Objective—To determine the effect of histamine on
the contractile elements of the respiratory tract in
neonatal calves and young adult cattle.
Sample Population—Samples of trachealis muscle,
bronchi, and intrapulmonary arteries and veins dissected
from the respiratory tracts of healthy bovids (2
to 8 days and 16 to 20 months old).
Procedure—Histamine cumulative concentrationeffect
curves (10–8 to 10–3M) were constructed in duplicate
smooth muscle samples mounted in organ
baths. Contractile responses to histamine were compared
with reference contractions elicited by methacholine
(10–5M) for airways or KCl (127mM) for vessels.
Results—In young adult cattle, trachealis muscle had
a substantial contractile response to histamine (84%
of methacholine-induced contraction), whereas
bronchi reacted slightly (15 and 20% for large and
small bronchi, respectively). Although contractile
responses to KCl were comparable in arteries and
veins, histamine-induced contractions were greater
for intrapulmonary veins than for arteries (202 vs 48%
of KCl-induced contraction). In neonatal calves, histamine-
induced contraction of veins also exceeded that
of arteries (230 vs 54% of KCl-induced contraction);
however, unlike in young adult cattle, histamine produced
notable contraction of large and small bronchi
(48 and 60% of methacholine-induced contraction,
Conclusions and Clinical Relevance—Compared
with intrapulmonary arteries, intrapulmonary veins
have greater contractile responses to histamine in
neonatal and young adult cattle. Data suggest loss of
histamine responsiveness in bronchial smooth muscle
as neonatal calves grow to young adults.
Venodilation may be useful in treatment of lung
edema in cattle. (Am J Vet Res 2003;64:819–822)
Objective—To evaluate leukotriene (LT) biosynthetic
capacity in lung tissue from healthy horses and horses
with recurrent airway obstruction (RAO).
Sample Population—Lung parenchyma and airway
specimens from 8 RAO-affected and 5 healthy horses.
Procedure—Horses were stabled for ≥ 72 hours.
Blood was drawn before euthanasia, after which lung
specimens were collected. Tissue strips from small
airways and parenchyma were incubated in organ
baths with the precursor LTA4 or stimulated with calcium
ionophore A23187 or the tripeptide N-formyl-
Met-Leu-Phe (fMLP), with or without exogenous
arachidonic acid, in the presence of isolated blood
Results—Stabling induced typical clinical signs of airway
obstruction in RAO-affected horses but not control
horses. When lung parenchyma or airway specimens
from both groups of horses were incubated
with calcium ionophore, with or without arachidonic
acid, they did not form LT. In contrast, addition of LTA4
to both tissues resulted in conversion to LTB4,
although concentrations of LTC4 were negligible in airways
and parenchymal strips from healthy and RAOaffected
horses. Incubation of airway and parenchymal
strips with suspensions of autologous neutrophils
did not influence formation of LT stimulated
by calcium ionophore or fMLP, with or without exogenous
Conclusion and Clinical Relevance—Results suggest
that lung parenchyma and airway tissues themselves
are not of substantial importance for LT formation
in the lungs, although these tissues possessed
some LTA4 hydrolase activity, enabling LTB4 formation.
It may be speculated that LTB4 originates primarily
from neutrophils and may play a role in the
inflammatory events of RAO. (Am J Vet Res 2002;
Objective—To use noninvasive respiratory inductance plethysmography (RIP) to investigate differences in breathing patterns between horses with and without recurrent airway obstruction (RAO) during the onset of airway obstruction induced through confinement to stables.
Animals—12 horses with no history or clinical signs of respiratory disease (control horses) and 7 RAO-affected horses.
Procedures—The study involved 2 phases. In phase 1, the optimal position of RIP bands for recording pulmonary function was investigated in 12 control horses. In phase 2, 7 RAO-affected and 7 control horses were confined to stables. Respiratory inductance plethysmography bands were applied to horses for 24 h/d to record respiratory rate and total displacement in 4-hour periods for 7 days or until RAO-affected horses developed signs of severe RAO that persisted for 2 consecutive days. Lung function was measured once daily.
Results—In phase 1, thoracic and abdominal cavity displacements were best represented by RIP bands positioned at intercostal spaces 6 and 17, respectively. In phase 2, pulmonary function indicated airway obstruction in the RAO-affected group on the final 2 days of stable confinement. Respiratory rate and total degree of respiratory displacement measured by RIP did not differ between the RAO-affected and control groups, but the SDs of these decreased significantly within 8 hours after stable confinement began in RAO-affected horses. Respiratory inductance plethysmography and pulmonary function findings became highly correlated as severity of disease progressed.
Conclusions and Clinical Relevance—The decrease in the SDs of RIP measurements indicated a lower degree of variability in breathing patterns of RAO-affected horses. This loss of variability may provide an early indicator of airway inflammation.
Objective—To determine whether the hyoepiglotticus
muscle has respiratory-related electromyographic
activity and whether electrical stimulation of this
muscle changes the position and conformation of the
epiglottis, thereby altering dimensions of the aditus
Animals—6 Standardbred horses.
Procedure—Horses were anesthetized, and a bipolar
fine-wire electrode was placed in the hyoepiglotticus
muscle of each horse. Endoscopic images of the
nasopharynx and larynx were recorded during electrical
stimulation of the hyoepiglotticus muscle in standing,
unsedated horses. Dorsoventral length and area
of the aditus laryngis were measured on images
obtained before and during electrical stimulation.
Electromyographic activity of the hyoepiglotticus
muscle and nasopharyngeal pressures were measured
while horses exercised on a treadmill at 50, 75,
90, and 100% of the speed that produced maximum
Results—Electrical stimulation of the hyoepiglotticus
muscle changed the shape of the epiglottis, displaced
it ventrally, and significantly increased the dorsoventral
length and area of the aditus laryngis. The
hyoepiglotticus muscle had inspiratory activity that
increased significantly with treadmill speed as a result
of an increase in phasic and tonic activity. Expiratory
activity of the hyoepiglotticus muscle did not change
with treadmill speed in 4 of 6 horses.
Conclusions and Clinical Relevance—Findings
reported here suggest that contraction of the
hyoepiglotticus muscle increases dimensions of the
airway in horses by depressing the epiglottis ventrally
during intense breathing efforts. The hyoepiglotticus
muscle may be an important muscle for dilating
the airway in horses, and contraction of the
hyoepiglotticus muscle may induce conformational
changes in the epiglottis. (Am J Vet Res
Objective—To determine the ex vivo leukotriene (LT)
biosynthesis in peripheral blood neutrophils (PBNs)
and inflammatory cells in bronchoalveolar lavage fluid
(BALF) obtained from horses affected with recurrent
airway obstruction (RAO).
Animals—6 RAO-affected and 6 control horses.
Procedure—Before and 6, 24, and 48 hours after
stabling, disease severity was determined subjectively
by clinical and mucus scores and measurement of
the maximal change in pleural pressure (ΔPplmax);
PBNs were isolated and BALF samples were examined
cytologically. The PBN and BALF cells were activated
with a calcium ionophore in the presence of
arachidonic acid, and production of LTC4 and LTB4
was measured per 106 cells.
Results—Clinical and mucus scores and ΔPplmax
increased during stabling in RAO-affected horses, but
not in control horses. In neutrophils and BALF cells
from both groups, production of LTB4 exceeded that
of LTC4. At all times, LTB4 production by PBNs was
less in RAO-affected horses than it was in control
horses. Before stabling, LTB4 production by cells in
BALF was low in RAO-affected horses, but increased
considerably after 6 hours of stabling. This increase
coincided with the migration of neutrophils into the
airways. In control horses, production of LTB4 did not
change during stabling.
Conclusions and Clinical Relevance—Results suggested
increased production of LTB4 in airways of
RAO-affected horses, compared with control horses,
that may contribute to the infiltration of neutrophils
into the lungs and the sustained inflammation associated
with RAO. ( Am J Vet Res 2004;65:289–295)
Objective—To determine the effect of a commercially
available nasal strip on airway mechanics in exercising
Animals—6 horses (5 Standardbreds and 1
Procedure—Horses exercised on a treadmill at
speeds corresponding to 100 and 120% of maximal
heart rate with and without application of a commercially
available nasal strip. Concurrently, tracheal pressures,
airflow, and heart rate were measured. Peak
inspiratory and expiratory tracheal pressures, airflow,
respiratory frequency, and tidal volume were recorded.
Inspiratory and expiratory airway resistances
were calculated by dividing peak pressures by peak
flows. Endoscopic examination of the narrowest point
of the nasal cavity (ie, nasal valve) was performed in
1 resting horse before, during, and after application of
a nasal strip.
Results—During exercise on a treadmill, peak tracheal
inspiratory pressure and inspiratory airway
resistance were significantly less when nasal strips
were applied to horses exercising at speeds corresponding
to 100 and 120% of maximal heart rate.
Application of the nasal strip pulled the dorsal conchal
fold laterally, expanding the dorsal meatus.
Conclusions and Clinical Relevance—The commercially
available nasal strip tented the skin over the
nasal valve and dilated that section of the nasal passage,
resulting in decreased airway resistance during
inspiration. The nasal strip probably decreases the
amount of work required for respiratory muscles in
horses during intense exercise and may reduce the
energy required for breathing in these horses.
(Am J Vet Res 2002;63:1101–1105)
Objective—To evaluate the safety and efficacy of thoracoscopically
guided pulmonary wedge resection in
Animals—10 horses (5 control horses and 5 horses
affected with recurrent airway obstruction [ie,
Procedure—Each horse underwent a thoracoscopically
guided pulmonary wedge resection. Before, during,
and after surgery, heart rate, respiratory rate,
arterial blood gases, and systemic and pulmonary
arterial pressures were measured. Physical examination,
CBC, and thoracic radiography and ultrasonography
were performed 24 hours before and 2 and 48
hours after surgery. Pulmonary specimens were
assessed by histologic examination. A second thoracoscopic
procedure 14 days later was used to evaluate
the resection site.
Results—The technique provided excellent specimens
for histologic evaluation of the lung. Heart and
respiratory rates decreased significantly after horses
were administered sedatives. A significant transient
decrease in PaO2 was detected immediately after pulmonary
wedge resection, but we did not detect significant
effects on arterial pH, Paco2, or mean arterial
and pulmonary arterial pressures. All horses except 1
were clinically normal after thoracoscopic surgery;
that horse developed hemothorax attributable to iatrogenic
injury to the diaphragm. The second thoracoscopy
revealed minimal inflammation, and there
were no adhesions.
Conclusion and Clinical Relevance—Thoracoscopically
guided pulmonary wedge resection provides
a minimally invasive method for use in obtaining specimens
of lung tissues from healthy horses and those
with lung disease. This technique may be useful for the
diagnosis of diseases of the lungs and thoracic cavity.
(Am J Vet Res 2002;63:1232–1240)
Objective—To record respiratory sounds in exercising
horses and determine whether spectrum analysis
could be use to identify sounds specific for laryngeal
hemiplegia (LH) and dorsal displacement of the soft
Animals—5 Standardbred horses.
Procedure—Respiratory sounds were recorded and
pharyngeal pressure and stride frequency were measured
while horses exercised at speeds corresponding
to maximum heart rate, before and after induction
of LH and DDSP.
Results—When airway function was normal, expiratory
sounds predominated and lasted throughout
exhalation. After induction of LH, expiratory sounds
were unaffected; however, all horses produced inspiratory
sounds characterized by 3 frequency bands
centered at approximately 0.3, 1.6, and 3.8 kHz. After
induction of DDSP, inspiratory sounds were unaffected,
but a broad-frequency expiratory sound, characterized
by rapid periodicity (rattling) was heard
throughout expiration. This sound was not consistently
detected in all horses.
Conclusions and Clinical Relevance—The technique
used to record respiratory sounds was well tolerated
by the horses, easy, and inexpensive.
Spectrum analysis of respiratory sounds from exercising
horses after experimental induction of LH or
DDSP revealed unique sound patterns. If other conditions
causing airway obstruction are also associated
with unique sound patterns, spectrum analysis of respiratory
sounds may prove to be useful in the diagnosis
of airway abnormalities in horses. (Am J Vet Res
Objective—To investigate relationships between
cough frequency and mucus accumulation, airway
obstruction, and airway inflammation and to determine
effects of dexamethasone on coughing and
Animals—13 horses with recurrent airway obstruction(
RAO and 6 control horses.
Procedure—6 RAO-affected and 6 control horses
were stabled for 3 days. Coughing was counted for 4
hours before and on each day horses were stabled.
Before and on day 3 of stabling, tracheal mucus accumulation
was scored, airway obstruction was
assessed via maximal change in pleural pressure
(ΔPplmax), and airway inflammation was evaluated by
use of cytologic examination of bronchoalveolar
lavage fluid (BALF). Effects of dexamethasone (0.1
mg/kg, IV, q 24 h for 7 days) were determined in 12
Results—To assess frequency, coughing had to be
counted for 1 hour. In RAO-affected horses, stabling
was associated with increases in cough frequency,
mucus score, and ΔPplmax. Control horses coughed
transiently when first stabled. In RAO-affected horses,
coughing was correlated with ΔPplmax, mucus
score, and airway inflammation and was a sensitive
and specific indicator of ΔPplmax > 6 cm H2O, mucus
score > 1.0, and > 100 neutrophils/µL and > 20% neutrophils
in BALF. Dexamethasone reduced cough frequency,
mucus score, and ΔPplmax, but BALF neutrophil
count remained increased.
Conclusions and Clinical Relevance—Because of its
sporadic nature, coughing cannot be assessed accurately
by counting during brief periods. In RAO-affected horses,
coughing is an indicator of airway inflammation and
obstruction. Corticosteroid treatment reduces cough frequency
concurrently with reductions in ΔPplmax and
mucus accumulation in RAO-affected horses. ( Am J Vet
Objective—To determine the effects of 2 weeks of intense exercise on expression of markers of pulmonary venous remodeling in the caudodorsal and cranioventral regions of the lungs of horses.
Procedures—Tissue samples of the caudodorsal and cranioventral regions of lungs were obtained before and after conditioning and 2 weeks of intense exercise. Pulmonary veins were isolated, and a quantitative real-time PCR assay was used to determine mRNA expression of matrix metalloproteinase-2 and −9, tissue inhibitor of metalloproteinase-1 and −2, collagen type I, tenascin-C, endothelin-1, platelet-derived growth factor, transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF). Protein expression of collagen (via morphometric analysis) and tenascin-C, TGF-β, and VEGF (via immunohistochemistry) was determined.
Results—Exercise-induced pulmonary hemorrhage was detected in 2 horses after exercise. The mRNA expression of matrix metalloproteinase-2 and −9, tissue inhibitor of metalloproteinase-2, TGF-β, and VEGF was significantly lower in pulmonary veins obtained after exercise versus those obtained before exercise for both the caudodorsal and cranioventral regions of the lungs. Collagen content was significantly higher in tissue samples obtained from the caudodorsal regions of the lungs versus content in samples obtained from the cranioventral regions of the lungs both before and after exercise. Exercise did not alter protein expression of tenascin-C, TGF-β, or VEGF.
Conclusions and Clinical Relevance—Results of this study indicated 2 weeks of intense exercise did not alter expression of marker genes in a manner expected to favor venous remodeling. Pulmonary venous remodeling is complex, and > 2 weeks of intense exercise may be required to induce such remodeling.