Acta physiologica et pharmacologica Bulgarica最新文献

Septic shock in humans is usually characterized by severe changes in the left ventricular function, while little is known about the dysfunction of the right ventricle. Rabbits were injected intraventricularly with endotoxin from Escherichia coli at a dose of 2 mg/kg following catheterization of both heart ventricles with the purpose of measuring their pressure, and determining a number of contractility indices. In the animals in which endotoxin shock developed very rapidly and death occurred between the 60th and the 90th min (shock development is called fulminant), we established significant changes in the function of both ventricles. At the 20th min, the intraventricular pressure, EDP and P-(dP/dtmax) increased, indicating a tension lead of the right ventricle. At the same time, there was a decrease in plus dP/dtmax, minus dP/dtmax, (dP/dtmax)/P and [(dP/dt)/P]max, considered evidence for impaired contractility and relaxation of the right ventricular myocardium. During the subsequent observation periods, some of the contractility indices returned to normal. At the 20th min, a reduction of intraventricular pressure, P-(dP/dtmax), plus dP/dtmax, minus dP/dtmax and (dP/dt)P was registered in the left ventricle. Pronounced bradycardia was observed from the 30th min to the end of the experiments. Fulminant endotoxin shock in rabbits occurs as a result of the impaired function of the right ventricle attributed to tension leading and endotoxin-induced biventricular myocardial dysfunction.

The aim of the study was to label TAM with radioactive iodine and to follow its distribution in different organs of rats. T-actemodulin is a thymic hormone isolated from calf thymus by a new technology. TAM was labeled according to the method of Greenwood and Hunter. Two major peaks were observed on the gel chromatography: The first peak contained the labeled TAM; the second peak contained 125I which was not bound to the organic compound. Additional purification of the first peak was performed on a Sephadex G-75 column, and the eluate was designated as purified peak I. After a radioimmune testing it could be concluded that TAM was labeled successfully and the peak I contained 125I-TAM. Peak I, purified peak I and the peak II were applied to young male Wistar rats. The radioactivity of pancreas, kidney, spleen, adrenals, liver, thymus, bone marrow, testis and thyroid were measured after killing the animals 10 min, 60 min, and 24 h after the injections. The pharmacokinetic study showed that all organs, except for the thyroid have a higher affinity for labeled TAM than for the free 125I. Higher accumulation of labeled TAM was observed in the pancreas, kidney, adrenals and spleen. A specific uptake of labeled TAM in these organs can be suggested. Functional interrelations between thymus and pancreas, spleen, adrenals are discussed.

The effects of nimodipine (3 micrograms/kg/min) and flunarizine (60 micrograms/kg/min) on the autoregulation of the regional cerebral blood flow (rCBF) in the cortex and thalamus of 28 cats were studied. The animals were anaesthetized with ether and alfa-chloralose. The rCBF was registered by the hydrogen clearance method with locally generated hydrogen. MABP elevation was performed by i.v. angiotensin infusion (0.2 +/- g/min). The initial values of the rCBF in the cortex were 71.1 ml/100g/min, and in the thalamus - 49.1 ml/100g/min. The limits of rCBF autoregulation in the cortex were: the absolute limit of autoregulation (La) 139 +/- 11 mm Hg, and the relative limit of autoregulation (Lr), 28 +/- 6 mm Hg. In the thalamus these values were: La 160 +/- 11 mm Hg, and Lr 47 +/- 7 mm Hg. Nimodipine increased the rCBF in the cortex by 58 per cent, and in the thalamus, by 38 per cent as compared to the initial values (p < 0.01). The limits of rCBF autoregulation in the cortex changed to 88 +/- 8 mm Hg for the La, and to 10 +/- 4 mm Hg for the Lr (p < 0.01); and in the thalamus, to 92 +/- 8 mm Hg for the La, and to 19 +/- 5 mm Hg for the Lr (p < 0.01). Flunarizine increased the rCBF in the cortex by 28 per cent, and in the thalamus by 24 per cent, as compared to the initial values (p < 0.01). The rCBF autoregulation in both cerebral structures was not influenced by flunarizine.

Nine paranoic schizophrenia patients and nine controls participated in the study aimed at revealing differences in their ability to discover a pattern of auditory stimuli and to react to changes in environmental probability structure. Two kinds of auditory stimuli were used: high--1200 Hz (H) and low--800 Hz (L), both of 50 msec duration and 60 dB intensity. The experimental series were: series 1 (S1)--simple motor reaction to 50 L tones; series 2 (S2) and series 3 (S3) were identical--a cycle signal pattern (HHLHLL) of 102 tones. In S2 the instruction required choice motor reaction to L tone and in S3, also discovering the tone sequence and its verbal announcement. Patients discovered the stimulus pattern at the 28th and controls at the 30th signal. RT of patients in all series was longer than that of controls. Each of the factors "group" (controls/patients) and "experimental series" had a significant influence on RT. The possibility of interpreting these results as connected with an extrasensor mechanism dysfunction is discussed.

Three beta-adrenergic blocking agents propranolol (50 mg/kg), pindolol (5mg/kg) and atenolol (150mg/kg) were administered orally in rats for 21 days. The duration of hexobarbital (HB) sleeping time and the activities of some liver monooxygenases and synthetases were studied. The HB sleeping time was not changed. Propranolol and pindolol decreased the ethylmorfin-N-demethylase (EMND) and benzphetamine-N-demethylase (BND) activities. The three beta-adrenergic blocking agents did not change the activities of anilinehydroxylase (AH), ethoxycoumarine-O-demethylase (ECOD), and glutathione-S-transferase (G-S-T), the total content of cytochrome P-450, b5 and microsomal heme. They increased the activities of uridinediphosphoglucuronil transferase (UDPGT) and NADPH-cytochrome C reductase. The participation of different mechanisms of the effects of the three beta-adrenergic blocking agents on the activity of drug-metabolizing enzyme systems was discussed.

Erythro- and leukopoiesis in rats after 10-day treatment with piracetam (2 x 200 mg/kg b.w.) were studied. Increase of reticulocytes and of 59-iron incorporation in newly formed erythrocytes accompanied by an increase of the index of maturation of erythroblasts in bone marrow were found suggesting a piracetam-induced stimulation of erythropoiesis. Piracetam also increased the number of small lymphocytes and the maturation of granulocytes in bone marrow. It is supposed that piracetam exerting a positive effect on the metabolic processes of erythroid, myeloid and lymphoid precursors stimulates their proliferation and differentiation.

The effects of subchronic (30 days) drinking water exposure of rats to ZnSO4 or Pb(CH3COO)2 alone or in combination on the adrenergically-mediated contractile responses of isolated vas deferens were studied. The contractile effects of the alpha 1, alpha 2-adrenoceptor agonist noradrenaline (NA) and to the alpha 1-adrenoceptor agonist 1-phenylephrine (1-PhE) were decreased after zinc exposure, whereas after lead exposure or lead plus zinc exposure they were not changed. The contractile responses to field electrical stimulation (FES, 0.1 Hz, 1 msec, 80 V) were diminished in amplitude in all metal-treated preparations as compared to controls. The yohimbine-induced restoration of the clonidine inhibited contractions in response to FES was decreased in both lead- and zinc-treated preparations, the EC50 for yohimbine being 0.018 +/- 0.001 microM in control preparations, 0.073 +/- 0.019 microM in lead-treated preparations and 0.056 +/- 0.021 microM in zinc-treated preparations. The calcium-channel blocker verapamil was found to inhibit at low concentrations and to increase at higher concentrations the FES-induced contractile responses in preparations from zinc-exposed rats. The inhibitory effect of cumulatively applied nitrendipine on the FES-induced contractions was increased in both lead- and zinc-treated smooth muscles, but was not altered in the preparations from lead plus zinc-treated rats. Therefore, subchronic exposure to subtoxic doses of lead of zinc led to different changes in the adrenergically-mediated contractility of isolated vas deferens. The changes induced by zinc exposure were not observed after lead plus zinc exposure. All these findings might be of pharmacological, toxicological or clinical importance.

Chronic experiments were performed on dogs with Biller II gastrectomy followed by Roux-Y gastrojejunostomy. Gastric mucosa valve was made in the region of the gastrointestinal anastomosis in order to prevent the rapid gastric evacuation. Electrical activity of the gastric remnant, duodenum and jejunum was led off by six bipolar, silver, ball-shaped electrodes, implanted subserously on the muscle wall. Continuous bursting of groups of spike potentials with the slow gastric potentials in the usual rhythm (4.5-5 cpm) occurred during the 1st month after surgery. However, at the end of the 2nd month after surgery there were periods of tachygastria. The frequency of the gastric potentials was lower (7.52 +/- 1.37 cpm, n = 26) or higher (20.40 +/- 0.68 cpm, n = 30) compared to that of the jejunal slow waves (14.11 +/- 0.18 cpm, n = 50), i.e., it was different from the frequency of the jejunal slow waves.

The potency of Ondansetron (Zofran, Glaxo), a highly specific 5HT3 antagonist in preventing the very unfavorable complication during introducing anesthesia, i.e. a Bezold-Jarisch reflex-like reaction, was studied in a clinical trial. A total of 20 patients (12 males and 8 females aged 19-65 years) admitted for clinical surgical treatment participated in the trial. Zofran (8 mg in 500 ml Ringer solution) was injected intravenously one hour before intubation at a flow rate of 8 ml. min-1. Systolic and diastolic blood pressure, central venous pressure, breathing frequency and minute ventilation, pCO2 and pO2 in venous blood, electrocardiogram monitoring (ECG) and several common features such as spontaneous muscle activity, palpebral reflexes, skin and mucose surfaces were continuously observed. Visual, auscultatory and X-ray control of the lungs was effected. It was found that blockade of 5HT3 receptors prevented the appearance of Bezold-Jarisch reflex-like reaction. The drug could successfully be used in anesthesiological practice.