Additional Dogs Research Articles

Extracellular Matrix as an Inductive Template for Temporomandibular Joint Meniscus Reconstruction: A Pilot Study

A device consisting of powdered porcine urinary bladder extracellular matrix (UBM-ECM) encapsulated within sheets of the same material was investigated as a scaffold for temporomandibular joint (TMJ) meniscus reconstruction. Five dogs underwent unilateral resection of the native meniscus and replacement with a UBM-ECM device. Necropsies were performed at 3, 4, 8, 12, and 24 weeks. Two additional dogs underwent bilateral resection of the meniscus with replacement with a UBM-ECM device on 1 side, leaving the contralateral side empty as a control. Necropsies were performed at 24 weeks for bilaterally treated animals. Macroscopically, the UBM-ECM implants were remodeled rapidly and were indistinguishable from newly deposited host tissue at all time points. Microscopically, remodeling was characterized by a dense infiltration of predominantly CD68(+) mononuclear cells and smooth muscle actin-positive fibroblast-like cells at early time points changing with time to a sparse population of smooth muscle actin-negative spindle-shaped cells resembling those of the native fibrocartilaginous TMJ meniscus. Furthermore, the remodeling process showed deposition of predominantly type I collagen, the density and organization of which resembled those of the native meniscus by the 24-week time point. Ingrowth of calsequestrin-positive skeletal muscle tissue was also observed at the periphery of the remodeled UBM-ECM device and was similar to that found at the attachment site of the native meniscus to the surrounding soft tissues. Histologic results were identical for samples excised from both unilaterally and bilaterally treated animals. No adverse changes in the articulating surfaces of the condyle or fossa were observed in UBM-ECM-implanted joints. In the bilaterally treated animals, the unimplanted control side was characterized by degeneration and pitting of the articulating surfaces of both the condyle and the fossa, with disorganized bands of fibrous connective tissue observed within the joint space. Results of this study suggest that the UBM-ECM device provides an effective interpositional material while serving as an inductive template for reconstruction of the TMJ meniscus.

Hepatotoxicosis in dogs consuming a diet of camel meat contaminated with indospicine

Four dogs presented with clinical signs of severe hepatic disease after consuming a commercial camel meat diet. Laboratory investigation revealed evidence of severe liver disease, including markedly increased serum alanine aminotransferase (ALT) activity and total bilirubin concentration, and prolonged clotting times. Two dogs deteriorated despite supportive therapy and were euthanased. Histologically, both livers appeared similar, with the main lesion being extensive periacinar necrosis and haemorrhage. Indospicine, a toxic amino acid of plant origin, was detected in the serum and/or plasma from all four dogs, as well as in tissues of a dog that was necropsied and in a sample of the camel meat fed to this animal. Serum biochemistry tests using blood samples collected from 15 additional dogs identified as having eaten the diet detected indospicine was in the serum of 14 and 3 had increased ALT activity. One of the latter dogs subsequently developed clinical signs of severe liver disease and was euthanased. To the authors' knowledge, this is the first published report of the detection of indospicine residues in camel meat and the occurrence of severe, sometimes fatal, liver disease in dogs that consumed this contaminated meat.

Longterm effects of cardiac mediastinal nerve cryoablation on neural inducibility of atrial fibrillation in canines

In canines, excessive activation of select mediastinal nerve inputs to the intrinsic cardiac nervous system induces atrial fibrillation (AF). Since ablation of neural elements is proposed as an adjunct to circumferential pulmonary vein ablation for AF, we investigated the short and long-term effects of mediastinal nerve ablation on AF inducibility. Under general anesthesia, in 11 dogs several mediastinal nerve sites were identified on the superior vena cava that, when stimulated electrically during the atrial refractory period, reproducibly initiated AF. Cryoablation of one nerve site was then performed and inducibility retested early (1–2 months post Cryo; n = 7) or late (4 months post Cryo; n = 4). Four additional dogs that underwent a sham procedure were retested 1 to 2 months post-surgery. Stimulation induced AF at 91% of nerve sites tested in control versus 21% nerve sites early and 54% late post-ablation (both P < 0.05). Fewer stimuli were required to induce AF in controls versus the Early Cryo group; this capacity returned to normal values in the Late Cryo group. AF episodes were longer in control versus the Early or Late Cryo groups. Heart rate responses to vagal or stellate ganglion stimulation, as well as to local nicotine infusion into the right coronary artery, were similar in all groups. In conclusion, focal damage to intrinsic cardiac neuronal inputs causes short-term stunning of neuronal inducibility of AF without major loss of overall adrenergic or cholinergic efferent neuronal control. That recovery of AF inducibility occurs rapidly post-surgery indicates the plasticity of intrathoracic neuronal elements to focal injury.

Genomic analysis of a pneumovirus isolated from dogs with acute respiratory disease

A previously unrecognized virus belonging to the subfamily Pneumovirinae and most closely related to murine pneumovirus (MPV) was identified in domestic dogs in 2 related animal shelters. Additional diagnostic testing yielded 3 new viral isolates and identified 6 additional PCR positive dogs from other USA locations indicating that its distribution is not geographically limited. Nucleotide sequences encompassing 9 of the 10 genes were compared to the only 2 available MPV strains, 15 and J3666. Several features distinguished the canine pneumovirus (CnPnV) from the murine strains. Two regions of diversity were identified in the amino-proximal region of P and the overlapping P2 ORF was only 54 amino acids (aa) compared to 137 aa in MPV. The G protein had an amino-terminal cytoplasmic tail 18 aa longer than in the MPV strains. The CnPnV SH protein showed the highest divergence with only 90.2% aa identity when compared to MPV strain 15. Like strain 15, the CnPnV SH ORF coded for a protein of 92 aa while J3666 has a 114 aa variant. Comparison of CnPnV isolates at culture passages 4 and 17 revealed 7 nt differences within the 8598 nt sequenced. Of note was a substitution at nt 364 in G resulting in a termination codon that would produce a truncated G protein of 122 aa. Analysis of early passage and ex vivo samples showed the termination codon in G to be predominant after 6 days in culture indicating rapid selection of the mutation in A72 cells.

Combined Effect of Disopyramide and Erythromycin on Ventricular Repolarization in Dogs With Complete Atrioventricular Block

The combined effects of disopyramide (DP) and erythromycin (EM) on ventricular repolarization and the inciden-ces of ventricular premature contractions (VPCs) and torsades de pointes (TdP) were investigated in 12 anesthetized dogs with complete atrioventricular block. Monophasic action potentials (MAPs) were measured from the left and right ventricular (LV and RV) endocardium. The right or left ventricle was paced at a cycle length of 750-1000 msec. Dogs were divided into 2 groups and given either intravenous DP at 3 mg/kg and then intravenous EM at 50 mg/kg (group 1, n = 8), or intravenous EM at 50 mg/kg and then intravenous DP at 3 mg/kg (group 2, n = 4). MAP duration at 90% repolarization (MAPD(90)) was measured before drug administration (baseline) and again after administration of each drug. RV MAPD(90) and LV MAPD(90) increased significantly (P < 0.02) after administration of each drug in group 1 (RV MAPD(90): from 247.0 ± 36.3 [baseline] to 283.5 ± 38.3 to 321.8 ± 56.7; LV MAPD(90): from 262.6 ± 49.1 (baseline) to 296.1 ± 58.8 to 351.0 ± 80.6). Early afterdepolarizations developed in 2 group 1 dogs after administration of DP and in 4 additional dogs after administration of EM. Frequent VPCs occurred in 1 dog after administration of DP and in 2 additional dogs after administration of EM, and TdP and ventricular tachycardias developed in 2 of the 3 dogs after administration of EM. Similar trends occurred in group 2. These results indicate a potentially fatal interaction between DP and EM administered in clinically relevant doses.

MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers

Mutations in the MTM1 gene encoding myotubularin cause X-linked myotubular myopathy (XLMTM), a well-defined subtype of human centronuclear myopathy. Seven male Labrador Retrievers, age 14-26 wk, were clinically evaluated for generalized weakness and muscle atrophy. Muscle biopsies showed variability in fiber size, centrally placed nuclei resembling fetal myotubes, and subsarcolemmal ringed and central dense areas highlighted with mitochondrial specific reactions. Ultrastructural studies confirmed the centrally located nuclei, abnormal perinuclear structure, and mitochondrial accumulations. Wild-type triads were infrequent, with most exhibiting an abnormal orientation of T tubules. MTM1 gene sequencing revealed a unique exon 7 variant in all seven affected males, causing a nonconservative missense change, p.N155K, which haplotype data suggest derives from a recent founder in the local population. Analysis of a worldwide panel of 237 unaffected Labrador Retrievers and 59 additional control dogs from 25 other breeds failed to identify this variant, supporting it as the pathogenic mutation. Myotubularin protein levels and localization were abnormal in muscles from affected dogs, and expression of GFP-MTM1 p.N155K in COS-1 cells showed that the mutant protein was sequestered in proteasomes, where it was presumably misfolded and prematurely degraded. These data demonstrate that XLMTM in Labrador Retrievers is a faithful genetic model of the human condition.

Congenital Ureteral Ectopia in Continent and Incontinent-Related Entlebucher Mountain Dogs: 13 Cases (2006-2009)

Ectopic ureters (EUs) associated with varying combinations of urinary incontinence, hydronephrosis, and urinary tract infection have been identified in related North American Entlebucher Mountain Dogs. To characterize the disease phenotype in affected dogs and evaluate possible modes of inheritance. Twenty client-owned Entlebucher Mountain Dogs. Nine dogs had clinical signs of urinary tract disease. Prospective case series in which 17 dogs were evaluated with excretory urography, ultrasonography, and urethrocystoscopy. Three additional dogs were evaluated by necropsy alone. Clinical and pedigree histories from 165 North American Entlebuchers were compiled for analysis. Eleven female and 2 male dogs were found to have EUs. Six females and 1 male were continent. Bilateral intravesicular ectopic ureters (IVEUs) were identified in 9 dogs, bilateral extravesicular ectopic ureters (EVEUs) in 3 dogs, and 1 dog had IVEU and EVEU. Hydronephrosis was identified in 5 dogs, 3 of which had bilateral IVEUs. Two necropsied dogs had bilateral hydronephrosis with presumed ureterovesical junction obstruction associated with chronic granulation tissue or lymphoplasmacytic inflammation. Twenty-six dogs with EUs were identified in the pedigree. Because of incomplete penetrance, mode of inheritance could not be determined. Ureteral ectopia is common in North American Entlebucher Mountain Dogs and clinical signs alone could not reliably predict disease phenotype. EVEUs were associated with urinary incontinence and occasionally hydronephrosis. IVEUs were clinically silent or associated with hydronephrosis. Further analyses are necessary to confirm and characterize the hereditary nature of the disorder.

An association study of 20 candidate genes with cryptorchidism in Siberian Husky dogs

Cryptorchidism (CO) as a common developmental defect in purebred dogs causes health concerns of reduced fertility and increases risk of testicular malignancies. A total of 49 single nucleotide polymorphisms (SNPs) discovered from 20 candidate genes was investigated to analyse their associations with CO in Siberian Huskies. The sibling-transmission disequilibrium test on 38 discordant full-sibs revealed seven SNPs in the collagen type II alpha 1 (COL2A1) gene were significantly (p < 0.05) or suggestively (p < 0.10) associated with CO. Further analyses showed that only one SNP (rs23358342) in this gene remained suggestively significant (p < 0.1) on a data set of full-sibs with additional related dogs, but not significant on all 156 Siberian Huskies. Based on the statistical results and the involvement of COL2A1 in the testicle development and descent, we could not exclude COL2A1 as a potential candidate gene for CO in Siberian Huskies. Further studies are necessary to clarify these results from our relatively small sample size.

Utilizing physiological measures to facilitate phobia treatment with individuals with autism and intellectual disability: A case study

AbstractDespite the conceptualization of phobic fear as a multi‐factorial response, the measurement and treatment of phobias is often not comprehensive. The extant literature on the treatment of phobias for individuals with intellectual disabilities has exclusively focused on indices of behavioral avoidance. The present study demonstrates the treatment of behavioral avoidance and physiological reactivity in a child diagnosed with autism, intellectual disability, and a dog phobia. The results indicate that the individual often experienced physiological reactivity in the presence of the feared stimulus despite engaging in behavioral approach. Treatment of both behavioral avoidance and physiological reactivity resulted in successful generalization of treatment effects across three additional dogs and maintenance of treatment effects during a six‐month follow‐up assessment. Implications for examining multiple aspects of the anxious response when treating children with intellectual disabilities and severe language delays are discussed. Copyright © 2010 John Wiley &amp; Sons, Ltd.

Localization of Canine Brachycephaly Using an Across Breed Mapping Approach

The domestic dog, Canis familiaris, exhibits profound phenotypic diversity and is an ideal model organism for the genetic dissection of simple and complex traits. However, some of the most interesting phenotypes are fixed in particular breeds and are therefore less tractable to genetic analysis using classical segregation-based mapping approaches. We implemented an across breed mapping approach using a moderately dense SNP array, a low number of animals and breeds carefully selected for the phenotypes of interest to identify genetic variants responsible for breed-defining characteristics. Using a modest number of affected (10–30) and control (20–60) samples from multiple breeds, the correct chromosomal assignment was identified in a proof of concept experiment using three previously defined loci; hyperuricosuria, white spotting and chondrodysplasia. Genome-wide association was performed in a similar manner for one of the most striking morphological traits in dogs: brachycephalic head type. Although candidate gene approaches based on comparable phenotypes in mice and humans have been utilized for this trait, the causative gene has remained elusive using this method. Samples from nine affected breeds and thirteen control breeds identified strong genome-wide associations for brachycephalic head type on Cfa 1. Two independent datasets identified the same genomic region. Levels of relative heterozygosity in the associated region indicate that it has been subjected to a selective sweep, consistent with it being a breed defining morphological characteristic. Genotyping additional dogs in the region confirmed the association. To date, the genetic structure of dog breeds has primarily been exploited for genome wide association for segregating traits. These results demonstrate that non-segregating traits under strong selection are equally tractable to genetic analysis using small sample numbers.

IMAGING DIAGNOSIS-CANINE MENINGIOANGIOMATOSIS

Meningioangiomatosis is a rare proliferative disorder of the central nervous system. It occurs sporadically in dogs and is characterized by a leptomeningeal plaque that extends from the subarachnoid space along the perivascular spaces into the adjacent parenchyma. We describe the clinical presentation, magnetic resonance (MR) imaging and neuropathologic characteristics of two additional dogs with meningioangiomatosis, and document involvement of the thoracolumbar spinal cord, a site not previously described for this condition. MR imaging findings were different from those previously described, most likely reflecting the degree of vascularity and collagen deposition. The MR imaging features of meningioangiomatosis are not specific.

Coagulation effects of low molecular weight heparin compared with heparin in dogs considered to be at risk for clinically significant venous thrombosis

Compare the effects of 3 anticoagulation protocols on anti-factor Xa activity (AXa). Prospective, randomized, double-blind study. University veterinary teaching hospital. Eighteen dogs considered to be at risk for venous thrombosis. Each dog was randomly assigned to 1 of the following 3 groups (n=6/group) and was treated for 24 hours: low-dose heparin (LDH), high-dose heparin (HDH), and dalteparin (DP). Dogs in the LDH group received a constant rate infusion (CRI) of unfractionated heparin (UFH) at 300 U/kg/d, the HDH group received a bolus of 100 U/kg of UFH IV, then a CRI of 900 U/kg/day, and the DP group received 100 U/kg DP SC at 0, 12, and 24 hours. A total of 54 samples for activated partial thromboplastin time (aPTT) and AXa assays were collected at 0, 4, and 28 hours. Six samples had an AXa >0.1 U/mL, 5 of those were from the HDH group at hour 4. Two samples from the HDH group at hour 4 had a prolonged aPTT (93 and 200 seconds) and the highest AXa (0.6 and 1.0 U/mL, respectively). Four additional dogs in the HDH group did not complete the study due to hemorrhage; none of the dogs completing the study showed signs of hemorrhage. Neither DP nor LDH increased AXa to values considered therapeutic in humans (0.5-1 and 0.35-0.75 U/mL, respectively), and both protocols appear to be inadequate to increase AXa in dogs with clinical illness. HDH increased AXa to this range in 2 of 6 dogs, but had unpredictable effects on aPTT and resulted in hemorrhage in some dogs.

Phase I Dose Escalation of Single‐Agent Vinblastine in Dogs

Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. Twenty-three dogs with lymphoma or cutaneous mast cell tumors. Dogs received 1 single-agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2-3 weeks. VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose-limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self-limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. In dogs, single-agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.

Abstract 4341: Dyssynchrony is a Prerequisite condition for Beta Reserve Upregulation By Cardiac Resynchronization Therapy

Background Dyssynchronous Heart failure (DHF) versus synchronous is characterized by unique cellular and molecular substrates involving stress kinase and cell survival signaling ( Chakir et al. Circulation 2008 ; 117 : 1369 –77 ). Hypothesis The impact of CRT may depend upon whether there was a preceding dyssynchrony. Here, we tested such dyssynchrony dependence on basal and beta-adrenergic stimulated myocyte function in a canine HF model. Methods Adult dogs (n=8) underwent LBB radio-frequency ablation; half then subjected to atrial tachypacing-induced dyssynchronous HF (DHF) for 6wks, while the others had 3 weeks DHF followed by 3-wks bi-ventricular tachypacing (CRT). 5 additional dogs were subjected to RV freewall tachypacing for 3wks (dyssynchrony) followed by 3 weeks right atrial tachypacing (resynchronization; V3A3), and 3 more were subjected to synchronous heart failure (RA tachypacing for 6 wks; A6). 3 non-paced dogs served as controls. Myocytes were enzymatically isolated from the LV free wall and field stimulated in a perfusion chamber. Sarcomere shortening and calcium transient were determined with and without 10 −7 M isoproterenol. Results: DHF, V3A3, A6 and CRT hearts had similar global failure, with dP/dtmax 1190.2±139.8 vs. 1111.8±131.6 vs. 1333.0±205.2 vs. 1195.3±137.6 mmHg/s, respectively (1900.3±176.8 in control). However, there were marked differences in basal and β-stimulated myocyte calcium transients and sarcomere shortening (Table , n=8 –30 cells/ group). Intriguingly, both DHF and A6 cells had reduced basal and β-AR stimulated sarcomere shortening and Ca transients versus control. In contrast, both V3A3 and CRT displayed enhanced rest and β-AR responses. Conclusion: HF resynchronization improves rest and β-AR cellular function over those never dyssynchronous. A particular substrate develops with DHF that when offset by CRT enhances cellular function beyond that with synchronous HF; explaining the CRT impact in targeted patients.

Rate-dependence of atrial tachycardia effects on atrial refractoriness and atrial fibrillation maintenance

Although atrial-tachycardia remodelling is a significant atrial fibrillation (AF) promoting factor, little information is available about how atrial-tachycardia rate determines remodelling effects. This study assessed the effects of atrial tachypacing (ATP) over a range of clinically relevant rates on atrial electrophysiology and AF. Chronically instrumented dogs underwent sequential 7 day ATP at 400, 300, 200, and 160 bpm in random order with 2 day recovery intervals between periods of ATP. ATP at 400, 300, and 200 bpm significantly decreased atrial effective refractory period (ERP) by 41 +/- 2, 37 +/- 3, and 7 +/- 1 ms, respectively, with no significant effects at 160 bpm. Mean duration of induced AF was increased by 400 and 300 bpm ATP (404 +/- 284 and 410 +/- 283 s on day 4, respectively, vs. 12 +/- 4 s at baseline, P < 0.01), but not by 200 or 160 bpm ATP. ATP effects developed slowly with 200 bpm pacing, so we studied 5 week ATP at 200 and 160 bpm in additional dogs. ERP shortened gradually over 3 weeks at 200 bpm (131 +/- 5 ms baseline vs. 112 +/- 4 and 105 +/- 4 ms at 2 and 3 weeks, respectively), but no decrease occurred thereafter (5-week value: 104 +/- 3 ms) and AF duration was not significantly affected. No change in ERP or AF duration occurred at 160 bpm. Because of the limited effects of 200 bpm ATP on AF duration despite significant effects on ERP, we tested 200 bpm ATP effects in the presence of AF substrates. When 200 bpm ATP was induced in the presence of a fibrotic AF substrate induced by 2 weeks of ventricular tachypacing followed by 1 week recovery, no change in AF duration or atrial vulnerability occurred. However, when 200 bpm ATP was followed by 400 bpm ATP, the onset of remodelling and AF duration increases was accelerated. There is a non-linear relationship between atrial rate and the extent of atrial electrical remodelling. Remodelling at rates equivalent to paroxysmal supraventricular tachycardias in man is insufficient to promote AF alone or in the presence of an atrial fibrotic substrate, but can accelerate the remodelling and stabilization of AF when followed by faster atrial tachyarrhythmias.

Feasibility and Safety of Targeted Cisplatin Delivery to a Select Lung Lobe in Dogs via the AeroProbe®Intracorporeal Nebulization Catheter

Delivery of drugs by airway can minimize systemic toxicity and maximize local drug concentrations. Most cancers metastasize to the lungs. Our purpose was to determine platinum concentrations in the lung after targeted delivery of cisplatin (CDDP) with an intracorporeal nebulizing catheter (INC), and to determine the safety of escalating doses of inhaled CDDP. In anesthetized and mechanically ventilated healthy dogs, the INC (AeroProbe) was introduced via flexible bronchoscope into the right caudal lung lobe (RCLL) and CDDP (10 mg/m2) administered. Tissue and serum platinum concentrations were compared to those after an equivalent intravenous dose of CDDP (n = 3 dogs/group). In three additional dogs, pharmacokinetics were performed after inhaled and intravenous CDDP. Increasing dosages of inhaled CDDP (10, 15, 20, and 30 mg/m2) were then administered every 2 weeks. Dogs were sacrificed for postmortem examination at week 10. One additional dog was treated with a single dose of 30 mg/m2 and sacrificed 2 weeks later. Immediately following a single inhaled dose, mean CDDP levels were 44 times greater in the RCLL than in most other tissues and 15.6 times lower in the serum compared to intravenous dosing. Pharmacokinetic comparison showed that the AUC0-24h was similar (p = 0.72), but maximum serum concentration was fivefold lower after inhalation than intravenous delivery (p = 0.02). Escalating doses of inhaled CDDP (cumulative 75 mg/m2) produced no significant clinical or hematological effects, but there was radiographic and histologic evidence of severe pneumonitis with mild to moderate fibrosis confined to the RCLL. Radiographic and histologic changes were similar in the single, high-dose dog. Targeted inhaled CDDP achieved high concentrations in the treated lobe, with lower peak serum levels than after intravenous administration. Escalating doses of inhaled CDDP produced focal pneumonitis and fibrosis in the treated lung lobe with minimal clinical and hematologic effects. Targeted inhaled chemotherapy could be a promising method of treatment for primary and secondary lung tumors.

Atrial sympathetic and parasympathetic nerve sprouting and hyperinnervation induced by subthreshold electrical stimulation of the left stellate ganglion in normal dogs

Subthreshold electrical stimulation of the left stellate ganglion (LSG) can induce nerve sprouting and sympathetic hyperinnervation in canine ventricles. It is unclear whether a similar neural plasticity involving both sympathetic and parasympathetic innervation also exists in the atria. We applied subthreshold electrical stimulation at 20 Hz (0.45 ms pulse width) or 5 Hz (1.9 ms pulse width) to the LSG in 6 normal mongrel dogs. After 41+/-9 days, the hearts were harvested and the right and left atrium stained for synaptophysin (SYN), growth-associated protein 43 (GAP43), sympathetic nerve markers tyrosine hydroxylase (TH), and parasympathetic marker choline acetyltransferase (ChAT). Tissues from 6 additional healthy dogs were used as controls. The hearts from dogs with LSG electrical stimulation had a higher density of nerve structures immunopositive to the SYN, GAP43, TH, and ChAT (P<.01) in both right and left atria. Nerve density was equal in right and left atria. There were more TH-positive nerve structures than ChAT-positive nerve structures (P<.01) for both right and left atria. No atrial arrhythmia was observed at the second surgery. Continuous subthreshold electrical stimulation to the LSG induces both sympathetic and parasympathetic hyperinnervation in both right and left atria in normal dogs.

Evaluation of a Deep Brain Stimulation Electrode for Laryngeal Pacing

The purpose of the present study was to evaluate the suitability of a deep brain stimulation electrode for laryngeal pacing. Of interest was whether the smaller and more closely spaced channels could provide sufficient channel redundancy, controlled current distribution, and discrete activation of the posterior cricoarytenoid (PCA) muscle. A study was conducted in dogs under differing states of PCA muscle innervation representing complete denervation to complete synkinetic reinnervation. In 3 animals, stimulated glottal opening was assessed in the innervated state and after chemical denervation by pancuronium bromide. In 3 additional dogs, the left side of the larynx was surgically denervated and compared to the innervated, right side to study an anatomic model of clinical paralysis. The thresholds were lower and the maximum level of abduction was greater for the innervated state. The stimulated glottal opening equaled that of a spontaneously breathing animal. Abductory responses were obtained across all channels in the array, demonstrating its anatomic and physiological compatibility for this application. In the denervated state, responses were only 20% of that of the innervated state with a pulse duration of 0.5 ms. The response could be enhanced to 40% and 60% by increasing the pulse duration to 1 and 2 ms. A deep brain stimulation electrode could effectively reanimate the PCA muscle to a normal level in a case of synkinetic reinnervation and to as much as 60% of the normal level in a case of complete denervation.

Vascular foramina of the metacarpophalangeal sesamoid bones of Greyhounds and their relationship to sesamoid disease

To apply a novel technique and use the number and size (diameter and mean area) of vascular foramina to estimate potential blood supply in the metacarpophalangeal bones of dogs. 28 Greyhounds. The forelimb sesamoid bones of 23 dogs were obtained after dogs were euthanized. Bones were isolated and examined by scanning electron microscopy. The number, diameter, and area of vascular foramina were determined by image analysis. Arterial distribution was assessed by use of resin injection in the sesamoid bones of 5 additional dogs. Sesamoids 2 and 7 had significantly fewer foramina (mean +/- SE, 38.9+/-2.5) and lower total foramen area (0.55+/-0.04 mm(2)), compared with values for other sesamoids (70.4+/-3.3 foramina and 1.43+/-0.06 mm(2), respectively). Mean area and diameter of foramina of sesamoids 2 and 7 were also smaller in some regions. Comparison of the foramen distribution in dogs with sesamoid disease and clinically normal dogs revealed that for sesamoids 2 and 7, intact sesamoids from dogs with sesamoid disease had a significantly lower total foramen area (20 sesamoids from 9 dogs, 0.45+/-0.04 mm(2)), compared with sesamoids in clinically normal dogs (59 sesamoids from 14 dogs, 0.58+/-0.03 mm(2)). However, for sesamoids other than 2 and 7, dogs with sesamoid disease had a significantly greater foramen area. The restriction of vascular foramina in sesamoids 2 and 7 appeared to mirror the disease distribution and disease risk for specific dogs.

The canine bilateral groove model of osteoarthritis

In studies aimed at local treatment of experimental osteoarthritis (OA) it is optimal to have an internal (untreated) OA control. Such an approach excludes interanimal variation, and allows paired statistical evaluation of treatment efficacy. For this purpose, we developed and characterized a bilateral version of the canine Groove model. We hypothesized that the bilateral version of the canine Groove model would show consistent and clear development of features of OA similar to those found in the unilateral version. In six Beagle dogs, grooves were surgically made in the articular cartilage of the femoral condyles of both knee joints. Six additional dogs underwent bilateral sham surgery. The degree of OA was quantified 20 weeks after surgery and was compared in retrospect to 23 animals that undergone the same procedure in a single knee joint with the contralateral knee serving as a non-OA control. Bilateral groove surgery resulted in OA. This was based on the observed ineffective repair response in which an increase in proteoglycan synthesis, a diminished retention of these newly formed proteoglycans, and an enhanced loss of resident proteoglycans resulted in a decreased cartilage proteoglycan content. These biochemical effects were corroborated by clear histological features of OA. All these effects were found in femor as well as in the (surgically untouched) tibia. Interestingly, features of OA were slightly more severe in the bilateral model than in the unilateral variant. The bilateral canine Groove model showed consistent and clear development of features of OA, comparable to the unilateral model.