Hypoxia in horses refers to a condition where there is a deficiency of oxygen in the tissues, which can occur due to various environmental, physiological, or pathological factors. This condition can impact a horse's respiratory and cardiovascular systems, influencing overall performance and health. Hypoxia may result from high altitudes, intense exercise, or respiratory diseases, and can lead to a range of physiological responses aimed at restoring oxygen balance. Studies on hypoxia in horses explore the mechanisms of oxygen transport and utilization, the adaptive responses to low oxygen levels, and the implications for equine health and athletic performance. This page compiles peer-reviewed research studies and scholarly articles that investigate the causes, effects, and management of hypoxia in equine species.
Cutler C, Viljanto M, Taylor P, Hincks P, Habershon-Butcher J, Gray B, Scarth J.FG-4592 is a hypoxia-inducible factor inhibitor that has been approved for therapeutic use in some countries. This class of compounds can increase the oxygen carrying capacity of the blood and thus have the potential to be used as performance enhancing agents in sports. The purpose of this study was to investigate the detection of FG-4592 and metabolites in equine plasma and mane hair following a multiple dose oral administration to two Thoroughbred racehorses, to identify the best analytical targets for doping control laboratories. Urine samples were also analysed, and the results compared to...
Ellerbrock M, Wehrend A.Dystocia represents a life-threatening condition for mare and foal. Morbidity and mortality rates due to a difficult birth, as well as the influence on fertility of the mare were analyzed, based on a review of publications. This was aggravated by the fact that no standardized diagnostic code was used and that most publications do not clearly describe how extensively the examinations were performed beforehand. Retentio secundinarum is the most common complication caused by dystocia. Other complications are injuries to the soft birth canal and the colon. These occur more frequently after surgica...
Davie A, Beavers R, Hargitaiová K, Denham J.This paper provides a comprehensive discussion on the physiological impacts of hypoxic training, its benefits to endurance performance, and a rationale for utilizing it to improve performance in the equine athlete. All exercise-induced training adaptations are governed by genetics. Exercise prescriptions can be tailored to elicit the desired physiological adaptations. Although the application of hypoxic stimuli on its own is not ideal to promote favorable molecular responses, exercise training under hypoxic conditions provides an optimal environment for maximizing physiological adaptations to ...
Verhaar N, de Buhr N, von Köckritz-Blickwede M, Dümmer K, Hewicker-Trautwein M, Pfarrer C, Dengler F, Kästner S.Hypoxia inducible factors (HIF) are widely researched in human medicine for their role in different disease processes. The aim of this study was to investigate the expression and distribution of HIF in experimental small intestinal ischemia in the horse. Unassigned: In 14 horses under general anesthesia, segmental jejunal ischemia with 90% reduction in blood flow was induced. The horses were randomly divided into two groups of seven horses, one subjected to ischemic postconditioning (IPoC) by delayed reperfusion, and a control group (group C) undergoing undelayed reperfusion. Intestinal sample...
Lanci A, Mariella J, Ellero N, Canisso IF, Dondi F, Castagnetti C.This study aimed to determine alpha-fetoprotein (AFP) concentrations in amniotic fluid, plasma of mares and respective foals: carrying normal pregnancies and delivering healthy foals (n = 20; Group 1); carrying apparently normal pregnancies and delivering sick foals (n = 15; Group 2); carrying high-risk pregnancies and delivering sick foals (n = 14; Group 3). High-risk pregnancy was defined by a history of premature udder development/lactation or increased of the combined thickness of the uterus and placenta, or vulvar discharge and/or mares' systemic illness. Sick foals were affected by...
Murase H, El-Sheikh Ali H, Ruby RE, Scoggin KE, Ball BA.Equine premature placental separation (PPS) is poorly understood and represents an important risk factor for fetal/neonatal hypoxia. Objective: To examine transcriptomic changes in the chorioallantois (CA) from mares with clinical PPS compared with the CA from normal foaling mares. Differential gene expression was determined and gene ontology as well as molecular pathways related to PPS were characterised. Methods: Retrospective case: control study. Methods: CA were collected from Thoroughbred mares with a clinical history of PPS (n = 33) and from control Thoroughbred mares (n = 4) with no...
Jørgensen E, Bjarnsholt T, Jacobsen S.In chronic wounds in humans, biofilm formation and wound chronicity are linked, as biofilms contribute to chronic inflammation and delayed healing. Biofilms are aggregates of bacteria, and living as biofilms is the default mode of bacterial life; within these aggregates, the bacteria are protected from both antimicrobial substances and the immune response of the host. In horses, delayed healing is more commonly seen in limb wounds than body wounds. Chronic inflammation and hypoxia are the main characteristics of delayed wound healing in equine limbs, and biofilms might also contribute to this ...
Stefanik E, Drewnowska O, Lisowska B, Turek B.Horses, due to their unique anatomy and physiology, are particularly prone to intraoperative cardiopulmonary disorders. In dorsally recumbent horses, chest wall movement is restricted and the lungs are compressed by the abdominal organs, leading to the collapse of the alveoli. This results in hypoventilation, leading to hypercapnia and respiratory acidosis as well as impaired tissue oxygen supply (hypoxia). The most common mechanisms disturbing gas exchange are hypoventilation, atelectasis, ventilation-perfusion (V/Q) mismatch and shunt. Gas exchange disturbances are considered to be an import...
Otto S, Michler JK, Dhein S, Mülling CKW.Distal axonopathy is seen in a broad range of species including equine patients. In horses, this degenerative disorder of the recurrent laryngeal nerve is described as recurrent laryngeal neuropathy (RLN). The dysfunctional innervation of the cricoarytenoideus dorsalis muscle (CAD) leads to a loss of performance in affected horses. In general, ex vivo models of the larynx are rare and for equine patients, just one short report is available. To allow for testing new therapy approaches in an isolated organ model, we examined equine larynges in a constant pressure perfused setup. In order to chec...
Pourali Dogaheh S, Boivin R, Lavoie JP.Severe equine asthma is characterized by airway hyperresponsiveness, neutrophilic inflammation and structural alterations of the lower airways. In asthmatic horses with neutrophilic inflammation, there is insensitivity to corticosteroids characterized by the persistence of neutrophils within the airways with therapy. We hypothesized that hypoxia or oxidative stress in the microenvironment of the lung contributes to this insensitivity of neutrophils to corticosteroids in asthmatic horses. Blood neutrophils isolated from horses with severe asthma (N = 8) and from healthy controls (N = 8)...
El-Sheikh Ali H, Dini P, Scoggin K, Loux S, Fedorka C, Boakari Y, Norris J, Esteller-Vico A, Kalbfleisch T, Ball B.Improved understanding of the molecular mechanisms underlying ascending equine placentitis holds the potential for the development of new diagnostic tools and therapies to forestall placentitis-induced preterm labor. The current study characterized the equine placental transcriptome (chorioallantois [CA] and endometrium [EN]) during placentitis (placentitis group, n = 6) in comparison to gestationally-matched controls (control group, n = 6). Transcriptome analysis identified 2953 and 805 differentially expressed genes in CA and EN during placentitis, respectively. Upstream regulator analys...
Ohmura H, Mukai K, Matsui A, Takahashi T, Jones JH.Supramaximal exercise while inspiring different O gases may induce different responses in cardiopulmonary function at the same relative and/or absolute exercise intensity. The purpose of this study was to compare the effects of supramaximal exercise in hypoxia, normoxia and hyperoxia on cardiopulmonary function in Thoroughbred horses. Using a crossover design, five well-trained horses were made to run up a 6% grade on a treadmill at supramaximal speeds sustainable for approximately 110 sec (approximately 115% Omax) while breathing normoxic gas (NO, 21% O) or hypoxic gas (LO, 15.3% O) in random...
de Castro RVG, Pieri NCG, Fantinato Neto P, Grizendi BM, Dória RGS, Meirelles FV, Smith LC, Garcia JM, Bressan FF.The cellular reprogramming into pluripotency is influenced by external and internal cellular factors, such as culture conditions (e.g., environmental oxygen concentration), and the aging process. Herein, we aimed to generate and maintain equine iPSCs (eiPSCs) derived from fibroblasts of a horse older than 20 years and to evaluate the effect of different levels of oxygen tension (atmospheric 20% O, 5% O, or 20% to 5% O) on these cells. Fibroblasts were reprogrammed, and putative eiPSCs were positive for positive alkaline phosphatase detection; they were positive for pluripotency-related genes ...
Sgorbini M, Freccero F, Castagnetti C, Mariella J, Lanci A, Marmorini P, Camillo F.Induction of parturition in horses is still not well accepted due to the potential peripartum complications for mares and newborn foals. We assessed differences after spontaneous and induced parturition with low doses of oxytocin (OX) in 1) incidence of peripartum complications in mares; 2) viability, behavioral, physical, and venous blood gas analyses in foals. In this study 61 mares were included; 45/61 were enrolled in the spontaneous foaling group (SF) and 16/61 in the induced foaling group (IF). In the IF group, when the calcium in mammary secretion reached concentrations of ≥250 ppm, ...
Wang W, Mukai K, Takahashi K, Ohmura H, Takahashi T, Hatta H, Kitaoka Y.The aim of this study was to investigate effects of short-term hypoxic training on lactate metabolism in the gluteus medius muscle of Thoroughbreds. Using crossover design (3 months washout), eight Thoroughbred horses were trained for 2 weeks in normoxia (F O = 21%) and hypoxia (F O = 18%) each. They ran at 95% maximal oxygen consumption (V̇O ) on a treadmill inclined at 6% for 2 min (3 days/week) measured under normoxia. Before and after each training period, all horses were subjected to an incremental exercise test (IET) under normoxia. Following the 2-week trainings, V̇O in IET ...
Mukai K, Ohmura H, Matsui A, Aida H, Takahashi T, Jones JH.We examined the effects of high-intensity training in normobaric hypoxia on aerobic capacity and exercise performance in horses and the individual response to normoxic and hypoxic training. Eight untrained horses were studied in a randomized, crossover design after training in hypoxia (HYP; 15.0% inspired O ) or normoxia (NOR; 20.9% inspired O ) 3 days/week for 4 weeks separated by a 4-month washout period. Before and after each training period, incremental treadmill exercise tests were performed in normoxia. Each training session consisted of 1 min cantering at 7 m/s and 2 min galloping ...
Dini P, Carossino M, Loynachan AT, El-Sheikh Ali H, Wolfsdorf KE, Scoggin KE, Daels P, Ball BA.Hydrallantois is the excessive accumulation of fluid in the allantoic cavities during the last trimester of pregnancy, leading to abdominal wall hernias, cardiovascular shock, abortion, and dystocia. It has been postulated that hydrallantois is associated with structural and/or functional changes in the chorioallantoic membrane. In the present study, we hypothesized that angiogenesis is impaired in the hydrallantoic placenta. Capillary density in the hydrallantoic placenta was evaluated in the chorioallantois via immunohistochemistry for Von Willebrand Factor. Moreover, the expression of angio...
Wu DD, Yang CP, Wang MS, Dong KZ, Yan DW, Hao ZQ, Fan SQ, Chu SZ, Shen QS, Jiang LP, Li Y, Zeng L, Liu HQ, Xie HB, Ma YF, Kong XY, Yang SL, Dong XX....Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the gene in these Tibetan domest...
Liu X, Zhang Y, Li Y, Pan J, Wang D, Chen W, Zheng Z, He X, Zhao Q, Pu Y, Guan W, Han J, Orlando L, Ma Y, Jiang L.High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7...
Gale AL, Mammone RM, Dodson ME, Linardi RL, Ortved KF.Joint injury is extremely common in equine athletes and post-traumatic osteoarthritis (PTOA), a progressive and debilitating disease, is estimated to affect 60% of horses in the USA. The limited potential for intrinsic healing of articular cartilage has prompted intense efforts to identify a cell-based repair strategy to prevent progression of PTOA. Mesenchymal stem cells (MSCs) have the potential to become an ideal source for cell-based treatment of cartilage lesions; however, full chondrogenic differentiation remains elusive. Due to the relatively low oxygen tension in articular cartilage, h...
Pfeiffenberger M, Bartsch J, Hoff P, Ponomarev I, Barnewitz D, Thöne-Reineke C, Buttgereit F, Gaber T, Lang A.Fractures in horses-whether simple fractures with just one clean break, or incomplete greenstick with stress fractures, or complications such as shattered bones can all be either minimal or even catastrophic. Thus, improvement in fracture healing is a hallmark in equine orthopedics. The fracture healing process implements a complex sequence of events including the initial inflammatory phase removing damaged tissue, re-establishment of vessels and mesenchymal stromal cells, a soft and hard callus phase closing the fracture gap as well as the remodeling phase shaping the bone to a scar-free tiss...
Davie AJ, Wen L, Cust ARE, Beavers R, Fyfe T, Zhou S.This study investigated the effects of six weeks of normobaric hypoxic training on transcriptional expression of the genes associated with mitochondrial and glycolytic activities in Thoroughbred horses. Eight horses were divided into two groups of four. They completed an identical incremental, moderate intensity training program, except that one group trained in a hypoxic chamber with 15% oxygen for 30 min on alternate days except Sundays (HT), while the other group trained in normal air (NC). Prior to and post training, heart rate and blood lactate were measured during an incremental treadm...
Ohmura H, Mukai K, Takahashi Y, Takahashi T, Jones JH.Hypoxic training is effective for improving athletic performance in humans. It increases maximal oxygen consumption (V̇Omax) more than normoxic training in untrained horses. However, the effects of hypoxic training on well-trained horses are unclear. We measured the effects of hypoxic training on V̇Omax of 5 well-trained horses in which V̇Omax had not increased over 3 consecutive weeks of supramaximal treadmill training in normoxia which was performed twice a week. The horses trained with hypoxia (15% inspired O) twice a week. Cardiorespiratory valuables were analyzed with analysis of varia...
Taylor PM, Luna S, Dye A.To determine the effects of surgery, hypoxia, hypercapnia and flunixin administration on plasma β-endorphin immunoreactivity (BEI) in anaesthetized horses. Methods: Prospective crossover study. Methods: Six healthy adult Welsh Mountain ponies and seven healthy adult Thoroughbreds. Methods: Ponies were anaesthetized with thiopentone and halothane or with pentobarbitone and the horses with guaiphenesin, thiopentone and halothane. Ponies were anaesthetized for 2 hours and on separate occasions underwent a period of hypoxia, hypercapnia, anaesthesia only, or were given flunixin at induction. The ...
Marr CM.Respiratory and cardiac diseases are common in older horses. Advancing age is a specific risk factor for cardiac murmurs and these are more likely in males and small horses. Airway inflammation is the most common respiratory diagnosis. Recurrent airway obstruction can lead to irreversible structural change and bronchiectasis; with chronic hypoxia, right heart dysfunction and failure can develop. Valvular heart disease most often affects the aortic and/or the mitral valve. Management of comorbidity is an essential element of the therapeutic approach to cardiac and respiratory disease in older e...
Griffon DJ, Cho J, Wagner JR, Charavaryamath C, Wei J, Wagoner Johnson A.Chitosan opens new perspectives in regenerative medicine as it enhances the properties of mesenchymal stem cells (MSCs) through formation of spheroids. Hypoxia has also been proposed to enhance stemness and survival of MSCs after in vivo implantation. These characteristics are relevant to the development of an off-the-shelf source of allogenic cells for regenerative therapy of tendinopathies. Umbilical cord-derived MSCs (UCM-MSCs) offer an abundant source of immature and immunoprivileged stem cells. In this study, equine UCM-MSCs (eqUCM-MSCs) conditioned for 3 and 7 days on chitosan films at 5...
Okabe K, Mukai K, Ohmura H, Takahashi T, Miyata H.We examined the effect of transient hypoxic exposure during high-intensity exercise on satellite cell activation and angiogenesis in Thoroughbred skeletal muscle. Methods: Six Thoroughbreds horses (6.3±0.8 years old) ran on a treadmill in normoxia (N; FIO2=21%) and hypoxia (H; FIO2=16%) at the same speed for the same duration, and oxygen consumption and plasma lactate and hemoglobin concentrations were measured. In addition, muscle biopsy samples were obtained from gluteus medius muscle before exercise and immediately, 4 hours, 24 hours, 3 days and 7 days after exercise, and immunohistochemic...
Wong A, Ghassemi E, Yellowley CE.The intermediate filament protein nestin is used as a marker for neural stem cells, and its expression is inversely correlated with cellular differentiation. More recently, nestin expression has also been described in other cell types including multipotential mesenchymal stromal cells (MSCs). In this study, we examined the expression of nestin in equine, canine and human bone marrow-derived MSCs undergoing osteogenic differentiation, to determine whether nestin levels were attenuated as the cells acquired a more mature phenotype. In addition, the expression of nestin may be under the influence...
Sørensen MA, Petersen LJ, Bundgaard L, Toft N, Jacobsen S.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...
Pawlak EA, Geor RJ, Watts MR, Black SJ, Johnson PJ, Belknap JK.Hypoxia-inducible factor-1α (HIF-1A) is an important protein in the regulation/induction of many genes in the cellular and tissue response to hypoxia and a central mediator in inflammatory signalling. As both hypoxia and inflammatory events are purported to occur in the lamellar epidermis in sepsis-related laminitis in the equid, HIF-1A may play a central role in this disease process. Objective: To assess the regulation of HIF-1A and HIF-1A-related genes in the equine keratinocyte in vitro and in the lamellar tissue of horses with sepsis-related laminitis. Methods: In vivo and in vitro experi...
Liu X, Zhang Y, Li Y, Pan J, Wang D, Chen W, Zheng Z, He X, Zhao Q, Pu Y, Guan W, Han J, Orlando L, Ma Y, Jiang L.High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7...
Bisgard GE, Forster HV, Orr JA, Buss DD, Rawlings CA, Rasmussen B.Seven ponies were subjected to carotid body denervation (CD) and two ponies were sham operated (S). Measurement of arterial blood gases and arterial blood and cerebrospinal fluid (CSF) acid-base balance were made prior to and 1,2,4,9, and 17 wks after surgery in unanesthetized animals. Resting ventilation and ventilatory responsiveness to hypoxia and NaCN infusion were assessed prior to and 2,9, and 17 wks after surgery. Alveolar hypoventilation in the CD ponies was marked 1-2 wk after surgery when VE and VA were reduced 40% and 10%, respectively, from control and PaCO2 was 12-15 mmHg above co...
Deschene K, Céleste C, Boerboom D, Theoret CL.Exuberant granulation tissue (EGT), a fibrotic healing disorder resembling the human keloid, occurs almost exclusively in limb wounds of horses and may be caused in part by a relative state of hypoxia within the wound. Objective: The objectives of this study were therefore to (1) assess the effects of hypoxia on equine dermal fibroblast (EDF) proliferation and apoptosis, (2) study the effects of hypoxia on the expression of key extracellular matrix (ECM) associated proteins and determine if such effects are dependent on hypoxia-inducible factor (HIF), and (3) determine if EDFs from the body or...
Wu DD, Yang CP, Wang MS, Dong KZ, Yan DW, Hao ZQ, Fan SQ, Chu SZ, Shen QS, Jiang LP, Li Y, Zeng L, Liu HQ, Xie HB, Ma YF, Kong XY, Yang SL, Dong XX....Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the gene in these Tibetan domest...
Milner PI, Wilkins RJ, Gibson JS.To examine the effect of O(2) and the role, and source, of reactive oxygen species (ROS) on pH regulation in articular chondrocytes. Methods: Cartilage from equine metacarpo/tarsophalangeal joints was digested (collagenase) to isolate chondrocytes and loaded with 2',7'-bis-2-(carboxyethyl)-5(6)-carboxylfluorescein, a pH-sensitive fluorophore. O(2) tension was maintained using Eschweiler tonometers and a Wosthoff gas mixer. Cells were exposed to agents which alter ROS levels, mitochondrial inhibitors and/or inhibitors of protein phosphorylation. ROS levels were determined by dichlorofluorescein...
Pfeiffenberger M, Bartsch J, Hoff P, Ponomarev I, Barnewitz D, Thöne-Reineke C, Buttgereit F, Gaber T, Lang A.Fractures in horses-whether simple fractures with just one clean break, or incomplete greenstick with stress fractures, or complications such as shattered bones can all be either minimal or even catastrophic. Thus, improvement in fracture healing is a hallmark in equine orthopedics. The fracture healing process implements a complex sequence of events including the initial inflammatory phase removing damaged tissue, re-establishment of vessels and mesenchymal stromal cells, a soft and hard callus phase closing the fracture gap as well as the remodeling phase shaping the bone to a scar-free tiss...
Cheeke PR.Plant toxins are the chemical defenses of plants against herbivory. Grasses have relatively few intrinsic toxins, relying more on growth habit to survive defoliation and endophytic fungal toxins as chemical defenses. Forage grasses that contain intrinsic toxins include Phalaris spp. (tryptamine and carboline alkaloids), sorghums (cyanogenic glycosides), and tropical grasses containing oxalates and saponins. Toxic effects of these grasses include neurological damage (Phalaris staggers), hypoxia (sudangrass), saponin-induced photosensitization (Brachiaria and Panicum spp.), and bone demineraliza...
Ranera B, Remacha AR, Álvarez-Arguedas S, Romero A, Vázquez FJ, Zaragoza P, Martín-Burriel I, Rodellar C.Mesenchymal stem cells (MSCs) derived from bone marrow (BM-MSCs) and adipose tissue (AT-MSCs) are being applied to equine cell therapy. The physiological environment in which MSCs reside is hypoxic and does not resemble the oxygen level typically used in in vitro culture (20% O2). This work compares the growth kinetics, viability, cell cycle, phenotype and expression of pluripotency markers in both equine BM-MSCs and AT-MSCs at 5% and 20% O2. Results: At the conclusion of culture, fewer BM-MSCs were obtained in hypoxia than in normoxia as a result of significantly reduced cell division. Hypoxi...
Barrey E, Mucher E, Jeansoule N, Larcher T, Guigand L, Herszberg B, Chaffaux S, Guérin G, Mata X, Benech P, Canale M, Alibert O, Maltere P, Gidrol X.Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorder...
Forster HV, Bisgard GE, Rasmussen B, Orr JA, Buss DD, Manohar M.The present study was designed to provide further insight into the role of the carotid and aortic chemoreceptors in ventilatory (VE) acclimatization during sojourn at altitude. Measurements were made: 1) on 10 ponies near sea level (SL, 740 Torr) under normal conditions, 2) on 6 of these at SL following chemoreceptor denervation (CD), and 3) subsequently on all 10 during 4 days of hypobaric hypoxia (PaO2 = 40-47 Torr). CD resulteo in hypoventilation at SL (deltaPaCO2 = d8 Torr, P less than 0.05), and it prevented hyperventilation normally observed with injection of NaCN and acute exposure to h...
Wong A, Ghassemi E, Yellowley CE.The intermediate filament protein nestin is used as a marker for neural stem cells, and its expression is inversely correlated with cellular differentiation. More recently, nestin expression has also been described in other cell types including multipotential mesenchymal stromal cells (MSCs). In this study, we examined the expression of nestin in equine, canine and human bone marrow-derived MSCs undergoing osteogenic differentiation, to determine whether nestin levels were attenuated as the cells acquired a more mature phenotype. In addition, the expression of nestin may be under the influence...
Celeste CJ, Deschene K, Riley CB, Theoret CL.Wound repair in horse limbs is often complicated by the development of exuberant granulation tissue (EGT) and excessive scarring while body wounds tend to repair uneventfully. EGT resembles the human keloid. While the events leading to keloid formation are not fully elucidated, tissue hypoxia has been proposed as a major contributing factor. The objective of this study was to investigate tissue oxygen saturation in healing full-thickness wounds created on the horse limb and body, using near-infrared spectroscopy. Spectroscopic reflectance data were collected from both anatomic sites at specifi...
Dickey EJ, Long SN, Hunt RW.Hypoxic ischemic encephalopathy (HIE) is a condition that occurs in both human newborns and foals. The condition is the subject of extensive current research in human infants, but there have been no direct studies of HIE in foals, and hence, knowledge of the condition has been extrapolated from studies in humans and other animal models. The purpose of this review article is to highlight the most up-to-date and relevant research in the human field, and discuss how this potentially might have an impact in the management of foals with HIE.
Birch HL, Rutter GA, Goodship AE.Hypoxia has been suggested as a possible cause of tissue degeneration and subsequent rupture in equine tendons. To determine whether low oxygen tension is likely to be detrimental to tendon cell function, experiments were designed to investigate oxidative energy metabolism in freshly isolated and cultured equine tendon cells. Freshly isolated tenocytes and cultured fibroblasts possessed activities of the mitochondrial enzyme citrate synthase similar to those of other mammalian cells, with well defined oxidative metabolism. D-[6(-14)C]-glucose oxidation was measurable in both freshly isolated a...
Gale AL, Mammone RM, Dodson ME, Linardi RL, Ortved KF.Joint injury is extremely common in equine athletes and post-traumatic osteoarthritis (PTOA), a progressive and debilitating disease, is estimated to affect 60% of horses in the USA. The limited potential for intrinsic healing of articular cartilage has prompted intense efforts to identify a cell-based repair strategy to prevent progression of PTOA. Mesenchymal stem cells (MSCs) have the potential to become an ideal source for cell-based treatment of cartilage lesions; however, full chondrogenic differentiation remains elusive. Due to the relatively low oxygen tension in articular cartilage, h...
Dunkel B, Palmer JE, Olson KN, Boston RC, Wilkins PA.Foals may present to a referral hospital with the primary diagnosis of uroperitoneum (UP), or they may develop UP while hospitalized for other reasons. Historical, physical, laboratory, and diagnostic variables of foals presenting with UP were compared to those developing UP while hospitalized. Emphasis was placed on the presence of electrolyte abnormalities, evidence of sepsis or infection, and development of anesthetic complications during surgical correction of the defect. Foals developing UP while in the hospital frequently had a history of dystocia and presented at a very young age (< ...
Sørensen MA, Petersen LJ, Bundgaard L, Toft N, Jacobsen S.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...
Dobson A, Gleed RD, Meyer RE, Stewart BJ.The distribution of blood flow to the lungs was measured with labelled microspheres injected into horses before and during anaesthesia. Anaesthesia was induced with glycerol guaiacolate ether and ketamine, and maintained with the spontaneous breathing of halothane in oxygen. In a preliminary group of six horses, flow distribution was observed during anaesthesia in sternal, dorsal and right lateral recumbency. In two other groups, each of four horses, the flow distribution with time during either sternal or right lateral recumbency was observed. A small, constant proportion of the 15 micron dia...
Roy TK, Popel AS.Characterizing the resistances to O2 transport from the erythrocyte to the mitochondrion is important in understanding potential transport limitations. A steady-state model of this process was developed to predict the minimum (critical) end-capillary PO2 required to prevent hypoxia at maximal O2 consumption (VO2max) in a circular region of tissue surrounding the venular end of a capillary. Capillary density was used as a measure of O2 delivery, and mitochondrial density was used as a measure of O2 consumption. The effects of oxyhemoglobin dissociation kinetics and diffusion facilitation by hem...
Vajdovich P.This article discusses the current understanding of the role of free radicals and antioxidants in inflammatory processes and in ischemia reperfusion injury. It begins by describing the manifestations of acute inflammation and outlining the cellular events that occur during inflammation. It then describes the biochemical mediators of inflammation with special attention to nitric oxide. It details the process of hypoxia reperfusion injury, the enzymes involved, its treatment, and studies involving specific hypoxia reperfusion injuries in various animal species.
Forster HV, Pan LG, Bisgard GE, Kaminski RP, Dorsey SM, Busch MA.We studied the effect of changes in inspired [O2] on partial pressure of CO2 in arterial blood (PaCO2) during treadmill exercise (3 mph, 3% grade) in normal, acute (+2-4 wk), and chronic (+1-2 yr) carotid body-denervated (CBD) ponies. In all studies, PaCO2 decreased (P less than 0.01) from rest during exercise, reaching a nadir usually between 15 and 30 s of exercise. During normoxia [partial pressure of O2 in arterial blood (PaO2) approximately 95 Torr], the PaCO2 nadir was 2.3 +/- 0.6 Torr below resting level in normal ponies, but the nadir was greater (P less than -0.01) in acute (delta = 6...
Mukai K, Ohmura H, Matsui A, Aida H, Takahashi T, Jones JH.We examined the effects of high-intensity training in normobaric hypoxia on aerobic capacity and exercise performance in horses and the individual response to normoxic and hypoxic training. Eight untrained horses were studied in a randomized, crossover design after training in hypoxia (HYP; 15.0% inspired O ) or normoxia (NOR; 20.9% inspired O ) 3 days/week for 4 weeks separated by a 4-month washout period. Before and after each training period, incremental treadmill exercise tests were performed in normoxia. Each training session consisted of 1 min cantering at 7 m/s and 2 min galloping ...
Griffon DJ, Cho J, Wagner JR, Charavaryamath C, Wei J, Wagoner Johnson A.Chitosan opens new perspectives in regenerative medicine as it enhances the properties of mesenchymal stem cells (MSCs) through formation of spheroids. Hypoxia has also been proposed to enhance stemness and survival of MSCs after in vivo implantation. These characteristics are relevant to the development of an off-the-shelf source of allogenic cells for regenerative therapy of tendinopathies. Umbilical cord-derived MSCs (UCM-MSCs) offer an abundant source of immature and immunoprivileged stem cells. In this study, equine UCM-MSCs (eqUCM-MSCs) conditioned for 3 and 7 days on chitosan films at 5...
Ohmura H, Mukai K, Takahashi Y, Takahashi T, Jones JH.Hypoxic training is effective for improving athletic performance in humans. It increases maximal oxygen consumption (V̇Omax) more than normoxic training in untrained horses. However, the effects of hypoxic training on well-trained horses are unclear. We measured the effects of hypoxic training on V̇Omax of 5 well-trained horses in which V̇Omax had not increased over 3 consecutive weeks of supramaximal treadmill training in normoxia which was performed twice a week. The horses trained with hypoxia (15% inspired O) twice a week. Cardiorespiratory valuables were analyzed with analysis of varia...
Dini P, Carossino M, Loynachan AT, El-Sheikh Ali H, Wolfsdorf KE, Scoggin KE, Daels P, Ball BA.Hydrallantois is the excessive accumulation of fluid in the allantoic cavities during the last trimester of pregnancy, leading to abdominal wall hernias, cardiovascular shock, abortion, and dystocia. It has been postulated that hydrallantois is associated with structural and/or functional changes in the chorioallantoic membrane. In the present study, we hypothesized that angiogenesis is impaired in the hydrallantoic placenta. Capillary density in the hydrallantoic placenta was evaluated in the chorioallantois via immunohistochemistry for Von Willebrand Factor. Moreover, the expression of angio...
Medina-Torres CE, Mason SL, Floyd RV, Harris PA, Mobasheri A.The aim of this study was to determine if hypoxia and the hypoxia mimetic cobalt chloride regulate the activity of matrix metalloproteinase (MMP)-2 and -9 in cultures of equine hoof keratinocytes. These effects were assessed in primary cultures of laminar keratinocytes using gelatin zymography. Incubation of keratinocytes with cobalt chloride significantly increased the levels of active MMP-2 compared to untreated controls. Hypoxia significantly increased the expression of active MMP-2 and -9 in keratinocyte cultures. This up-regulation was observed after 6h and peaked at 24h. The study findin...
Vaala WE, Sertich PL.Perinatal death accounts for a large percentage of foal mortality. The most serious threats to perinatal survival remain septicemia, hypoxia, and dysmaturity. Topics discussed in this article include biochemical indices of fetoplacental function and evaluation and management of the high-risk mare.
Brooks AC, Menzies-Gow N, Bailey SR, Cunningham FM, Elliott J.Hypoxia may enhance the deleterious effects of lipopolysaccharide (LPS) in the endotoxaemic horse. This study has examined some of the actions of LPS and hypoxia, alone and in combination, on cultured equine digital vein endothelial cells (EDVEC) and the signalling molecules involved. Methods: EDVEC were exposed to LPS, 5% O(2) and LPS then 5% O(2) for up to 24 h. HIF-1alpha stabilisation, neutrophil adhesion and EDVEC permeability were assessed by immunoblotting, measurement of myeloperoxidase and movement of FITC-dextran, respectively. Pharmacological inhibitors were used to assess the roles...
Okabe K, Mukai K, Ohmura H, Takahashi T, Miyata H.We examined the effect of transient hypoxic exposure during high-intensity exercise on satellite cell activation and angiogenesis in Thoroughbred skeletal muscle. Methods: Six Thoroughbreds horses (6.3±0.8 years old) ran on a treadmill in normoxia (N; FIO2=21%) and hypoxia (H; FIO2=16%) at the same speed for the same duration, and oxygen consumption and plasma lactate and hemoglobin concentrations were measured. In addition, muscle biopsy samples were obtained from gluteus medius muscle before exercise and immediately, 4 hours, 24 hours, 3 days and 7 days after exercise, and immunohistochemic...
Ohmura H, Mukai K, Matsui A, Takahashi T, Jones JH.Supramaximal exercise while inspiring different O gases may induce different responses in cardiopulmonary function at the same relative and/or absolute exercise intensity. The purpose of this study was to compare the effects of supramaximal exercise in hypoxia, normoxia and hyperoxia on cardiopulmonary function in Thoroughbred horses. Using a crossover design, five well-trained horses were made to run up a 6% grade on a treadmill at supramaximal speeds sustainable for approximately 110 sec (approximately 115% Omax) while breathing normoxic gas (NO, 21% O) or hypoxic gas (LO, 15.3% O) in random...
