Controls Dogs Research Articles

Canine Visceral Leishmaniasis: A Histological and Immunohistochemical Study of Fibropoiesis in Chronic Interstitial Pneumonitis.

We studied some fibrotic aspects of chronic interstitial pneumonitis in the lungs of dogs infected with Leishmania infantum. The lungs of eleven naturally infected dogs, twelve experimentally infected with two distinct strains of L. infantum (BH401 and BH46), and six uninfected (controls) dogs, were analyzed by histological, parasitological, and immunohistochemical studies. Conventional histology (HE), collagen deposition (Gomori's silver staining for reticulin collagen fibers), and immunohistochemistry for myofibroblast characterization were carried out based on the cellular expression of alpha-smooth muscle actin, vimentin, cytokeratin, E-cadherin, snail antigen homologue 1 (SNAI1) (Snail), and the cytokine expression of transforming growth factor-beta (TGF-β). Parasitological screening was carried out using conventional polymerase chain reaction (PCR) and the immunohistochemical reaction of streptavidin-peroxidase for visualizing Leishmania amastigotes. Dogs naturally infected with L. infantum and experimentally infected with L. infantum BH401 strains showed intense interstitial pneumonitis characterized by thickening of the alveolar septa as a consequence of an intense diffuse and focal (plaques) chronic exudate of mononuclear cells associated with fibrogenesis. The expression of alpha-actin, vimentin, and TGF-β was higher in the lung interstitium of all infected dogs than in the other two groups (BH46 strain and controls). Moreover, in both the naturally and experimentally infected dog (BH401 strain) groups, the expression of Snail was moderate to intense in contrast to the other groups. Based on these immunohistochemical results, we concluded that mesenchymal cells are active in promoting changes in the extracellular matrix in the lungs of dogs naturally and experimentally infected with L. infantum, but it depends on the virulence of the parasite.

Videofluoroscopic swallow study abnormalities identify aerodigestive disorders in dogs with respiratory disease versus healthy controls

Aerodigestive diseases (AeroD) pathologically link respiratory and alimentary tracts. Dogs with respiratory signs lacking dysphagia, vomiting, or regurgitation typically do not undergo diagnostic testing that identifies comorbid alimentary disease. A videofluoroscopic swallow study (VFSS) identifies defects in swallowing, reflux, and aspiration. We hypothesized that dogs with respiratory and no alimentary disease (RESP) would have significantly more abnormal VFSS metrics versus controls (CON). We hypothesized RESP dogs with pulmonary parenchymal disease would have more reflux and higher penetration-aspiration score (PAS) than those with airway disease. Client-owned dogs: RESP (n=45) and CON (n=15) groups. Prospectively, all dogs underwent VFSS. The RESP dogs had advanced respiratory diagnostic testing. Eight subjective and 3 objective VFSS metrics (pharyngeal constriction ratio [PCR], PAS, and esophageal transit time [ETT]) were assessed. Fisher's exact test compared differences between groups (presence or absence of VFSS abnormalities). The Mann-Whitney rank sum test was used to compare PCR and PAS. Subjective VFSS abnormalities were present in 34/45 (75%) RESP and 2/15 (13%) CON dogs, with RESP dogs significantly more likely to have VFSS abnormalities (P=.01). No difference in PCR was found between groups. Pathologic PAS was more common in RESP than CON dogs (P=.03). The RESP dogs with airway disease had higher PAS than CON dogs (P=.01) but not RESP dogs with parenchymal disease (P=.25). Most (75%) RESP dogs had VFSS abnormalities, emphasizing that AeroD are common. The VFSS has value in diagnostic evaluation of respiratory disease.

Circulating hyaluronan as a marker of endothelial glycocalyx damage in dogs with myxomatous mitral valve disease and dogs in a hypercoagulable state

The endothelial glycocalyx (eGlx) lines the luminal surface of endothelial cells, maintaining vascular health. Glycocalyx damage is pathophysiologically important in many diseases across species however few studies have investigated its breakdown in naturally occurring disease in dogs. The aims of the study were to investigate eGlx damage in dogs with myxomatous mitral valve disease (MMVD) diagnosed on echocardiography, and dogs in a hypercoagulable state diagnosed using thromboelastography (TEG), by measuring serum hyaluronan concentrations. Serum hyaluronan was quantified in dogs with MMVD (n = 27), hypercoagulability (n = 21), and in healthy controls dogs (n = 18). Serum hyaluronan concentrations were measured using a commercially-available ELISA validated for use in dogs. Hyaluronan concentrations were compared among groups using Kruskal-Wallis tests, and post-hoc with Dunn’s tests. Serum hyaluronan concentrations (median [range]) were significantly increased in dogs with MMVD (62.4 [22.8–201] ng/mL; P = 0.031) and hypercoagulability (92.40 [16.9–247.6] ng/mL; P < 0.001) compared to controls (45.7 [8.7–80.2] ng/mL). Measurement of serum hyaluronan concentration offers a clinically applicable marker of eGlx health and suggests the presence of eGlx damage in dogs with MMVD and dogs in a hypercoagulable state.

T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma.

Investigation of canine T cell immunophenotypes in canine melanomas as prognostic biomarkers for disease progression or predictive biomarkers for targeted immunotherapeutics remains in preliminary stages. We aimed to examine T cell phenotypes and function in peripheral blood mononuclear cells (PBMC) and baseline tumor samples by flow cytometry, and to compare patient (n = 11–20) T cell phenotypes with healthy controls dogs (n = 10–20). CD3, CD4, CD8, CD25, FoxP3, Ki67, granzyme B, and interferon-γ (IFN-γ) were used to classify T cell subsets in resting and mitogen stimulated PBMCs. In a separate patient cohort (n = 11), T cells were classified using CD3, CD4, CD8, FoxP3, and granzyme B in paired PBMC and single cell suspensions of tumor samples. Analysis of flow cytometric data of individual T cell phenotypes in PBMC revealed specific T cell phenotypes including FoxP3+ and CD25+FoxP3- populations that distinguished patients from healthy controls. Frequencies of IFN-γ+ cells after ConA stimulation identified two different patient phenotypic responses, including a normal/exaggerated IFN-γ response and a lower response suggesting dysfunction. Principle component analysis of selected T cell immunophenotypes also distinguished patients and controls for T cell phenotype and revealed a clustering of patients based on metastasis detected at diagnosis. Findings supported the overall hypothesis that canine melanoma patients display a T cell immunophenotype profile that is unique from healthy pet dogs and will guide future studies designed with larger patient cohorts necessary to further characterize prognostic T cell immunophenotypes.

Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs

Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.

Prevalence of antibodies against Borrelia burgdorferi, Anaplasma phagocytophilum, and Leptospira interrogans serovars in Bernese Mountain Dogs.

Bernese Mountain Dogs (BMD) have a higher prevalence of Borrelia burgdorferi sensu lato (Bbsl) antibodies than other breeds, but it is not known whether this is the case for other pathogens. Therefore, the aim of the study was to determine the frequency and level of specific antibodies against members of the Bbsl group, Anaplasma phagocytophilum (Ap), and Leptospira (L.) interrogans serovars in BMD and compare the results with those found in dogs of other breeds. A total of 171 healthy BMD and 57 healthy control dogs of other breeds were included in the study. Controls were large dogs (>30kg) with long, dark hair coats. A two-tiered testing method consisting of computerized kinetic enzyme-linked immunosorbent assay (KELA) and Western blotting was used for detection of antibodies against Bbsl, an immunofluorescence assay (IFA) was used for detection of antibodies against Ap, and microscopic agglutination test (MAT) for antibodies to 18 different serovars of L.interrogans. The prevalence of anti-Bbsl antibodies was significantly higher in BMD (43.3%) than in controls (17.5%) (p<0.001). Antibodies to Bbsl attributable to vaccination were excluded from the calculation of prevalence. Antibodies to Ap were found in 50.3% of BMD, whereas only 24.6% of the controls dogs were tested positive for Ap (p<0.001). Antibody titers of the 18 different serovars of L.interrogans antibodies did not differ significantly between BMD and control dogs except for L.copenhageni antibody titers which were higher in BMD. Significantly higher antibody titers to L.canicola (p=0.003), L.copenhageni (p=0.005), L.grippothyphosa (p=0.029) and L. vanderhoedoni (p=0.035) were seen in BMD compared to control dogs. BMD had a higher prevalence of anti-Bbsl, anti-L.copenhageni and anti-Ap antibodies than control dogs. Significantly higher antibody titers against L.canicola (p=0.003), L.copenhageni (p=0.005), L.grippothyphosa (p=0.029) and L. vanderhoedoni (p=0.035) were seen in BMD compared with control dogs, but the reason for this and potential clinical implications are not known.

EFFECTS OF CORN OIL ADMINISTERED ORALLY ON CONSPICUITY OF ULTRASONOGRAPHIC SMALL INTESTINAL LESIONS IN DOGS WITH LYMPHANGIECTASIA

Lymphangiectasia is one of the causes of protein-losing enteropathy in dogs and characteristic ultrasonographic small intestinal lesions have been previously described. The purpose of this study was to determine whether corn oil administered orally (COAO) would result in increased conspicuity of these characteristic small intestinal ultrasonographic lesions in dogs with lymphangiectasia. Affected dogs were included if they underwent corn oil administered orally and had a surgical full-thickness intestinal biopsy diagnosis of lymphangiectasia. Control dogs had normal clinical examination and standard laboratory test findings. Ultrasound images of duodenum, jejunum, and ileum were obtained prior to and 30, 60, 90, and 120 min after corn oil administered orally for all dogs. Parameters recorded for each ultrasound study were intestinal wall thickness, mucosal echogenicity, and presence or absence of hyperechoic mucosal striations (HMS) and a parallel hyperechoic mucosal line (PHML). Nine affected and five controls dogs were included in the study. Seven of the nine dogs with lymphangiectasia had hyperechoic mucosal striations prior to corn oil administered orally. Jejunal hyperechoic mucosal striations were significantly associated with lymphangiectasia at multiple time points (P < 0.05) and were best identified in dogs with lymphangiectasia 60 or 90 min after corn oil administered orally. Increased mucosal echogenicity was observed in all dogs at multiple time points after corn oil administered orally. A parallel hyperechoic mucosal line was present in the jejunum in 4/5 healthy and 6/9 dogs with lymphangiectasia at one or more time points after corn oil administered orally. Findings indicated that corn oil administered orally improves conspicuity of characteristic ultrasonographic lesions in dogs with lymphangiectasia, however some of these lesions may also be present in healthy dogs that recently received a fatty meal.

ESTUDIO RETROSPECTIVO DE CASO-CONTROL DE EHRLICHIOSIS CANINA EN LA FACULTAD DE MEDICINA VETERINARIA DE LA UNIVERSIDAD NACIONAL MAYOR DE SAN MARCOS: PERIODO 2002-2005

Canine ehrlichiosis is a worldwide well known infectious disease and potentially lethal to dogs and other members of the Canidae family. It is caused by Ehrlichia canis and transmitted by the brown dog tick Rhipicephalus sanguineus. The aim of this work was to carry out a retrospective case-control study in order to evaluate the risk factors associated with the presence of canine ehrlichiosis in dogs that have been patients at the Clinic of Small Animals and at the Clinical Pathology Laboratory of the Veterinary Faculty, San Marcos University, Lima. For this purpose, cases (dogs with ehrlichiosis: n=50) as well as controls (dogs without ehrlichiosis: n=100) from clinical records in the period of 2002-2005 were used. Data was grouped by breed, sex, age, history of tick presence, and home location. Chi square, odds ratio (OR), and logistic regressions were performed. Among the cases, 50% were of large breeds, 72% were males, 64% were ³2 years old, and 82% had ticks. The risk factors associated with the disease were large breeds (OR=12.8, p=0.024), German Shepherd dog (OR=12.2, p&lt;0.01), age (³2-4 years: OR= 4.0, p=0.008) and tick history [82% (48/50) for the cases and 1% (1/100) for the controls].

Testing the Efficacy of a Multi-Component DNA-Prime/DNA-Boost Vaccine against Trypanosoma cruzi Infection in Dogs

Background Trypanosoma cruzi, the etiologic agent of Chagas Disease, is a major vector borne health problem in Latin America and an emerging infectious disease in the United States.MethodsWe tested the efficacy of a multi-component DNA-prime/DNA-boost vaccine (TcVac1) against experimental T. cruzi infection in a canine model. Dogs were immunized with antigen-encoding plasmids and cytokine adjuvants, and two weeks after the last immunization, challenged with T. cruzi trypomastigotes. We measured antibody responses by ELISA and haemagglutination assay, parasitemia and infectivity to triatomines by xenodiagnosis, and performed electrocardiography and histology to assess myocardial damage and tissue pathology.ResultsVaccination with TcVac1 elicited parasite-and antigen-specific IgM and IgG (IgG2>IgG1) responses. Upon challenge infection, TcVac1-vaccinated dogs, as compared to non-vaccinated controls dogs, responded to T. cruzi with a rapid expansion of antibody response, moderately enhanced CD8+ T cell proliferation and IFN-γ production, and suppression of phagocytes’ activity evidenced by decreased myeloperoxidase and nitrite levels. Subsequently, vaccinated dogs controlled the acute parasitemia by day 37 pi (44 dpi in non-vaccinated dogs), and exhibited a moderate decline in infectivity to triatomines. TcVac1-immunized dogs did not control the myocardial parasite burden and electrocardiographic and histopatholgic cardiac alterations that are the hallmarks of acute Chagas disease. During the chronic stage, TcVac1-vaccinated dogs exhibited a moderate decline in cardiac alterations determined by EKG and anatomo-/histo-pathological analysis while chronically-infected/non-vaccinated dogs continued to exhibit severe EKG alterations.ConclusionsOverall, these results demonstrated that TcVac1 provided a partial resistance to T. cruzi infection and Chagas disease, and provide an impetus to improve the vaccination strategy against Chagas disease.

N-3 Polyunsaturated fatty acids alter expression of fibrotic and hypertrophic genes in a dog model of atrial cardiomyopathy

We previously showed that omega-3 polyunsaturated fatty acids (PUFAs) reduce vulnerability to atrial fibrillation (AF). The mechanisms underlying this effect are unknown. The purpose of this study was to use a genome-wide approach to identify gene expression profiles involved in a new model of AF vulnerability and to determine whether they were altered by PUFA therapy. Thirty-six dogs were randomized evenly into three groups. Two groups were paced using simultaneous atrioventricular pacing (SAVP) at 220 bpm for 14 days to induce atrial enlargement, fibrosis, and susceptibility to AF. One group was supplemented with oral PUFAs (850 mg/day) for 21 days, commencing 7 days before the start of pacing (SAVP-PUFAs). The second group received no PUFAs (SAVP-No PUFAs). The remaining dogs were unpaced, unsupplemented controls (CTRL). Atrial tissue was sampled at the end of the protocol. Gene expression was analyzed in four dogs randomly selected from each group (n = 12) via microarray. Results were confirmed with quantitative real-time polymerase chain reaction (RT-PCR) and histology on all 36 dogs. Microarray or quantitative RT-PCR results showed that SAVP-No PUFAs dogs had significantly increased mRNA levels of protein kinase B (Akt), epidermal growth factor (EGF), JAM3, myosin heavy chain alpha (MHCalpha), and CD99 and significantly decreased levels of Smad6 compared with CTRL dogs. Quantitative RT-PCR showed that PUFA supplementation was associated with significant down-regulation of Akt, EGF, JAM3, MHCalpha, and CD99 levels compared with SAVP-No PUFAs dogs. The effect of PUFAs on these fibrosis, hypertrophy, and inflammation related genes suggests that, in this model, PUFA-mediated prevention of AF may be due to attenuation of adverse remodeling at the genetic level in response to mechanical stress.

Toxoplasma gondii: Evidence for the transmission by semen in dogs

Ten male dogs were distributed into three experimental groups for infection with Toxoplasma gondii: GI – three dogs inoculated with 2.0 × 10 5 P strais oocysts, GII – three dogs infected with 1.0 × 10 6 RH strain tachyzoites, and GIII – four controls dogs. Several clinical parameters were evaluated. IFAT was performed to detect anti- T. gondii antibodies. Presence of the parasite in semen was evaluated by PCR and bioassay techniques. Tissue parasitism was examined using bioassays and immunohistochemistry in testicle and epididymis fragments collected after orchiectomy. In semen samples collected from these two groups, the presence of T. gondii was verified by bioassays and PCR. T. gondii was detected by immunohistochemistry in tissues (testicle and epididymis fragments) of all six experimentally infected dogs. The T. gondii-positive seminal samples were used in the artificial insemination (AI) of four female dogs free of toxoplasmic infection. Seven days after AI, all of the female dogs presented serologic conversion (IFAT). Fetal reabsorption occurred in two of the dogs, while the others sustained full-term gestation. Several T. gondii cysts were detected in the brains of four offspring. These results suggest that T. gondii can be sexually transmitted in domestic dogs.

Prednisone Prevents Inducible Atrial Flutter in the Canine Sterile Pericarditis Model

Atrial fibrillation (AF) and atrial flutter (AFL) are common following cardiac surgery and are associated with significant morbidity. We tested the hypothesis that suppression of the inflammatory response with steroids would significantly modify the inducibility of postoperative AF/AFL in the canine sterile pericarditis model. Twenty-three dogs were studied daily from creation of pericarditis to the fourth postoperative day: 11 dogs were treated with oral prednisone (PRED) starting 2 days preoperatively until the end of the study; 12 dogs were controls (CON). EP testing was performed daily using epicardial electrodes placed at initial surgery. High-resolution (404 sites) epicardial mapping was performed during the terminal study. Baseline and daily CRP levels were obtained in all dogs. Sustained AFL was absent in PRED (0%) versus CON dogs (91%; P < 0.001); AF induced in the early postoperative course in PRED dogs was of very short CL (mean 66 ms). Tissue inflammation was significantly attenuated in PRED dogs. Thresholds were lower in PRED versus CON dogs, significantly so on postoperative day (POD) 3. There was a trend toward lower ERPs in the PRED group at all CLs. CRP levels were markedly reduced in PRED versus CON dogs (peak CRP 78 +/- 7 mg/L vs 231 +/- 21 mg/L, P < 0.001), and returned to baseline in PRED dogs by POD 4, correlating with a virtual absence of sustained arrhythmia. During open chest mapping studies on POD 4, PRED dogs showed only nonsustained AF/AFL. Prednisone eliminated postoperative AFL, affected all EP parameters studied, and attenuated the inflammatory response associated with pericarditis.

Evaluation of the Vascular Targeting Agent Combretastatin A-4 Prodrug on Retinal Neovascularization in the Galactose-Fed Dog

Combretastatin A-4 (CA-4) is a vascular targeting agent known to rapidly shut off blood flow in new vessels and, as a result, regress neovascularization. In this pilot study, the ability of CA-4 to modify retinal neovascularization, which results in altered retinal vessel blood flow and retinal permeability, was evaluated in aphakic long-term galactose-fed beagles, an animal model that develops diabetes-like retinal neovascularization. Two (2) groups of aphakic dogs, each group comprised of 4 galactose-fed dogs and 2 age-matched controls dogs, were utilized. Each group initially received the combretastatin A-4-phosphate prodrug (CA-4P) as either sub-Tenon's injections, administered at the corneoscleral junction, or intravitreal injections. Six (6) weeks after this treatment, all dogs also received systemic (intravenous) injections of CA-4P. Retinal vascular changes were monitored at 2-week intervals by fluorescein angiography. All galactose-fed dogs demonstrated the presence of retinal neovascular lesions by fluorescein angiograms. Fluorescein leakage or perfusion through neovascular vessels was not altered by either sub-Tenon's, intravitreal, or systemic CA-4P administration. Whereas CA-4P was well tolerated by the healthy eyes of the control animals, its administration to some galactose-fed dogs was associated with corneal edema and increases in intraocular pressure following sub-Tenon's and intraocular injections. Neovascularization in the galactose-fed dog progresses over a period of years, similar to that observed with clinical diabetic retinopathy. The failure of CA-4P to ameliorate neovascularization suggests that chronic, long-term administration may be required to destroy the slowly growing retinal endothelial cells.

Selective Aortic Arch Perfusion During Cardiac Arrest: Enhanced Resuscitation Using Oxygenated Perflubron Emulsion, With and Without Aortic Arch Epinephrine

Study objective: To evaluate selective aortic arch perfusion (SAAP) with an oxygenated fluorocarbon emulsion, with and without aortic arch epinephrine during cardiac arrest. Methods: This randomized, controlled study, undertaken at a university research laboratory, involved 15 mixed-breed dogs. After 10 minutes of ventricular fibrillation and 30 seconds of CPR, the dogs were randomized to three groups, each comprising five dogs. Group 1 (controls) dogs were given CPR and intravenous epinephrine, .01 mg/kg, at 10.5 minutes and then every 3 minutes. Group 2 dogs (IVE-SAAP) were treated with CPR and intravenous epinephrine (IVE) in the same fashion as the control group but were also subjected to SAAP with 275 mL of oxygenated 60% wt/vol perflubron emulsion over 30 seconds. Group 3 dogs (AoE-SAAP) received the same treatment as the IVE-SAAP group, except that the first epinephrine dose was given intraaortically. Results: Coronary perfusion pressure (CPP) increased during SAAP in both the IVE-SAAP and AoE-SAAP groups but was greater in the AoE-SAAP group. CPR diastolic CPP after SAAP was significantly greater in the AoE-SAAP group than in the control group. Return of spontaneous circulation (ROSC) occurred in two control dogs, all five IVE-SAAP dogs, and all five AoE-SAAP dogs. The time elapsed from the initiation of CPR to ROSC was 6.1±1.9 minutes in the AoE-SAAP group, compared with 11.0±5.8 minutes in the IVE-SAAP group. Conclusion: SAAP with oxygenated perflubron emulsion improved ROSC, both with and without aortic arch epinephrine. The combination of SAAP with perflubron emulsion and aortic arch epinephrine resulted in higher CPP and more rapid ROSC. [Manning JE, Batson DN, Payne FB, Adam N, Murphy CA, Perretta SG, Norfleet EA: Selective aortic arch perfusion during cardiac arrest: Enhanced resuscitation using oxygenated perflubron emulsion, with and without aortic arch perfusion. Ann Emerg Med May 1997; 29:580-587.]

Prostaglandin E 2 levels in cerebrospinal fluid of normal and narcoleptic dogs

It has been shown that endogenous prostaglandin D 2 and prostaglandin E 2 (PGE 2) are involved in sleep-wake regulation. Our recent experimental result that exogenously administered PGE 2 significantly reduces canine cataplexy (a pathological equivalent of rapid-eye-movement sleep atonia and a symptom of narcolepsy) suggests that PGE 2 is involved in the pathophysiology of canine narcolepsy. In order to further investigate the role of prostaglandins (PGs) in this disorder, PG levels in cerebrospinal fluid (CSF) of genetically homozygous narcoleptic, heterozygous (unaffected), and control Doberman pinschers were studied. PGE 2 levels were measured by direct radioimmunoassay (RIA) and after high-grade purification using PG affinity columns and high-performance liquid chromatography. PGD 2 and PGF 2α levels were measured by RIA after high-grade purification. There was no significant difference in PGE 2 levels between homozygous narcoleptic and heterozygous or controls dogs, and PGD 2 and PGF 2α levels were undetectable in most cases. Our results do not favor the hypothesis that central PGE 2 levels are modified in canine narcolepsy, assuming that PGE 2 levels in cisternal CSF properly reflect PGE 2 production in the brain.

"Reperfusion injury" by oxygen-derived free radicals? Effect of superoxide dismutase plus catalase, given at the time of reperfusion, on myocardial infarct size, contractile function, coronary microvasculature, and regional myocardial blood flow.

Do oxygen-derived free radicals, generated at the time of reperfusion, lethally injure viable, previously ischemic myocardium, damage vascular endothelium, and impair recovery of postischemic contractile function? To address these issues, 23 anesthetized open-chest dogs underwent 2 hours of left anterior descending coronary artery occlusion followed by 4 hours of reperfusion. Immediately prior to reflow, each dog was randomized to receive either the free radical scavenging agents superoxide dismutase (SOD) + catalase, or saline alone. SOD + catalase had no significant beneficial effect on infarct size measured by triphenyltetrazolium staining: area of necrosis averaged 38.5 +/- 6.1% vs. 46.3 +/- 6.2% of the area at risk in treated compared with control animals respectively (p = NS). Furthermore, infusion of SOD + catalase did not alter contractile function of the viable subepicardium: mean segment shortening (measured using sonomicrometry) at 4 hours postreperfusion was -23 +/- 5% of baseline, preocclusion values in controls dogs and -24 +/- 9% of preocclusion values in animals that received the scavenging agents. However, SOD + catalase treatment preserved the endocardial microvasculature (assessed by semiquantitative electron microscopic analysis) and enhanced regional myocardial blood flow after reperfusion. Specifically, mean score for microvascular injury was 0.41 +/- 0.14 vs. 0.10 +/- 0.08 (p less than 0.05) in control compared with SOD + catalase treated groups, and blood flow averaged 0.56 +/- 0.11 vs. 1.27 +/- 0.33 ml/min/g tissue (p less than 0.05), respectively, in the previously ischemic endocardium at 2 hours postreflow. Thus, SOD + catalase given at the time of reperfusion had no acute beneficial effect on either the extent of myocyte necrosis or postischemic contractile function in this canine model. SOD + catalase did, however, attenuate both endocardial vascular injury and the "low reflow" phenomenon. These data suggest that microvascular injury and low reflow following prolonged (2 hour) but transient coronary occlusion may be mediated by oxygen-derived free radicals generated at the time of reperfusion.

Dirofilaria immitis: Fate and immunogenicity of irradiated infective stage larvae in beagles

Experiments were conducted on the fate of irradiated infective larvae of Dirofilaria immitis in dogs, and on the effect of these infections on a challenge dose of nonirradiated larvae administered at a later date. Six dogs were inoculated with 200 to 296 irradiated larvae; in no case was a patent infection established. No living worm was recovered beyond 66 days. Eight dogs inoculated with 200 to 2401 irradiated larvae over varying periods of time were exposed 57 to 190 days after the final inoculation of irradiated larvae, to a challenge infection of 200 to 250 nonirradiated (normal) larvae. The results showed that the number of worms which developed to maturity in these dogs was sharply reduced compared to that in the 5 controls (dogs inoculated with normal larvae only). The most striking effect was seen in “vaccinated” dogs which were challenged 3 months or more after the final administration of irradiated larvae.