Biomedical subjects

M Adamcová

Publications and source records attributed to M Adamcová.

At least 19 recordsLinked to original sources

PubMed2006

Early detection of anthracycline cardiotoxicity in a rabbit model: left ventricle filling pattern versus troponin T determination.

Anthracycline cardiotoxicity represents a serious risk of anticancer chemotherapy. The aim of the present pilot study was to compare the potential of both the left ventricular (LV) filling pattern evaluation and cardiac troponin T (cTnT) plasma levels determination for the early detection of daunorubicin-induced cardiotoxicity in rabbits. The echocardiographic measurements of transmitral LV inflow as well as cTnT determinations were performed weekly for 10 weeks in daunorubicin (3 mg/kg weekly) and control groups (n=5, each). Surprisingly, no significant changes in LV-filling pattern were observed through the study, most likely due to the xylazine-containing anesthesia, necessary for appropriate resolving of the E and A waves. In contrast to the echographic measurement, the dP/dt(min) index obtained invasively at the end of the study revealed a significant impairment in LV relaxation, which was further supported by observed disturbances in myocardial collagen content and calcium homeostasis. However, at the same time cTnT plasma levels were progressively rising in the daunorubicin-treated animals from the fifth week (0.024+/-0.008 microg/l) until the end of the experiment (0.186+/-0.055 microg/l). Therefore, in contrast to complicated non-invasive evaluation of diastolic function, cTnT is shown to be an early and sensitive marker of anthracycline-induced cardiotoxicity in the rabbit model.

Anesthetics↗

PubMed2005

Study of daunorubicin cardiotoxicity prevention with pyridoxal isonicotinoyl hydrazone in rabbits.

Risk of cardiotoxicity is the most serious drawback of the clinical usefulness of anthracycline antineoplastic antibiotics, which however, remain among the most powerful and widely employed anticancer drugs. In this study we have used daunorubicin-induced cardiomyopathy in rabbits as a model to investigate possible cardioprotective effects of pyridoxal isonicotinoyl hydrazone (PIH)-a principal representative of a novel group of aroylhydrazone iron chelators. Three groups of animals were used: a control group (n=11; i.v. saline), daunorubicin-treated animals (n=11; 3mg/kg, i.v.), and animals pretreated with PIH (n=9, 25 mg/kg, i.p.) 60 min before daunorubicin administration. All substances were administered once weekly for 10 weeks. Repeated administration of daunorubicin caused premature death in four animals and induced conspicuous histopathological changes in the myocardium, progressive and significant impairment of systolic heart function (a decrease in left ventricular dP/dt(max), ejection fraction, an increase in the pre-ejection period/left ventricular ejection time index), and a gradual increase in cardiac troponin T plasma concentrations. On the contrary, all the PIH-treated animals have survived all daunorubicin applications. Furthermore, in this group, the daunorubicin-induced cardiac changes were in most functional, biochemical as well as morphological parameters less pronounced than in the group receiving daunorubicin alone. Hence, PIH and other aroylhydrazones merit further investigation as potentially protective agents against anthracycline-induced cardiotoxicity.

Animals↗

PubMed2005

Safety and tolerability of repeated administration of pyridoxal 2-chlorobenzoyl hydrazone in rabbits.

Recently, pyridoxal 2-chlorobenzoyl hydrazone (o-108) has been identified as an effective iron chelator [Link et al., Blood 2003; 101: 4172-79]. Since chronic treatment would be necessary in its potential indications, in the present study, the safety and tolerability of this agent after repeated administration was determined. Three doses of o-108 (25, 50, 100 mg/kg, in 10% Cremophor EL) were administered intraperitoneally, once weekly, for 10 weeks to three groups (n=5 each) of Chinchilla male rabbits. The effects on biochemical, haematological and cardiovascular parameters were examined during the experiment; histopathological examination was performed at the end of the experiment. Results were compared with control (saline 2 mL/kg, n=11) and vehicle groups (10% Cremophor EL, 2 mL/kg, n=12). No premature deaths occurred; the well-being of animals was evidenced by their body weight gain, although lower gain was observed with the highest dose (100 mg/kg). Significant elevations of cardiac troponin T plasma concentrations were observed with the highest dose of o-108, but no abnormalities were found in the cardiovascular function and only minor and inconsistent changes in haematological and biochemical parameters were observed. Histopathological examinations of selected organs revealed only weak and reversible changes through all studied groups. Thus, the data from this study suggest that o-108 remains a promising drug from the standpoint of the possibility of its repeated administration and warrants further investigation.

Animals↗

PubMed2003

Troponins in children and neonates.

UNLABELLED: Cardiac troponin T and cardiac troponin I--the biochemical markers of myocardial injury--are characterized by high specificity and sensitivity in comparison with other markers used in the past. CONCLUSION: Troponins have been studied in a wide range of clinical settings. Some of them are unique to paediatric care, but many questions, mainly concerning laboratory limitations and data interpretation in paediatrics, are still open to debate.

Biomarkers↗

PubMed2003

Protein profiling in daunorubicin-induced cardiomyopathy.

The aim of this paper was to study the protein remodelling of the left ventricle following repeated administration of either daunorubicin (DNR) or DNR in combination with the cardioprotective agent dexrazoxane (DXZ). The experiment was carried out on three groups of Chinchilla male rabbits: 1. DNR (3 mg/kg i.v.), 2. DNR (3 mg/kg i.v.) + DXZ (60 mg/kg i.p.), and 3. the control group (saline 1 ml/kg i.v. in the same schedule). The drugs were given once weekly, max. 10 administrations. Protein fractions were isolated by stepwise extraction from the samples of the left ventricle. In the DNR-group, the concentrations of both, metabolic and contractile proteins were significantly reduced, while the amount of collagen was significantly higher in comparison with the control group. In the group treated with DNR and DXZ, the concentrations of individual protein fractions (except metabolic proteins) were comparable to those of the control group, which confirms a significant cardioprotective effect of DXZ. The changes of protein profiling corresponded to functional examination of both cardiac parameters (EF, dP/dt(max), PEP: LVET index) and histological examination. These data should be used in further studies dealing with evaluation of cardiotoxic and, possibly, cardioprotective effects of new drugs.

Animals↗

PubMed2002

Cardiac troponin T following repeated administration of pyridoxal isonicotinoyl hydrazone in rabbits.

Pyridoxal isonicotinoyl hydrazone (PIH) is a new tridentate Fe-chelating agent that should be very promising in many pathological states resulting from both an iron-overload and formation of free radicals. The aim of our study was to investigate the effect of PIH on the cardiovascular system focusing to the regulatory protein -- cardiac troponin T (cTnT). The study was carried out in two groups of Chinchilla male rabbits: 1) PIH (50 mg/kg dissolved in 10 % Cremophor i.p., once a week, 10 administrations, n=8) and 2) Cremophor (2 ml/kg i.p. in the same schedule, n=7). Plasma concentrations of cTnT (as a marker of myocardial damage) were measured using a commercial kit (Roche). cTnT was within the physiological range (i.e. < 0.1 microg/l) during the whole experiment in the Cremophor group. In the PIH group, the cTnT levels were not significantly increased when compared with the control group or with the initial values (except with those before the 5th administration). Furthermore, we analyzed the cytosolic and myofibrillar fraction of cTnT in the left ventricular myocardium. Using SDS-PAGE and Western blot we resolved three isoforms. The profiling of TnT did not differ significantly between the PIH-treated group and the Cremophor-treated group. Our data concerning cTnT support the opinion that the possible cardiotoxicity of PIH is very low.

Animals↗

PubMed2001

Evaluation of cardiac effects of the new antineoplastic drug --dimethoxybenfluron--in the rabbit.

Cardiotoxicity ranks among the most serious adverse effects of some cytostatics. The cardiac effects of repeated i.v. administration of a new antineoplastic agent, dimethoxybenfluron (once a week, 10 administrations), were investigated in rabbits with respect to cardiac function and the release of cardiac troponin T (cTnT). Different doses of dimethoxybenfluron were administered to two groups of animals (12 mg/kg; n = 7 and 24 mg/kg; n = 6) and compared with either a control group (saline 1 ml/kg; n = 6) or a group with experimentally induced cardiomyopathy (daunorubicin 50 mg/m2; n = 13). In daunorubicin-induced cardiomyopathy, cTnT levels in animals with premature deaths were significantly higher (0.31 +/-0.11 microg/l) in comparison with the surviving animals (0.04 +/- 0.03 microg/l). However, cardiac TnT levels after the administration of dimethoxybenfluron in both doses were within the physiological range (lower than 0.1 microg/l) during the whole experiment as it was in the control group. The lack of cardiotoxicity of this new antineoplastic drug was supported by the absence of alterations in PEP:LVET ratio, left ventricle dP/dtmax or histological heart examination as well as by the fact that no premature death of animals occurred following repeated administration of dimethoxybenfluron. It is possible to conclude that no signs of cardiotoxicity were observed following repeated i.v. administration of dimethoxybenfluron.

Animals↗

PubMed2001

[Myocardial regulatory proteins in children with congenital heart defects].

The purpose of this study was to compare the protein profiling of the regulatory proteins. The samples of myocardial tissue were obtained during surgical intervention from children (age 8.2 +/- 1.8 years) operated for different types of congenital heart diseases. The arterial oxygen saturation was 95.5 +/- 0.07% in normoxaemic patients (ventricular and atrial septal defects), resp. 76.9 +/- 2.1% in hypoxaemic patients (tetralogy of Fallot). The both cytosolic and myofibrillar fractions of cardiac troponin T (cTnT) were isolated by stepwise extraction (4) from the both right ventricular and right atrial musculature. The concentration of proteins was measured using Coomasie Plus Protein Reagent Kit (Pierce). After isolation, one-dimensional SDS polyacrylamide gel electrophoresis was carried out according to a modified version of the method of Laemmli (1970), using a 12% separating gel and a 4% stacking gel. In some cases after SDS-PAGE, proteins were electroblotted onto nitrocellulose membrane for immunoblotting and analysed using the JLT-12 monoclonal antibodies (Sigma Chemicals). The cytosolic pool of cTnT (measured by commercial kit Elecsys Troponin T STAT Immunoassay--Roche) represents about 12.5%, the myofibrillar pool of cTnT was about 87.5%; hypoxaemia did not affect this proportion.

Child↗

PubMed2001

[Plasma levels of troponin T in rabbits after administration of new antineoplastic agents (Oracin and Dimefluron) and daunorubicin].

Recently, cardiac troponin T (cTnT) has been shown to be a sensitive marker of anthracycline-induced cardiomyopathy. In our study, the cardiotoxicity of repeated i.v. administration (once a week, 10 administrations) of daunorubicin combined with new antineoplastic drugs (with mild side-effects) were followed in two groups of rabbits: 1) Dimefluron (3,9-dimethoxybenfluron hydrochloride-12 mg/kg) + daunorubicin (3 mg/kg), 2) Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H- indeno[1,2c]isoquinoline hydrochloride--10 mg/kg) + daunorubicin (3 mg/kg) and compared with the control group (saline--1 ml/kg) and the group with experimentally induced cardiomyopathy (daunorubicin--3 mg/kg). The concentration of cTnT in heparinized plasma samples was measured using commercial kit (Roche). In the control group, plasma levels of cTnT were always within the physiological range (i.e. lower than 0.1 microgram/l) during the experiment. During the development of daunorubicin-induced cardiomyopathy, after the eighth administration of drug, cTnT was significantly higher (0.31 +/- 0.11 microgram/l) in animals with premature deaths compared with the rest of the group (0.04 +/- 0.03 microgram/l). The animals with pathological values of cTnT were at higher risk of premature deaths (P = 0.0006). The combination of daunorubicin either with Oracin or with Dimefluron caused neither significant changes of cTnT levels nor significant deterioration of other followed-up parameters (especially, functional and toxicological parameters). Similarly to the daunorubicin group, the animals with pathological levels of cTnT after the eighth administration of antineoplastic drugs were at higher risk of premature death (P = 0.025). Our results show that the plasma concentration of cardiac troponin T could be a suitable predictive marker of cardiotoxicity of antineoplastic drugs.

Animals↗

PubMed2000

Cardiac troponin T in neonates after acute and long-term tocolysis.

The present study was designed to determine the levels of cardiac troponin T (cTnT) in cord blood of neonates exposed in utero to tocolytic therapy by beta-sympathomimetics. cTnT in 40 neonates after acute tocolysis (0.24 +/- 0.05 microg/l) was significantly higher (p < 0.05) in comparison with the control group (0.05 +/- 0.01 microg/l). The maximal values were reached in about the 3rd day of therapy (0.39 +/- 0.11 microg/l). cTnT in 30 neonates after long-term tocolysis was 0.12 +/- 0.03 microg/l. No correlation was found between cTnT and CK and its isoenzyme CK-MB or ECG. CK, unlike cTnT, significantly correlated with gestational age (r = 0.57, p < 0.05) and birth weight (r = 0.55, p < 0.05). It is possible to conclude that acute tocolytic therapy by beta-sympathomimetics increases the cTnT levels in cord blood and cardiac troponin T is more useful for the laboratory diagnosis of neonatal myocardial injury than CK-MB.

Adrenergic beta-Agonists↗

PubMed2000

Anthracycline-induced cardiotoxicity.

Anthracycline antibiotics are among the most effective and widely used antineoplastic drugs. Their usefulness is limited by a cumulative dose-related cardiotoxicity, whose precise mechanisms are not clear as yet. The principal role is possibly exerted by free oxygen radicals generated by "redox-cycling" of anthracycline molecule and/or by the formation of anthracycline-ferric ion complexes. The iron catalyzes the hydroxyl radical production via Haber-Weiss reaction. The selective toxicity of ANT against cardiomyocytes results from high accumulation of ANT in cardiac tissue, appreciable production of oxygen radicals by mitochondria and relatively poor antioxidant defense systems. Other additional mechanisms of the anthracycline cardiotoxicity have been proposed--calcium overload, histamine release and impairment in autonomic regulation of heart function. The currently used methods for an early identification of anthracycline cardiotoxicity comprise ECG measurement, biochemical markers, functional measurement and morphologic examination. Among a plenty of studied cardioprotective agents only dexrazoxane (ICRF-187) has been approved for clinical use. Its protective effect likely consists in intracellular chelating of iron. However, in high doses dexrazoxane itself may cause myelotoxicity. This fact encourages investigation of new cardioprotectants with lower toxicity. Orally active iron chelators and flavonoids attract more attention. Modification of dosage schedule and synthesis of new anthracycline analogues may represent alternative approaches to mitigate anthracycline cardiotoxicity while preserving antitumour activity.

Animals↗

PubMed2000

[Effects of new antineoplastic agents (dimethoxybenflurone and Oracin) on the cardiovascular system and other parameters in the rabbit in vivo].

Anthracycline derivatives belong among the most effective antineoplastic drugs but their therapeutic use is limited by their side effects--a dose-related cardiotoxicity. The influence of repeated i.v. administration (once weekly, max. 10 weeks) of new antineoplastic agents--dimethoxybenfluron (DMB) (3,9-dimethoxybenfluron hydrochloride, C23H24O4NCl, M.w. 413.9, Institute of Experimental Biopharmaceutics, Czech Academy of Sciences, Hradec Králové, Czech Republic; 12 or 24 mg base/kg) and Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H- indeno[1,2c]isoquinoline hydrochloride), C20H19N2O3Cl, M.w. 370.84, Research Institute for Pharmacy and Biochemistry, Prague, Czech Republic; 5 or 10 mg/kg) on cardiovascular, biochemical, haematological and histological parameters were studied in rabbits in vivo. Data obtained in these groups were compared with the group with experimentally induced cardiomyopathy (daunorubicin 50 mg/m2 i.v.) and with the control group (saline 1 ml/kg). Only mild and mostly no significant changes of the cardiovascular parameters (DMB 12 group: PEP:LVET ratio--0.408-0.502, LV dP/dtmax.--1337.0 kPa/s; DMB 24 group: PEP:LVET ratio--0.407-0.433, LV dP/dtmax.--1438.2 kPa/s), biochemical parameters (decrease in natrium, ALP and increase in glucose, GPX and GSH levels) and haematological parameters (increase in erythrocytes and decrease in leukocytes after the larger dose of the drug) were found in the dimethoxybenfluron groups. Repeated administration of the lower dose of Oracin induced only mild and mostly no significant changes of parameters (PEP:LVET ratio--0.393-0.475, LV dP/dtmax.--1092.4 kPa/s) in comparison with the control group. Though significant in some intervals, only a mild oscillation of the PEP:LVET ratio (0.368-0.446), decrease in LV dP/dtmax. (991.2 kPa/s) and--in comparison with control group--significantly higher blood pressure and lower heart rate were found after the higher dose of Oracin. In the most of haematological and biochemical parameters (with the exception of chlorides, protein and albumin levels) no significant changes were present. Histological examination of the heart revealed normal structure of the myocardium including minute changes of myocardium following administration of antineoplastic agents in all groups. Administration of new antineoplastic agents induced mostly mild changes of the followed-up parameters (PEP:LVET ratio, LV dP/dtmax., heart rate, levels of cardiac troponin T, survival of animals, haematological and biochemical parameters); the values of parameters were mostly significantly different from those in rabbits with daunorubicin-induced cardiomyopathy. On the basis of our results it is possible to conclude that the administration of dimethoxybenflurone and Oracin did not induce signs of cardiotoxicity in rabbits in vivo. This observation is considered to be important from the viewpoint of possible further clinical use of these new antineoplastic agents.

Animals↗

PubMed1999

Cardiac troponin T in pregnant women having intravenous tocolytic therapy.

We studied drug-induced cardiotoxic effects in 22 pregnant women having tocolysis with intravenous fenoterol and verapamil. Because CK-MB is released from the uterus and placenta, we used the determination of cardiac troponin T (cTnT) as it is one of the most sensitive and specific indicators of myocardial necrosis. Cardiac troponin T levels were within physiological range (0.08 +/- 0.01 microgram/l) in all healthy pregnant women tested between 32 and 36 weeks of gestation (control group). In the pregnant women having tocolysis cTnT levels started to increase slightly during the first day of treatment (0.10 +/- 0.03 microgram/l) and were significantly higher (p < 0.05) during the third day (0.35 +/- 0.14 microgram/l) of tocolytic therapy. The cTnT levels in cord blood (0.13 +/- 0.03 microgram/l) did not correspond with maternal cTnT concentrations.

Adult↗

PubMed1999

Cardiac troponin T as a marker of myocardial damage caused by antineoplastic drugs in rabbits.

Anthracycline derivatives are among the most effective antineoplastic drugs but their therapeutic use is limited by their adverse effects. The cardiac side-effects of antineoplastic drugs were investigated in rabbits in vivo from the viewpoint of release of cardiac troponin T (cTnT) measured by Elecsys Troponin T STAT immunoassay (Boehringer Mannheim, Germany). No increase in cTnT was found following administration of a single dose of daunorubicin (3 mg/kg i.v., n = 4). During development of daunorubicin-induced cardiomyopathy (daunorubicin 3 mg/kg i.v., once a week; maximum nine administrations, n = 7), the levels of cTnT were within the physiological range (i.e. cTnT <0.1 microg/l) at the beginning of the experiment and before and after the 5th administration, but the pathological values of cTnT after the 8th administration in 43% animals (0.22+/-0.08 microg/l) correlated with their premature death. In the control group, the levels of cTnT were always lower than 0.1 microg/l during the experiment. Following administration of a new antineoplastic drug - Oracin [6-[2-(2-hydroxyethyl) aminoethyl]-5,11-dioxo-5,6-dihydro-11H-indeno [1,2-c]-isoquinoline hydrochloride, 10 mg/kg i.v., once weekly, ten administrations, n = 7], there was no increase in cTnT levels. These findings correlated with the PEP: LVET index, histological examination and no animal succumbing to premature death. It is possible to conclude that cTnT is a useful marker for the prediction of experimentally induced anthracycline cardiomyopathy and for the evaluation of cardiotoxic (and, possibly, cardioprotective) effects of new drugs in rabbits.

Animals↗

PubMed1999

Isoforms of troponin in normal and diseased myocardium.

The regulatory protein troponin (Tn) located on actin filament consists of three subunits: TnT--binds troponin to tropomyosin, TnC--binds divalent calcium ions, and TnI--affects myosin-actin interactions. Tn subunits display several molecular and calcium binding variations. During ontogenetic development of cardiac and skeletal muscles the synthesis of multiple isoforms of Tn subunits was detected. Expression of Tn isoforms and the extent of phosphorylation of both TnT and TnI via protein kinase C or protein kinase A under different pathological situations (e.g. ischemia, congenital heart disease, heart failure) can affect the Ca2+-stimulated contraction function and the myofibrillar ATPase activity of the heart.

Amino Acid Sequence↗

PubMed1997

Clinical utility of cardiac troponin I and cardiac troponin T measurements.

The measurement of CK-MB remains the test of choice for confirmation or exclusion of AMI and probably will remain the test of choice for routine diagnosis in the near future. Nowadays determination of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) as a method relatively expensive and time-consuming should be restricted to clinical settings that really require their high specificity.

Biomarkers↗

PubMed1996

[Troponin T levels in cord blood after tocolysis with Bricanyl].

The present study was designed to evaluate the side-effects of preventive tocolysis by Bricanyl on the foetal myocardium using the new serological marker of myocardial damage-troponin T (TnT). The cardiac troponin T concentration was measured by means of commercial kits (Enzymun-Test System, Boehringer Mannheim, Germany) in the cord blood of 15 neonates. TnT serum concentration of neonates exposed in utero to Bricanyl was not significantly higher (mean 0.12 +/- 0.20 microgram/l) in comparison with the normal cardiac troponin T level but 4 of 15 neonates had an elevated TnT concentration (above 0.1 microgram/l). No correlation was found between TnT and CK or CK-MB.

Female↗

PubMed1995

Troponin T levels in the cord blood of healthy term neonates.

Troponin T (TnT) is recently being considered to be an important diagnostic marker of myocardial damage in adults, but this marker has not yet been used in neonates. The present study was designed to determine the normal level of cardiac TnT in the cord blood of healthy term neonates. Cardiac troponin T concentration in cord blood was measured in 15 healthy term neonates using commercial kit (Enzymun-Test System, Boehringer, Mannheim). TnT serum concentration was 0.05 +/- 0.04 micrograms/l in 10 of 15 babies whereas in the remaining 5 haemolysed samples its concentration was elevated (mean 0.19 +/- 0.07 micrograms/l). It is important to consider that incidental haemolysis of blood samples can mimic pathological elevation of TnT by interfering with the assay.

Age Factors↗