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.
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...
Borer-Weir KE, Bailey SR, Harris PA, Menzies-Gow NJ, Elliott J.Digital vasoconstriction, ischaemia and hypoxia may predispose to acute laminitis. Laminitis incidence varies seasonally, peaking in spring and summer. Direct seasonal influences on equine digital artery (EDA) contractility have not been investigated. This study assessed seasonal variation in maintenance of phenylephrine (PHE)-induced tone in isolated EDAs under hypoxic (95% nitrogen) and hyperoxic (95% oxygen) conditions. The objective was to measure change in arterial tone over time after constriction to a plateau with PHE. Tone was measured at plateau and over time and percentage change cal...
Milner PI, Smith HC, Robinson R, Wilkins RJ, Gibson JS.Hypoxia and acidosis are recognized features of inflammatory arthroses. This study describes the effects of IGF-1 and TGF-β(1) on pH regulatory mechanisms in articular cartilage under hypoxic conditions. Acid efflux, reactive oxygen species (ROS), and mitochondrial membrane potential were measured in equine articular chondrocytes isolated in the presence of serum (10% fetal calf serum), IGF-1 (1, 10, 50, 100 ng/ml) or TGF-β(1) (0.1, 1, 10 ng/ml) and then exposed to a short-term (3 h) hypoxic insult (1% O(2)). Serum and 100 ng/ml IGF-1 but not TGF-β(1) attenuated hypoxic regulation of pH hom...
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...
Borer KE, Bailey SR, Harris PA, Elliott J.The underlying pathophysiological triggers for equine acute laminitis are unknown, although digital vasoconstriction, ischaemia, hypoxia and reperfusion injury may be involved. The contractile responses of isolated equine digital arteries (EDAs), harvested from the hindlimbs of normal horses postmortem at an abattoir, were studied acutely (up to 3 h) under hyperoxic (95% oxygen, 5% CO2 ) and hypoxic (95% nitrogen, 5% CO2 ) conditions in organ baths. Phenylephrine (PHE; 10(-6) m), 5-hydroxytryptamine (5-HT; 10(-7) m) and high potassium (K(+) ; 118 mm) caused contraction in EDAs which was signif...
Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P.Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-α in myeloid cells in ho...
Suagee JK, Corl BA, Geor RJ.Understanding the mechanisms involved in the development of insulin resistance in horses should enable development of effective treatment and prevention strategies. Current knowledge of these mechanisms is based upon research in obese humans and rodents, in which there is evidence that the increased production of pro-inflammatory cytokines by adipose tissue negatively influences insulin signaling in insulin-responsive tissues. In horses, plasma concentrations of the cytokine, tumor necrosis factor-α, have been positively correlated with body fatness and insulin resistance, leading to the hypo...
Crumley MN, Hodgson DS, Kreider SE.To measure the effects of tidal volume, ventilatory frequency, and oxygen insufflation flow on the fraction of inspired oxygen in cadaveric horse heads attached to a lung model. Methods: 8 heads of equine cadavers. Methods: Each cadaveric horse head was intubated with a nasotracheal tube that extended into the proximal portion of the trachea. Oxygen was delivered through an oxygen catheter contained within and extending to the tip of the nasotracheal tube. The trachea was connected to the lung model by use of a spiral-wound hose with a sampling adaptor. Eight treatment combinations involving 2...
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.
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...
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...
Deschene K, Céleste C, Boerboom D, Theoret CL.As a transient hypoxic state exists within skin wounds in horses and may be important for the healing process, this study sought to identify a molecular hypoxia response occurring in horse limb and body wounds healing by second intention. Hypoxia-inducible factor 1α (HIF1α) protein expression was studied throughout repair by Western blotting and immunofluorescence. Paradoxically, HIF1α was strongly expressed in intact skin and its expression decreased dramatically following wounding (p<0.01), despite the expected hypoxic state within the wounded tissue. HIF1α levels reincreased in parallel...
De Ceulaer K, Delesalle C, Van Elzen R, Van Brantegem L, Weyns A, Van Ginneken C.Strangulation colic often leads to surgery. We aimed to document the molecular response in the non-resected intestine in these horses using quantitative Western blot analysis, and immunohistochemistry. The expression of hypoxia-inducible factor 1-alpha (HIF1α) was investigated together with two molecular pathways initiated after protein destruction: proteasome degradation via ubiquitin chain formation and protein restoration via molecular chaperones such as inducible heat shock protein 70 (HSP70). In addition, the expression of c-fos and c-jun could indicate an early proinflammatory response....
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...
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...
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...
Faleiros RR, Leise BB, Westerman T, Yin C, Nuovo GJ, Belknap JK.C-X-C motif ligand 1 (CXCL1) is an important chemokine of epithelial origin in rodents and humans. Objective: To assess in vivo and in vitro the regulation of CXCL1 in equine laminitis. Methods: Twenty adult horses. Methods: Real-time quantitative polymerase chain reaction (PCR) was used to assess expression of CXCL1 in samples of laminae, liver, skin, and lung from the black walnut extract (BWE) model of laminitis, and in cultured equine epithelial cells (EpCs). Tissue was obtained from control animals (CON, n = 5), and at 1.5 hours (early time point [ETP] group, n = 5), at the onset of leuko...
Portier K, Crouzier D, Guichardant M, Prost M, Debouzy JC, Kirschvink N, Fellmann N, Lekeux P, Coudert J.To evaluate whether a period of hyperoxia or after a period of hypoxia produced changes attributable to reactive oxygen species in anaesthetized horses. Methods: Prospective randomized experimental study. Methods: Six healthy (ASA I) geldings, aged 4.5-9.5 years and weighing 510-640 kg(-1). Methods: After 30 minutes breathing air as carrier gas for isoflurane, horses were assigned randomly to breathe air as carrier gas (CG0.21) or oxygen as carrier gas (CG1.00) for a further 90 minutes. After an interval of 1 month each horse was re-anaesthetized with the other carrier gas for the 90 minute te...
Ellenberger C, Müller K, Schoon HA, Wilsher S, Allen WR.Anovulatory haemorrhagic follicles (AHFs) are often the reason for ovulation failure in the mare. As the underlying factors that lead to AHF development are not well understood, it was of interest to investigate the vascularization of AHFs compared with normal follicles and corpora lutea (controls). In the present study, the ovarian cell populations investigated immunohistochemically included granulosa and luteal cells as well as various vascular structures. None of these cell types showed differences in the expression of vascular endothelial growth factor A (VEGF-A) between control ovaries co...
Giguère S, Slade JK, Sanchez LC.Despite a lack of data regarding their efficacy, both caffeine and doxapram have been recommended for treatment of hypercapnia in equine neonates with central nervous system damage. Objective: Caffeine and doxapram alleviate hypercapnia in foals with hypoxic-ischemic encephalopathy. Methods: Sixteen foals treated with either caffeine (n = 8) or doxapram (n = 8). Methods: Information on age, body temperature, heart rate, respiratory rate, arterial blood gas parameters, duration of therapy, and outcome was abstracted from each medical record. Results: Therapy with doxapram resulted in a signific...
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.
Dip RG.Adenosine is a purine nucleoside whose concentration increases during inflammation and hypoxia and the many roles of this molecule are becoming better understood. Increased reactivity to adenosine of the airways of asthmatic but not of normal subjects underlines the role of adenosine in airway inflammation. The identification and pharmacological characterisation of different adenosine receptors have stimulated the search for subtype-specific ligands able to modulate the effects of this molecule in a directed way. Several compounds of different chemical classes have been identified as having po...
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...
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 (< ...
MacEachern KE, Smith GL, Nolan AM.Hypoxaemia accompanies dorsal recumbency in the horse and frequently complicates general anaesthesia. The physiology associated with this phenomenon is poorly understood. One possible cause of poor tolerance to dorsal recumbency is an absent or reduced response to hypoxic pulmonary vasoconstriction (HPV). This study compared the HPV response in isolated pulmonary artery vessels from equivalent regions of equine and bovine lung. Methods: Equine and bovine, in vitro study. Methods: Equine and bovine pulmonary arteries were removed from the lungs of euthanased horses and cattle. Measurements of i...
Meyer C, Gerber R, Guthrie AJ.A 4-year-old Thoroughbred gelding racehorse was referred to the Onderstepoort Veterinary Academic Hospital (OVAH) with a history of post-race distress and collapse. In the absence of any obvious abnormalities in the preceding diagnostic work-up, a standard exercise test was performed to determine an underlying cause for the post-race distress reported. In this particular case oxygen desaturation became evident at speeds as slow as 6 m/s, where PO2 was measured at 82.3 mm Hg. Similarly at a blood pH of 7.28, PCO2 had dropped to 30.0 mm Hg indicating a combined metabolic acidosis and respiratory...
Bettschart-Wolfensberger R, Bowen MI, Freeman SL, Feller R, Bettschart RW, Nolan A, Clarke KW.To determine cardiopulmonary effects of total IV anesthesia with propofol and medetomidine in ponies and effect of atipamezole on recovery. Methods: 10 ponies. Methods: After sedation was induced by IV administration of medetomidine (7 microg/kg of body weight), anesthesia was induced by IV administration of propofol 12 mg/kg) and maintained for 4 hours with infusions of medetomidine (3.5 microg/kg per hour) and propofol 10.07 to 0.11 mg/kg per minute). Spontaneous respiration was supplemented with oxygen. Cardiopulmonary measurements and blood concentrations of propofol were determined during...
Benamou AE, Marlin DJ, Lekeux P.Elevated concentrations of endothelin (ET), a potent endothelium-derived vasoactive peptide, have been reported in a number of pathophysiological conditions associated with pulmonary hypertension, both in the horse and other species. We have previously shown, both in vitro and in vivo, that the pulmonary and systemic vascular response to exogenous ET is mediated predominantly via ET(A) receptors. Our hypothesis in the present study was that ET is involved in the equine hypoxic pulmonary vasoconstrictive response to acute hypoxia. In this study, we investigated the effects of a selective ET(A) ...
Greene HM, Wickler SJ, Anderson TP, Cogger EA, Lewis CC, Wyle A.Arterial and venous blood were analysed at rest and post exercise for pH, PCO2, and PO2, and bicarbonate ([HCO3-]), base excess (BE), and strong ion difference (SID) were calculated in response to a 10 day sojourn to 3800 m. Pulmonary artery pressures (PAP) were measured at rest. Post exercise samples were restricted to venous blood. The equids (n = 6) experienced a profound hypoxia-hypocapnia and a respiratory alkalosis. PaO2 decreased 42% and PaCO2 41%. PaCO2 increased to 80% of initial values after 8 days at altitude. Arterial [HCO3-] decreased by 34%; however, it returned to normal by Day ...
Erickson BK, Seaman J, Kubo K, Hiraga A, Kai M, Yamaya Y, Wagner PD.In a previous study we evaluated the mechanism of alveolar-arterial PO2 (AaPO2) reduction when nitrogen is replaced with helium in normoxia (FIO2 = 0.21). The reduction in AaPO2 was not due to changes in VA/Q inequality, pulmonary O2 diffusing capacity, or cardiac output, but to more complete diffusion equilibration as a consequence of the higher ventilation and thus PAO2 (which reduced the average slope of the hemoglobin O2 dissociation curve (ODC), and thus enhanced diffusive equilibration). We hypothesized that hypoxic He/O2 breathing in contrast would not reduce the AaPO2 because PAO2 and ...
Brown DR, Forster HV, Greene AS, Lowry TF.Periodic oscillations in pulmonary ventilation (VI), tidal volume (VT), and inspiratory and expiratory times (TI and TE) were studied during normoxia (arterial PO2 = 95 Torr) and 48 h of hypoxia (arterial PO2 = 40-50 Torr) in awake intact (n = 8) and carotid body-denervated (CBD; n = 8) ponies. Periodic oscillations were identified by fast-Fourier transformation of breath-by-breath data and quantitated by determining the power ratio of significant periodic oscillations to total power of data sequence. Periodic oscillations of 0.063-0.500 cycles/breath were observed in all parameters during bot...
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...
Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P.Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-α in myeloid cells in ho...
Manohar M, Bisgard GE, Bullard V, Will JA, Anderson D, Rankin JH.Hemodynamics, myocardial function, and regional myocardial blood flow (MBF) were measured in 6 closed-chest ponies anesthetized with ketamine hydrochloride before (control) and after creation of acute right ventricular systolic hypertension (RVSH) during normoxia and isocapnic hypoxia. The right ventricular (RV) systolic pressure during each RVSH approached 90 mmHg. There were significant alterations in the pattern of total ventricular MBG distribution in favor of the RV. Because RV myocardium received proportionate increments to its endocardium as well as epicardium, it is concluded that auto...
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...
Portier K, Crouzier D, Guichardant M, Prost M, Debouzy JC, Kirschvink N, Fellmann N, Lekeux P, Coudert J.To evaluate whether a period of hyperoxia or after a period of hypoxia produced changes attributable to reactive oxygen species in anaesthetized horses. Methods: Prospective randomized experimental study. Methods: Six healthy (ASA I) geldings, aged 4.5-9.5 years and weighing 510-640 kg(-1). Methods: After 30 minutes breathing air as carrier gas for isoflurane, horses were assigned randomly to breathe air as carrier gas (CG0.21) or oxygen as carrier gas (CG1.00) for a further 90 minutes. After an interval of 1 month each horse was re-anaesthetized with the other carrier gas for the 90 minute te...
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, ...
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...
Orr JA, Bisgard GE, Forster HV, Buss DD, Dempsey JA, Will JA.Unanesthetized adult female ponies were studied near sea level (250 m) and during sojourns to 3400 m (N=6) and 4300 m (N=7) altitude. The pH, PCO2, and PO2 of arterial blood and pH and PCO2 of cerebrospinal fluid (CSF) were measured under conditions of acute (1 hr) and chronic (1-45 days) hypoxia. Cerebrospinal fluid was sampled from the cisterna magna of the awake pony and arterial blood withdrawn from an indwelling arterial catheter. In both groups of animals, PaCO2 decreased slightly after 1 hr of hypoxia (delta PaCO2= - 0.6 mm Hg at 3400 m; - 3.9 mm Hg at 4300 m), decreased further after 1...
Bettschart-Wolfensberger R, Bowen MI, Freeman SL, Feller R, Bettschart RW, Nolan A, Clarke KW.To determine cardiopulmonary effects of total IV anesthesia with propofol and medetomidine in ponies and effect of atipamezole on recovery. Methods: 10 ponies. Methods: After sedation was induced by IV administration of medetomidine (7 microg/kg of body weight), anesthesia was induced by IV administration of propofol 12 mg/kg) and maintained for 4 hours with infusions of medetomidine (3.5 microg/kg per hour) and propofol 10.07 to 0.11 mg/kg per minute). Spontaneous respiration was supplemented with oxygen. Cardiopulmonary measurements and blood concentrations of propofol were determined during...
Pelletier N, Leith DE.Thoroughbred horses (TB) have no ventilatory response to added CO2 during near-maximal exercise. To see whether that reflects mechanical limits to ventilation or the control of breathing, we examined the effects of varying inspired O2 fraction (0.16, 0.21, or 0.30) in five normal TB standing quietly and galloping at 10 and 14 m/s on a level treadmill. We measured gas exchange (O2 consumption and CO2 production) and ventilation with a flow-through mask system. We also measured PO2, PCO2, and O2 contents in arterial and mixed venous blood and calculated cardiac output by using the Fick equation....
Elliott AR, Steffey EP, Jarvis KA, Marshall BE.The hypoxic pulmonary vasoconstrictor response to unilateral hypoxia was analyzed in pentobarbital anesthetized dogs (n = 5), miniature swine (n = 5), and ponies (n = 5). The left and right lungs (LL, RL) were separately ventilated with the LL exposed to inspired oxygen concentrations (CIO2) of 100%, 12%, 8% or 4%, while the RL always received a CIO2 = 100%. Pulmonary blood flow distribution was measured using 15 microns radioactive microspheres. LL PAO2, and percent pulmonary blood flow diversion (%FD) were calculated at each CIO2. At CIO2 of 4% there were significant differences (P greater t...
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 ...
De Ceulaer K, Delesalle C, Van Elzen R, Van Brantegem L, Weyns A, Van Ginneken C.Strangulation colic often leads to surgery. We aimed to document the molecular response in the non-resected intestine in these horses using quantitative Western blot analysis, and immunohistochemistry. The expression of hypoxia-inducible factor 1-alpha (HIF1α) was investigated together with two molecular pathways initiated after protein destruction: proteasome degradation via ubiquitin chain formation and protein restoration via molecular chaperones such as inducible heat shock protein 70 (HSP70). In addition, the expression of c-fos and c-jun could indicate an early proinflammatory response....
Bisgard GE, Orr JA, Will JA.Hemodynamic measurements were made in 6 ponies at low altitude (Madison, WI, altitude, 250 m) and after 1, 2, 4, and 6 weeks at high altitude (Climax, CO, altitude, 3,400 m). The salient findings were that ponies maintain an increased heart rate and cardiac output and develop significant pulmonary hypertension at high altitude. The average control resting mean pulmonary artery pressure (BPpul) was 25.1 mm of Hg at 250 m; this value increased to 56.3 mm of Hg after 6 weeks at 3,400 m. An additional finding was that the pulmonary vascular response to acute hypoxia seemed to increase with time at...
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...
Green SL, Conlon PD, Mama K, Baird JD.The effects of hypoxia and azotaemia on the pharmacokinetics of amikacin were evaluated in 20 full-term neonatal critically ill foals which required 24-h supportive care, antibiotics and dextrose-supplemented polyionic fluids given intravenously, nasal insufflation with oxygen and nutritional supplementation. There was no association between sepsis score or survival and pharmacokinetic parameters. Concurrent hypoxia and azotaemia were associated with significantly decreased clearance and increased peak and trough serum concentrations of amikacin; however, peaks or troughs did not exceed toxic ...
Giguère S, Slade JK, Sanchez LC.Despite a lack of data regarding their efficacy, both caffeine and doxapram have been recommended for treatment of hypercapnia in equine neonates with central nervous system damage. Objective: Caffeine and doxapram alleviate hypercapnia in foals with hypoxic-ischemic encephalopathy. Methods: Sixteen foals treated with either caffeine (n = 8) or doxapram (n = 8). Methods: Information on age, body temperature, heart rate, respiratory rate, arterial blood gas parameters, duration of therapy, and outcome was abstracted from each medical record. Results: Therapy with doxapram resulted in a signific...
Greene HM, Wickler SJ, Anderson TP, Cogger EA, Lewis CC, Wyle A.Arterial and venous blood were analysed at rest and post exercise for pH, PCO2, and PO2, and bicarbonate ([HCO3-]), base excess (BE), and strong ion difference (SID) were calculated in response to a 10 day sojourn to 3800 m. Pulmonary artery pressures (PAP) were measured at rest. Post exercise samples were restricted to venous blood. The equids (n = 6) experienced a profound hypoxia-hypocapnia and a respiratory alkalosis. PaO2 decreased 42% and PaCO2 41%. PaCO2 increased to 80% of initial values after 8 days at altitude. Arterial [HCO3-] decreased by 34%; however, it returned to normal by Day ...
Tate LP, Corbett WT, Bishop BJ, Foreman JH.The physiologic effects of exercise were studied in four horses with complete laryngeal hemiplegia. Right carotid arteries were surgically elevated to a subcutaneous position for percutaneous catheterization. Each horse was fitted with a device designed to obtain multiple arterial samples while the horse was exercised over a 1.6-km course. After each horse completed 10 test gallops, the laryngeal hemiplegia was treated using a laryngeal prothesis and ventriculectomy. The horses were then reconditioned, and the exercise test and sampling were repeated. Horses with laryngeal hemiplegia became ac...
Korducki MJ, Forster HV, Lowry TF, Forster MM.To determine the effect of hypoxia on metabolic rate (VO2) of ponies, on 2 days we studied ponies that were breathing room air for 1 h followed by 5 h of either hypoxic hypoxia (fractional concn of inspired O2 = 0.126) or 5 h of CO hypoxia. Control arterial PO2 was 103 +/- 1.2 Torr, and at 5 min and 5 h of hypoxic hypoxia, arterial PO2 was 53.1 +/- 1.8 and 41.0 +/- 1.8 Torr, respectively. There was a time-dependent hypocapnia and alkalosis during hypoxic hypoxia. During CO hypoxia, carboxyhemoglobin increased to 25% after 30 min and remained constant thereafter. With increased carboxyhemoglobi...
Santschi EM, Slone DE, Gronwall R, Juzwiak JS, Moll HD.The records of 105 pregnant mares and 105 nonpregnant horses with colic admitted to an equine hospital were reviewed. The 2 groups had similar types of colic and short-term survivability. Of the 105 pregnant mares, 31 were treated medically and 74 required surgical intervention. Thirty-three of the 105 mares died or were euthanatized. Thirteen (18%) of the 72 remaining mares aborted. Of 4 mares with severe medical cases, 2 died, 1 aborted, and 1 aborted and died. Of 27 horses with medical cases that required less intensive treatment, none died and 2 aborted. Of the 74 horses that required surg...
Borer KE, Bailey SR, Harris PA, Elliott J.The underlying pathophysiological triggers for equine acute laminitis are unknown, although digital vasoconstriction, ischaemia, hypoxia and reperfusion injury may be involved. The contractile responses of isolated equine digital arteries (EDAs), harvested from the hindlimbs of normal horses postmortem at an abattoir, were studied acutely (up to 3 h) under hyperoxic (95% oxygen, 5% CO2 ) and hypoxic (95% nitrogen, 5% CO2 ) conditions in organ baths. Phenylephrine (PHE; 10(-6) m), 5-hydroxytryptamine (5-HT; 10(-7) m) and high potassium (K(+) ; 118 mm) caused contraction in EDAs which was signif...
Suagee JK, Corl BA, Geor RJ.Understanding the mechanisms involved in the development of insulin resistance in horses should enable development of effective treatment and prevention strategies. Current knowledge of these mechanisms is based upon research in obese humans and rodents, in which there is evidence that the increased production of pro-inflammatory cytokines by adipose tissue negatively influences insulin signaling in insulin-responsive tissues. In horses, plasma concentrations of the cytokine, tumor necrosis factor-α, have been positively correlated with body fatness and insulin resistance, leading to the hypo...
Anderson BG, Anderson WD.The use of methyl methacrylate corrosion-casts has made it possible to examine the intracranial microvasculature on a three-dimensional scale with the scanning electron microscope. By this means we have compared regions of four cerebral and cerebellar arteries among three domestic animal species. The results of this study suggest that there are from one to three different levels of interarteriolar anastomosis between branches of the same or adjacent vessels. In the horse and ox anastomoses were demonstrated (1) at the level of the precapillary arterioles, (2) along the arterioles, and (3) betw...
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)...
Milner PI, Smith HC, Robinson R, Wilkins RJ, Gibson JS.Hypoxia and acidosis are recognized features of inflammatory arthroses. This study describes the effects of IGF-1 and TGF-β(1) on pH regulatory mechanisms in articular cartilage under hypoxic conditions. Acid efflux, reactive oxygen species (ROS), and mitochondrial membrane potential were measured in equine articular chondrocytes isolated in the presence of serum (10% fetal calf serum), IGF-1 (1, 10, 50, 100 ng/ml) or TGF-β(1) (0.1, 1, 10 ng/ml) and then exposed to a short-term (3 h) hypoxic insult (1% O(2)). Serum and 100 ng/ml IGF-1 but not TGF-β(1) attenuated hypoxic regulation of pH hom...
Dixon PM.Horses clinically affected with chronic obstructive pulmonary disease (COPD) were found to have pulmonary artery hypertension which was associated with systemic arterial hypoxia. The pulmonary hypertension in symptomatic COPD-affected horses was partially reversible upon remission of clinical signs or by oxygen administration. The induction of acute hypoxaemia caused an increase in pulmonary artery pressure in both normal and COPD-affected horses.
