Influence of centrally administered diltiazem on behavioural responses, clinical symptoms, reticulo-ruminal contractions and plasma catecholamine level after experimentally induced duodenal distension in sheep.

A different role of L-type antagonists for voltage-gated calcium channels (VGCC) has been previously identified in different types of experimental and clinical pain in man and animals. Present study examined the role of VGCC blocker - diltiazem administered icv (0.25, 0.5, 1.0 and/or 2.0mg in toto) on the development of pain related symptoms, clinical signs, plasma catecholamine level and the inhibition of reticulo-rumen motility caused by 5min lasting mechanical duodenum distension (DD) in the sheep. Experimental DD was conducted by insertion (during surgery) of rubber balloon into the duodenum and the distension by 40ml of warm water. Duodenal distension resulted in a significant increase of behavioural pain responses, tachycardia, hyperventilation, inhibition of reticulo-rumen contractions rate (from 85% to 45% during 15-20min), an increase of plasma catecholamine concentration (over sevenfold increase of epinephrine during 2h following DD, two-times norepinephrine and 84% increase of dopamine). Diltiazem infusion given 10min before DD decreased intensity of visceral nocifensive responses such as: behavioural changes, tachycardia, hyperventilation, reticulo-rumen motility and efficiently prevented appearance of catecholamine release. These data demonstrated that the development and persistence of acute duodenal pain depends on the activation of Ca(2+) ion flux leading to neurotransmitters release and modulation of membrane excitability. It seems that diltiazem given icv 10min prior to DD (as a source of acute visceral pain), inhibited specific receptors α(1) subunits of VGCCs in target tissues, prevent depolarization of cell membranes and release of neurotransmitters responsible for pain sensitivity in sheep. The observed antinociceptive action of VGCCs type-L blockers suggests that these channels play a crucial role in the modulation of acute visceral pain in sheep.

Centrally administered PD 140.548 N-methyl-D-glucamine prevents the autonomic responses to duodenal pain in sheep.

Cholecystokinin (CCK) released in the CNS inhibits the analgesic action of exogenous opioids and may antagonize analgesia resulting from the activation of an endogenous pain inhibitory system. The aim of this study was to analyse the central action of PD 140.548 N-methyl-D-glucamine--a peptide antagonist of a specific peripheral type CCK receptor--on animal behaviour, catecholamines (CA) and cortisol concentration, as well as clinical symptoms of visceral pain induced by duodenal distension (DD). A 5 min distension of the duodenum wall, using a 10 cm long balloon filled with 40 and/or 80 ml of water (DD 40 and/or DD 80) at animal body temperature, produced a significant increase in plasma CA and cortisol levels, an increase in the heart rate, hyperventilation and other clinical symptoms (inhibition of rumen motility, bleating, teeth grinding, prostration, urination, defecation) that may be related to pain, proportionally to the degree of intestinal distension. Intracerebroventricular administration of PD 140.548 at the dose of 1 or/and 2 mg in toto 10 min before applying DD 40 completely blocked the increase in blood plasma cortisol, epinephrine (E), norepinephrine (NE) and dopamine (DA) concentration. It is suggested that the central inhibitory action of CCK antagonist on the cortisol and catecholamine release produced by visceral pain is due to the inhibition of peripheral CCK1 type receptors in the central centrifugal descending pain facilitatory system in sheep perhaps via the hypothalamic-pituitary-adrenal axis.

Intracerebroventricular administration of PD 140.548 N-methyl-D-glucamine attenuates the release of cortisol and catecholamines induced by duodenal distension in the sheep.

The aim of this study was to determine the influence of mechanically induced duodenal distension (DD) and PD 140.548 N-methyl-D-glucamine (a specific peptide antagonist of a CCK1 receptor) premedication on mechanographical reticulo-ruminal activity, animal general behaviour, catecholamines (CA) and the blood plasma cortisol levels, as well as the clinical symptoms of visceral pain induced by DD in sheep. After 24 h fasting, 6 animals, Polish merino sheep were praeanaesthetised by i.m. injection of ketamine (20 mg x kg(-1) b.w.) and anaesthetised with i.v. infusion of pentobarbital (20 mg x kg(-1) b.w.) and a permanent stainless steel cannula (gate cannula) was inserted inside the lateral cerebral ventricle (controlled by cerebrospinal fluid efflux) 10 mm above the bregma and 5 mm laterally from the midline suture using stereotaxic method. Under the same general anaesthesia and analgesia a T-shaped silicon cannula, was inserted into the duodenum (12 cm from pylorus) and a second one was inserted into the dorsal sac of the rumen. During 7 consecutive days after surgery each animal was treated i.m. with procaine penicillin (300000 I.U..kg(-1) b.w.), dihydrostreptomycine (DHS, 10 microg x kg(-1) b.w.), prednisolone acetate 1.2 mg x kg(-1) b.w.) together and i.m. injection of ketamine (20 mg x kg(-1) b.w.), separetely. The influence of PD 140.548 N-methyl-D-glucamine on the unfavourable effects of duodenal distension using a 10 cm long balloon filled with 40 and 80 ml (DD40 and DD80) water at animal body temperature was investigated in this study. Five minutes DD40 and DD80 caused an immediate and compete inhibition of the reticulo-ruminal frequency, a significant increase in plasma CA and cortisol levels, an increase in the heart rate, hyperventilation and other symptoms of pain, proportionally to the degree of intestinal distension. Intracerebroventricular (i.c.v.) administration of PD 140.548 alone at a dose of 0.25, 0.5, 1 or 2 mg in toto did not significantly change the reticulo-ruminal motility, CA and cortisol concentrations, but 10 min after the i.c.v. infusion (or 10 min before DD) at a dose 1 and 2 mg in toto , it completely blocked the increase of blood plasma cortisol, epinephrine (E), norepinephrine (NE) and dopamine (DA) concentrations for 20 min. In the some time it prevented the reticulo-ruminal atony provocked by DD. It is concluded that PD 140.548 N-methyl-D-glucamine--an antagonist of the central CCK1 receptor can be an effective analgesic agent in duodenal pain. This action is due to the inhibition of peripheral CCK1 type receptor in the central descending nerve pathway, facilitating pain transmission in sheep perhaps in the hypothalamic-pituitary-adrenal axis.

[The effect of carbimazole on lactate dehydrogenase isoenzymes and thyroid hormone levels in sheep]. / Efekt karbimazolu na izoenzýmy laktátdehydrogenázy a koncentrácie tyreoideálnych hormónov u oviec.

The oxidative processes in the organism are activated by hormones of the thyroid gland. The pyruvate-lactate component catalyzed by lactate dehydrogenase presents one of the important oxidic-reductive systems in the animal organism of biochemical importance (EC. 1.1.1.27). In certain cases of the thyroid gland disturbances antithyroid drugs, such as derivatives of thiouracil, mercaptoimidazole and some others may be used for the treatment of men and animals (Marchant et al., 1979; Negwer, 1987). In the present study, the activity changes of lactate dehydrogenase isoenzymes in the blood plasma of young rams and ewe hoggets in experiments with carbimasole [carbimasolum(1-carbaethoxy-3-methyl-2-thioimidazolum) ] have been studied. The dose of carbimasole at the time of sampling (May, 1993) was 7O mg per animals and day. In May, no significant differences in T3 and T4 concentrations in the serum of experimental and control animals in males and females were found (Tab. 1). The T3 concentrations in the experimental group of young rams were 0.56 +/- 0.21 nmol/l (n = 3), in ewe hoggets 0.70 +/- 0.19 nmol/l (n = 6). The T4 concentrations in young rams were 39.15 +/- 24.15 nmol/l (n = 3), in ewe hoggets 48.6 +/- 15.3 nmol/l (n = 6). Out of lactate dehydrogenase isoenzymes, only LD4 exhibited significant differences (P < 0.02) in the blood plasma of ewe hoggets (Tab. I). In the course of these months, no clinical signs of hypothyrosis were observed in experimental animals.

[Lactate dehydrogenase isoenzymes in purebred sheep and rams]. / Izoenzýmy laktátdehydrogenázy u plemenných oviec a barancekov.

In farm animals the questions of clinical and mainly heritable health receive increased attention. In this work the activity of the polymorphous system of lactate dehydrogenase was observed in some pure- and crossbred ewes and rams under field conditions. The isoenzyme of lactate dehydrogenase were separated on 5.5% polyacrylamide gel as reported Dietz, Lubrano (1967). Age- and sex-related determinations of the isoenzyme spectrum of lactate dehydrogenase revealed increased LD3 activity in yearling ewes, and increased LD4 and LD5 activity in yearling rams (Tab. I). Significant differences of LD4 isoenzyme activity (P < 0.05) were observed between the Stavropol Merino and the Stavropol Merino x Merino x Corriedale crossbreds (Tabs II and III). In the blood plasma of Stavropol Merino rams the following quantities of LD isoenzymes were determined: LD1 = 48.0 +/- 10.6%, LD2 = 12.1 +/- 5.2%, LD3 = 25.9 +/- 7.02%, LD4 = 4.0 +/- 2.2% and LD5 = 10.0 +/- 3.5%. In the activity of some isoenzymes breed differences were recorded in 2-5-year-old ewes (Tabs IV and V). For LD1, significant differences (P < 0.01) were found between the Merino and Ascan Merino x Merino sheep breeds as well as between the Merino x Corriedale sheep and the crossbreds of Merino with a certain share of Lincoln. Differences in LD1 activity between Merino and Merino x Corriedale sheep as well as between the Ascan Merino and Merino crossbreds with a certain share of Lincoln were significant at the level of P < 0.02. For LD2, no significant differences were stated in the pure- and crossbred animals under examination.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparative study of the protective effects of 3 carboxylic acids on urea and ammonia toxicity in sheep]. / Porovnávacie stúdium protektívneho úcinku troch karboxylových kyselín na toxicitu cpavku a mocoviny pri ovciach.

Three carboxylic acids (acetic, propionic and citric) were compared as to their protective effect in controlling the toxic and lethal action of urea in sheep. It was derived from the metabolic and clinical studies that citric acid was the most effective of all the acids studied and can be used in the preventive treatment of sheep against the toxic lethal action of urea and ammonia. The mechanism of the action of citric acid is also discussed in relation with other findings.