The concentrations of immunoreactive cortisol were monitored over 24 hours in the serum of a total of 23 dogs. The dogs were divided into three groups: (a) control group with no exercise, (b) experimental group, (c) working dogs. Blood was collected from each dog at the intervals of 90-180 min. The cortisol concentrations in different time periods were mutually compared using the Kruskal-Wallis test for the analysis of variance. Circadian pattern was found in the study. Cortisol concentrations found between 10.00 and 13.00 (46.5 ± 17.0 nmol/l) were significantly higher (P < 0.05) than those found between 19.00 and 22.00 (38.9 ± 16.0 nmol/l). The results differed within individual groups. Diurnal rhythms were confirmed in control group but not found in experimental group and in working dogs. In experimental group, other significant (P < 0.05) differences were also found between various time intervals compared to the total pattern but no diurnal rhythm was established. In working dogs no significant differences (P < 0.05) were found between cortisol concentrations in different time intervals. The results suggest that cortisol concentrations in the dog are subject to considerable changes during the day. Depending on the characteristics of day and night activities a diurnal rhythm can be found in some dogs.

No abstract

The aim of this study was in vivo testing of the action of three newly synthesized potential ultrashort acting beta-blockers on the heart rate in the laboratory rat. The tested substance 44Bu was administered to animals with induced tachycardia, in the form of an intravenous bolus in general anaesthesia.Doses at concentrations of 1.5 mg⋅kg -1 , 2.5 mg⋅kg -1 , and 3.5 mg⋅kg -1 of body mass were tested and the efficacy was compared with placebo. For the heart rate monitoring a computer electrocardiograph was used. Significant (p < 0.05) heart rate decrease was recorded for all three tested doses, minimally up to the 14 th minute following the intravenous administration.Bradycardic effect of the compound 44Bu was compared with the action of esmolol under the same experimental conditions. The effects of the compound 44Bu and esmolol were not different in the onset, but in the depth of the heart rate decrease, above all at higher concentrations. It was experimentally verified, that the compound 44Bu has the properties of an ultrashort acting beta adrenergic receptor blocker.Pharmacology, ester-functional group, bradycardic effect, heart rate, rats

The anti-arrhythmic effect was tested on the model of aconitine-induced arrhythmia. The experiment was performed in vivo with 31 male Wistar laboratory rats. Group A was first administered aconitine and, after the onset of the first sinus rhythm disorders, the 44Bu compound was administered. Group B was first administered the 44Bu compound and only after that the aconitine. The control group was administered aconitine and saline as a replacement of the tested compound. In group A, there was a decrease in the ventricular fibrillation occurrence from 100 % to 8 % (p < 0.001) after the administration of the 44Bu compound. In the B group, the onsets of all monitored arrhythmia types were delayed by an average of 15.6 min. Ventricular rhythm occurrence was decreased from 100 to 20 %, as well as ventricular fibrillations, from 100 to 0 % (p < 0.001).

, J. Neãas: Ultrashort Bradycardic Effect of Newly Synthesized Compounds. Acta Vet. Brno 2006, 75: 183-196. Changes in the heart rate induced by four different doses of two newly synthesized potential ultrashort-action antagonists of beta adrenergic receptors were tested in 90 male laboratory Wistar rats. The isoprenaline-induced tachycardia model was used. Their effects were compared with those of esmolol. In the second part of the study, approximate electro-physiological measurements were made in vitro to assess the influence of the compounds tested on ion membrane currents in isolated ventricular cardiomyocytes. Both compounds demonstrated significant bradycardic effects in all concentrations tested compared with the control group, but they differed in the time of the onset of their action. Both newly synthesized compounds induced blockade of the fast sodium current (I Na ) and potassium currents (I to, I K1, I K,end ). Experimental pharmacology, rats, heart rate, ester-functional group, bradycardic effect, membrane currents, esmololAlthough attempts at using beta sympatolytic antagonists (beta blockers, beta adrenolytics, beta adrenergic receptors) have been made in many areas of medicine, they have gained a particularly important position in the treatment of cardiovascular diseases. They are indicated for the treatment of myocardial infarction, hypertension, arrhythmias and hyperthrophic cardiomyopathy (Frishman et al. 1984;McDevitt 1986;Hampton 1994). Beta blockers, however, have also a number of side effects, e.g., bradycardia, hypotension, and they may have an aggravating effect on the heart failure, or rather, bronchospasm, peripheral vasoconstriction, fatigue, insomnia and depression. In order to avoid prolonged action, beta blocking agents with assumed ultra-short-acting period have been developed. Their pharmacological effects last only several minutes, and their administration as intravenous infusions in indicated patients in critical care situations is much safer than the use of longeracting beta-adrenergic blocking agents (Reilly et al. 1985; Gray 1988).Ultra-short-acting beta blocking agents still form only a small fraction of a large group of beta-adrenolytics. At present, two ultra-short-acting beta blockers have been registered: esmolol ( Brevibloc ® inj.) (Gorczynski 1985) and landiolol (Onoact ® inj.) (Barton et al. 1986). A third one, flestolol (Atarashi et al. 2000), is now being clinically tested. What they all have in common is a short elimination half-life achieved by the insertion of an ester group in the side chain on the aromatic core. This group is very rapidly hydrolyzed by plasma cholinesterases or by esterases present in the cytosole or erythrocyte membranes. With compounds of this type, gradual beta-blockade titration is possible and their clinical effects rapidly subside with the facultative termination of the therapy (Murthy et al. 1988). In the ACTA VET. BRNO 2006, 75: 183-196