W. E. van den Brom

Secretion pattern of thyroid-stimulating hormone in dogs during euthyroidism and hypothyroidism.

In as many as one third of dogs with primary hypothyroidism a plasma thyrotropin (TSH) concentration within the reference range for euthyroid dogs is found. To determine whether this is due to fluctuations in the release of TSH, the plasma profiles of TSH were analyzed in 7 beagle bitches by collecting blood samples every 10 min for 6 hr, both before and after induction of primary hypothyroidism. After induction of primary hypothyroidism, a 37-fold increase in mean basal plasma TSH concentration and a 34-fold increase in mean area under the curve for TSH were found. Analysis by the Pulsar program demonstrated pulsatile secretion of TSH in the hypothyroid state, characterized by relatively low amplitude pulses (mean [+/-SEM]) amplitude 41 +/- 3% of basal plasma TSH level) and a mean pulse frequency of 2.0 +/- 0.5 pulses/6 hr. In the euthyroid state, significant TSH pulses were identified in only 2 dogs. The mean basal plasma TSH level correlated positively (r = 0.84) with the mean amplitude of the TSH pulses, and correlated negatively (r = -0.88) with the TSH pulse frequency. The results of this study demonstrate pulsatile secretion of TSH in dogs during hypothyroidism and only small fluctuations in plasma TSH concentrations during euthyroidism. The findings also suggest that the low TSH values occasionally found in dogs with spontaneous primary hypothyroidism may in some cases in part be the result of ultradian fluctuations.

Improvement of chronic hepatic encephalopathy in dogs by the benzodiazepine-receptor partial inverse agonist sarmazenil, but not by the antagonist flumazenil

Therapeutic modulation of the increased GABAergic tone in chronic hepatic encephalopathy (HE) by the benzodiazepine receptor (BR) antagonist flumazenil (F) has led to conflicting results in humans and animal models for HE. The BR inverse agonist sarmazenil (S) has only been used in animal models of acute HE. Therefore we investigated the effects of intravenous injection of F and S in dogs with chronic HE 8 to 12 weeks after placement of a portocaval shunt and 40% hepatectomy (n=7), compared to sham-operated pair-fed controls (n=7). The HE dogs had hyperammonemia (298±48 μM v 33±3 before surgery (mean±SEM)) and signs of HE at the start of the experiments (0.9±0.1 (scale 0-4)). Three (S3) and 8 (S8) mg/kg of S resulted in a significant improvement of encephalopathy (grade 0.9±0.2 immediately before v 0.5±0.1 after injection (S3) and 0.7±0.1 v 0.3±0.1 (S8)) and increase in mean dominant frequency of the EEC (MDF; 9.1±0.7 Hz v 11.1±0.3 (S3) and 8.9±0.5 v 11.0±0.3 (S8)) in HE dogs, whereas 15 mg/kg of S, 3 and 8 mg/kg of F, and the vehicle had no significant effects. The efficacy of S in these dogs is consistent with an increased GABAergic tone in the pathogenesis of chronic HE. The lack of effects of F makes a role for endogenous benzodiazepines herein unlikely.

Quantitation of portosystemic shunting in dogs by ultrasound-guided injection of 99MTc-macroaggregates into a splenic vein

A technique is described for the ultrasound-guided injection of 99mTc-macroaggregates into a splenic vein in order to quantitate portosystemic collateral circulation. The fraction of portal blood by-passing the liver was derived from the radioactivity trapped in the liver and lungs and was expressed as the shunt index (SI). The method was tested in healthy dogs without shunting, and in dogs with single hereditary portosystemic shunts before and one month after surgical closure of the shunt. The mean SI was 0.01 (range 0.01 to 0.05) in healthy dogs and 0.94 (0.69 to 1.00) in dogs with hereditary shunts. After partial closure of the shunts the SI decreased to 0.25 (0.03 to 0.70). There was a significant positive correlation between the logarithms of the concentration of ammonia in plasma and the SI (r = 0.87, P < 0.001).

Effects of methods used for blood collection on plasma concentrations of luteinising hormone, testosterone, and cortisol in male dogs.

The effects of two putative stressors relative to the collection of blood, namely the environment of the treatment room and the pain associated with venepuncture, on plasma levels of luteinising hormone (LH), testosterone and cortisol were examined in six trained male experimental dogs. Blood samples were collected from the dogs in a treatment room as well as in the kennels (control), and by venepuncture as well as via an indwelling intravenous catheter (control). No significant influence of either stressor on plasma levels of LH, testosterone or cortisol was found. Plasma concentrations of these hormones varied considerably both between and within dogs. Mean (+/- SEM; n = 6) plasma concentrations were 4.3 +/- 1.0 micrograms/l for LH, 4.6 +/- 1.9 nmol/l for testosterone and 68 +/- 10 nmol/l for cortisol. It was concluded that the putative stressors, the environment of the treatment room and the pain associated with venepuncture, did not significantly influence plasma levels of LH, testosterone or cortisol in trained male experimental dogs. This conclusion implies that under the experimental conditions described, the validity of results will not be affected by the method of blood collection used.

In vivo studies on the effects of ovine corticotrophin-releasing hormone, arginine vasotocin, arginine vasopressin, and haloperidol on adrenocortical function in the racing pigeon (Columba livia domestica)

This study investigates the effects of in vivo administration of pituitary stimulants in racing pigeons (Columba livia domestica). Plasma corticosterone concentrations were measured following intravenous administration of ovine corticotrophin-releasing hormone (oCRH) (0.1, 1, 10, and 100 micrograms/kg), arginine vasopressin (AVP) (0.01, 0.1, 1, and 10 micrograms/kg), arginine vasotocin (AVT) (0.01, 0.1, 1, and 5 micrograms/kg), and haloperidol (0.05, 0.5, and 5 micrograms/kg). Compared with mammals the pituitary-adrenocortical system of the pigeon appeared to be less sensitive to stimulation with oCRH, although high doses were well tolerated and gave a clear response. Both AVP and AVT stimulated corticosterone secretion, AVT in a more pronounced dose-dependent manner than AVP. The natural neurohypophysial peptide in birds, AVT, was less well tolerated in high doses than AVP. The clear response to haloperidol indicates that the hypothalamo-pituitary-adrenocortical system is under dopaminergic inhibition. Of the pituitary stimulants tested AVP (10 micrograms/kg) and oCRH (100 micrograms/kg) are the most appropriate for testing the integrity of the pituitary-adrenocortical system in the pigeon.

Effect of methadone on plasma arginine vasopressin level and urine production in conscious dogs.

The aim of this study was to examine the effect of i.v. methadone on the plasma arginine-vasopressin (AVP) levels and urine production in 9 conscious dogs. A highly significant increase from the baseline plasma AVP values of below 3 pg/ml occurred within 5 min following methadone administration. Maximum levels were reached within 30-50 min post-injection and varied from 18.5 to 100 pg/ml. A significant decrease in urine production was not seen under these experimental conditions. Mean arterial blood pressure did not change significantly during the experiment. Apart from the partial influence of the methadone-induced respiratory acidosis, we postulate a direct relationship between i.v. administration of methadone and the increased plasma AVP levels in dogs.

Effects of aging on brainstem responses to toneburst auditory stimuli: a cross-sectional and longitudinal study in dogs.

BACKGROUND It is assumed that the hearing of dogs becomes impaired with advancing age, but little is known about the prevalence and electrophysiologic characteristics of presbycusis in this species. HYPOTHESIS As in humans, hearing in dogs becomes impaired with aging across the entire frequency range, but primarily in the high-frequency area. This change can be assessed quantitatively by brainstem-evoked response audiometry (BERA). ANIMALS Three groups of 10 mixed-breed dogs with similar body weights but different mean ages were used. At the start of the study, the mean age was 1.9 years (range, 0.9-3.4) in group I, 5.7 years (3.5-7) in group II, and 12.7 years (11-14) in group III. METHODS In a cross-sectional study, the BERA audiograms obtained with toneburst stimuli were compared among the 3 groups. In a longitudinal study, changes in auditory thresholds of group II dogs were followed for 7 years. RESULTS Thresholds were significantly higher in group III than in groups I and II at all frequencies tested, and higher in group II than in group I at 4 kHz. The audiograms in group II indicated a progressive increase in thresholds associated with aging starting around 8-10 years of age and most pronounced in the middle- to high-frequency region (8-32 kHz). CONCLUSIONS AND CLINICAL IMPORTANCE Age-related hearing loss in these dogs started around 8-10 years of age and encompassed the entire frequency range, but started and progressed most rapidly in the middle- to high-frequency area. Its progression can be followed by BERA with frequency-specific stimulation.

Effects of age and breed on the phospholipid composition of canine surfactant

To investigate possible age- and breed-related changes in the composition of canine pulmonary surfactant, we determined the phospholipid patterns of surfactants isolated by bronchoalveolar lavage of 3 age categories of beagles (3–7 months; 3–7 years; 12 years and older) and of 1 group of greyhounds (4–14 years). There was a significant (p=0.01) increase in the proportion of phosphatidylcholine in surfactant with age, whereas the proportions of phosphatidylserine and sphingomyelin were significantly lower in old beagles compared to young dogs. Although the differences were generally rather small, they may nevertheless be of biological importance, as was indicated by comparing the minimal surface tensions of lavage fluids obtained from young and old beagles. It is attractive to speculate that the shift in surfactant lipid composition could be 1 of the mechanisms that permit efficient lung function in old dogs, despite changes in morphology and mechanics in the aging lung. The phospholipid composition of surfactant isolated from greyhounds differed significantly from that in beagles. The surfactant of greyhounds was enriched in phosphatidylglycerol compared to all age groups of beagles. The degree of saturation of surfactant phosphatidylcholine was also higher in greyhounds, although this difference was significant only when compared to young and middle-aged beagles.

Relationship between atrial fibrillation and primary hypothyroidism in the dog

Atrial fibrillation (AF) and primary hypothyroidism are most often diagnosed in middle-aged and older dogs of large and giant breeds. We hypothesized that the frequency of primary hypothyroidism may be higher in dogs with AF than in those without AF. Two groups were investigated. Group 1 (March 1987-June 1990) consisted of 128 dogs with AF. A thyroid-stimulating hormone (TSH) stimulation test was performed in dogs with a low voltage on the ECG and low uptake of pertechnetate on a thyroid scan. Group 2 (July 1990-July 1991) consisted of both dogs with AF (n = 38) and control dogs (n = 235) in which plasma thyroxine (T4) was measured. If T4 was below 15 nmol/l, a TSH stimulation test was performed. The frequencies of primary hypothyroidism in group 1 (8/128) and in the group 2 AF dogs (3/38) were not different, but were higher than in the control animals (3/235) (P < 0.05). The group 1 and the group 2 AF dogs were found to be comparable, and pooling of the data of the two groups enhanced the significance of the frequency of primary hypothyroidism in dogs with AF versus the control animals (11/166 versus 3/235) (P < 0.01). We concluded that the frequency of primary hypothyroidism in dogs with AF is higher than in the group of control dogs without AF. This may be due to the additional cardiovascular changes accompanying primary hypothyroidism in dogs that already have heart disease.

Transient metabolic hyperammonaemia in young Irish wolfhounds

Inherited portosystemic shunts occur in 2 to 3 per cent of Irish wolfhounds and are associated with high venous ammonia concentrations and signs of hepatic encephalopathy. Moreover, the vast majority of Irish wolfhound pups without signs of hepatic encephalopathy have moderate hyperammonaemia. The aim of this study was to investigate whether the increased ammonia levels in these clinically healthy dogs are caused by low-grade portosystemic shunting, and whether the hyperammonaemia persists in adulthood. The fasting venous ammonia concentration and the fraction of portal blood by-passing the liver, expressed as the shunt index (si) were measured in 42 Irish wolfhound pups, and the dogs with high si values were examined post mortem. The ammonia concentration was also measured in 25 adult Irish wolfhounds in which it had been measured when they were seven to eight weeks old. Eleven of the 42 pups had a portosystemic shunt, as evidenced by a high Si (mean 0.82, range 0.12 to 1.00, normal range 0.01 to 0.05) and by post mortem examination. Their mean ammonia concentration was 249 pmolllitre (range 121 to 350). The 31 pups with a normal si (mean 0.025, range 0.00 to 0.05) had a mean ammonia concentration of 93 μmol/litre (range 51 to 125). In the 25 dogs in which the ammonia concentration was measured twice, the mean concentration at seven to eight weeks of age was 77,mol/litre (range 47 to 115) and in the adults it was 17 μmol/litre (range 6 to 27) at a mean age of 3-1 years (range 1.0 to 8.9). These results show that Irish wolihounds with ammonia concentrations >125 μmol/litre had a portosystemic shunt, whereas the hyperammonaemia in dogs with ammonia concentrations <120 gmolllitre was transient and of metabolic origin.