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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.
Voltage-gated ion channelopathies: inherited disorders caused by abnormal sodium, chloride, and calcium regulation in skeletal muscle. The pathological genetic defects in the inherited myotonias and periodic paralyses were recently elucidated using molecular genetic studies. These disorders are usually transmitted as a dominant trait from an affected parent to a child. The many clinical symptoms include cold-induced uncontrollable contraction of muscle, potassium-induced contraction and paralysis, myotonia with dramatic muscular hypertrophy, muscle stiffness, and insulin-induced paralysis (in males). Horses afflicted with the disorder can suddenly collapse, despite an impressive physique. In the past three years, these clinic...
Respiratory emergencies in the adult horse. Responding to an equine respiratory emergency requires rapid localization of the problem and appropriate choices for therapy. Localizing the cause of respiratory distress is aided by history and thorough physical examination. When examining the patient, one must focus on the presenting signs as indicators of URT or LRT dysfunction. Table 3 summarizes the characteristic presenting signs based on respiratory tract location and suggests the initial treatment course indicated. Respiratory distress in the absence of signs related to the pulmonary system suggests inadequate oxygen delivery secondary...
Pathogenic aspects of circulatory shock. Shock has been described and defined by the inciting cause. This method of categorization does little to clarify common pathophysiologic changes known to occur regardless of the etiology. Each type of shock involves different stages that are determined by the inciting cause, its duration, severity of the initial result, susceptibility of the patient, and adequacy of treatment.
Regulation of equine fibrinolysis in blood and peritoneal fluid based on a study of colic cases and induced endotoxaemia. Much of the pathophysiology associated with equine gastrointestinal diseases is attributed to the effects of endotoxin on haemostasis. Because little is known about the responses of the equine fibrinolytic system to endotoxin, regulation of the system was investigated. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were identified as the primary plasminogen activator and plasminogen activator inhibitor, respectively, in equine blood. Under experimental conditions, the equine fibrinolytic system responded to endotoxin in a manner similar to that repo...
Modulation of bronchial smooth muscle function in horses with heaves. Four mechanisms that modulate airway smooth muscle function in normal horses were studied in the bronchi of horses affected by the airway obstructive disease heaves. Results were compared with data from historical controls studied by the same personnel in the same laboratory. Rings from the left cranial lobar bronchus (LB1) and small bronchi (5 mm OD) were suspended in muscle baths, and the isometric tension were measured. The inhibitory nonadrenergic noncholinergic (iNANC) function was studied in LB1. After the LB1 segments were pretreated with atropine and contracted with histamine, electric...
Endotoxin-induced platelet aggregation in heparinised equine whole blood in vitro. Endotoxaemia is a leading cause of death among horses. Thrombocytopenia is a common finding in clinical and experimentally-induced cases of endotoxaemia and can lead to coagulopathies, including disseminated intravascular coagulopathy which is usually fatal. In this study it was shown that endotoxin (3 ng ml-1 to 25 micrograms ml-1) can aggregate equine platelets in heparinised whole blood in vitro. The endotoxin-induced aggregation (EIA) was shown to be dependent on the presence of leucocytes in the blood and did not occur when detoxified endotoxin was used, suggesting that lipid A was necess...
Stress failure of pulmonary capillaries as a mechanism for exercise induced pulmonary haemorrhage in the horse. Exercise induced pulmonary haemorrhage (EIPH) is a serious problem in the Thoroughbred industry. The condition apparently occurs essentially in all Thoroughbreds in training but the mechanism has proved elusive. There is now strong evidence that the condition is caused by mechanical failure of the walls of the pulmonary capillaries when the pressure inside them rises to very high levels. It is well known that pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently we have shown that the wall stresses are very large when the capillary t...
Distribution of SP- and CGRP-like immunoreactive nerve fibers in the lower respiratory tract of neonatal foals: evidence for loss during development. The lungs of neonatal foals contain many nerves immunoreactive for substance P and calcitonin gene-related peptide. These nerves are closely associated with the epithelium, bronchial and pulmonary vessels and the airway smooth muscle of all intrathoracic airways, including non-cartilaginous bronchioles. Activation of sensory nerves in the respiratory epithelium could thus potentially affect, via local axon reflexes, vascular and respiratory smooth muscle in neonatal equine airways. Nerves immunoreactive for these peptides are much more widely distributed within the lung than in adult horses; t...
Histopathologic evidence of reperfusion injury in the large colon of horses after low-flow ischemia. Effects of low-flow ischemia and reperfusion of the large colon on mucosal architecture were determined in horses. Twenty-four adult horses were randomly allocated to 3 groups: sham-operated (n = 6), 6 hours of ischemia (n = 9), and 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline values. Systemic hemodynamic and metabolic variables were maintained constant and in a normal physiologic range. Full-thickness biopsy specimens were obtained from the left ventral colon for his...
Decrease in the alpha 1-proteinase inhibitor Spi3 in equine bronchoalveolar lavage fluid. The alpha 1-proteinase inhibitors of trypsin, Spi1, Spi3A, and Spi3B, in bronchoalveolar lavage fluid (BALF) and serum of horses were separated by electrophoresis, and their proportions were quantified in 12 control horses and 12 with chronic obstructive pulmonary disease (COPD). A significantly lower proportion of Spi3B (P < 0.05) and higher proportion of Spi1 (P < 0.02 to P < 0.01) were detected in BALF, compared with serum, in control and COPD-affected horses and appeared to be attributable to reduced Spi3 activity in BALF. There was no significant difference between the control an...
Neutrophil accumulation in the large colon of horses during low-flow ischemia and reperfusion. Histomorphologic/morphometric evaluation, leukocyte scintigraphy, and myeloperoxidase activity were used to determine whether neutrophils accumulate in the large colon of horses during low-flow ischemia and reperfusion. Twenty-four adult horses were assigned to 1 of 3 groups: group 1, sham-operated (n = 6); group 2, 6 hours of ischemia (n = 9); and group 3, 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia of the large colon was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. Radiolabeled (99mTc) autogenous neutrophils wer...
Characterization of the hemodynamic and metabolic alterations in the large colon of horses during low-flow ischemia and reperfusion. Effects of low-flow ischemia and reperfusion of the large colon on systemic and colonic hemodynamic and metabolic variables were determined in horses. Twenty-four adult horses were randomly allocated to 3 groups: sham-operated (n = 6), 6 hours of ischemia (n = 9), and 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia was induced in groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. Heart rate, arterial blood pressures, cardiac index, pulmonary artery pressure, right atrial pressure, and colonic blood flow were monitored. Arterial, mixed-venous, a...
[Direct approach for demonstrating free radical phenomena during equine postanesthetic myopathy: preliminary study]. This preliminary study demonstrated the existence of a free radical generation during an experimental postischemic muscular reperfusion in a halothane anesthetized horse. The authors used alpha-phényl-N-tert-butylnitrone as a spin trap agent and the electronic paramagnetic resonance method to observe in vivo a free radical generation. This preliminary study demonstrated the existence of a free radical generation during an experimental postischemic muscular reperfusion in a halothane anesthetized horse. The authors used alpha-phényl-N-tert-butylnitrone as a spin trap agent and the electronic ...
In vitro effects of tachykinins on the smooth musculature of horse gut. The contractile effects of the tachykinins eledoisin, substance P and neurokinin A and B were investigated in vitro on circular and longitudinal muscle strips from horse duodenum, ileum and colon. Circular smooth muscle of the small intestine was highly responsive, large intestine circular smooth muscle less so, while longitudinal muscle from all gut segments was much less sensitive. pD2 values and intrinsic activities on small intestine circular muscle indicated differences in receptor distribution between the duodenum and ileum: NK3 and a smaller number of NK2 receptors being present in the ...
The role of nitric oxide in the responses of equine digital veins to vasodilator and vasoconstrictor agents. Isolated equine digital veins were examined in vitro to study the importance of the endothelium in the responses to both vasodilator and vasoconstrictor agents and to characterise the endothelial-derived mediators involved. Carbachol (Cch; 1 microM) and bradykinin (Bk; 1 nM) caused relaxation of U44069-induced tone by 79.5 +/- 0.35% and 73.7 +/- 4.0% respectively. Mechanical removal of the endothelium completely prevented relaxant responses to Cch and to Bk showing they were mediated by the endothelium. Treatment of veins with NG-nitro-L-arginine methyl ester (L-NAME; 30 and 300 microM) inhibi...
Quantitation of alpha-1 proteinase inhibitor in the pulmonary epithelial lining fluid of horses with chronic obstructive pulmonary disease. The concentration of alpha-1 proteinase inhibitor (API) was measured in the pulmonary epithelial lining fluid (PELF) of horses with chronic obstructive pulmonary disease (COPD) while they had clinical signs and while they had none. The concentrations of total protein, albumin and API were significantly higher in the PELF of animals with clinical signs of COPD. The correlation between albumin and API in the PELF suggested that most of the API was derived from the serum.
Equine motor neuron disease: findings in 28 horses and proposal of a pathophysiological mechanism for the disease. Over a three and one-half year period, 28 adult horses were diagnosed with equine motor neuron disease (EMND). The most commonly identified environmental risk factors for a horse having EMND were absence of grazing for more than a year and provision of poor quality hay. Quarter Horses were 5.4 times more at risk than other breeds but this was thought to be an epiphenomenon related to the frequency of Quarter Horses at boarding stables. Weight loss, excessive recumbency and/or trembling were the first signs noted. Other clinical diagnostic signs included: constant shifting of the weight in the ...
Pathophysiology of sodium channelopathies: correlation of normal/mutant mRNA ratios with clinical phenotype in dominantly inherited periodic paralysis. It is often suggested that polygenic or environmental factors are responsible for clinical variability between patients with identical mutations. However, most dominant diseases are caused by a change-of-function alteration in the mutant allele's protein product. All patients are heterozygous and presumably express both mutant and normal proteins from the corresponding genes. Thus, a possible molecular mechanism for clinical variability could be the difference in relative levels of mutant vs. normal mRNA in different patients with the same mutation. To investigate this hypothesis, it is necess...
The pathobiology and repair of tendon and ligament injury. Injury of the collagenous structures comprising tendons and ligaments, either from acute trauma or from repetitive strain lesions, results in protracted periods of disability. The resolution of such injuries often fails to restore the normal morphologic and functional characteristics of the structure and, therefore, either compromises the future performance of the individual or predisposes to an increased risk of recurrent injury.
Molecular weight alterations of alpha-1 proteinase inhibitor in equine bronchoalveolar lavage fluid. The equine alpha-1 proteinase inhibitor (alpha 1PI) system differs from that of man in that the equine system consists of four closely-linked genes (Spi1-Spi4) whereas in man, a single gene encodes for alpha 1PI. We have previously found differences in the proportion of the Spi proteins in equine serum and bronchoalveolar lavage fluid (BALF). We therefore wished to determine whether, as reported in man, there was any molecular weight difference between the Spi proteins in serum and BALF. alpha 1PI and albumin from equine BALF migrated further towards the anode compared with serum alpha 1PI on ...
Comparative aspects of the strength of pulmonary capillaries in rabbit, dog, and horse. In previous studies of rabbit and dog lung, we demonstrated stress failure of pulmonary capillaries at high transmural pressures (Ptm). The Ptm necessary to elicit stress failure was 40 cmH2O higher in dog than rabbit, and the total blood-gas barrier (BGB) thickness was greater in dog than rabbit. This suggests that stress failure may be related to BGB thickness, and is consistent with the Laplace relationship which states that wall stress is proportional to capillary radius but inversely proportional to wall thickness. In the present studies, we compared BGB thickness and an index of capillar...
Tidal breathing flow-volume loops in horses with recurrent airway obstruction (heaves). Tidal breathing flow-volume (TBFV) loops were determined in a group of control horses and in horses affected with recurrent airway obstruction (heaves). The latter group was studied when the condition was in remission and under increasing amounts of airway obstruction as reflected by measurements of change in pleural pressure, pulmonary resistance, and dynamic compliance. The TBFV loops of control horses had biphasic inspiratory and expiratory patterns; peak inspiratory and peak expiratory flows were detected early in inspiration and expiration, respectively. Tidal volume was unaffected by hea...
Evaluation of a technique for detection of pulmonary hemorrhage in horses, using carbon monoxide uptake. The diffusing capacity for carbon monoxide (DLCO) and the functional residual capacity (FRC) of the lung were measured in 5 healthy Thoroughbreds before and after instillation of autologous blood into their lungs, in an attempt to develop a method to quantitate extravascular blood in the lungs of horses with exercise-induced pulmonary hemorrhage. Mean (+/- SD) baseline values of DLCO and FRC were 333.8 +/- 61.9 ml/min/mm of Hg and 21.464 +/- 4.156 L, respectively. Blood instillation resulted in decreases in DLCO and FRC. The paradoxic decrease in DLCO (we were expecting to find an increase owi...
Albumin quotient, IgG concentration, and IgG index determinations in cerebrospinal fluid of neonatal foals. Total protein (TP), albumin, and IgG concentrations were measured in CSF from the atlanto-occipital (AO) and lumbosacral (LS) sites and in serum of 15 clinically normal neonatal foals < or = 10 days old (mean, 7.0 days). The albumin quotient (AQ; CSF albumin/serum albumin x 100) and IgG index ([CSF IgG/serum IgG] x [serum albumin/CSF albumin]), indicators of blood-brain barrier permeability and intrathecal IgG production, respectively, were then calculated. Mean +/- SD values obtained from the foals of this study were: serum albumin, 2,900 +/- 240 mg/dl; serum IgG, 1,325 +/- 686 mg/dl; AO CSF ...
Characterization of muscarinic receptor subtype mediating contraction and relaxation in equine coronary artery in vitro. In coronary arterial rings isolated from horses, 10(-8)-10(-6) mol/l acetylcholine (ACh) induced concentration-dependent contractions which were potentiated by the removal of endothelium and by pretreatment with L-nitro-arginine (LNAG) or methylene blue (MB). Relatively lower concentrations of ACh (10(-14)-10(-8) mol/l) induced relaxation when the coronary rings were contracted by phenylephrine (PE). ACh-induced contractions in the coronary rings without endothelium were competitively inhibited by each muscarinic subtype selective antagonist in the following order of potency: 4-diphenylacetoxy...
Structural and functional characterization of elastases from horse neutrophils. In order better to understand the pathophysiology of the equine form of emphysema, two elastinolytic enzymes from horse neutrophils, referred to as proteinases 2A and 2B, have been extensively characterized and compared with the human neutrophil proteinases, proteinase-3 and elastase. Specificity studies using both the oxidized insulin B-chain and synthetic peptides revealed that cleavage of peptide bonds with P1 alanine or valine residues was preferred. Further characterization of the two horse elastases by N-terminal sequence and reactive-site analyses indicated that proteinases 2A and 2B ha...
Microvascular thrombosis associated with onset of acute laminitis in ponies. The hypothesis that equine laminitis is caused by thrombosis of vessels in the laminar corium (dermis) was investigated. Hemostatic alterations were evaluated by determining platelet count, platelet survival, platelet adhesiveness to vascular subendothelium, activated clotting time, and whole blood recalcification time. Thrombosis of vessels in the hoof wall was evaluated by scintigraphic studies of the hoof wall after administration of indium-111 (111In)-labeled platelets, contrast arteriography, and histologic examination. Platelet count remained constant before and at the onset of lameness;...
A silver-impregnation and immunocytochemical study of innervation of the distal sesamoid bone and its suspensory ligaments in the horse. The innervation of the navicular bone (os sesamoideum distale) and its suspensory ligaments (ligamenta sesamoidea collateralia) (CSL) or proximal suspensory ligament and the ligamentum sesamoideum distale impar or the distal sesamoidean impar ligament (DS-impar ligament) was examined using combined anatomical techniques of silver impregnation and immunocytochemistry. Silver impregnation studies revealed an abundance of nerve fibres present in both the CSL and DS-impar ligament with the latter having relatively more nerve fibres. These silver-impregnated nerves coursed parallel to and were asso...
Vascular perfusion in horses with chronic laminitis. Vascular perfusion casts were used to define and characterise the macroscopic perfusion defects present in the distal digit of 11 horses affected by chronic laminitis. Five clinically normal horses were used as controls. Based on clinical history and clinical status, horses with chronic laminitis were classified as being potentially treatable or clinically refractory. Eleven macroscopic vascular defects were noted in the casts from horses with laminitis. Four types of lesions were identified in the submural laminar circulation, 3 in the coronary bed and 4 were associated with the solar circula...
