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J Sedivý

Publications and source records attributed to J Sedivý.

At least 19 recordsLinked to original sources
PubMed1999

The effect of the ultrashort beta-blocker esmolol on cardiac function recovery: an experimental study.

OBJECTIVE: This is an experimental work designed to determine, using the isolated perfused rat heart, the effect of the ultra-short acting beta-blocker esmolol on cardiac arrest and cardiac function recovery following esmolol withdrawal. METHODS: Changes in heart rate, coronary flow, diastolic pressure and the rate pressure product were evaluated on the isolated heart (Langendorff model). Esmolol concentrations of 125, 250, and 500 mg/l were tested. In another experiment using esmolol concentration of 250 mg/l, cardiac function recovery was assessed after 20- and 45-min arrest. RESULTS: While concentrations of 250 and 500 mg/l are necessary to produce cardiac arrest, the concentration of 500 mg/l does not result in full cardiac function recovery following esmolol withdrawal. After the highest concentration of esmolol, coronary flow, heart rate and the rate-pressure product recovered to about 80, 70 and 60% of the initial control values, respectively. When comparing 20- and 45-min arrests we found cardiac function normalization occurs later after 45-min arrest. CONCLUSION: The induction of cardiac arrest by esmolol is optimal at a concentration of 250 mg/l. A concentration of 125 mg/l does not result in cardiac arrest and produces bradycardia only, a concentration of 500 mg/l may be dangerous on account of persisting undesirable effects on the rat heart.

Adrenergic beta-Antagonists↗
PubMed1999

Nephrotoxicity of cyclosporin A in hereditary hypertriglyceridemic rats.

It has been suggested that cyclosporin A (CsA) nephrotoxicity can be reduced by the concomitant administration of omega-3 fatty acids or vitamin E. The present study was designed to establish whether the effect of the above substances can also be demonstrated in rats with hereditary hypertriglyceridemia (HTG) whose sensitivity to the nephrotoxic effect is greater than in control AVN rats. CsA administration at a dose of 10 mg/kg/day to HTG rats resulted in a significant rise (p<0.001) in serum levels of creatinine (from 66.0+/-7.6 to 108.4+/-11.6 micromol/l) and urea (from 8.3+/-0.7 to 22.3+/-18 mmol/l) which was not found in AVN rats. The baseline values of systolic blood pressure (SBP) were significantly higher in HTG rats. However, in both strains CsA administration was associated with a similar SBP increase which was not prevented by omega-3 fatty acids (EPAX) or vitamin E administration. Concomitant administration of CsA with EPAX at a dose of 600 mg/kg b.w./day in HTG rats prevented the rise in the serum levels of creatinine (65.4+/-14.7 micromol/l) and reduced the increase in the serum urea levels (11.9+/-7.6 mmol/l). Concomitant administration of CsA and vitamin E (at a dose of 25 mg/kg/day) also reduced the increase (p<0.05) in the serum levels of creatinine (70.7+/-14.3 micromol/l) and urea (9.8+/-3.4 mmol/l) compared to the effects elicited by the administration of CsA alone (p<0.05). Administration of CsA alone or in combination with EPAX or vitamin E did not have a marked effect on diuresis, proteinuria, urinary osmolality, urinary excretion of urea, creatinine and potassium. Under all experimental conditions, the rate of urinary excretion of sodium in HTG rats was significantly lower (p<0.01) than in AVN rats. The results obtained support the assumption that omega-3 fatty acids and vitamin E at the doses used reduce CsA nephrotoxicity in rats with hereditary hypertriglyceridemia whose sensitivity to the nephrotoxic effect of CsA is significantly higher than in AVN rats.

Animals↗
PubMed1994

[An experimental model of the effect of uremia on cyclosporin A availability].

BACKGROUND: The aim of the study was to determine whether or not uraemia has an effect on cyclosporine A intestinal resorption. METHODS AND RESULTS: Model experiments were conducted in rats to monitor the effect of acute uraemia (bilateral nephrectomy) on the kinetics of cyclosporine A. Using intragastric tube, Cyclosporine A was administered to one group of rats in the form of Consupren (Galena, Czech Republic) and to another group in the form of Sandimmune (Sandoz, Switzerland), at a dose of 10 mg/kg/24 h either case. Blood levels of cyclosporine A were determined using RIA and specific and non-specific antibodies (cyclosporine and its metabolites). Cyclosporine A kinetics in nephrectomized rats was compared with that in control rats and in rats undergoing sham nephrectomy. The blood levels of cyclosporine A were significantly lower, and the area under the curve (AUC) of blood cyclosporine A in nephrectomized rats significantly smaller than in control rats. No significant differences in the evaluated parameters after Consupren or Sandimmune were observed. CONCLUSIONS: Our findings support the hypothesis that uraemia decreases cyclosporine A availability. The results suggest that the changes in cyclosporine A kinetics in nephrectomized rats following Consupren and Sandimmune administration are of the same character.

Acute Disease↗
PubMed1993

[Cetirizine].

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Cetirizine↗
PubMed1990

[Preclinical modeling of the possible effect of acute uremia on drug resorption in the gastrointestinal tract].

The authors investigated in experiments on rats the course of serum concentrations of sulfisoxazole (S) and acetylsulfisoxazole (AS) in normal rats and in rats after bilateral nephrectomy after intra gastric administration of S. Serum concentrations of S and AS during the first three hours following administration did not differ significantly or were very close. During the subsequent hours the serum concentrations of S and AS in uraemic animals were significantly higher than in controls. The value of the absorption constant in the uraemic animals was on average higher and the absorption half-life lower than in controls. The assembled results suggest that in acute uraemia in rats the intestinal reabsorption of S and its metabolism in the liver are not reduced. The findings support the idea that the model used could be useful in preclinical research of drugs used in the treatment of acute uraemia.

Acute Disease↗
PubMed1990

Pharmacokinetics of roxithromycin in kidney grafted patients under cyclosporin A or azathioprine immunosuppression and in healthy volunteers.

The pharmacokinetics of roxithromycin was studied in 9 kidney grafted patients under cyclosporin A immunosuppression, in 10 transplanted patients with azathioprine, and in 6 healthy volunteers. The biological half-life (beta-phase) of roxithromycin in cyclosporin patients was 34.4 (+/- 12.25) h (mean +/- SD), in azathioprine patients 23.4 (+/- 8.18) h and in healthy volunteers 17.0 (+/- 3.8) h. The total elimination constant (k10) was 0.046 (+/- 0.014), 0.068 (+/- 0.019) and 0.084 (+/- 0.036) h, respectively. The total clearance was 0.79 (+/- 0.21), 1.45 (+/- 0.66) and 1.84 (+/- 0.56) l/h, respectively. The areas under the serum level curves were 407.6 (+/- 118.3), 251.0 (+/- 106.6) and 180.7 (+/- 73.2) mg.h/l, respectively. The differences in these parameters between healthy volunteers and cyclosporin patients were statistically significant, as well as those between cyclosporin and azathioprine patients. The differences between healthy volunteers and azathioprine patients were not statistically significant. The results cannot be interpreted unambiguously as an interaction between roxithromycin and cyclosporin; the effect of cyclosporin on the function of eliminating organs which causes the slowed-down elimination of roxithromycin could be taken into account.

Adult↗
PubMed1985

Physical activity of different intensities and the development of myocardial resistance to injury.

The conditions under which increased motor activity leads to raised resistance of the myocardium to injury were studied. Motor activity was raised by running on a treadmill; myocardial resistance was evaluated quantitatively from the extent of isoprenaline (ISO)-induced lesions. After 3 weeks of forced running (5 days a week), using an adequate daily dose, the cardiotoxic effect of ISO was reduced. Adequacy of the daily dose of exercise depended both on the distance run per day and on the rate at which the animals ran. If the training regimen was continued for further weeks, with the same daily dose of exercise, there was no significant increase in protection of the myocardium. In animals aged less than 3 months, myocardial resistance changed after higher daily doses of running than those needed in older animals. The cardioprotective effect of increased motor activity was not conditioned by increase in the weight of the myocardium.

Age Factors↗
PubMed1983

Influence of motor activity on the development of isoprenaline induced heart lesions.

The influence of spontaneous motor activity on the development of isoprenaline-induced heart lesions was studied in male rats of different ages. The extent of the lesions was evaluated quantitatively from raised accumulation of 203HgCl2 in the damaged tissue. Spontaneous activity in rotation cages rose with the animals, age and attained maximum values (6 562 m/d) at 3 months. The increase in motor activity in 10 months was very low and attained only 561 m/d. In all the experimental groups in which spontaneous activity was higher than this limit, a decrease in the cardiotoxic effect of isoprenaline was found after 2--3 weeks. The extent of the heart lesions in the individual animals was not proportional to the degree of their motor activity. The smallest myocardial damage was not found in animals which ran the most metres and vice versa. A marked decrease in the extent of the heart lesions occurred when the motor regimen was prolonged to 70 days. After a three days' break in the motor regimen, reduction of the cardiotoxic effect was still maintained. The extent of the heart lesions after 14 days' interruption corresponded to the values found in animals which were not allowed increased motor activity.

Aging↗
PubMed1983

Protective effect of isoprenaline pretreatment on the cardiotoxic effect of the same drug.

The study deals with the development of increased resistance of the rat myocardium to ISO-induced injury after pretreatment with the same drug. Reduced sensitivity already developed after the first dose of ISO, whose effect was only slightly increased by subsequent repeated doses. The development of myocardial injury was completed significantly sooner in pretreated animals, and this resulted in a decrease of the extent of the lesion. The reduction of cardiotoxic effect of ISO could be achieved by pretreatment with very small doses of ISO (0.01 mg/kg). An increase in the pretreatment dose augmented the protective effect and, in particular, prolonged the duration of reduced sensitivity. The effect of pretreatment in older animals, which responded to ISO by greater damage, was more pronounced.

Age Factors↗
PubMed1980

The effect of pregnancy and lactation on the development of experimental heart lesions.

The authors studed the effect of pregnancy and lactation on the resistance of myocardium against damage. Lesions of the heart were induced by isoprenaline in vivo. The extent of lesions was evaluated macroscopically and quantitatively according to the increased accumulation of 203HCl2 in the damaged heart tissue. In vitro, the damage of the isolated right ventricle was induced by anoxia and the resistance of heart tissue was evaluated according to the recovery of contractility. During the first week after delivery, the extent of isoprenaline-induced heart lesions was increased in nursing mothers as compared with virgin females of the same age. The mortality did not change significantly. Restitution of contractility of the right ventricle in vitro and anoxia was lower than in virgin females. In nursing mothers 35 days after delivery, the mortality and the extent of heart lesions induced by isoprenaline was significantly reduced as compared with virgin females. Furthermore, the resistance to anoxia of their isolated right ventricle was higher than that of virgin females. The reduced effect of isoprenaline lasted for several months after devlivery. The mortality and the extent of isoprenaline-induced heart lesions were not reduced significantly 35 days after delivery in non-lactating mothers, which were deprived of their young.

Animals↗
PubMed1980

Quantitative evaluation of the development of isoprenaline-induced heart lesions.

The development of heart lesions induced by isoprenaline (ISO) was quantitatively evaluated by 203Hg-Mercurascan (MSC) which was taken up and retained in the damaged cells. After the administration of ISO, the MSC uptake increased immediately at a constant rate, which was independent of the dose of ISO. A higher cardiotoxic effect of increased doses of ISO was caused by prolongation of the time during which the development of heart lesions proceeded. Later, when the damaged cells were subjected to cytolysis, MSC uptake decreased. The blockade of the effect of ISO by methypranol immediately stopped any further increase of MSC uptake. The accumulation of other labelled substances (Neohydrin, HgCl2, CaCl2) in the damaged myocardium was compared with the uptake of MSC. MSC and HgCl2 in particular are suitable for the observation of early changes; relatively less CaCl2 accumulated in the damaged hearts, but it can be used for the detection of more advanced lesions.

Animals↗
PubMedDate not supplied

Genetic differences in the resistance of rats to isoprenaline-induced heart lesions.

Two strains of rats were obtained by selective breeding: the IR strain, resistant to isoprenaline-induced myocardial lesions and the IS strain, sensitive to this damage. The IR rats grew more slowly, the weight of their adipose tissue was higher and the weight of m. soleus was less than that of the IS rats. The IR rats had a higher content of triglycerides in the serum and a lower isoprenaline-stimulated lipolytic activity of adipose tissue in vitro. The basal NEFA level in the serum and its rise after the administration of isoprenaline in vivo did not differ between the strains. The IR rats had a higher content of glycogen in the heart and in the muscle. After the administration of isoprenaline the glycogen content decreased more slowly in IR rats. The findings indicate a considerable importance of the glycogen stores in the heart for the resistance of myocardium to damage.

Adipose Tissue↗
PubMedDate not supplied

Studies on isoprenaline-induced myocardial lesions. 1. Quantitative evaluation by mercurascan uptake.

For the quantitative evaluation of myocardial damage induced by isoprenaline (ISO) a method based on the uptake of 203Hg-labelled Mercurascan (MSC) in the heart was used. The increase of myocardial uptake of MSC in ISO-treated rats over control values was very rapid and might be directly proportional to the number of damaged myocardial cells actually present in the heart. MSC-uptake method of myocardial damage evaluation was more sensitive and precise than other methods tested (macroscopic evaluation according to Rona, increase of heart weight). Different modifications of MSC-uptake test may be selected in relation to experimental conditions. MSC test is especially useful for evaluation of early myocardial lesions induced by small doses of ISO (0.01 mg/kg).

Animals↗