Objective—To determine whether small intestinal
ischemia and reperfusion induces bacterial translocation
and proinflammatory cytokine response in either
the systemic or portal circulation in dogs.
Animals—17 healthy adult Beagles.
Procedure—The superior mesenteric artery (SMA)
was occluded for 0 (group-3 dogs), 30 (group-1 dogs),
or 60 (group-2 dogs) minutes, followed by reperfusion
for 180 minutes; serum lactate and endotoxin concentrations
and tumor necrosis factor-α (TNF-α), interleukin-
1β (IL-1β), and IL-6 activities in the systemic and
portal circulation and intramucosal pH were measured
at various time points.
Results—In group-2 dogs, TNF-α activity was found
to be significantly increased in the portal circulation,
peaking at 60 minutes of reperfusion; TNF-α activity,
in the systemic circulation, gradually increased from
60 minutes of reperfusion to the end of the experiment;
however, the increase was not significant. In
group-1 and -2 dogs, IL-6 activities significantly and
gradually increased in the systemic and portal circulation
during the reperfusion phase, and the magnitude
of these increases was dependent on the duration of
the ischemic phase. There were no significant
changes in IL-1β activity or endotoxin concentration in
any dog group.
Conclusions and Clinical Relevance—Results of the
our study indicate that intestinal ischemia and reperfusion
leads to significant increases of the circulating
TNF-α and IL-6 activities, depending on the duration of
the ischemia phase, in the absence of detectable
endotoxin in the circulation. This finding suggests that
intestinal ischemia and reperfusion induces a systemic
proinflammatory cytokine response in dogs.
(Am J Vet Res 2002;63:1680–1686)
Objective—To determine whether small intestinal
ischemia and reperfusion affects intestinal intramucosal
pH (pHi), arterial and portal venous blood gas
values, and intestinal blood flow (IBF) and to investigate
relationships between regional intestinal tissue
oxygenation and systemic variables in dogs.
Animals—15 healthy adult Beagles.
Procedure—Occlusion of superior mesenteric artery
(SMA) for 0, 30, or 60 minutes, followed by reperfusion
for 180 minutes, was performed; IBF, pHi, arterial and
portal venous blood gas values, arterial pressure, and
heart rate were measured at various time points; and
intestinal mucosal injury was histologically graded.
Results—Occlusion of the SMA induced significant
decreases in pHi and IBF. After the release of the
occlusion, IBF returned rapidly to baseline values, but
improvement in pHi was slow. Arterial and portal
venous blood gas analyses were less sensitive than
tonometric measurements of pHi, and there was no
correlation between results of blood gas analyses and
tonometric measurements. Histologic score for intestinal
mucosal injury increased significantly, depending
on duration of ischemia, and there was a correlation
between tonometric results and the histologic score.
Conclusion and Clinical Relevance—Results suggest
that it is difficult to accurately evaluate local oxygenation
disorders by monitoring at the systemic
level, whereas clinically pHi is the only reliable indicator
of inadequate regional intestinal tissue oxygenation
in dogs. (Am J Vet Res 2002;63:804–810)
Objective—To determine whether continuous infusion
of a low dose of lipopolysaccharide (LPS) to
induce a condition mimicking septic shock in dogs
would affect systemic and hepatosplanchnic circulation
Animals—12 healthy adult Beagles.
Procedure—Dogs received a low dose of LPS
(Escherichia coli O55:B5) by continuous IV infusion at
a rate of 1 µg/kg/h for 8 hours. Systemic hemodynamics;
systemic oxygenation; blood flow in the cranial
mesenteric artery, common hepatic artery, and
portal vein; intestinal and hepatic tissue blood flow;
mesenteric oxygenation; and intramucosal PCO2 were
examined before and at selected time points after
onset of the LPS infusion.
Results—After onset of the LPS infusion, cardiac
index increased and mean arterial pressure (MAP)
and systemic vascular resistance decreased, which is
characteristic of the hyperdynamic state in septic
patients. Hepatosplanchnic blood flow increased during
the hyperdynamic state. Intestinal PCO2 was
increased even when blood flows increased. During
the latter half of the experimental period, MAP was
maintained but hepatosplanchnic blood flows
decreased and intestinal PCO2 increased further.
Conclusions and Clinical Relevance—Analysis of
the results suggested that hepatosplanchnic blood
flow enters the hyperdynamic state during the early
stages of sepsis and that intestinal tissue oxygenation
is threatened even when hepatosplanchnic blood
flow is increased or maintained. Hence, improvement
of hepatosplanchnic circulation and intestinal tissue
oxygenation is important in dogs with clinical evidence
of a septic condition. (Am J Vet Res
Objective—To determine the effects of continuous
low-dose infusion of lipopolysaccharide (LPS) on the
expression of E-selectin and intercellular adhesion
molecule-1 (ICAM-1) mRNA and neutrophil accumulation
in the lungs, liver, spleen, small intestine, and
pancreas in dogs.
Animals—11 healthy adult Beagles.
Procedure—Dogs received a continuous infusion of a
low dose (10 µg/kg/h, IV) of LPS ( Escherichia coli055:B5)
or saline (0.9% NaCl) solution (20 mL/kg/h, IV) for 8
hours. Activity levels of tumor necrosis factor-α (TNF-α),
interleukin-1β (IL-1β), and interleukin-6 (IL-6) and the number
of WBCs in circulation were examined before and 1,
2, 4, and 8 hours after the onset of LPS infusion.
Expression of E-selectin and ICAM-1 mRNA and the
number of neutrophils in each tissue were examined.
Results—After the onset of LPS infusion, serum
TNF-α and IL-1β activities transiently increased.
Thereafter, IL-6 activity increased, and high IL-6 activity
was maintained throughout the experiment. In
dogs in the LPS group, expression of E-selectin
mRNA increased only in the lungs, and expression of
ICAM-1 mRNA increased in the lungs and liver; the
number of neutrophils in the tissue increased in the
lungs and liver.
Conclusions and Clinical Relevance—Results suggested
that expression of E-selectin and ICAM-1
mRNA increased during sepsis, particularly in the
lungs and liver, and that this increase was associated
with neutrophil accumulation. Hence, inhibiting the
activation of endothelial cells in the lung and liver may
decrease organ damage caused by accumulated neutrophils
and help regulate multiple-organ dysfunction.
(Am J Vet Res 2005;66:1259–1266)
Objective—To investigate the relationship between runt-related transcription factor 2 (RUNX2) expression in canine nucleus pulposus (NP) cells and intervertebral disk aging in chondrodystrophoid dogs.
Animals—7 healthy Beagles (mean age, 35.6 months) and 11 Dachshunds with herniated disks (mean age, 61 months).
Procedures—All dogs underwent MRI examination of the thoracic and lumbar vertebral column immediately before sample collection under general anesthesia. The disk center–to–CSF T2-weighted signal intensity ratio was determined for healthy Beagles. Samples of NP were obtained from nonherniated disks in healthy Beagles and from herniated disks during surgical treatment of hospitalized Dachshunds. Samples were evaluated for RUNX2 and matrix metalloproteinase 13 transcript expression via reverse transcriptase PCR assay; RUNX2 protein expression was evaluated via immunohistochemical analysis, and correlation between these variables and age of dogs was evaluated. A 3′ and 5′ rapid amplification of cDNA ends method was used to identify the RUNX2 coding region.
Results—RUNX2 cDNA had > 97% conservation with the human cDNA sequence and approximately 95% conservation with the mouse cDNA sequence; RUNX2 and matrix metalloproteinase 13 mRNA expression and RUNX2 protein expression in NP cells were positively correlated with age. The disk center–to–CSF T2-weighted signal intensity ratio was negatively correlated with RUNX2 protein expression in the NP of healthy dogs.
Conclusions and Clinical Relevance—Results indicated that RUNX2 mRNA and protein expression in the NP are enhanced in aging intervertebral disks in dogs.
Objective—To evaluate effects of long-term administration of carprofen on healing of a tibial osteotomy in dogs.
Animals—12 healthy female Beagles.
Procedures—A mid-diaphyseal transverse osteotomy (stabilized with an intramedullary pin) of the right tibia was performed in each dog. The carprofen group (n = 6 dogs) received carprofen (2.2 mg/kg, PO, q 12 h) for 120 days; the control group (6) received no treatment. Bone healing and change in callus area were assessed radiographically over time. Dogs were euthanized 120 days after surgery, and tibiae were evaluated biomechanically and histologically.
Results—The osteotomy line was not evident in the control group on radiographs obtained 120 days after surgery. In contrast, the osteotomy line was still evident in the carprofen group. Callus area was significantly less in the carprofen group, compared with the area in the control group, at 20, 30, and 60 days after surgery. At 120 days after surgery, stiffness, elastic modulus, and flexural rigidity in the carprofen group were significantly lower than corresponding values in the control group. Furthermore, histologic evaluation revealed that the cartilage area within the callus in the carprofen group was significantly greater than that in the control group.
Conclusions and Clinical Relevance—Long-term administration of carprofen appeared to inhibit bone healing in dogs that underwent tibial osteotomy. We recommend caution for carprofen administration when treating fractures that have delays in healing associated with a reduction in osteogenesis as well as fractures associated with diseases that predispose animals to delays of osseous repair.
Objective—To determine the effects of intestinal ischemia and reperfusion on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNAs in the jejunum, liver, and lungs of dogs.
Animals—8 healthy adult Beagles.
Procedures—In each dog, the cranial mesenteric artery was occluded for 0 (control group; n = 4) or 60 (I-R group; 4) minutes, followed by reperfusion for 480 minutes; serum TNF-α and IL-6 activities and expression levels of TNF-α and IL-6 mRNAs in jejunal, hepatic, and lung tissues were measured before and at the end of the ischemic period and at intervals during reperfusion. For each variable, values were compared between the control and I-R groups at each time point.
Results—Compared with the control group, serum IL-6 activity increased significantly after 180 minutes of reperfusion in the I-R group; also, jejunal TNF-α mRNA expression increased significantly after 60 (peak) and 180 minutes of reperfusion. In the I-R group, expressions of IL-6 mRNA in the liver and TNF-α and IL-6 mRNAs in the lungs increased significantly at 480 minutes of reperfusion, compared with the control group. Serum TNF-α activity, expression of IL-6 mRNA in the jejunum, and expression of TNF-α mRNA in the liver in the control and I-R groups did not differ.
Conclusions and Clinical Relevance—Results indicated that the liver, lungs, and jejunum contributed to the production of TNF-α and IL-6 after intestinal ischemia and reperfusion in dogs, suggesting that intestinal ischemia and reperfusion induce a systemic proinflammatory cytokine response in dogs.
Objective—To evaluate the effects of mitotane administration on the function and morphology of pituitary corticotrophs in clinically normal dogs.
Animals—12 clinically normal adult Beagles.
Procedures—Dogs were randomly assigned to the control group or the mitotane treatment group. In mitotane treatment group dogs, mitotane was administered for 1 month. In both groups, ACTH stimulation testing and corticotrophin-releasing hormone (CRH) stimulation testing were performed. Magnetic resonance imaging (MRI) of the pituitary gland and brain was performed in mitotane treatment group dogs before and after administration of mitotane. After CRH stimulation testing and MRI, dogs were euthanatized and the pituitary gland and adrenal glands were excised for gross and histologic examination.
Results—ACTH concentrations in mitotane treatment group dogs were significantly higher than in the control group dogs following CRH stimulation. Magnetic resonance imaging revealed that pituitary glands were significantly larger in treatment group dogs after administration of mitotane, compared with before administration. On gross and histologic examinations, the adrenal cortex was markedly atrophied. Immunohistochemistry revealed hypertrophy of corticotrophs in pituitary glands of mitotane treatment group dogs.
Conclusions and Clinical Relevance—These findings indicate that inhibition of the adrenal cortex by continuous administration of mitotane leads to functional amplification and morphologic enhancement of corticotrophs in clinically normal dogs. In instances of corticotroph adenoma, hypertrophy of individual corticotrophs induced by mitotane may greatly facilitate enlargement of the pituitary gland and increases in ACTH secretion.
Objective—To compare activities of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and matrix
metalloproteinase (MMP)-3 and contents of sulfated
glycosaminoglycan (S-GAG) in joint fluid obtained
from dogs with hip dysplasia (HD) and clinically normal
dogs, evaluate correlations among these markers
in joint fluid obtained from dogs with HD, and evaluate
correlations between each marker and clinical and
Animals—26 dogs with HD (clinical group) and 43
clinically normal Beagles (control group).
Procedure—Joint fluid was aseptically collected from
the hip joints of all dogs. For each dog in the clinical
group, age, duration of lameness, radiographic
osteoarthritis (OA) score, and Norberg angle in each
affected joint were recorded. Activities of IL-1β, IL-6,
TNF-α, and MMP-3 and S-GAG contents were measured.
Values were compared between groups by use
of Mann-Whitney U tests, and the Spearman rank correlation
test was used to evaluate correlations among
markers and between each marker and clinical or
Results—Values of all markers were significantly
higher for the clinical group, compared with values for
the control group. There was a moderate positive correlation
between lameness duration and IL-6 activity
and a strong negative correlation between the
Norberg angle and IL-1β activity.
Conclusions and Clinical Relevance—Analysis of
our results indicated that there was a significant
increase in markers of OA in dogs with HD. Activities
of IL-1β and IL-6 in joint fluid of dogs with HD may be
influenced by the severity of laxity in the hip joint and
lameness duration, respectively. (Am J Vet Res