Objective—To compare the mechanisms of heartworm
(HW) extract-induced shock and endotoxininduced
shock in dogs by determination of serum
tumor necrosis factor (TNF) concentrations.
Animals—11 mixed-breed dogs (7 without and 4 with
Procedure—Eight dogs were treated with 2 ml of
HW extract IV, and 3 dogs were given endotoxin
(Escherichia colili popolysaccharide [LPS]) at 40 or 400
μg/kg of body weight, IV. Changes in clinical and
hematologic findings and serum TNF concentrations
were examined from before treatment to 120 minutes
after treatment in dogs given HW extract or from
before treatment to 180 minutes after treatment in
dogs given LPS. Tumor necrosis factor concentration
was determined by cytotoxic assay, using WEHI-164
murine sarcoma cells, and plasma endotoxin concentration
was determined in 2 dogs treated with HW
extract, using the endotoxin-specific chromogenic
Results—Eight dogs developed shock 3 to 16 minutes
after HW extract treatment. Rectal temperature
did not change during examination. Serum TNF concentration
was detected at a low concentration only
60 and 120 minutes after HW extract treatment, and
plasma endotoxin was not detected during examination.
In dogs treated with LPS, rectal temperature
increased to > 40 C in 2 of 3 dogs, and serum TNF
concentration began to increase 30 minutes after LPS
treatment, reaching a maximum concentration by 60
Conclusions—The cause and mechanism of HW
extract-induced shock may be different from those of
endotoxin-induced shock, because TNF, which was a
pivotal mediator in endotoxin-induced shock,
increased minimally in serum of dogs treated with
HW extract. (Am J Vet Res 2001;62:765–769)
Objective—To determine whether heartworm (HW)
extract-induced shock in dogs is consistent with anaphylactic
shock by examining the role of histamine.
Animals—6 mixed-breed dogs (3 without and 3 with
HW infections) and 4 specific pathogen-free (SPF)
Procedure—Four experiments were performed as
follows: 1) 6 mixed-breed dogs were treated IV with 2
ml of HW extract, and plasma histamine concentrations
were determined; 2) 4 SPF dogs were treated IV
with 2 ml of HW extract and examined for shock; 3)
sera from 6 dogs of experiment 1 and from 4 SPF
dogs of experiment 2 that were obtained before HW
extract treatment were tested for heterologous passive
cutaneous anaphylaxis (PCA), using rabbits during
a sensitization period of 48 to 72 hours; and 4)
mast cell degranulation by HW extract was tested,
using rat mesentery and canine cultured mast cells.
Results—Experiment 1: 6 dogs developed shock, and
plasma histamine concentrations increased significantly
from 0.3 ± 0.2 (mean ± SD) ng/ml before HW
extract treatment to 44.6 ± 68.9 ng/ml at the onset of
shock; experiment 2: all SPF dogs developed shock
and had an increase in plasma histamine concentrations;
experiment 3: sera from mixed-breed dogs
without HW infection and from SPF dogs had negative
PCA reactions; experiment 4: HW extract degranulated
rat mesentery mast cells and released histamine
directly from canine mast cells.
Conclusions and Clinical Relevance—Results of our
study indicate that an unknown mast cell-degranulating
substances contained in HW extract may degranulate
mast cells directly, consequently releasing histamine
that may participate in the onset of shock in
HW extract-induced shock in dogs. (Am J Vet Res
Objective—To investigate effects of short- and long- term administration of glucocorticoids, feeding status, and serum concentrations of insulin and cortisol on plasma leptin concentrations in dogs.
Animals—20 nonobese dogs.
Procedure—For experiment 1, plasma leptin concentrations and serum concentrations of insulin and cortisol were monitored for 24 hours in 4 dogs administered dexamethasone (0.1 mg/kg, IV) or saline (0.9% NaCl) solution for fed and nonfed conditions. For experiment 2, 11 dogs were administered prednisolone (1 mg/kg, PO, q 24 h for 56 days [7 dogs] and 2 mg/kg, PO, q 24 h for 28 days [4 dogs]) and 5 dogs served as control dogs. Plasma leptin and serum insulin concentrations were monitored weekly.
Results—For experiment 1, dexamethasone injection with the fed condition drastically increased plasma leptin concentrations. Furthermore, injection of saline solution with the fed condition increased plasma leptin concentrations. These increases in plasma leptin concentrations correlated with increases in serum insulin concentrations. Dexamethasone injection with the nonfed condition increased plasma leptin concentrations slightly but continuously. Injection of saline solution with the nonfed condition did not alter plasma leptin concentrations. For experiment 2, prednisolone administration at either dosage and duration did not alter plasma leptin concentrations in any dogs.
Conclusions and Clinical Relevance—Dexamethasone injection and feeding increased plasma leptin concentrations in dogs. In addition, dexamethasone administration enhanced the effect of feeding on increases in plasma leptin concentrations. Daily oral administration of prednisolone (1 or 2 mg/kg) did not affect plasma leptin concentrations in dogs.
Objective—To evaluate postprandial changes in the leptin concentration of CSF in dogs during development of obesity.
Animals—4 male Beagles.
Procedures—Weight gain was induced and assessments were made when the dogs were in thin, optimal, and obese body conditions (BCs). The fat area at the level of the L3 vertebra was measured via computed tomography to assess the degree of obesity. Dogs were evaluated in fed and unfed states. Dogs in the fed state received food at 9 AM. Blood and CSF samples were collected at 8 AM, 4 PM, and 10 PM.
Results—Baseline CSF leptin concentrations in the thin, optimal, and obese dogs were 24.3 ± 2.7 pg/mL, 86.1 ± 14.7 pg/mL, and 116.2 ± 47.3 pg/mL, respectively. In the thin BC, CSF leptin concentration transiently increased at 4 PM. In the optimal BC, baseline CSF leptin concentration was maintained until 10 PM. In the obese BC, CSF leptin concentration increased from baseline value at 4 PM and 10 PM. Correlation between CSF leptin concentration and fat area was good at all time points. There was a significant negative correlation between the CSF leptin concentration–to–serum leptin concentration ratio and fat area at 4 PM; this correlation was not significant at 8 AM and 10 PM.
Conclusions and Clinical Relevance—Decreased transport of leptin at the blood-brain barrier may be 1 mechanism of leptin resistance in dogs. However, leptin resistance at the blood-brain barrier may not be important in development of obesity in dogs.