Evaluation of acepromazine-induced hemodynamic alterations and reversal with norepinephrine infusion in standing horses.

The effects of norepinephrine (NOR) infusion on hemodynamic alterations induced with sedative doses of acepromazine (ACP) were evaluated. Infusion of NOR at 1 µg/kg body weight (BW)/minute for 15 min was administered to 5 standing horses 45 min (T45) after intravenous injection of ACP at 0.1 mg/kg BW. Systolic arterial blood pressure (SAP) and hemodynamic parameters were evaluated on the median artery. Parameters were evaluated every 5 min from 45 to 65 min (T65) at 75 (T75), 90 (T90), and 105 (T105) minutes after ACP administration, and the vessel's surface (SURF), diameter (DIAM), circumference (CIRC), peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV), volumetric flow (VF) and resistivity index (RI) of the flow were calculated. Acepromazine induced hypotension and vasodilation with a significant rise in SURF, DIAM, CIRC, PSV, EDV, MV, and VF and a reduction in RI and SAP, which were significantly counteracted from T50 to T60 for EDV, VF, MV and RI, and to T65 for SAP, from T50 to T90 for CIRC and SURF and to T60 for DIAM. These findings demonstrate that a 1 µg/kg BW/minute NOR infusion can reverse ACP's vasodilatory effects, restoring hemodynamic parameters and blood pressure in horses.

Évaluation d'altérations hémodynamiques induites par l'acépromazine et inversion par une infusion de norépinéphrine chez des chevaux debout. Les effets d'une infusion de norépinéphrine (NOR) sur les altérations hémodynamiques induites avec des doses sédatives d'acépromazine (ACP) ont été évalués. Une infusion de NOR à 1 µg/kg poids corporel (PC)/minute pendant 15 minutes a été administrée à 5 chevaux debout 45 minutes (T45) après une injection intraveineuse d'ACP à 0,1 mg/kg PC. La tension artérielle systolique (TAS) et les paramètres hémodynamiques ont été évalués sur l'artère médiane. Les paramètres ont été évalués toutes les 5 minutes, de 45 à 65 minutes (T65), puis 75 (T75), 90 (T90) et 105 (T105) minutes après l'administration d'ACP et la surface (SURF), le diamètre (DIAM), la circonférence (CIRC), le pic de vélocité systolique (PVS), la vélocité en fin de diastole (VFD), la vélocité moyenne (VM) et l'écoulement volumétrique (EV) du vaisseau ainsi que l'indice de résistivité (IR) du débit ont été calculés. L'hypotension et la vasodilatation induites par l'acépromazine causant une hausse significative de SURF, de DIAM, de CIRC, de PVS, d'EV, de VM et de EV ainsi qu'une réduction d'IR et de TAS ont été significativement compensées de T50 à T60 pour EDV, VF, MV et RI, à T65 pour SAP, de T50 à T90 pour CIRC et SURF et à T60 pour DIAM. Ces constatations démontrent qu'une infusion de 1 µg/kg PC/minute NOR peut inverser les effets vasodilatoires d'ACP, rétablissant les paramètres hémodynamiques et la tension artérielle chez les chevaux.(Traduit par Isabelle Vallières).

Effect of strenuous exercise and ex vivo TLR3 and TLR4 stimulation on inflammatory gene expression in equine pulmonary leukocytes.

The effects of strenuous exercise and ex vivo stimulation of TLR3 and TLR4 pathways on the expression of six inflammatory genes in equine pulmonary leukocytes were investigated. The genes tested were interferon-beta (IFN-ß), interleukin-1-beta (IL-1ß), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), chemokine (c-c motif) ligand 5 (RANTES) and tumor necrosis factor-alpha (TNF-α). We hypothesized that strenuous exercise would modulate basal gene expression on one hand and modulate the response to bacterial lipopolysaccharide (LPS) and to polyinosinic:polycytidylic acid (Poly IC) on the other hand. Eight young Thoroughbred mares were selected for the experiment. Bronchoalveolar lavages were performed on horses 48 h before and 24h after the completion of treadmill exercise until fatigue. Differential counts were performed on the bronchoalveolar lavage cells. Real-time PCR was used to quantify cytokine expression in pulmonary leukocytes. Target gene expression was normalized to the expression of three housekeeping genes (HKG). There were no significant differences in the mRNA expression of the six cytokines between pre-exercise and post-exercise cells. LPS and Poly IC induced respectively significant increases of TNF-α, IFN-ß, IL-6, IL-1ß, and TNF-α, IFN-ß, IP-10 and RANTES, both before and after exercise. However, exercise induced a significant decrease of the genes response to LPS and Poly IC. These findings may suggest that strenuous treadmill exercise exerts a deleterious effect on part of the pulmonary immune response in horses 24h following an intense physical activity.

The oxidant/antioxidant equilibrium in horses.

Since "free radical research" started in 1954, understanding the role of oxidants and antioxidants in physiological and pathological conditions has increased continuously. Oxidants are essentially generated by metabolic enzymes, inflammatory cells and mitochondrial electron leakage; they are indispensable for the cellular redox regulation and may, under certain conditions, have a pro-inflammatory stimulatory role. Endogenous and exogenous antioxidants counterbalance the oxidative processes and so maintain the oxidant/antioxidant equilibrium. Excessive oxidant generation or antioxidant insufficiency can lead to oxidative stress. The aims of this review are: (1) to provide an insight into the concept of the oxidant/antioxidant equilibrium by briefly introducing the oxidant and the antioxidant systems; (2) to describe how the oxidant/antioxidant equilibrium or oxidative stress can be evaluated in horses, and (3) to summarise current knowledge about oxidative stress in equine medicine and equine exercise physiology.

Change in blood antioxidant status of horses moved from a stable following diagnosis of equine motor neuron disease.

The antioxidant status of 10 horses living in stable 1 where 2 cases of equine motor neuron disease had previously been diagnosed was assessed before and 9 weeks after moving to another stable. Duration of residence in stable 1, subsequent moving, or both, significantly affected several parameters of the antioxidant status.

Myeloperoxidase concentration in bronchoalveolar lavage fluid from healthy horses and those with recurrent airway obstruction.

The aim of this work was to measure the myeloperoxidase (MPO) concentration in bronchoalveolar lavage (BAL) fluid collected from horses with recurrent airway obstruction (RAO), both in crisis and in remission, as well as from healthy horses. Seven horses with RAO were exposed to moldy hay until the maximum change in pleural pressure was greater than 1.5 kPa. At that point, BAL was performed, and the total cell counts and percentages in the fluid were immediately determined. To measure the MPO concentration in BAL-fluid supernatant, we used a specific enzyme-linked immunosorbent assay with polyclonal antibodies against equine MPO. The tests were repeated on the horses with RAO after they had spent 2 mo on pasture. Six healthy horses serving as controls underwent the same tests. The absolute and relative neutrophil counts and the MPO concentration in the BAL fluid were significantly greater in the horses with an RAO crisis than in the control horses. After 2 mo on pasture, the horses that had been in RAO crisis were clinically normal, and their neutrophil counts and MPO levels in BAL fluid had significantly decreased; during remission their neutrophil counts were not significantly different from those in the healthy horses, but their MPO concentration remained significantly higher. This study showed that determining the MPO concentration in a horse's BAL fluid is technically possible and that during remission from RAO the concentration remains higher than normal. Thus, MPO may be a marker of neutrophil presence and activation in the lower airways.

DNA binding activity of transcription factors in bronchial cells of horses with recurrent airway obstruction.

Horses with recurrent airway obstruction (RAO) present many similarities with human asthmatics including airway inflammation, hyperresponsiveness, reversible obstruction, and increased NF-kappaB expression. Studies in experimental asthma models have shown that transcriptions factors such as activator protein-1 (AP-1), GATA-3, cyclic AMP response element binding protein (CREB) and CAAT/enhancer binding protein (C/EBP) may also play an important role in airway inflammation. The purpose of this study was to measure DNA binding activity of these transcription factors in the airways of horses with RAO and to compare it to pulmonary function and bronchoalveolar lavage fluid (BALF) cytology. Seven horses with RAO and six control animals were studied during a moldy hay challenge and after 2 months at pasture. Pulmonary function, BALF cytology and transcription factors' activities in bronchial brushings were measured during hay and pasture exposures. During moldy hay challenge, RAO-affected horses developed severe airway obstruction and inflammation and a significantly higher airway AP-1 binding activity than in controls. After 2 months on pasture, pulmonary function and airway AP-1 binding activity were not different between RAO and control horses. The DNA binding activity of CREB in airways of RAO-affected horses increased significantly after 2 months at pasture and became higher than in controls. A significant positive correlation was detected between AP-1 binding activity and indicators of airway obstruction and inflammation. Airway GATA-3, CEBP and CREB binding activities were negatively correlated with indices of airway obstruction. However, contrarily to CREB binding activity, GATA-3 and CEBP binding activities were not different between RAO and control horses and were unaffected by changes in environment. These data support the view that AP-1 and CREB play a role in modulating airway inflammation in horses with RAO.

Effect of atropine-dobutamine stress test on left ventricular echocardiographic parameters in untrained warmblood horses.

The aim of this study was to investigate the effect of combined atropine low-dose dobutamine stress test on left ventricular parameters in adult warmblood horses, to establish a potential protocol for pharmacological stress echocardiography. Seven healthy untrained warmblood horses aged 9 to 22 years were used. Heart rate (HR) and left ventricular B- and M-mode dimensions were recorded at baseline and during stress testing with 35 microg/kg atropine IV followed by incremental dobutamine infusion of 2 to 6 microg/kg/min. HR increased significantly (P < .05) during the pharmacological challenge, and a maximal HR of 156.6 +/- 12.5 bpm was reached at maximal dobutamine infusion rate. Systolic and diastolic interventricular septum thickness, systolic and diastolic left ventricular free wall thickness, and fractional shortening increased significantly and reached a maximum at the highest infusion rate (mean +/- SD: 4.51 +/- 0.27 versus 5.65 +/- 0.31 cm, 2.89 +/- 0.19 versus 3.78 +/- 0.10 cm, 3.72 +/- 0.34 versus 4.77 +/- 0.18 cm, 2.44 +/- 0.28 versus 3.11 +/- 0.34 cm, 34.98 +/- 3.82 versus 50.56 +/- 3.42%, respectively). Systolic and diastolic left ventricular internal diameter decreased significantly during dobutamine infusion. Left ventricular external and internal area were significantly lower at a dobutamine infusion rate of 2 microg/kg/min but no further decrease was observed during the subsequent steps. Systolic and diastolic myocardial area was significantly lower after the administration of dobutamine but not significantly different during dobutamine infusion, when compared to baseline values. This pharmacological stress test induced significant changes in left ventricular echocardiographic parameters in adult warmblood horses. Additional research should evaluate the value of this stress test in horses suffering from cardiac disease.

Effect of beclomethasone dipropionate and dexamethasone isonicotinate on lung function, bronchoalveolar lavage fluid cytology, and transcription factor expression in airways of horses with recurrent airway obstruction.

Glucocorticoid (GC) therapy is recognized to be effective for the treatment of recurrent airway obstruction (RAO) in horses. Anti-inflammatory properties of GC are thought to be mediated by suppression of inflammatory gene expression via inhibition of transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). The purpose of this study was to evaluate the effect of low-dose inhaled beclomethasone dipropionate and injectable dexamethasone 21-isonicotinate on clinical signs, pulmonary function, airway cytology, and activity of NF-kappaB and AP-1 in bronchial cells of RAO-affected horses. Seven horses with RAO were exposed to moldy hay until they developed airway obstruction on 3 separate occasions. In a crossover design, they were then treated with a placebo (injection on day 1), inhaled beclomethasone (500 microg q12h for 10 days), or dexamethasone (0.06 mg/kg, IM on day 1) and monitored for 10 days. Pulmonary function, bronchoalveolar lavage fluid cytology, and NF-kappaB and AP-1 activity in bronchial brushing cells were measured before (day 1) and after treatment (day 10). Treatment with beclomethasone resulted in significantly improved pulmonary function of RAO-affected horses compared with placebo and dexamethasone treatments. However, none of the treatments had an effect on bronchoalveolar lavage fluid cytology or NF-kappaB and AP-1 activity. These findings reveal that, in a model of severe RAO, the benefits of low-dose inhaled beclomethasone on pulmonary function are not accompanied by a decrease in airway inflammatory cells or a suppression of transcription factors NF-kappaB and AP-1 DNA-binding activity.