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OBJECTIVE 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). DESIGN Retrospective study from 2000-2010. SETTING Emergency service of an urban university teaching hospital. ANIMALS One hundred forty-six cats presented for rodenticide exposure. MAIN RESULTS 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 (P < 0.001), sexually intact (P < 0.001), 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. CONCLUSIONS 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.

Objective 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. Design Systematic evaluation of the literature gathered via medical databases searches of Medline, CAB abstracts, and Google Scholar. Synthesis 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. Conclusions 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 describe the most common reasons for emergency medical visits in working police dogs. Design Retrospective case control study. Animals Two hundred three German Shepherd dogs (GSDs); 138 police dog visits by 74 dogs and 138 pet (control) dog visits by 129 dogs. Procedures 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. Results 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. Conclusions and Clinical Relevance 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.

Objective To characterize derangements in the hemostatic profiles of dogs with naturally occurring septic peritonitis and determine if such derangements were predictive of survival. Design Prospective, observational single cohort study. Setting University veterinary teaching hospital. Animals A total of 27 client-owned dogs with naturally occurring septic peritonitis. Interventions 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. Measurements and Main Results 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%; P < 0.001) and AT (53 ± 9% versus 32 ± 16%; P < 0.001) 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 (P < 0.01), with the maximum amplitude being the most specific predictor of survival (100%). Conclusions 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.

Objective – To identify hemostatic abnormalities in dogs with protein-losing nephropathies (PLN) that represent risk factors for pathologic thrombosis. Design – Cross-sectional observational study of client-owned dogs with PLN, nonprotein losing renal failure (RF), and systemic illness (SI) exclusive of primary renal disease. Setting – Urban University Referral Center. Animals – 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. Interventions – 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. Results – 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. Conclusions – 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.

Objective – To perform a qualitative evaluation of procalcitonin gene (CALCA) expression in a tissue-specificmanner 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 diedwith a diagnosis of parvoviral infection or SIRS were collected and immediately stored at –801C. Diagnosis ofparvoviral infection was based on clinical signs, positive fecal antigen test, and confirmed by polymerasechain reaction (PCR). Clinical diagnosis of SIRS was based on the clinical criteria reported in veterinaryliterature. Necropsy was performed on all subjects in the study. Furthermore, thyroid, lung, liver, spleen werecollected from 5 normal research dogs immediately postmortem for testing. The 9 dogs with a clinicaldiagnosis of SIRS died from either parvovirus (n55), bacterial sepsis (n53), or neoplasia (n51). CALCAwasamplified by PCR in the following samples: thyroid (9/9), spleen (6/9), lung (4/9), liver (3/9). Only thyroidexpressed CALCA in the 5 normal dogs.Conclusions – In SIRS, extrathyroidal transcription of CALCA was documented. Quantitative analysis (real-time polymerase chain reaction) in a wider population of SIRS and normal dogs will provide essentialinformation about the extent and source of extrathyroidal expression of canine CALCA induced by septic andnonseptic systemic inflammation.(J Vet Emerg Crit Care 2010; 20(5): 523–527) doi: 10.1111/j.1476-4431.2010.00575.x

OBJECTIVE: To evaluate population characteristics, injuries, emergency diagnostic testing, and outcome of dogs with blunt trauma requiring intensive care in an urban hospital. DESIGN: Retrospective study 1997-2003. SETTING: All data obtained from the University of Pennsylvania - Matthew J. Ryan Veterinary Hospital. ANIMALS: Dogs admitted to the intensive care unit for treatment following blunt trauma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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 (P Language: en

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 effect of gastrointestinal (GI) decontamination on the incidence of prolonged prothrombin time (PT) in dogs after anticoagulant rodenticide ingestion. Design: Retrospective study. Setting: Urban emergency room. Animals: One hundred and fifty-one client-owned dogs. Measurements: Dogs presented to the emergency room within 6 hours of ingestion of an anticoagulant rodenticide and had a PT measured within 2–6 days of toxicant ingestion before initiating vitamin K therapy were included. Dogs were categorized as treated or untreated based on the institution of vitamin K therapy following PT testing. The signalment, body weight, type of rodenticide ingested, time elapsed between ingestion and initial presentation, method(s) of GI decontamination, and the times elapsed between both toxicant ingestion and initial hospital presentation until determination of PT were recorded. The PT results were recorded as well as any treatment received following the recheck examination. Any reported incidents of bleeding or untoward effects between exposure and reexamination were recorded. Main results: Of 151 dogs, only 11 dogs (8.3%) developed prolonged PT requiring vitamin K supplementation. None of the 11 dogs with prolonged PTs exhibited signs of bleeding or required transfusion therapy. No differences in age, weight, or time elapsed between treated and untreated patients were found. Conclusions: The incidence of prolonged PT is low in dogs receiving GI decontamination within 6 hours of anticoagulant rodenticide ingestion. Delaying vitamin K therapy until a PT has been assessed 48–72 hours after initial exposure appears to be safe and sensitive in dogs following anticoagulant rodenticide ingestion.

Background: As veterinary medicine has become more sophisticated, with greater numbers of veterinary patients receiving intensive care, more patients with an acute respiratory distress (ARDS)-like syndrome have been recognized. Methods: A consensus definition meeting was held for the purpose of developing veterinary-specific definitions for acute lung injury (ALI) and ARDS. Results/conclusions: Three clinically based definitions for acute lung injury and acute respiratory distress-like syndromes occurring in veterinary patients were described. Neonatal equine respiratory distress syndrome (NERDS) was defined separately due to the specific requirement for primary developmental surfactant dysfunction and lack of an inflammatory component. Five diagnostic criteria categories were established for Veterinary ALI/ARDS (Vet ALI/ARDS) with 4 required and a fifth highly recommended criteria. A strong consensus was reached that onset of respiratory distress must have been acute and that known risk factors must be present. Additional criteria included evidence of pulmonary capillary leak with no evidence of increased pulmonary capillary pressure, evidence of inefficient gas exchange and, finally, evidence of inflammation. Some features of ALI/ARDS in the neonatal horse were recognized as unique, therefore, equine neonatal ALI/ARDS (EqNALI/EqNARDS) was similarly defined but with a graded gas exchange inefficiency table to allow for normal developmental changes in gas exchange. Use of these definitions in planning prospective studies of these problems in veterinary patients should allow for more direct comparisons of studies and clinical trials, with a larger goal of improving outcome in veterinary patients.

Objective: To provide evidence that naturally occurring sepsis in dogs provides a unique opportunity to test new therapies in clinically relevant settings. Data sources: Human and veterinary literature. Human data synthesis: Sepsis is a devastating condition responsible for most intensive care unit deaths. Most clinical trials targeting inflammatory mediators of sepsis have failed to improve outcome in clinical patients despite promising results in laboratory animal models. Animal models of sepsis fail to reproduce the clinical syndrome and therefore lead to conclusions that may not be relevant to clinical care. Veterinary data synthesis: Sepsis is recognized but not well-characterized in companion animal species. Despite some species variability, the cardiopulmonary response to sepsis in dogs is similar to humans. Additionally, inflammatory and coagulation changes that accompany canine sepsis are consistent with those documented in humans. Sepsis secondary to canine parvoviral infection offers the advantages of relative population homogeneity, predictable course, and easy early diagnosis. The disadvantages of canine parvovirus are that it affects a predominantly young and healthy population and results in low mortality with aggressive supportive care. Septic peritonitis and pneumonia have high mortality but can be challenging to diagnose, have a variable course, and affect a heterogeneous population, which can be an advantage or a disadvantage. Conclusions: Similar to trials currently being performed in canine cancer patients, veterinary clinical trials of new sepsis therapeutics may provide a unique opportunity to advance the treatment of sepsis in dogs, humans, and other species. Spontaneous sepsis from canine parvovirus, peritonitis, and pneumonia are common clinical conditions in which therapeutics can be tested.

Objective: To describe and compare the patient population, treatment, and outcome in dogs with septic peritonitis from 2 time periods at the same institution. Design: Retrospective study. Setting: The Matthew J. Ryan Veterinary Hospital at the University of Pennsylvania. Animals: Dogs treated surgically for septic peritonitis between 1988–1993 and 1999–2003. Interventions: None. Measurements: Preoperative physical and clinicopathologic data, surgical findings, anesthetic parameters, treatment, and outcome. Main results: No significant difference in survival among dogs treated surgically for septic peritonitis between 1988 and 1993 (21/33 [64%]) and 1999–2003 (29/51 [57%]) was detected. The patient populations of the two time periods were similar. Changes in treatment between the study periods reflected availability of new antibiotics and synthetic colloids, as well as greater attention to pain management and ulcer prevention. Duration of hospitalization was not significantly different between the two time periods, but the daily cost adjusted to 2005 dollars was higher in 1999–2003. Potential prognostic indicators were compared between survivors and non-survivors after combining the data from both time periods, and although several parameters reached statistical significance, of greatest clinical significance were the higher blood pressure and preoperative serum albumin in survivors. Conclusions: Although new treatments were added to the supportive care of dogs with septic peritonitis, survival did not change sufficiently to detect a significant difference between the time periods evaluated. Identifying reliable prognostic indicators for septic peritonitis remains a challenge, but hypotension and decreased preoperative serum albumin were associated with non-survival in this group of dogs.

Objective: To describe the technique of thromboelastography (TEG) and review the applications of this coagulation test in humans and small animals. Data sources: Data sources included scientific reviews and original research publications. Human data synthesis: TEG in humans has been used for documentation of hypercoagulable and hypocoagulable states and has been shown to be beneficial in patient management. Veterinary data synthesis: Clinical evaluation of TEG in veterinary medicine is limited; however, recent reports have documented evidence of hypercoagulability in dogs with parvovirus and protein-losing nephropathy. Additionally, many of the research models may be relevant to veterinary patients. Conclusions: TEG provides information about coagulation that is not available through routine coagulation tests. The application of TEG monitoring to veterinary patients shows promise; however, prospective clinical studies are needed.

Objective: To establish normal parameters of thromboelastography (TEG) in healthy adult cats. Background: Thromboelastography (TEG) is an in vitro test of coagulation that has been shown to be useful in humans, dogs and select species to identify and quantify alterations of hemostasis (e.g., hypercoagulable and hypocoagulable states). It has also been demonstrated to be useful in monitoring effects of anticoagulant therapies. This test has not been evaluated in cats. Methods: Blood was collected from 25 clinically normal cats by venipuncture using a 21 gauge×3 1/2 inch butterfly catheter and syringe for medial saphenous or jugular venipuncture. A single 1.8 mL sample in 3.8% Sodium Citrate (9:1) was collected from each cat. Recalcified whole blood was analyzed 30 minutes following collection with the TEG® 5000 analyzer (Haemoscope, Niles, IL). Analysis temperature was 37.6°C. TEG parameters recorded included: R-value (represents initial fibrin formation), K (time from R to standard fixed measure of clot firmness which represents contributions of platelets and fibrinogen), maximum amplitude (MA; represents absolute clot strength), and alpha angle (α; the slope of TEG tracing which represents rate of clot formation). The coagulation index (CI) was derived from the formula generated for humans to provide an overall assessment of whether the sample was hyper- or hypocoagulable. Results: Values for the 25 normal cat samples are reported as mean ±2 standard deviations. R=2.97; 1.23–4.72; K=1.54, 0.38–2.71; α=70.70, 57.76–83.65; MA=58.50, 45.26–71.74 and CI=2.27, 0.07–4.46. Compared to historical information obtained on normal dogs, cats have significantly shorter R and K and larger α, MA and CI. Conclusions: TEG does have reproducible performance when used to evaluate coagulation status in normal cats. Compared to dogs, normal cats favor a hypercoagulable state. Species-specific normal values are necessary for interpretation of TEG results. This test bears potential value for use in future experimental and clinical work to investigate hemostasis in cats receiving anticoagulant therapies or in cats suffering from diseases such as cardiomyopathy which are thought to be associated with altered coagulation status.

Objectives: 1) Validate a chromogenic assay to measure Factor Xa inhibitory activity (anti-Xa activity) in normal feline plasma and following administration of low molecular weight heparins and unfractionated heparin. 2) Compare the effects of two commercially available low molecular weight heparins (LMWH), unfractionated heparin (UFH), and placebo on TEG, anti-Xa activity, PT/aPTT, PCV/TS and platelet count in healthy cats. Methods: Our study consisted of two phases: 1) the evaluation of a commercially available chromogenic anti-Xa assay (Rotachrom Heparin, Diagnostic Stago) for use in cats, and 2) the evaluation of hemostatic effects of LMWH in healthy cats. Phase 1: The anti-Xa assay was validated for use in cats using feline plasma and serial dilutions of the plasma spiked with UFH, enoxaparin, and dalteparin. Phase 2: Five healthy cats were included in a randomized Latin Squares model crossover-design to compare the effects of UFH and LMWH in cats. The cats then received one of the following subcutaneously: 1) 250 IU/kg UFH QID, 2) 100 IU/kg dalteparin BID, 3) 1 mg/kg enoxaparin BID, 4) 0.25 mL/kg 0.9% saline (placebo) QID. A minimum of a two-week washout period separated each treatment period. Each drug was administered for 5 days. Blood samples were obtained to measure anti-Xa, TEG, PT/aPTT, platelet count, and PCV/TS on Days 1, 3, 5, and 6 of each treatment cycle. Samples were collected at time 0 on each sample day for all parameters and on select days at hours 4, 8, and 12 for anti-Xa and TEG. Results: Preliminary results using the validated anti-Xa assay (from the first part of this study) demonstrate that LMWH treatment results in peak anti-Xa activity at the 4-hour sampling time that returned toward baseline by 8 hours (in 5/6 cats treated with LMWH thus far). Similar anticoagulant effects were noted in the TEG parameters of cats receiving LMWH (i.e., peak effects were noted at 4 hours). Analysis of current data by linear regression identifies a relationship between anti-Xa measurements and TEG parameters for cats treated with all heparin therapies (p

Objective: To determine plasma β-d-glucuronidase (βG) activity in the first 4 hours following injury in dogs struck by a motor vehicle, and to evaluate whether the degree of enzyme activity is correlated with the severity of injury. Design: A prospective clinical study. Setting: Veterinary Medical Teaching Hospital. Animals: Thirteen client-owned dogs that were presented to the Veterinary Hospital of the University of Pennsylvania between June and August 1999 for blunt vehicular trauma. Ten healthy student and staff-owned dogs served as controls. Interventions: None. Measurements: Plasma was analyzed for βG enzyme activity at the time of presentation (n=13), and 1 and 4 hours (n=7) following presentation to the Emergency Service for blunt vehicular trauma. The results were compared with enzyme activity from healthy controls evaluated serially over 4 hours. Fluorometric analysis using 96-well microtiter plates was used to perform the enzyme assays. The relationships between presentation (n=13) and 4 hours (n=7) of enzyme activity and 3 indices of metabolic and physical disturbance (serum pH, serum lactate and Animal Trauma Triage (ATT) score) at the time of presentation were also investigated. Main results: Of the 13 dogs, 7 fulfilled the inclusion criteria for comparison of enzyme activity of the trauma over time. A statistically significant difference in βG activity was found in the trauma group (mean 75.6±10.4 U) at 4 hours following presentation compared with controls (mean 48.0±6.4 U). This difference was suggested by 1 hour following presentation (trauma group, mean 70.4±10.9 U; control group, mean 49.8±5.5 U), although it did not reach statistical significance. Thirteen dogs fulfilled the inclusion criteria for comparison of only presentation enzyme activity with trauma severity score, serum lactate, and serum pH. No statistically significant relationship was found between the βd-glucuronidase activity and the presenting ATT score, serum lactate concentration, or serum pH at either presentation or 4 hours, although the power of these analyses was low. Conclusions: These results demonstrate that the activity of βG, a lysosomal enzyme, increases significantly in the systemic circulation in dogs 4 hours following blunt trauma. Additional research to include more severely injured dogs, a larger number of dogs, and to follow the course of injury for a longer period of time would be beneficial to further characterize βG activity following blunt trauma.

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.

Objective: Myocardial dysfunction has been shown to play a major role in the mortality associated with sepsis. Tumor necrosis factor-α (TNF-α) has been implicated as a key factor in this dysfunction, and the sphingomyelin pathway is a membrane-signaling pathway by which TNF-α exerts many of its negative inotropic effects. The purpose of this manuscript is to review the physiology of TNF-α and sphingosine, etiology of increased levels of myocardial TNF-α and sphingosine, as well as the effects of these increased levels on the myocardium. In addition, both in vivo and in vitro studies looking at the effects of blocking TNF-α will be presented. Data sources: Data sources included scientific reviews and original research publications. Human data synthesis: It is well documented that levels of TNF-α are elevated in many human patients with sepsis. However, clinical trials evaluating the effects of blocking TNF-α have not shown a statistically significant decrease in the mortality of sepsis. Veterinary data synthesis: No clinical research has been performed on TNF-α and myocardial dysfunction in veterinary medicine, although many of the research models may be relevant to our patient population. In these models, myocardial TNF-α and sphingosine are elevated in sepsis. Treatment of experimental animals with TNF-α antibodies has shown variable results, while blockage of sphingosine has been shown to completely reverse the myocardial effects of increased TNF-α. Conclusions: Tumor necrosis factor-α and the sphingomyelin pathway are an important part of the myocardial compromise that accompanies sepsis. Further research into these pathways may provide new understandings and treatment options for veterinary patients.

Objective: To review the principles and practice of cardiopulmonary cerebral resuscitation (CPCR) in veterinary medicine, and to incorporate recommendations from the human International Guidelines 2000 Conference on cardiopulmonary resuscitation and emergency cardiovascular care. Data sources: Both clinical and experimental studies from the human and veterinary literature were reviewed for this manuscript. Summary: Cardiopulmonary cerebral resuscitation consists of basic life support measures, advanced life support measures, and post-resuscitation care. Part I of this article introduced the evidence-based recommendations from human medicine and reviewed basic life support. Part II of this article reviews advanced life support, including drug therapy and electrical defibrillation based upon the electrocardiographic rhythm present at the time of cardiopulmonary arrest (CPA). Post-resuscitation care is discussed, with a particular focus on optimizing perfusion to the brain, kidneys, and gastrointestinal tract. Several currently investigational methods that may improve future patient outcomes are also addressed. Conclusions: Advanced life support techniques provide methods to augment CPCR efforts. As with basic life support, recent recommendations to improve advanced life support in humans may be also be applied to veterinary patients. However, clinical research evaluating these interventions in veterinary CPCR is necessary. Post-resuscitation care requires vigilant monitoring and aggressive support to ensure vital organ perfusion and maximize patient outcomes.

Objective: To provide a synthesis of information learned by the veterinary community during the care and treatment of search and rescue dogs in a large-scale urban disaster. Summary: Disaster medicine requires several stages. The most important stage is the planning stage. To function effectively and safely in a disaster situation, a disaster response plan and prior training in disaster response are essential. The execution of a disaster plan requires coordination and communication with multiple agencies. Treatment of search and rescue dogs involves front line field care for life-threatening emergencies, a first aid station or MASH unit in close proximity to the disaster and/or base of operations for stabilization and general medical care, and local full service veterinary hospitals for specialty and extended care. New or Unique information provided: This report is a summary of experiences gained in preparing for and implementing veterinary care in a major disaster. Medical conditions that affected search and rescue dogs and were treated by veterinary disaster responders at the World Trade Center are presented.

Objective:To determine the clinical efficacy of abdominal fluid to peripheral blood ratios of creatinine and potassium concentrations to diagnose uroperitoneum in dogs. Design:Records of 13 dogs with confirmed uroabdomen were retrospectively analyzed. Prospective evaluation of 8 dogs with nonrenal ascites provided data for a control population. Setting:Veterinary Medical Teaching Hospital. Animals:Client owned dogs. Interventions:None Measurements and Main Results:Abdominal fluid potassium (mEq/L) and creatinine concentrations (mg/dl) were recorded. Peripheral blood potassium and creatinine concentrations were also recorded. Ratios were calculated based on these values. An abdominal fluid creatinine concentration to peripheral blood creatinine concentration ratio of > 2:1 was predictive of uroabdomen in dogs (specificity 100%, sensitivity 86%). An abdominal fluid potassium concentration to peripheral blood potassium concentration of > 1.4:1 is also predictive of uroabdomen in dogs (specificity 100%, sensitivity 100%). All dogs with uroabdomen had an abdominal fluid creatinine concentration that was at least 4 times normal peripheral blood levels. Conclusion:Abdominal fluid to peripheral blood potassium and creatinine ratios provide a means to diagnose uroperitoneum in dogs without elevated peripheral blood creatinine.

We evaluated the ability of an antimicrobial and endotoxin-neutralizing agent, the recombinant amino terminal fragment of bactericidal permeability-increasing protein (rBPI21), to decrease plasma endotoxin concentration and severity of clinical signs of canine parvovirus and to improve survival. This randomized, double-blinded, placebo-controlled clinical trial included 40 client-owned dogs and 9 normal puppies from a closed research colony. Dogs weighing >5 kg (11 lb) with fecal antigen-confirmed parvovirus and clinical signs of vomiting and diarrhea were randomly assigned to receive placebo or rBPI21 infusion over 6 hours. Plasma endotoxin concentration was measured at 0, 3, and 6 hours of infusion. Owners chose continued medical care with either the Veterinary Hospital of the University of Pennsylvania Internal Medicine Service or a local veterinarian. Telephone follow-up was conducted at 14 days. Surviving dogs were reevaluated at >30 days (recovered group), at which time plasma samples for measurement of endotoxin concentration were obtained. Plasma endotoxin concentrations were significantly higher in dogs with parvovirus than in normal or recovered dogs. Despite 90% survival, the rBPI21 treatment did not have a significant effect on outcome, duration of hospitalization, or plasma endotoxin concentrations. Treatment in a tertiary care hospital, however, significantly improved survival but resulted in a significantly increased duration of hospitalization. Endotoxemia occurs in dogs with parvovirus enteritis, but rBPI21 is not associated with improved survival.

Objective: To compare the incidence of clinically evident post-operative complications, financial cost and length of hospital stay for Dachshunds with acute intervertebral disc disease treated with decompressive surgery with and without the use of methylprednisolone sodium succinate (MPSS). Design: Retrospective clinical study Setting: Veterinary Teaching Hospital Animals: Dachshunds that presented to the Veterinary Hospital of the University of Pennsylvania between January 1994 and December 1999 with acute intervertebral disc disease that were treated with decompressive surgery. Intervention: None Measurements and Main Results: Dogs were divided into 2 groups dependent upon whether they had received MPSS. Medical records were examined for evidence of post-operative complications. Other parameters recorded included details of drugs administered (principally corticosteroids and gastrointestinal protectant drugs), length and cost of hospital stay and neurological status at 24 hours post-operatively and at suture removal. Compared to other corticosteroids, dogs receiving MPSS had a significantly higher incidence of clinically evident post-operative gastrointestinal complications, an increased use of gastrointestinal protectant drugs, and an increased cost for hospital stay (p

Summary Over the past ten years, nitric oxide has been shown to be important in a number of biological systems. This article is a review of the literature on nitric oxide and its affects on hemodynamics in the kidney. Nitric oxide is a major contributor to basal vasodilatory tone in the renal vasculature and systemic vasculature. It also has effects on the mechanisms which comprise the tubuloglomerular feedback loop. (Vet Emerg & Crit Care, 1998; 8: 7–18)

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.

Ascites with accumulation of a true or modified transudate, is relatively uncommon in young dogs. When it does occur, congenital defects of the cardiovascular, gastrointestinal, or renal systems, infectious diseases and trauma must be considered. Cor triatrium dexter, an abnormal membrane obstructing the caudal vena cava at the level of the right atrium, was diagnosed in an eight-month-old cocker spaniel presented with ascites.