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Biomedical subjects

V Gersl

Publications and source records attributed to V Gersl.

At least 37 records · Page 2Linked to original sources
PubMed1996

Toxicities of O-alkyl S-(2-dialkylaminoethyl) methyl phosphonothiolates (V-compounds).

Toxicities expressed as LD50 values of O-alkyl S-(2-dialkylaminoethyl) methyl phosphonothiolates in different species and different routes of administration were determined. Rats were more sensitive to these compounds than mice, rabbits and guinea-pigs were more sensitive than mice and rats. The most sensitive to these compounds were dogs. LD50 values varied in a wide range, however, a decrease of toxicity was observed in the following rank: i.v., i.m., s.c., i.p., p.o. and p.c., respectively. Depending on the route of administration, LD50 values varied from 5 g/kg (i.m., dogs) through tens of microgram/kg for the most part of compounds and routes of administration to hundreds, rarely thousands of g/kg (some chemicals, p.c. administration).

Animals↗
PubMed1996

Acute haemodynamic effects of diltiazem and its distribution in relation to the myocardial infarction size.

The aim of this study was to contribute to an elucidation of some possible mechanisms underlying harmful haemodynamic effects of calcium antagonist diltiazem in large myocardial infarctions in rats. Acute haemodynamic effects of i.v. diltiazem in a single dose of 0.5 mg/kg and the distribution of diltiazem in selected tissues was measured four weeks after surgical imposition of myocardial infarction in urethane (1.2 g/kg i.p.) anaesthetized rats. Hypotensive effect of diltiazem was significantly (r = 0.624) attenuated with an increasing infarction size. A significant relationship (r = -0.697) between change in stroke index and infarction size was observed. In rats with small infarctions (< 32% of the left ventricle circumference) there was an absolute increase, and in rats with large infarctions (> 32%) there was an absolute decrease in the stroke index. From the results obtained it seems likely that dilatation of ventricles without appropriate hypertrophy accompanying large infarctions is one of the main determinants of manifestation of negative inotropic potential of diltiazem.

Animals↗
PubMed1995

Changes of some biochemical and hematological parameters following administration of daunorubicin in rabbits.

The effects of the repeated i.v. administration of daunorubicin (50 mg/m2, once weekly, max. 9 weeks) were investigated in rabbits in vivo to analyze biochemical and hematological changes. Noninvasive polygraphic records were used to evaluate the function of the heart. The administration of daunorubicin induced changes especially in levels of protein (decrease in total protein and albumin) and of some ions (decrease in calcium, magnesium and phosphorus) as well as in hematological parameters (decrease in erythrocytes, leukocytes and thrombocytes). The results obtained correlate with data on mechanisms of daunorubicin toxicity.

Animals↗
PubMed1994

Noninvasive polygraphic cardiac changes in daunorubicin-induced cardiomyopathy in rabbits.

The use of anthracycline antitumour agents (e.g., adriamycin and daunorubicin) is limited by their dose-related cardiotoxicity. The effects of the repeated i.v. administration of daunorubicin (50 mg/m2, once weekly, max. 11 weeks)) were investigated in rabbits in vivo from the point of view of the occurrence of cardiotoxicity and compared with a control group of animals. Noninvasive polygraphic records (in ketamine anaesthesia, 50 mg/kg i.m.) were used for the measurement of systolic time intervals (especially the PEP:LVET ratio) to evaluate the function of the heart. The administration of daunorubicin induced a significant, progressive increase in the PEP:LVET ratio (0.3775-0.9473) and in the PEP:LVETcorr. ratio, as well as a lengthening of the preejection period PEP and a shortening of the left ventricular ejection time LVET without significant changes in the electromechanical systole Q-2. The values in the daunorubicin group were mostly significantly different from the control group of animals. The results of polygraphic records reflect thus a presence of cardiac dysfunction on the basis of daunorubicin-induced cardiomyopathy. It is thus possible to conclude that the results obtained in the study confirm the adequacy of the rabbit model of daunorubicin-induced cardiomyopathy and the methods used in the study.

Animals↗
PubMed1993

Comparison of two substances with a possible alpha-adrenoceptor blocking and calcium channel blocking activity in rabbits in vivo under the paced and non-paced heart conditions. I. The effects on cardiac contractility (left ventricular dP/dtmax.).

The effects of substances--which in the isolated preparations possess calcium channel and alpha-adrenoceptor blocking activity--on cardiac contractility (dP/dtmax. of the blood pressure in the left ventricle) were evaluated. Substances VUFB 17951 (0.046 and 0.46 mg/kg) and VUFB 17959 (0.045 and 0.45 mg/kg) were administered intravenously in rabbits in vivo in pentobarbital anaesthesia under the conditions of the paced and non-paced heart rate. VUFB 17951 induced dose-dependent, immediately after the administration onsetting, progressive and significant decrease in dP/dtmax. (max. 50.5% in the paced and 51.4% in the non-paced heart). The effects of substance VUFB 17959 were less marked. On the basis of the results obtained in the present study it is possible to consider the participation of more mechanisms of the action (inc. calcium-channel antagonistic ones) related to negative inotropic effects of the substances. The absence of significant differences in the reaction of dP/dtmax. between the paced and non-paced heart conditions may then indicate a presence of a direct cardiodepressant action of substances VUFB 17951 and 17959.

Adrenergic alpha-Antagonists↗
PubMed1993

Comparison of two substances with a possible alpha-adrenoceptor blocking and calcium channel blocking activity in rabbits in vivo under the paced and non-paced heart conditions. II. The hemodynamic effects.

The effects of i. v. administration of substances VUFB 17951 (0.046 and 0.46 mg/kg) and VUFB 17959 (0.045 and 0.45 mg/kg) on hemodynamics of rabbits in vivo have been determined under the paced and non-paced heart conditions. The substances (N-arakyl derivatives of 2-aminomethyl-1, 4 benzodioxane) used in our study possessed calcium-channel and alpha-adrenoceptor blocking activity in the isolated preparations. The administration of VUFB 17951 (in the non-paced heart) induced a dose-dependent decrease in blood pressure (max. 62.2%), a mild slowing-down of the heart rate (max. 83.6%), a progressive and marked decrease in the values of the minute (max. 40.6%) and stroke (max. 41.4%) blood flow in the abdominal aorta. The administration of the lower dose of VUFB 17959 induced a mild increase in the blood pressure (max. 115.6%), after the higher dose a mild decrease in blood pressure was found (max. 83.1%). VUFB 17959 induced a mild slowing down of the cardiac frequency (max. 88.2%) and a progressive and marked decrease in minute (max. 45.3%) and stroke (max. 43.2%) blood flow in the abdominal aorta. In most intervals (during 120 min observation) no significant differences in the followed parameters were found between the conditions of the paced and non-paced hearts. The effects of VUFB 17951 were mostly more marked compared with those of VUFB 17959. From the point of view of a further study of the substances under examination the fact that premature death of animals occurred seems to be substantial. The premature death (followed up to the 240th min after the administration of substances) occurred in about 2/3 of animals and was accompanied with signs of an acute cardiac and hemodynamic failure. The observed hemodynamical changes may be manifestations of a presence of calcium-channel antagonistic effects of substances, possibly in combination with their alpha-adrenergic blocking activity. However, they do not exclude other possible mechanisms of their action or toxicity. On the basis of the results obtained in our study a need follows to investigate the effects of substances during a long period after their administration. A consideration should be paid to other routes of administration as well as a necessity of further detailed study concerning the pharmacodynamics and pharmacokinetics of substances.

Adrenergic alpha-Antagonists↗
PubMed1992

The effects of chelating agents on the left ventricular dP/dtmax. of the paced and non-paced heart in rabbits in vivo.

The effects of i. v. administration of Na2H2EDTA and a novel chelator MgNa2EDTA (both drugs in doses of 0.05 and 0.1 mg. kg-1) on the left ventricular dP/dtmax. of the paced and non-paced heart were investigated in rabbits in vivo. Both chelators induced a decrease in cardiac contractility which was, especially after the lower doses of the drugs, significantly less pronounced after MgNa2EDTA (max. 69.6% in the non-paced and 75.2% in the paced heart) in comparison with Na2H2EDTA (max. 51.3% in the non-paced and 52.9% in the paced heart). The decrease in dP/dtmax. was similar both under the paced and non-paced heart conditions after administration of both doses of the drugs. On the basis of the results obtained, it is possible to assume that the negative inotropic effects of the new chelator MgNa2EDTA may be lower in comparison with those of Na2H2EDTA and that cardiac pacing does not influence the inotropic response to the chelators in a negative manner. Premature deaths of a number of animals after the administration of both chelators show a necessity of further studies concerning especially cardiac intracellular ion concentrations.

Animals↗
PubMed1990

Trimepranol increases a negative inotropic effect of MgNa2EDTA in rabbits in vivo.

The effect of a pre-treatment with the chelator MgNa2EDTA (0.5 mg.kg-1 i.v.) on the influencing of cardiac contractility by Trimepranol (0.3 mg.kg-1 i.v.) was studied in rabbits in vivo under pentobarbital anaesthesia in the conditions of the spontaneous and paced heart rates and compared with the effects of the administration of the chelator MgNa2EDTA (0.5 mg.kg-1 i.v.) alone. The administration of the chelator alone induced especially commencing with the end of the first hour of observation, a progressive decrease in the left ventricular dP/dtmax. both in the paced heart (max. 67.0 % in the 170th min) and in the nonpaced heart conditions (max. 60.9 % in the 180th min). The administration of Trimepranol (120 min after the pre-treatment with the chelator) resulted in a pronounced increase in a negative inotropic effect (max. 43.1% in the paced and 35.3 % in the non-paced heart, always in the 130th min, i.e., 10 min after the administration of the beta-blocker), which was in most intervals significantly different from the values of dP/dtmax. after the administration of the chelator alone. A significant increase in the negative inotropic effect was manifested also by deaths of a number of experimental animals before the end of observation. On the basis of the results obtained, it is possible to assume that the combination of the administration of MgNa2EDTA with beta-blockers may especially result in an increase in the cardiodepressive action and in an occurrence of adverse effects on the hemodynamics of the organism.

Animals↗
PubMed1990

The effects of calcium channel blockers on the cardiovascular system of rabbits in vivo.

The effects of i.v. administration of the calcium channel blockers--verapamil (0.045 and 0.45 mg.kg-1) and Mepamil (2-methylphenyl-derivative of verapamil; 0.0445 and 0.445 mg.kg-1) on the cardiovascular system of rabbits in vivo under the paced and non-paced heart conditions were investigated. Verapamil induced--in the dose-dependent manner--a decrease in blood pressure (max. 65.2%), a significant decrease in dP/dtmax. (max. 46.0%), a bradycardia (max. 79.4%), a decrease in minute blood flow (max. 63.9 %) and stroke blood flow (max. 71.5%). The administration of Mepamil did not induce important changes in heart rate; changes in other parameters were--again in the dose-dependent manner--of a similar qualitative character as after verapamil administration, but they were quantitatively less expressed (especially marked in the effect on dP/dtmax, where the maximum decrease was only to 71.5%). The results show a less pronounced cardiodepressive activity of Mepamil compared to verapamil in rabbits.

Animals↗
PubMed1989

[Effect of metipranolol on the cardiovascular system of the rabbit in vivo during spontaneous and paced heart rhythm].

The effects of i.v. administration of metipranolol (Trimepranol, Biotika; 0.03; 0.15 and 0.3 mg.kg-1) and saline (1.0 ml.kg-1) on the cardiovascular system of rabbits in vivo have been determined under the conditions of the paced and non-paced heart. The administration of saline in the control group led to a mild decrease of dP/dtmax, minute blood flow through the abdominal aorta and slowing-down the cardiac frequency without significant changes in blood pressure in a. femoralis and stroke blood flow through the abdominal aorta. No practically important differences between the paced and non-paced conditions were found. The administration of Trimepranol led to a significant, dose dependent decrease in dP/dtmax, which was less expressed in the paced heart (in comparison with the non-paced heart) after the lowest dose of the drug; no such a difference was found after higher doses of Trimepranol. Reactions of blood pressure (no significant changes) and minute blood flow through the abdominal aorta (a mild decrease) to the administration of Trimepranol were similar both in the paced and in non-paced heart. A significant slowing-down of the spontaneous cardiac frequency after Trimepranol was dose-dependent and, in relation to this fact, a significant increase in stroke blood flow through the abdominal aorta was found. On the basis of the above-mentioned results, it is possible to conclude that the paced heart conditions do not unfavourably influence the effects of Trimepranol on the cardiovascular system of rabbits in vivo.

Animals↗
PubMed1981

The occurrence of gastrin-17 in the heart.

Radioimmunoassay revealed gastrin-like immunoreactivity in extracts of the heart muscle from cat, guinea pig, rabbit and hog. The immunoreactivity was unevenly distributed, the highest levels being observed in extracts from the atria of the cat heart: in the right atrium approximately 1,000 pg/g or 450 pmol/kg and in the left atrium approximately 4,400 pg/g or 2,000 pmol/kg. In extracts from the cat atria the gastrin-like immunoreactivity was identified as Gastrin-17. The preponderant localization of gastrin to the atria is suggested to be due to the distribution of gastrin containing vagal fibres and nerve terminals in that area, even if a possible localization to specific receptors, Purkinje fibres etc. cannot be excluded. A modulating action on the vagal influence on the heart, either on neurotransmission or on the receptor level, or a direct (perhaps trophic) effect on biochemical processes in the muscle are suggested as possible biological functions of the heart gastrin.

Animals↗