Topic:Pathophysiology
Pathophysiology in horses involves the study of functional changes that occur in the body as a result of disease or injury. This field examines the mechanisms through which diseases develop and progress, as well as how they affect the body's normal physiological processes. In equine research, pathophysiology encompasses a wide range of conditions, including respiratory disorders, musculoskeletal injuries, gastrointestinal diseases, and metabolic syndromes. Understanding these processes helps in identifying potential therapeutic targets and developing effective treatment strategies. This page collects peer-reviewed research studies and scholarly articles that explore the underlying mechanisms, clinical manifestations, and implications of various pathophysiological conditions in equine health.
Isolation of equine endothelial cells and life cell angiogenesis assay. Arterial or venous thromboses are frequent clinical complications with the risk of fatal progression. Recent studies suggest the disruption of angiogenesis in the course of thrombus resolution as the underlying pathomechanism. Very similar to the situation in human patients, equine vessels have been described to be particularly susceptible to thrombosis. In contrast to humans, equine donors are readily available to obtain organs and tissues for isolation of endothelial cells. Objective of this study was to isolate equine endothelial cells and develop an angiogenesis assay from primary cultures...
Next-generation sequencing identifies equine cartilage and subchondral bone miRNAs and suggests their involvement in osteochondrosis physiopathology. MicroRNAs (miRNAs) are an abundant class of small single-stranded non-coding RNA molecules ranging from 18 to 24 nucleotides. They negatively regulate gene expression at the post-transcriptional level and play key roles in many biological processes, including skeletal development and cartilage maturation. In addition, miRNAs involvement in osteoarticular diseases has been proved and some of them were identified as suitable biomarkers for pathological conditions. Equine osteochondrosis (OC) is one of the most prevalent juvenile osteoarticular disorders in horses and represents a major concern f...
Laminar inflammatory events in lean and obese ponies subjected to high carbohydrate feeding: Implications for pasture-associated laminitis. Acute, massive enteral carbohydrate overload is associated with laminar inflammation in equids; it is unclear if the same is true for a more prolonged period of moderate dietary carbohydrate intake. Objective: To characterise laminar inflammation in ponies exposed to a dietary carbohydrate challenge meant to mimic acute pasture exposure. Methods: In vivo experiment. Methods: Mixed-breed ponies (n = 22) received a diet of hay chop (nonstructural carbohydrate [NSC] ∼7% on a dry matter [DM] basis) for 4 weeks prior to initiation of the experimental feeding protocol. Following dietary acclimatio...
The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae. An increased incidence of metabolic disease in horses has led to heightened recognition of the pathological consequences of insulin resistance. Laminitis, failure of the weightbearing digital lamellae, is an important consequence. Altered trafficking of specialised glucose transporters (GLUTs), responsible for glucose uptake, is central to the dysregulation of glucose metabolism and may play a role in the pathophysiology of laminitis. Objective: We hypothesised that prolonged hyperinsulinaemia alters the regulation of glucose transport in insulin-sensitive tissue and digital lamellae. Our obje...
Descemet’s membrane detachment in horses; case series and literature review. The aim of this article was to describe Descemet's membrane detachment (DMD) following phacoemulsification in five equine eyes and to review the human literature on this topic. In the last decade, there has been increased reporting of DMD in the human literature, in particular following cataract surgery. The natural history of DMD remains unknown and although various medical and surgical treatments have been advocated there is no recognized 'gold standard' treatment for DMD. This case series reports the diagnosis of DMD in four horses (5 eyes) in association with phacoemulsification surgery. T...
Application of stem cells for the treatment of joint disease in horses. Stem cells in the form of mesenchymal stromal cells derived from various sources have been identified to have the potential of supporting the therapy of joint disease in the horse, and preliminary data has been published about the clinical application of stem cells in horses suffering from clinical joint disease. Furthermore, the horse is recognized to be the ideal large animal model for the preclinical study of cell therapy in joints. The advantage of this species in this respect is the size of the joints, which makes surgical applications practically feasible in analogy to human surgery. Add...
Equine sarcoid: In situ demonstration of matrix metalloproteinase expression. Sarcoids are the most prevalent equine skin tumours and remain a therapeutic challenge due to their differing clinical morphology, local aggressive behaviour, and high recurrence following surgical treatment. In vitro, sarcoid derived fibroblasts are invasive and express matrix metalloproteinase (MMP) -1, -2 and -9. It was hypothesised that the MMPs produced by neoplastic cells play a role in both their local invasiveness and interaction with the overlying epidermis (picket fence formation). The objective of this morphological study was to investigate the local behaviour and in situ MMP expres...
Transcriptome-wide analysis of messenger RNA decay in normal and osteoarthritic human articular chondrocytes. Messenger RNA (mRNA) decay rates control not only gene expression levels, but also responsiveness to altered transcriptional input. We undertook this study to examine transcriptome-wide posttranscriptional regulation in both normal and osteoarthritic (OA) human articular chondrocytes. Methods: Human articular chondrocytes were isolated from normal or OA tissue. Equine articular chondrocytes were isolated from young or old horses at a commercial abattoir. RNA decay was measured across the transcriptome in human cells by microarray analysis following an actinomycin D chase. Messenger RNA levels ...
Administration of trimethoprim-sulphadimidine does not improve healing of glandular gastric ulceration in horses receiving omeprazole: a randomised, blinded, clinical study. Interest in Equine Gastric Ulcer Syndrome (EGUS) has recently increased in part due to a growing awareness of the differences between squamous and glandular disease. The pathophysiology and epidemiology of squamous and glandular disease are different and recently it has been shown that the response of glandular gastric ulceration to monotherapy with omeprazole is poor. Given these differences it has been recommended that specific treatment guidelines be formulated for equine glandular disease and that adjunctive therapies be investigated. Along these lines it has been suggested that the additi...
Calcium homeostasis in myogenic differentiation factor 1 (MyoD)-transformed, virally-transduced, skin-derived equine myotubes. Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human an...
The effect of the laryngeal tie-forward procedure and soft palate cautery on nasopharyngeal diameter in horses. The laryngeal tie-forward (LTF) procedure has been shown to move the larynx rostrally and dorsally whilst repositioning the basihyoid bone caudally and dorsally. Other studies have shown that the position of the hyoid bones influences the size of the nasopharynx. The effect of the LTF procedure on the size of the nasopharynx is unknown. It was hypothesised that the LTF procedure would result in a decrease in dorsoventral nasopharyngeal diameter. Twenty-five thoroughbred horses which underwent LTF with or without soft palate cautery (LTF±SPC) for treatment of dorsal displacement of the soft pa...
Morphologic and morphometric features of the calcaneal insertions of the superficial digital flexor tendon in the horse. Accurate description of the calcaneal insertions of the superficial digital flexor tendon (SDFT) is lacking and inconsistent. The aim of this study was to undertake morphologic and morphometic evaluations of these structures to assist in elucidating their functional and pathogenic roles in displacement of the SDFT from the calcaneal tuber. Methods: Dissections were performed on 10 normal cadaveric hindlimbs. The anatomy was photographed to allow measurements at repeatable locations and differences in SDFT dimensions at the various locations were compared using a paired student t-test. Results:...
Histomorphometric parameters and fractal complexity of the equine placenta from healthy and sick foals. Computer-based digital image analysis of tissue samples shows promise both to reduce the subjectivity of traditional manual tissue assessments and potentially to shorten the time required to analyze each sample. The present study used digital image analysis to investigate the histomorphometric parameters and fractal complexity of the equine placenta from healthy and sick foals. We hypothesized that the placentas of sick foals could have a different growth pattern and complexity that could be objectively estimated by their fractal dimension (FD). Fourteen placentas from 30 mares were selected i...
Vasorelaxation responses to insulin in laminar vessel rings from healthy, lean horses. Hyperinsulinemia causes laminitis experimentally and is a risk factor for naturally occurring laminitis. The aim of this study was to investigate the effects of insulin on laminar vascular relaxation and to induce insulin-associated vascular dysfunction in vitro. Relaxation responses of isolated laminar arterial and venous rings to acetylcholine and insulin were evaluated. To alter vascular function in response to insulin, all vessel rings were incubated with insulin or vehicle, submaximally contracted, administered insulin again and relaxation responses recorded. Laminar arteries were also in...
Wheat germ agglutinin as a counterstain for immunofluorescence studies of equine hoof lamellae. Equine laminitis is a common, painful, debilitating condition of the hoof that is a leading cause of disability in horses, often necessitating euthanasia. The equine hoof represents an extreme evolutionary adaptation of an epidermal structure homologous to the human or murine nail units. Immunohistochemistry is frequently utilized in the study of the pathophysiology of laminitis. The complex, multilayered, extensively interdigitated epidermal-dermal lamellar interface renders precise interpretation of immunofluorescence localization difficult, especially when effective technique and reagents r...
In situ cell surface proteomics reveals differentially expressed membrane proteins in retinal pigment epithelial cells during autoimmune uveitis. Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye and plays an important role in pathogenesis of the sight threatening disease equine recurrent uveitis (ERU). ERU is a spontaneous autoimmune mediated inflammatory disease characterised by the breakdown of the outer blood-retinal barrier and an influx of autoaggressive T-cells into the inner eye. Therefore, identification of molecular mechanisms contributing to changed function of blood-retinal barrier in ERU is important for the understanding of pathophysiology. Cell surface proteins of RPE collected from health...
Achilles tendon injuries in elite athletes: lessons in pathophysiology from their equine counterparts. Superficial digital flexor tendon (SDFT) injury in equine athletes is one of the most well-accepted, scientifically supported companion animal models of human disease (i.e., exercise-induced Achilles tendon [AT] injury). The SDFT and AT are functionally and clinically equivalent (and important) energy-storing structures for which no equally appropriate rodent, rabbit, or other analogues exist. Access to equine tissues has facilitated significant advances in knowledge of tendon maturation and aging, determination of specific exercise effects (including early life), and definition of some of the...
Regional disturbances in blood flow and metabolism in equine limb wound healing with formation of exuberant granulation tissue. As in other fibroproliferative disorders, hypoxia has been suggested to play a key role in the pathogenesis of exuberant granulation tissue (EGT). The purpose of this study was to investigate metabolism and blood flow locally in full-thickness wounds healing with (limb wounds) and without (body wounds) formation of EGT. Microdialysis was used to recover endogenous metabolites from the wounds, and laser Doppler flowmetry was used to measure blood flow. Measurements were performed before wounding and 1-28 days after wounding. Blood flow was consistently lower in limb wounds than in body wounds t...
Coagulopathies in horses. Although primary coagulopathies are rare in horses, changes in coagulation and fibrinolysis are commonly associated with inflammatory diseases. A clear understanding of the pathophysiology of normal and abnormal hemostasis is required to be able to choose and interpret diagnostic tests evaluating coagulation and fibrinolysis. After diagnosis, treatment of the underlying disease must occur regardless of whether clinical manifestations (excessive bleeding or thrombosis) of the coagulopathy are present or not. Specific treatment may be initiated if there are clinical signs of coagulopathy.
Metabolic syndrome: is equine disease comparable to what we know in humans? This review summarizes similarities and differences between the metabolic syndromes in humans and equines, concerning the anatomy, symptoms, and pathophysiological mechanisms. In particular, it discusses the structure and distribution of adipose tissue and its specific metabolic pathways. Furthermore, this article provides insights and focuses on issues concerning laminitis in horses and cardiovascular diseases in humans, as well as their overlap.
Equine lamellar energy metabolism studied using tissue microdialysis. Failure of lamellar energy metabolism may contribute to the pathophysiology of equine laminitis. Tissue microdialysis has the potential to dynamically monitor lamellar energy balance over time. The objectives of this study were to develop a minimally invasive lamellar microdialysis technique and use it to measure normal lamellar energy metabolite concentrations over 24 h. Microdialysis probes were placed (through the white line) into either the lamellar dermis (LAM) (n = 6) or the sublamellar dermis (SUBLAM) (n = 6) and perfused continuously over a 24 h study period. Probes were pl...
Impact of tetrodotoxin application and lidocaine supplementation on equine jejunal smooth muscle contractility and activity of the enteric nervous system in vitro. By blocking the enteric nervous system (ENS) using tetrodotoxin (TTX), previous studies have documented the contractility-enhancing (CE) effects of lidocaine in equine intestinal smooth muscle (SM) at the level of SM cells and/or interstitial cells of Cajal (ICC). The present study examined the impact of ENS deactivation on CE lidocaine effects, and investigated the effects of lidocaine on ENS activity. TTX application did not affect the CE effects of lidocaine, indicating that these were not mediated by TTX-sensitive sodium channels. Application of TTX or ≥100 mg/L lidocaine reduced ENS a...
Colonic gastrointestinal stromal tumor resulting in recurrent colic and hematochezia in a warmblood gelding. A 14-year-old Trakehner gelding was evaluated for recurrent colic, with episodes occurring over 1 year. Signs were consistent with intermittent ascending colon obstruction and hematochezia. Necropsy examination revealed an ulcerated mass extending into the lumen of the right dorsal ascending colon. Gross and histologic appearance and immunoreactivity to c-kit (CD117), desmin, vimentin, and smooth muscle actin, were consistent with a diagnosis of gastrointestinal stromal tumor. Tumeur ventrale gastro-intestinale du côlon produisant des coliques et de l’hématochézie et des coliques récurre...
The effect of tumour necrosis factor-α and insulin on equine digital blood vessel function in vitro. Insulin and inflammatory cytokines may be involved in equine laminitis, which might be associated with digital vascular dysfunction. This study determined the effects of TNF-α and insulin on the endothelial-dependent relaxant responses of equine digital blood vessels and on equine digital vein endothelial cell (EDVEC) cGMP production. Methods: Isolated rings of equine digital arteries (EDAs) and veins (EDVs) were obtained and EDVECs were cultured from horses euthanized at an abattoir. Methods: The effect of incubation with TNF-α (10 ng/ml) and/or insulin (1,000 μIU/ml) for 1.5 h or overn...
Evaluation of the effect of onlay mesenteric flaps on end-to-end jejunojejunostomy healing in horses. To evaluate the effect of onlay mesenteric flaps (MFs) with end-to-end jejunojejunostomy on stomal diameter, length of jejunum with reduced stomal diameter, abdominal adhesion formation, and healing. Methods: Experimental study. Methods: Healthy adult horses (n = 6). Methods: Two hand sewn end-to-end jejunal anastomoses using a 1 layer simple continuous serosubmucosal suture pattern were performed in each horse ∼ 2 and 5 m oral to the ileocecal fold. Using a random design for selection anastomosis location (oral or aboral), 1 anastomosis was covered with 2 adjacent onlay MFs secured with int...
Involvement of mitochondrial dysfunction and ER-stress in the physiopathology of equine osteochondritis dissecans (OCD). Osteochondrosis (OC) is a developmental bone disorder affecting several mammalian species including the horse. Equine OC is described as a focal disruption of endochondral ossification, leading to osteochondral lesions (osteochondritis dissecans, OCD) that may release free bodies within the joint. OCD lesions trigger joint swelling, stiffness and lameness and affects about 30% of the equine population. OCD is considered as multifactorial but its physiopathology is still poorly understood and genes involved in genetic predisposition are still unknown. Our study compared two healthy and two OC-a...
Treatment of idiopathic headshaking in horses with pulsed high-dose dexamethasone. Treatment of idiopathic headshaking in horses is complicated by an incomplete understanding of underlying pathophysiology and partially effective treatments. If an inflammatory etiology exists, corticosteroids could be beneficial. Objective: An anti-inflammatory dose of dexamethasone reduces the signs of idiopathic headshaking in a field setting. Methods: Convenience sample of 20 adult horses with idiopathic headshaking syndrome. Cases were recruited from the general population and diagnosed by attending veterinarians. Methods: Prospective, blinded clinical trial. Pulsed dosing was with oral d...
Pharmacological characterization of muscarinic receptors in the contractions of isolated bronchi in the horse. We investigated the effects of nonselective muscarinic antagonist (atropine) and of selective muscarinic subtype 1 (M1), 2 (M2), 3 (M3) antagonists (VU0255035, methoctramine, pFHHSiD, respectively) on the contractions evoked by electrical field stimulation (EFS) or by exogenous ACh in isolated horse bronchial muscle. Atropine completely inhibited neurogenic contractions in a concentration-dependent fashion, whereas selective muscarinic antagonists induced relevant modifications only at the highest concentration tested. Experiments with selective muscarinic antagonists in combination showed tha...