranges. No pulmonary abnormalities were detected on radiographs, and no significant differences in behavior or medical history were detected between groups. Conclusions and Clinical Relevance—Within the first year following the September 11 attacks, there was no evidence that responding dogs developed adverse effects related to their work. Mild but significantly higher serum concentrations of globulin and bilirubin and activity of alkaline phosphatase in deployed dogs suggested higher antigen or toxin exposure. These dogs will be monitored for delayed effects for at least 3 years. (J Am Vet Med Assoc 2004;225:861–867)

Highlights • Real time detection of cyclical atelectasis is fundamental for individualised mechanical-ventilation therapy in ARDS. • Intra-arterial oxygen sensors could be used to detect the breath-by-breath oscillations in PO2 during cyclical atelectasis. • The fidelity with which oxygen sensors can detect these arterial PO2 oscillations depends on the sensors’ speed of response. • We present a system for testing fast-response fibre optic oxygen sensors under simulated conditions of cyclical atelectasis. • We show that a prototype fibre optic oxygen sensor, compatible with clinical use, can detect rapid PO2 changes in vitro., Two challenges in the management of Acute Respiratory Distress Syndrome are the difficulty in diagnosing cyclical atelectasis, and in individualising mechanical ventilation therapy in real-time. Commercial optical oxygen sensors can detect PaO2 oscillations associated with cyclical atelectasis, but are not accurate at saturation levels below 90%, and contain a toxic fluorophore. We present a computer-controlled test rig, together with an in-house constructed ultra-rapid sensor to test the limitations of these sensors when exposed to rapidly changing PO2 in blood in vitro. We tested the sensors’ responses to simulated respiratory rates between 10 and 60 breaths per minute. Our sensor was able to detect the whole amplitude of the imposed PO2 oscillations, even at the highest respiratory rate. We also examined our sensor's resistance to clot formation by continuous in vivo deployment in non-heparinised flowing animal blood for 24 h, after which no adsorption of organic material on the sensor's surface was detectable by scanning electron microscopy.

Companion animals with sepsis and multiple organ dysfunction can be the most challenging of all patients to treat. Current research in humans and laboratory models offers some exciting insights into the pathophysiology behind some of our most frustrating clinical challenges. This article applies several current concepts to a clinical case of pancreatitis and secondary sepsis to illustrate some of the cardiovascular, immune, and coagulation abnormalities commonly seen.

Objective—To determine whether hyperglycemia is associated with head trauma in dogs and cats and whether the degree of hyperglycemia corresponds to severity of neurologic injury or outcome. Design—Retrospective study. Animals—52 dogs and 70 cats with head trauma and 122 age- and species-matched control dogs and cats. Procedure—Severity of head trauma was classified as mild, moderate, or severe. Blood glucose concentrations recorded within 1 hour after admission were compared between case and control animals and among groups when case animals were grouped on the basis of severity of head trauma or outcome. Results—Blood glucose concentration was significantly associated with severity of head trauma in dogs and cats and was significantly higher in dogs and cats with head trauma than in the control animals. However, blood glucose concentration was not associated with outcome. Conclusions and Clinical Relevance—Results suggest that dogs and cats with head trauma may have hyperglycemia and that degree of hyperglycemia was associated with severity of head trauma. However, degree of hyperglycemia was not associated with outcome for dogs and cats with head trauma. Because hyperglycemia can potentiate neurologic injury, iatrogenic hyperglycemia should be avoided in patients with head trauma. (J Am Vet Med Assoc 2001;218:1124–1129)

Two 13-amino-acid peptides were synthesized based on the putative feline tumor necrosis factor (FeTNF) sequence. The synthesized peptides were conjugated to keyhole limpet hemocyanin, emulsified in complete Freund's adjuvant, and injected into rabbits. The gene for FeTNF was cloned into the FLAG (International Biotechnologies Inc. [IBI], Kodak, New Haven, Conn.) fusion protein expression vector. The expressed fusion protein was purified by using the M-1 anti-FLAG octapeptide monoclonal antibody (IBI, Kodak). The fusion protein was emulsified in complete Freund's adjuvant and injected into chickens. The immune sera generated to the synthetic peptides and the fusion protein recognized the recombinant FeTNF fusion protein on Western or dot blot assay. The preimmune and immune sera were incubated with naturally occurring FeTNF (supernatants from lipopolysaccharide-stimulated cultured feline peritoneal exudate or peripheral mononuclear cells). The antibody raised to the recombinant FeTNF fusion protein and N-terminal synthetic peptide neutralized bioactivity of native FeTNF and recombinant human TNF. Preimmune sera did not have any neutralizing activity. The polyclonal antibodies were not specific for FeTNF, since both porcine and human recombinant TNF were neutralized by the fusion protein antibodies. The synthetic peptide antibodies recognized recombinant feline and equine TNF on a Western blot.

A prospective, nonrandomized study was performed to evaluate the role of endotoxin and tumor necrosis factor (TNF) in dogs with parvoviral enteritis. Seventeen dogs with naturally occurring parvoviral enteritis were enrolled in the study. Plasma samples were obtained for quantification of endotoxin and TNF on presentation and at 3 and 6 hours after therapy with either fluids prior to antibiotics, or fluids concurrently with antibiotics. All dogs received standard supportive therapy. Fourteen of 17 dogs had endotoxin in their plasma during the study period; 7 of 17 dogs had measurable TNF. No endotoxin or TNF was detectable in plasma from normal puppies. An increase in TNF activity was predictive of mortality (P = .041). There was a trend for increasing endotoxin activity to predict mortality (P = .0769). Animals that received antibiotics with fluids were significantly older than those that received fluids prior to antibiotics, and there was a trend for animals that received antibiotics with fluids to have a decrease in endotoxin activity after treatment (P = .054). Endotoxin and activation of the cytokine cascade are integral to the pathophysiology of parvoviral enteritis. Measures to limit endotoxemia and the systemic inflammatory response may improve survival.

The tumor necrosis factor (TNF) genes from cats, horses, and pigs have all been cloned into the pFLAG-1 fusion protein expression vector (International Biotechnologies, Inc., Kodak, New Haven, Conn.). Growth curves for Escherichia coli containing the pFLAG-1 vector alone and the pFLAG-1 vector containing the TNF gene from each species were determined by visible light spectrophotometry (at 600 nm). Porcine TNF, equine TNF, and feline TNF cultures had slower doubling rates than cultures containing the pFLAG-1 vector alone. Cultures of cells transformed with feline TNF reached peak densities at 3 to 4 h and then decreased to near initial densities prior to the recovery of growth. The induction of expression with isopropyl-beta-D-thiogalactopyranoside (IPTG) arrested the growth of fresh feline TNF cultures for 6 h, which was followed by complete recovery. This inhibition occurred in two strains of E. coli (LL308 and JM101). Induced feline TNF cultures expressed the TNF-FLAG fusion protein for the first 6.5 h. Uninduced cultures expressed low levels of fusion protein. The feline TNF-pFLAG-1 vector was purified from cells expressing fusion protein and from cells with recovered growth curves. Sequencing the vector demonstrated the complete feline TNF gene and tac promoter in cells expressing the fusion protein and a deletional mutation of the tac promoter site in recovered cells. In contrast to equine and porcine TNF, the expression of recombinant feline TNF is toxic to E. coli. Alterations in protein folding and the prevention of secretion of the feline protein may explain the toxic effect.

Objective—To evaluate risk factors for gastric dilatation-volvulus (GDV) in a large number of privately owned dogs across a wide geographic area. Design—Internet-based, cross-sectional study. Animals—2,551 privately owned dogs. Procedures—A questionnaire addressed dog-specific, management, environmental, and personality-associated risk factors for GDV in dogs. Respondents were recruited through the posting of the electronic link to the questionnaire on websites for dog owners; the information was also disseminated at meetings of dog owners and via newsletters, e-mail lists for dog owners and breeders, owner-oriented dog publications, and e-mails forwarded by participants. Descriptive statistics and logistic regression analysis were performed. Results—Factors significantly associated with an increased risk of GDV were being fed dry kibble, anxiety, residence in the United Kingdom, being born in the 1990s, being a family pet, and spending at least 5 hours a day with the owner. Factors associated with a decreased risk of GDV were playing with other dogs and running the fence after meals, fish and egg dietary supplements, and spending equal time indoors and outdoors. A significant interaction between sex and neuter status was observed, with sexually intact females having the highest risk for GDV. Conclusions and Clinical Relevance—In dogs with a high risk of GDV, regular moderate daily and postprandial activity appeared to be beneficial. Feeding only commercial dry dog food may not be the best choice for dogs at risk; however, supplements with fish or eggs may reduced this risk. The effect of neuter status on GDV risk requires further characterization.

Background Canine influenza virus (CIV) H3N8 infection is thought to be highly contagious and potentially deadly. Low seroprevalence in dogs participating in the sport of flyball in 2009 was reported. It remains unknown if prevalence is changing in dogs at risk. Objective To determine seroprevalence of antibodies to CIV H3N8 in a population of pet dogs that participated in an indoor flyball tournament in Pennsylvania in November 2010. Animals Dogs participating in a flyball tournament. Methods Medical, travel, and activity histories for previous 10.5 months were obtained from consenting owners and serum samples were collected from dogs. Antibodies to CIV H3N8 were measured using hemagglutination inhibition. Results Of 251 competing dogs, 103 dogs were tested. Overall, seroprevalence of CIV H3N8 in dogs participating in flyball was 1.9% (95% CI, 0.05–6.8%). Thirty-five dogs were tested in both 2009 (all titers 8) and both had been vaccinated twice in the previous month. Titers in remaining 8 vaccinated dogs were undetectable. Seroprevalence in vaccinated dogs was 20% (95% CI, 5.7–50.1%), whereas in unvaccinated dogs it was 0% (95% CI, 0–4.0%). Although 7 dogs had history of respiratory signs, only 1, which was vaccinated, was serologically positive for CIV H3N8. Conclusions Consistent with low prevalence of CIV H3N8 exposure previously reported in flyball dogs, unvaccinated dogs had 0% prevalence, suggesting a stable exposure rate. However, low seroprevalence may result in unprotected flyball dogs at risk for developing CIV H3N8.

To describe the most common reasons for emergency medical visits in working police dogs.Retrospective case control study.Two hundred three German Shepherd dogs (GSDs); 138 police dog visits by 74 dogs and 138 pet (control) dog visits by 129 dogs.Medical records of all GSDs seen in the emergency service (ES) at the University of Pennsylvania Veterinary Hospital from July 2008 to July 2010 were reviewed. The recorded diagnoses from police GSD ES visits (defined as a new problem or new episode of a recurrent problem) were compared to those of randomly chosen pet GSD ES visits.There were significantly more intact male police GSDs than pet GSDs. Police GSDs were significantly younger than pet GSDs. The most common presenting complaint in both groups was gastrointestinal disease (eg, vomiting, diarrhea, gastric dilatation and volvulus). Pet GSDs were significantly more likely to present for geriatric conditions (eg, central nervous system disease, cardiovascular disease, and neoplastic conditions). Orthopedic issues were significantly more common in police GSDs.Police GSDs are more likely to present for orthopedic injuries and less likely to present for geriatric diseases. Gastrointestinal disease is not unique to the working GSD and was equally represented in both populations. Preventative measures for all GSDs should focus on minimizing gastrointestinal disease. Preventive strategies focusing on physical fitness and conditioning as well as selective breeding programs may help reduce orthopedic injuries in police GSDs.

To characterize derangements in the hemostatic profiles of dogs with naturally occurring septic peritonitis and determine if such derangements were predictive of survival.Prospective, observational single cohort study.University veterinary teaching hospital.A total of 27 client-owned dogs with naturally occurring septic peritonitis.Standard treatment included fluid resuscitation, antimicrobial therapy, supportive care, and surgery provided at the discretion of the primary clinician. Blood was collected preoperatively and on days 1 and 3 postoperatively for platelet count, prothrombin time, activated partial thromboplastin time, D-dimer and fibrinogen concentrations, total protein C (PC) and antithrombin (AT) activities, and thromboelastography.Sixteen of 27 (59%) dogs survived. Preoperative PC deficiency was identified in 10 of 11 (91%) nonsurvivors and 2 of 15 (13%) survivors. Preoperative AT deficiency was identified in 10 of 11 (91%) nonsurvivors and 14 of 15 (93%) survivors. Compared to survivors, nonsurvivors had lower mean preoperative PC (98 ± 24% versus 49 ± 26%; P0.001) and AT (53 ± 9% versus 32 ± 16%; P0.001) activities. Anticoagulant activities decreased on day 1 postoperatively. As a predictor of survival, preoperative PC activity of more than 60% achieved a sensitivity of 93% and specificity of 82%. Preoperative AT activity of more than 41.5% achieved a sensitivity of 100% and specificity of 82%. The maximum amplitude, α angle, and coagulation index from preoperative thromboelastograms of survivors were significantly greater (more hypercoagulable) than nonsurvivors (P0.01), with the maximum amplitude being the most specific predictor of survival (100%).Deficiencies of PC and AT and hypercoagulability appear to be consistent features of naturally occurring canine sepsis and may be useful prognostic indicators in canine septic peritonitis.

To identify hemostatic abnormalities in dogs with protein-losing nephropathies (PLN) that represent risk factors for pathologic thrombosis.Cross-sectional observational study of client-owned dogs with PLN, nonprotein losing renal failure (RF), and systemic illness (SI) exclusive of primary renal disease.Urban University Referral Center.A total of 29 dogs (n=11 PLN, n=7 RF, n=11 SI) were enrolled between January 2001 and July 2002. Samples were also collected from 20 clinically normal dogs to serve as hemostasis assay controls.None. HEMOSTASIS TESTING: Citrate anticoagulated blood was collected for point-of-care testing with a viscoelastic monitor (thromboelastograph [TEG]) and citrate plasma was prepared for coagulation screening tests and specific assay of the following hemostatic proteins: antiplasmin, antithrombin, D-dimer, Factor VIII, fibrinogen, plasminogen, protein C, and von Willebrand factor.Dogs with PLN and RF demonstrated TEG abnormalities consistent with hypercoagulability (eg, short clotting time, high clot amplitude) and both groups had significantly lower antithrombin than the SI group. The PLN dogs had significantly higher protein C than either the RF or SI group. Hyperfibrinogenemia was a consistent finding among all 3 disease groups, and the coagulation index a measure of hypercoagulability derived from TEG parameters, directly correlated with fibrinogen values of all study dogs.Hemostatic abnormalities consistent with systemic hypercoagulability are common in dogs with RF and PLN, however, no prothrombotic factors unique to PLN were identified in our study. The thrombotic tendency of PLN may therefore involve parameters we did not directly assess such as platelet reactivity, fibrinolysis, perturbations in blood flow, and/or endothelial dysfunction. High protein C is a novel finding in PLN dogs of unknown clinical relevance.

In response to the terrorist attacks of September 11, 2001, at the World Trade Center and Pentagon, almost 50,000 rescue workers and approximately 300 search and rescue dogs participated in rescue and recovery operations. The dogs were exposed to the same hazards as the human workers, but did not have any of the personal protective gear. This prospective double cohort observational study compared annual medical history, blood biochemical and hematologic results, and thoracic radiographic findings in 95 search and rescue dogs that responded to the terrorist attacks at the World Trade Center or the Pentagon on September 11, 2001, to a control group of 55 search and rescue dogs that were not involved in the 9/11 response. Compared to controls, the deployed search dogs demonstrated mild changes in blood work and a higher incidence of radiographic cardiac abnormalities. Species differences may explain the lack of pulmonary findings in the dogs. These dogs may provide early evidence of nonpulmonary complications of the 9/11 response. Continued surveillance of all responders is warranted.

Objective – To perform a qualitative evaluation of procalcitonin gene (CALCA) expression in a tissue-specific manner in dogs with signs of the systemic inflammatory response syndrome (SIRS). Design – Observational study. Setting – University Veterinary Teaching Hospital. Animals – Nine clinical cases and 5 research dogs. Interventions – None. Measurements and Main Results – Fresh tissue samples (thyroid, lung, liver, spleen) from 9 dogs that died with a diagnosis of parvoviral infection or SIRS were collected and immediately stored at –801C. Diagnosis of parvoviral infection was based on clinical signs, positive fecal antigen test, and confirmed by polymerase chain reaction (PCR). Clinical diagnosis of SIRS was based on the clinical criteria reported in veterinary literature. Necropsy was performed on all subjects in the study. Furthermore, thyroid, lung, liver, spleen were collected from 5 normal research dogs immediately postmortem for testing. The 9 dogs with a clinical diagnosis of SIRS died from either parvovirus (n55), bacterial sepsis (n53), or neoplasia (n51). CALCAwas amplified by PCR in the following samples: thyroid (9/9), spleen (6/9), lung (4/9), liver (3/9). Only thyroid expressed CALCA in the 5 normal dogs. Conclusions – In SIRS, extrathyroidal transcription of CALCA was documented. Quantitative analysis (realtime polymerase chain reaction) in a wider population of SIRS and normal dogs will provide essential information about the extent and source of extrathyroidal expression of canine CALCA induced by septic and nonseptic systemic inflammation.

Five hybridomas (4F4, 14H1, 9B4, 6E10, and 8G7) secreting antibodies to porcine tumor necrosis factor alpha (PTNF-alpha) were obtained from one fusion. Four of the 5 monoclonal antibodies (Mab) recognized recombinant PTNF-alpha (rPTNF-alpha) on western blot and were able to neutralize both rPTNF-alpha and native (released by porcine macrophages) PTNF (nPTNF-alpha, only 4F4, 14H1, and 9B4 tested for the neutralization of nPTNF-alpha) in vitro. A sandwich enzyme-linked immunosorbent assay (ELISA) for PTNF-alpha was developed using Mab 4F4 and purified rabbit polyclonal antibodies against PTNF-alpha. The test detected PTNF-alpha concentrations as low as 400 pg/ml and did not cross react with native porcine TNF-beta, recombinant human TNF-alpha, recombinant mouse TNF-beta or native mouse TNF-alpha. The Mabs and the ELISA should be useful for assessing PTNF-alpha levels in swine serum during disease processes and possibly for alleviation of toxic effects of TNF-alpha.

To evaluate population characteristics, injuries, emergency diagnostic testing, and outcome of dogs with blunt trauma requiring intensive care in an urban hospital.Retrospective study 1997-2003.All data obtained from the University of Pennsylvania - Matthew J. Ryan Veterinary Hospital.Dogs admitted to the intensive care unit for treatment following blunt trauma.None.Of the 235 dogs that met inclusion criteria, 206 (88%) survived and 29 (12%) did not survive. Blunt vehicular trauma accounted for 91.1% of cases. Mild hyperglycemia and hyperlactatemia was common in both survivors and nonsurvivors. The chest was the most common region traumatized and the prevalence of polytrauma was 72.3%. Initial weight, vital signs, PCV, total plasma protein, BUN, glucose, lactate, acid-base status, and electrolytes did not differ between survivors and nonsurvivors. Nonsurvivors were significantly more likely to have had head trauma (P=0.008), cranium fractures (P0.001), recumbency at admission (P0.001), development of hematochezia (P0.001), clinical suspicion of acute respiratory distress syndrome (P0.001), disseminated intravascular coagulation (P0.001), multiorgan dysfunction syndrome (P0.001), development of pneumonia (P0.001), positive-pressure ventilation (P0.001), vasopressor use (P0.001), and cardiopulmonary arrest (P0.001).Outcome of severe blunt trauma in dogs treated with intensive care is very good. Despite the high survival rate, several features associated with poor outcome were identified. Neither admission lactate nor glucose was able to predict outcome.

Objective – To analyze thromboelastograms (TEGs) of naturally occurring cases of immune-mediated hemolytic anemia (IMHA) in order to identify whether a hypercoagulable state was present and whether its presence was associated with differences in survival. Design – Retrospective study spanning January 2000 to June 2008. Medical records of dogs were evaluated. Endpoints were considered death or discharge from the hospital. Setting – Academic teaching hospital. Animals – Thirty-nine dogs with a diagnosis of IMHA and at least one TEG performed during hospitalization were included. Interventions – None. Measurements and Main Results – Four values were evaluated from the TEG: the R time (R), K time (K), alpha angle (α), and maximum amplitude. From these values, a coagulation index (CI) was calculated to classify patients as normocoagulable, hypercoagulable, or hypocoagulable. Thirty-three of 39 patients were hypercoagulable based on the CI. The 6 remaining dogs were normocoagulable. The patients with a normocoagulable CI had an increased mortality rate (100%) when compared with the hypercoagulable patients using Fisher's exact test (P=0.02). Additionally, prolongation of partial thromboplastin time did not preclude hypercoagulable TEG values. Conclusions – The majority of dogs with IMHA were hypercoagulable as measured by TEG. A normal CI was associated with a worse outcome in this patient population. TEG may provide additional and complementary information to prothrombin time and partial thromboplastin time relating to coagulation status in dogs with IMHA and may help predict prognosis and potentially guide clinical decisions to utilize anticoagulant drugs.

A long-term surveillance study was conducted on 95 search-and-rescue (S&R) dogs deployed to the September 11, 2001, terrorist attack sites; an additional 55 nondeployed S&R dogs served as controls. After 5 years of surveillance, 32% of the deployed dogs have died and 24% of the nondeployed dogs. The mean age at the time of death in these 2 groups of dogs is not significantly different. Causes of death in both groups of dogs include inflammatory, degenerative, and proliferative conditions. No primary pulmonary tumors have been identified to date nor has any significant level of toxicant been found in the tissues from these dogs using assays for general organic compounds and metals or, specifically, for polychlorinated biphenyls. However, significant numbers of both deployed and nondeployed dogs have evidence of inhaled matter as demonstrated by the presence of anthracotic pigments or refractile particulate matter in pulmonary tissue. Although S&R activities in response to the 9/11 terrorist attacks exposed dogs to a wide variety of potentially toxic compounds, to date, these dogs do not appear to suffer from higher mortality or increased pulmonary disease compared with nondeployed dogs. To the authors' knowledge, the current survey represents the first long-term and large-scale survey of the pathology and toxicology of S&R dogs deployed to a major disaster site.

Fluid therapy in the patient with vomiting and diarrhea is essential to correct hypovolemia, dehydration, acid-base imbalance, and serum electrolyte abnormalities. Prediction of acid-base or electrolyte disturbances is difficult; therefore, point of care testing is beneficial to optimize therapy. This article focuses on the pathophysiology and treatment of hypovolemia, dehydration, electrolyte disturbances, and acid-base derangements resulting from and associated with vomiting and diarrhea.

Volutrauma and atelectrauma have been proposed as mechanisms of ventilator-associated lung injury, but few studies have compared their relative importance in mediating lung injury. The objective of our study was to compare the injury produced by stretch (volutrauma) vs. cyclical recruitment (atelectrauma) after surfactant depletion. In saline-lavaged rabbits, we used high tidal volume, low respiratory rate, and low positive end-expiratory pressure to produce stretch injury in nondependent lung regions and cyclical recruitment in dependent lung regions. Tidal changes in shunt fraction were assessed by measuring arterial Po2 oscillations. After ventilating for times ranging from 0 to 6 h, lungs were excised, sectioned gravitationally, and assessed for regional injury by evaluation of edema formation, chemokine expression, upregulation of inflammatory enzyme activity, and alveolar neutrophil accumulation. Edema formation, lung tissue interleukin-8 expression, and alveolar neutrophil accumulation progressed more rapidly in dependent lung regions, whereas macrophage chemotactic protein-1 expression progressed more rapidly in nondependent lung regions. Temporal and regional heterogeneity of lung injury were substantial. In this surfactant depletion model of acute lung injury, cyclical recruitment produced more injury than stretch.

Nitric oxide (NO) production by inducible NO synthase (iNOS) is dependent on O2availability. The duration and degree of hypoxia that limit NO production are poorly defined in cultured cells. To investigate short-term O2-mediated regulation of NO production, we used a novel forced convection cell culture system to rapidly (response time of 1.6 s) and accurately (±1 Torr) deliver specific O2tensions (from 2availability rapidly (≤30 s) and reversibly decreased NO production with an apparent KmO2of 22 (SD 6) Torr (31 μM) and a Vmaxof 4.9 (SD 0.4) nmol·min−1·10−6cells. To explore potential mechanisms of decreased NO production during hypoxia, we investigated O2-dependent changes in iNOS protein concentration, iNOS dimerization, and cellular NO consumption. iNOS protein concentration was not affected ( P = 0.895). iNOS dimerization appeared to be biphasic [6 Torr ( P = 0.008) and 157 Torr ( P = 0.258) >36 Torr], but it did not predict NO production. NO consumption was minimal at high O2and NO tensions and negligible at low O2and NO tensions. These results are consistent with O2substrate limitation as a regulatory mechanism during brief hypoxic exposure. The rapid and reversible effects of physiological and pathophysiological O2tensions suggest that O2tension has the potential to regulate NO production in vivo.

Hyperglycemia is common in critically ill humans. Recent clinical trials have shown a significant reduction in morbidity and mortality rates with the use of intensive insulin therapy to maintain strict normoglycemia in critically ill patients. Hyperglycemia is associated with many detrimental effects, including reduced immune function, increased inflammation and coagulation, and modulation of the endothelium. Most of the evidence regarding the adverse effects of hyperglycemia is derived from humans with diabetes, cardiac failure, or traumatic brain injury. In addition to its anabolic effects on metabolism, insulin has antiinflammatory properties. To define the potential risks and benefits of intensive insulin therapy in critically ill animals, prospective, randomized clinical trials are necessary.

Low-molecular-weight heparin (LMWH) has potential benefit in cats at risk for thromboembolic disease. However, LMWH pharmacokinetics has not been characterized in the cat. Drug effect with LMWH may be evaluated with analysis of factor Xa inhibition (anti-Xa) or thromboelastography (TEG).Administration of LMWH at previously recommended dosages and schedules to healthy cats will result in inhibition of factor Xa and hypocoagulable TEG.In vivo research with heparin was performed in 5 purpose-bred cats.In a prospective study with randomized crossover design, heparin or placebo was administered. Treatments were unfractionated heparin (UFH), 250 IU/kg q6h; dalteparin, 100 IU/kg q12h; enoxaparin, 1 mg/kg q12h; or 0.9% saline, 0.25 mL/kg q6h. Each drug was administered for 5 consecutive days followed by a minimum washout of 14 days. Baseline and post-treatment analyses included anti-Xa, TEG, and prothrombin time/activated partial thromboplastin time.Mean anti-Xa activity 4 hours after enoxaparin (0.48 U/mL) approached the human therapeutic target (0.5-1.0 U/mL); however, mean trough anti-Xa activity was below detection limits. Mean anti-Xa activity 4 hours after dalteparin was lower, and only 1 cat attained therapeutic target at a single time point. Cats receiving UFH attained target anti-Xa activity and changes in TEG at trough and 4 hours.Cats have rapid absorption and elimination kinetics with LMWH therapy. On the basis of pharmacokinetic modeling, cats will require higher dosages and more frequent administration of LMWH to achieve human therapeutic anti-factor Xa activity of 0.5-1 U/mL. Peak anti-Xa activity is predicted at 2 hours after administration of LMWH.

Cyclical recruitment of atelectasis with each breath is thought to contribute to ventilator-associated lung injury. Extrinsic positive end-expiratory pressure (PEEPe) can maintain alveolar recruitment at end exhalation, but PEEPe depresses cardiac output and increases overdistension. Short exhalation times can also maintain end-expiratory recruitment, but if the mechanism of this recruitment is generation of intrinsic PEEP (PEEPi), there would be little advantage compared with PEEPe. In seven New Zealand White rabbits, we compared recruitment from increased respiratory rate (RR) to recruitment from increased PEEPe after saline lavage. Rabbits were ventilated in pressure control mode with a fraction of inspired O2 (FiO2) of 1.0, inspiratory-to-expiratory ratio of 2:1, and plateau pressure of 28 cmH2O, and either 1) high RR ( 24 ) and low PEEPe (3.5) or 2) low RR ( 7 ) and high PEEPe ( 14 ). We assessed cyclical lung recruitment with a fast arterial Po2 probe, and we assessed average recruitment with blood gas data. We measured PEEPi, cardiac output, and mixed venous saturation at each ventilator setting. Recruitment achieved by increased RR and short exhalation time was nearly equivalent to recruitment achieved by increased PEEPe. The short exhalation time at increased RR, however, did not generate PEEPi. Cardiac output was increased on average 13% in the high RR group compared with the high PEEPe group ( P < 0.001), and mixed venous saturation was consistently greater in the high RR group ( P < 0.001). Prevention of end-expiratory derecruitment without increased end-expiratory pressure suggests that another mechanism, distinct from intrinsic PEEP, plays a role in the dynamic behavior of atelectasis.

Objectives—To determine characteristics, variables associated with deployment morbidity, and injuries and illnesses of search-and-rescue dogs associated with the Sept 11, 2001, terrorist attacks. Design—Historical cohort study. Animals—96 dogs. Procedure—Data collected included previous medical or surgical history, physical attributes of dogs, type and number of years of training, site of deployment, shift and hours worked, and number of days deployed. Combined morbidity was defined as 1 or more abnormalities of body systems, including traumatic injuries. Results—Handlers of 96 of the 212 dogs responded to the surveys. Fifty-nine dogs were deployed by the Federal Emergency Management Agency, 10 by police forces, and 27 as members of other search-and-rescue teams. Sixty-five dogs (incidence rate, 17 events/1,000 dog search hours) had combined morbidity during deployment. System-specific morbidity rates included gastrointestinal tract signs (5 events/1,000 dog search hours), cuts and abrasions mostly on the feet (5 events/1,000 dog search hours), fatigue (6 events/1,000 dog search hours), change in appetite (6 events/1,000 dogs search hours), dehydration (5 events/1,000 dog search hours), respiratory tract problems (2 events/1,000 dog search hours), heat exhaustion (2 events/1,000 dog search hours), and orthopedic or back problems (2 events/1,000 dog search hours). Dogs deployed to the World Trade Center were 6.6 times more likely to have combined morbidity, compared with dogs at the Pentagon. Conclusions and Clinical Relevance—Injury and illnesses occurred in most dogs and affected several organ systems, but all were minor. (J Am Vet Med Assoc 2004;225:868–873)

Intermittent hypoxia has been implicated in morbidities associated with sleep apnea, and may be a novel cellular signal for inflammation [J. Appl. Physiol. 90 (2001) 1986]. Standard cell culture has two major limitations for studying the effects of steady-state P O 2 and intermittent hypoxia. First, convective mixing in the culture media can be variable, making precise control of cellular P O 2 difficult. Second, diffusion of oxygen through the culture media slows changes in cellular P O 2 after rapid changes in the gas phase P O 2 . Our estimates of diffusional transients for standard cell culture suggest significant restrictions in the ability to cycle P O 2 at frequencies relevant to intermittent hypoxia. We present a novel system for forced convection cell culture with adherent cells inside capillary tubing. Steady state cellular P O 2 is regulated to an accuracy of approximately 1 Torr. The response time for cycling of P O 2 is less than 1.6 sec. This system is ideally suited for studies of intermittent hypoxia in adherent cells.

The effects of physiologically relevant hypoxia on the catalytic activity of cytochrome c oxidase (CytOX), mitochondrial gene expression, and both nuclear and mitochondrial encoded CytOX mRNA levels were investigated in murine monocyte macrophages, mouse C2C12 skeletal myocytes and rat adrenal pheochromocytoma PC12 cells. Our results suggest a coordinated down regulation of mitochondrial genome-coded CytOX I and II and nuclear genome-coded CytOX IV and Vb mRNAs during hypoxia. Hypoxia also caused a severe decrease in mitochondrial transcription rates, and associated decrease in mitochondrial transcription factor A. The enzyme from hypoxia exposed cells exhibited altered subunit content as revealed by blue native gel electrophoresis. There was a generalized decline in mitochondrial function that led to a decrease in total cellular heme and ATP pools. We also observed a decrease in mitochondrial heme aa3 content and decreased levels of CytOX subunit I, IV and Vb, though the catalytic efficiency of the enzyme (TN for cytochrome c oxidase) remained nearly the same. Increased glycolytic flux and alterations in the kinetic characteristics of the CytOX might be the two mechanisms by which hypoxic cells maintain adequate ATP levels to sustain life processes. Reoxygenation nearly completely reversed hypoxia-mediated changes in CytOX mRNA contents, rate of mitochondrial transcription, and the catalytic activity of CytOX enzyme. Our results show adaptive changes in CytOX structure and activity during physiological hypoxia.