Spurious hyperbicarbonatemia and a negative anion gap in a cat and a dog with severe rhabdomyolysis.

A 3-year-old male neutered domestic shorthair cat and a 2-year-old male neutered Labrador-mix dog were separately presented to the Veterinary Medical Center for evaluation after sustaining significant muscle trauma due to a dog attack and seizure activity, respectively. In both cases, biochemical analysis was consistent with rhabdomyolysis. Additionally, a markedly increased measured serum bicarbonate concentration and negative calculated anion gap were observed. As these biochemical abnormalities were not expected and deemed incompatible with life, an interference with the analyzer measurement of bicarbonate involving marked increases in pyruvate and lactate dehydrogenase (LDH) following myocyte injury was suspected. Venous blood gas analysis calculated bicarbonate concentration and anion gap were within reference interval, while measured LDH activity was markedly increased. These findings supported an analyzer-generated interference. This is the first published report of a previously described chemistry analyzer interference of markedly increased LDH activity with serum bicarbonate concentration measurement in dogs and cats. Awareness of this interference is important, particularly in the emergency setting, as it may influence case management.

Retrospective evaluation of the clinical course and outcome of zinc toxicosis due to metallic foreign bodies in dogs (2005-2021): 55 cases.

OBJECTIVE: To describe the overall clinical course of zinc toxicosis in dogs including source, time to source control, incidence of hemolytic anemia, acute liver injury (ALI), acute kidney injury (AKI), and pancreatitis. DESIGN: Retrospective case series from 2005 to 2021. SETTING: Six university veterinary teaching hospitals. ANIMALS: Fifty-five client-owned dogs with known zinc toxicosis due to metallic foreign body (MFB) ingestion. MEASUREMENTS AND MAIN RESULTS: The most common source of zinc was US pennies minted after 1982 (67.3%). Forty-five of 55 (81.8%) dogs survived and 10 of 55 (18.2%) died or were euthanized. Median length of hospitalization for survivors and nonsurvivors was 3 days. The most common clinical sequelae of zinc toxicosis were anemia (87%), ALI (82%), coagulopathy (71%), thrombocytopenia (30.5%), AKI (26.9%), and acute pancreatitis (5.5%). Most dogs (67.3%) required blood products and 83% of dogs achieved a stable HCT or PCV in a median of 24 hours after MFB removal. The median duration of illness prior to presentation was 48 hours for both survivors and nonsurvivors and there was no impact of time to presentation on the incidence of ALI, AKI, or pancreatitis. CONCLUSIONS: Zinc toxicosis secondary to MFB ingestion should be considered a differential diagnosis for dogs with gastrointestinal signs, hemolytic anemia, ALI, hemostatic abnormalities, AKI, and pancreatitis. AKI may be a more common sequela of zinc toxicosis than previously suspected. Acute pancreatitis is a rare but potentially serious sequela to zinc toxicosis.

Retrospective evaluation of fluid production at the time of thoracostomy tube removal following elective and emergency surgery in dogs (2010-2017): 185 cases.

OBJECTIVE: To report the rate of fluid production at the time of removal of thoracostomy tubes placed intraoperatively and to determine the association of this rate with specific patient factors, surgical factors, or clinical diagnosis. The secondary objective was to determine whether identification of pleural effusion within 2 weeks of thoracostomy tube removal was associated with the same variables. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: One hundred eighty-five client-owned dogs with thoracostomy tubes placed intraoperatively between January 2010 and March 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thoracostomy tubes were removed at a median fluid production of 0.09 mL/kg/h (range, 0-7.0 m L/kg/h). Median fluid production at the time of thoracostomy tube removal was significantly higher in dogs with preoperative pleural effusion compared to dogs without preoperative pleural effusion (0.21 vs 0.05 mL/kg/h; P = 0.0001) and in dogs that had a median sternotomy compared to dogs that had a lateral thoracotomy (0.14 vs 0.09 mL/kg/h; P = 0.04). Of the 169 dogs available for follow-up, 12 (7.1%) had pleural effusion within 2 weeks of removal of the thoracostomy tube. Detection of pleural effusion during the follow-up period was significantly associated with the presence of preoperative pleural effusion (P = 0.0019) and the diagnosis (P = 0.01). A greater proportion of dogs with a lung lobe torsion (4/9, 44.4%) and idiopathic chylothorax (2/7, 28.5%) had pleural effusion within 2 weeks compared to other diagnoses. Reintervention was performed in 4.7% of dogs. CONCLUSIONS: Thoracostomy tubes were removed at pleural fluid production rates that frequently exceeded current veterinary guidelines. However, the fluid production rate at the time of thoracostomy tube removal was not associated with the detection of pleural effusion within 2 weeks of thoracostomy tube removal, and the overall need for reintervention following thoracostomy tube removal was low (4.7%).

Use of a platelet-rich plasma-collagen scaffold as a bioenhanced repair treatment for management of partial cruciate ligament rupture in dogs.

Dogs are commonly affected with cruciate ligament rupture (CR) and associated osteoarthritis (OA), and frequently develop a second contralateral CR. Platelet rich plasma (PRP) is a component of whole blood that contains numerous growth factors, which in combination with a collagen scaffold may act to promote bioenhanced primary repair of ligament. This study tested the hypothesis that treatment of partial stable CR stifles with an intra-articular collagen scaffold and PRP would decrease the disease progression, synovitis and risk of complete CR over a 12-month study period. We conducted a prospective cohort study of 29 client-owned dogs with an unstable stifle due to complete CR and stable contralateral stifle with partial CR. All dogs were treated with tibial plateau leveling osteotomy (TPLO) on the unstable stifle and a single intra-articular application of PRP-collagen in the stable partial CR stifle. Dogs were evaluated at the time of diagnosis, and at 10-weeks and 12-months after treatment. We evaluated correlation between both development of complete CR and time to complete CR with diagnostic tests including bilateral stifle radiographs, 3.0 Tesla magnetic resonance (MR) imaging, and bilateral stifle arthroscopy. Additionally, histologic evaluation of synovial biopsies, C-reactive protein (CRP) concentrations in serum and synovial fluid, and synovial total nucleated cell count, were determined. Results indicated that a single application of PRP-collagen in partial CR stifles of client owned dogs is not an effective disease-modifying therapy for the prevention of progression to complete CR. Radiographic effusion, arthroscopic evaluation of cranial cruciate ligament (CrCL) damage, and MR assessment of ligament fiber tearing in partial CR stifles correlated with progression to complete CR over the 12-month follow-up period. We determined that the best predictive model for development of complete CR in PRP-collagen treated partial CR stifles included variables from multiple diagnostic modalities.

Radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture.

Cruciate ligament rupture (CR) and associated osteoarthritis (OA) is a common condition in dogs. Dogs frequently develop a second contralateral CR. This study tested the hypothesis that the degree of stifle synovitis and cranial cruciate ligament (CrCL) matrix damage in dogs with CR is correlated with non-invasive diagnostic tests, including magnetic resonance (MR) imaging. We conducted a prospective cohort study of 29 client-owned dogs with an unstable stifle due to complete CR and stable contralateral stifle with partial CR. We evaluated correlation of stifle synovitis and CrCL fiber damage with diagnostic tests including bilateral stifle radiographs, 3.0 Tesla MR imaging, and bilateral stifle arthroscopy. Histologic grading and immunohistochemical staining for CD3+ T lymphocytes, TRAP+ activated macrophages and Factor VIII+ blood vessels in bilateral stifle synovial biopsies were also performed. Serum and synovial fluid concentrations of C-reactive protein (CRP) and carboxy-terminal telopeptide of type I collagen (ICTP), and synovial total nucleated cell count were determined. Synovitis was increased in complete CR stifles relative to partial CR stifles (P<0.0001), although total nucleated cell count in synovial fluid was increased in partial CR stifles (P<0.01). In partial CR stifles, we found that 3D Fast Spin Echo Cube CrCL signal intensity was correlated with histologic synovitis (SR = 0.50, P<0.01) and that radiographic OA was correlated with CrCL fiber damage assessed arthroscopically (SR = 0.61, P<0.001). Taken together, results of this study show that clinical diagnostic tests predict severity of stifle synovitis and cruciate ligament matrix damage in stable partial CR stifles. These data support use of client-owned dogs with unilateral complete CR and contralateral partial CR as a clinical trial model for investigation of disease-modifying therapy for partial CR.

Role of calcitonin gene-related peptide in functional adaptation of the skeleton.

Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRPα and CGRPß. Sensory fibers are a potential means by which the nervous system may detect and respond to loading events within the skeleton. However, the functional role of the nervous system in the response of bone to mechanical loading is unclear. We used the ulna end-loading model to induce an adaptive modeling response in CGRPα and CGRPß knockout mouse lines and their respective wildtype controls. For each knockout mouse line, groups of mice were treated with cyclic loading or sham-loading of the right ulna. A third group of mice received brachial plexus anesthesia (BPA) of the loaded limb before mechanical loading. Fluorochrome labels were administered at the time of loading and 7 days later. Ten days after loading, bone responses were quantified morphometrically. We hypothesized that CGRP signaling is required for normal mechanosensing and associated load-induced bone formation. We found that mechanically-induced activation of periosteal mineralizing surface in mice and associated blocking with BPA were eliminated by knockout of CGRPα signaling. This effect was not evident in CGRPß knockout mice. We also found that mineral apposition responses to mechanical loading and associated BPA blocking were retained with CGRPα deletion. We conclude that activation of periosteal mineralizing surfaces in response to mechanical loading of bone is CGRPα-dependent in vivo. This suggests that release of CGRP from sensory peptidergic fibers in periosteum and bone has a functional role in load-induced bone formation.

Functional adaptation in female rats: the role of estrogen signaling.

BACKGROUND: Sex steroids have direct effects on the skeleton. Estrogen acts on the skeleton via the classical genomic estrogen receptors alpha and beta (ERα and ERß), a membrane ER, and the non-genomic G-protein coupled estrogen receptor (GPER). GPER is distributed throughout the nervous system, but little is known about its effects on bone. In male rats, adaptation to loading is neuronally regulated, but this has not been studied in females. METHODOLOGY/PRINCIPAL FINDINGS: We used the rat ulna end-loading model to induce an adaptive modeling response in ovariectomized (OVX) female Sprague-Dawley rats. Rats were treated with a placebo, estrogen (17ß-estradiol), or G-1, a GPER-specific agonist. Fourteen days after OVX, rats underwent unilateral cyclic loading of the right ulna; half of the rats in each group had brachial plexus anesthesia (BPA) of the loaded limb before loading. Ten days after loading, serum estrogen concentrations, dorsal root ganglion (DRG) gene expression of ERα, ERß, GPER, CGRPα, TRPV1, TRPV4 and TRPA1, and load-induced skeletal responses were quantified. We hypothesized that estrogen and G-1 treatment would influence skeletal responses to cyclic loading through a neuronal mechanism. We found that estrogen suppresses periosteal bone formation in female rats. This physiological effect is not GPER-mediated. We also found that absolute mechanosensitivity in female rats was decreased, when compared with male rats. Blocking of adaptive bone formation by BPA in Placebo OVX females was reduced. CONCLUSIONS: Estrogen acts to decrease periosteal bone formation in female rats in vivo. This effect is not GPER-mediated. Gender differences in absolute bone mechanosensitivity exist in young Sprague-Dawley rats with reduced mechanosensitivity in females, although underlying bone formation rate associated with growth likely influences this observation. In contrast to female and male rats, central neuronal signals had a diminished effect on adaptive bone formation in estrogen-deficient female rats.

Are bacterial load and synovitis related in dogs with inflammatory stifle arthritis?

It has been proposed that small quantities of microbial material within synovial joints may act as a trigger for development of synovitis. We have previously identified an association between intra-articular bacteria and development of inflammatory stifle arthritis and cranial cruciate ligament rupture (CCLR) in dogs, and now wished to quantify bacterial load and markers of synovitis in dogs with and without stifle arthritis and CCLR. Joint tissues were collected from dogs with CCLR (n=51) and healthy dogs with normal stifles (n=9). Arthritis was assessed radiographically in CCLR dogs. Bacterial load was assessed using qPCR and broad-ranging 16S rRNA primers. qRT-PCR was used to estimate expression of the T lymphocyte antigen receptor (TCR Vß), CD3ɛ, tartrate-resistant acid phosphatase (TRAP), IL-4, IL-17, and TNF-α genes. Severity of synovitis was assessed histologically. Bacterial load was increased in arthritic stifles, when compared with healthy stifles. Histologic synovitis in arthritic stifles was mononuclear and was significantly correlated with bacterial load (1 of 2 primer sets) (S(R)=0.49, p<0.001). In arthritic stifles, expression of TRAP in synovium was increased relative to healthy stifles. Expression of pro-inflammatory genes was not correlated with bacterial load, histologic inflammation, or radiographic arthritis. Translocation of bacterial material to the canine stifle is related to the presence of joint inflammation. The lack of a strong positive correlation suggests that bacterial load is unlikely to be a primary pro-inflammatory factor. However, dysregulation of immune responses within synovial tissues may be dependent upon an environmental microbial trigger.

Systemic effects of ulna loading in male rats during functional adaptation.

Functional skeletal adaptation is thought to be a local phenomenon controlled by osteoctyes. However, the nervous system also may have regulatory effects on adaptation. The aim of this study was to determine the effects of loading of a single bone on adaptation of other appendicular long bones and whether these responses were neuronally regulated. Young male Sprague-Dawley rats were used. The right ulna was loaded to induce a modeling response. In other rats, a second regimen was used to induce bone fatigue with a mixed modeling/remodeling response; a proportion of rats from each group received brachial plexus anesthesia to induce temporary neuronal blocking during bone loading. Sham groups were included. Left and right long bones (ulna, humerus, tibia, and femur) from each rat were examined histologically 10 days after loading. In fatigue- and sham-loaded animals, blood plasma concentrations of TNF-α, RANKL, OPG, and TRAP5b were determined. We found that loading the right ulna induced an increase in bone formation in distant long bones that were not loaded and that this effect was neuronally regulated. Distant effects were most evident in the rats that received loading without bone fatigue. In the fatigue-loaded animals, neuronal blocking induced a significant decrease in plasma TRAP5b at 10 days. Histologically, bone resorption was increased in both loaded and contralateral ulnas in fatigue-loaded rats and was not significantly blocked by brachial plexus anesthesia. In young, growing male rats we conclude that ulna loading induced increased bone formation in multiple bones. Systemic adaptation effects were, at least in part, neuronally regulated.