Biomedical subjects

V Pelouch

Publications and source records attributed to V Pelouch.

At least 19 recordsLinked to original sources

PubMed2004

Phospholipid composition of myocardium in children with normoxemic and hypoxemic congenital heart diseases.

Samples of myocardial tissue were obtained during cardiac surgery from children operated for different types of normoxemic and hypoxemic congenital heart diseases. The phospholipid composition was analyzed by thin layer chromatography. The concentration of total phospholipids (PL), phosphatidylcholine and phosphatidylethanolamine (PE) was found lower in atrial tissue of both normoxemic and hypoxemic groups in comparison with the ventricles. When comparing the difference between hypoxemic and normoxemic defects, hypoxemia was found to increase the concentration of total PL, PE and phosphatidylserine in ventricles and total PL and PE in the atria. The increased level of particular phospholipid species may represent adaptive mechanisms to hypoxemia in children with congenital heart diseases.

Child↗

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

Captopril fails to reverse hypertrophy of the left ventricle induced by aortic insufficiency in rabbits.

Angiotensin converting enzyme (ACE) inhibition has been reported to induce regression of hypertrophy in several models of hemodynamic pressure overload. The aim of the present study was to determine whether the ACE inhibitor captopril can reduce hypertrophy of the left ventricle induced by a chronic volume overload and modify collagen composition of the hypertrophied myocardium. Rabbits with four months lasting aortic insufficiency were divided into two groups: treated with captopril (20 mg/kg/day) for five weeks and treated with placebo. The respective control groups were represented by sham-operated animals. Aortic insufficiency induced a decrease of diastolic pressure, an increase of systolic and pulse pressure, hypertrophy of the left and right ventricle, and an increase of hydroxyproline content in the left ventricle without a change of hydroxyproline concentrations in either ventricle. Captopril treatment further enhanced pulse pressure by decreasing diastolic blood pressure. Hypertrophy of the left ventricle, hydroxyproline content and concentration in both ventricles were unaffected by captopril treatment. It is concluded that ACE inhibition did not reverse the left ventricular hypertrophy developed as a result of overload induced by aortic insufficiency. We suggest that mechanisms different from activation of the renin-angiotensin system may play a decisive role in the maintenance of hypertrophy in this particular model of volume hemodynamic overload.

Angiotensin-Converting Enzyme Inhibitors↗

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

[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↗

PubMed2000

Regression of chronic L -NAME-treatment-induced left ventricular hypertrophy: effect of captopril.

Long-term administration of N(G)-nitro- L -arginine methyl ester (L -NAME) induces development of NO-deficient hypertension and left ventricular (LV) hypertrophy. In this work, we examined the effect of spontaneous and captopril-induced recovery on LV hypertrophy and protein composition in rats with developed L -NAME-induced hypertension. Four groups of rats were investigated: control L -NAME 40 mg/kg/day for 4 weeks (L -NAME) L -NAME 40 mg/kg/day for 4 weeks followed by 3-week spontaneous recovery (L -NAME+R) L -NAME 40 mg/kg/day for 4 weeks followed by 3 weeks of captopril treatment at a dose of 100 mg/kg/day (L -NAME+C). LV hypertrophy in the L -NAME group was associated with an increase in content and concentration of left ventricular DNA and RNA, concentration of metabolic proteins (MP) and soluble collagenous proteins (SCP). Spontaneous recovery period reduced the hypertension, without regression of LV hypertrophy. Left ventricular DNA and RNA content were increased in the L -NAME+R group. In this group, concentrations of MP, contractile proteins (CP), and collagenous proteins did not differ from those in the L -NAME group. Captopril treatment caused total regression of hypertension and LV hypertrophy and decreased both content and concentration of DNA and RNA, as well as the contents of MP, CP and SCP v the L -NAME group. However, after captopril treatment, concentration of collagenous and non-collagenous protein fractions remained increased v control. We conclude that spontaneous regression of L -NAME-induced hypertension is not associated with regression of LV hypertrophy. LV hypertrophy was regressed only in captopril-treated animals.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Effect of angiotensin-converting enzyme inhibitors on non-diseased myocardium of experimental animals: potential clinical implications.

Angiotensin-converting enzyme (ACE) inhibitors protect the hearts of patients with different levels of cardiac disorder. The greatest benefit seems to be achieved in subjects with most severe heart failure. Moreover, ACE inhibition is protective also in patients without manifested heart failure but with severe systolic left ventricular dysfunction. Data are presented that ACE inhibitors can alter the composition of the myocardium also in control: healthy animals. In rats and rabbits with non-diseased heart, chronic ACE inhibition reduced fibrotic tissue concentration in the left ventricle. We speculate that if this were applied to humans, ACE inhibition may prove to be of potential benefit in subjects with normal systolic function but with a trend to left ventricular filling abnormalities caused by increased ventricular stiffness. In these patients reduction of myocardial fibrotic tissue might prevent deterioration of diastolic function.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Activity of cytochrome c oxidase in the right and left ventricular myocardium of male and female rats exposed to intermittent high altitude hypoxia.

The aim of the present study was to compare the capacity of the oxidative metabolism (total activity of cytochrome c oxidase, COX) in the right and left ventricular myocardium of adult rats exposed to intermittent high altitude (IHA) hypoxia simulated in a barochamber (5,000 m, 8 h/day, 5 days/wk, for a total of 32 exposures). In male and female rats, IHA induced significant increases of the right ventricular (RV) weight and protein content, whereas left ventricular (LV) weight and protein content remained unaffected. Consequently, the RV/LV ratio in both sexes markedly increased. Similarly, IHA induced an increase of the total activity of COX in RV in both sexes. The specific activities of COX in homogenate as well as in isolated mitochondria were not changed in IHA-exposed animals, which indicates that the increase of total activity of COX is proportional to the increase of total protein content and RV weight.

Altitude↗

PubMed1999

L-NAME-induced protein remodeling and fibrosis in the rat heart.

The aim of the present study was to determine whether NO deficiency itself or rather the elevation of systolic blood pressure is responsible for the protein and structural remodeling of the heart during hypertension induced by long-term treatment by nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Three groups of rats were investigated. The first group served as control. In the second group L-NAME was given in the dose of 20 mg/kg/day in the drinking water and in the third group L-NAME was given in the dose of 40 mg/kg/day during 4 weeks. While L-NAME treatment in both doses caused essentially the same increase in systolic blood pressure (SBP), NO synthase activity and cGMP concentration in the left ventricle decreased by 17% and 13%, respectively in the 20 mg/kg/day L-NAME group and by 69% and 27%, respectively in the 40 mg/kg/day L-NAME group. The protein profile of the left ventricle in both L-NAME groups was characterized by an increased concentration of metabolic proteins. Nevertheless, a significant increase in the concentration of pepsin-soluble collagenous proteins and the concentration of hydroxyproline in pepsin-insoluble collagenous proteins was found only in the group receiving 40 mg/kg/day L-NAME. The morphometric evaluation revealed a significant increase in myocardial fibrosis in both L-NAME groups. However, this was more pronounced in the 40 mg/kg/day L-NAME group. It is concluded that NO deficiency resulted in significant enhancement of fibrotic tissue growth in proportion to the administered L-NAME dose, while SBP was increased similarly in both L-NAME groups. Thus, NO deficiency rather than hemodynamic changes appears to be crucially involved in collagenous protein and fibrotic tissue changes of the left ventricle in hypertension induced by L-NAME.

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↗

PubMed1998

Thyroid control of sarcolemmal Na+/Ca2+ exchanger and SR Ca2+-ATPase in developing rat heart.

Thyroid hormone (TH) levels increase in the postnatal life and are essential for maturation of myocardial Ca2+ handling. During this time, the sarcolemmal (SL) Na+/Ca2+ exchanger (NCX) function decreases and the sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA2) function increases. We examined the effects of postnatal hypo- or hyperthyroidism on NCX and SERCA2 in rat hearts. Animals were rendered hypothyroid by 0.05% 6-n-propyl-2-thiouracil in drinking water given to nursing mothers from days 2 to 21 postpartum. Hyperthyroidism was induced by daily injections of 10 microg/100 g body weight of 3,3',5-triiodo-L-thyronine during this period. Ventricular steady-state mRNA and protein levels of NCX and SERCA2 were analyzed by Northern and Western blotting. These were compared with SL Na+ gradient-induced and SR oxalate-supported Ca2+ transports in isolated membranes. In hypothyroidism, NCX mRNA and protein were elevated by 66 and 80%, respectively, and SERCA2 mRNA and protein were reduced to 55 and 70%, respectively (P < 0.05 vs. euthyroid). Corresponding differences were observed in the respective Ca2+ transports. Conversely, reduced NCX (by 50%) and elevated SERCA2 (by 150%) activities were found in hyperthyroidism (P < 0.05). The levels of NCX and SERCA2 mRNA and protein were, however, unchanged in hyperthyroidism, indicating that functional changes are not due to altered NCX and SERCA2 expression. In this case, a decline in noninhibitory phosphorylated phospholamban is a likely explanation for the elevated SR Ca2+ transport. In conclusion, physiological TH levels appear to be essential for normal reciprocal changes in the expression and function of myocardial NCX and SERCA2 during postnatal development.

Animals↗

PubMed1998

Pressure overload induced in newborn rats: effects on left ventricular growth, morphology, and function.

Gradual pressure overload was induced by abdominal aortic constriction in male rats on postnatal d 6 (AC6) or 2 (AC2). At the age of 8 wk, the systemic blood pressure was measured, and the contractile performance of the left ventricle (LV) was assessed after acute ligation of the ascending aorta in open chest anesthetized animals. The LV free wall was used for the determination of collagen concentration and morphometric analysis of cardiac myocytes and capillaries. Aortic constriction resulted in LV hypertrophy, which was more pronounced in AC2 (by 71%) as compared with AC6 (by 34%) groups and correlated closely with the degree of pressure overload (r = 0.88 and 0.80, respectively). The right ventricular weight was increased by 13% in the AC2 group only. Contractile performance of the LV of aortic constricted rats was significantly higher before as well as after the acute load, but the average functional reserve was unchanged in both experimental groups. Although the maximum value of the rate of pressure development increased linearly with the degree of ventricular hypertrophy in the AC6 group (r = 0.82), a negative correlation was observed in the AC2 animals (r = -0.61). The density of myocytes was decreased, and the calculated average myocyte cross-sectional area was increased in aortic constricted rats, but the coronary capillary density and myocardial concentration of collagen remained constant. Thus, in spite of the larger cardiac growth response in the younger age group, the capillary proliferation and collagen formation were proportional to the ventricular hypertrophy. Therefore, the degrees of overload and hypertrophy do not seem to be limiting factors. Pressure overload induced in newborn rats can be a useful model for the study of mechanisms that control either the growth and differentiation of myocardium soon after birth, as well as the transition from compensated to decompensated hypertrophy at later stages.

Animals↗

PubMed1997

Protein remodelling of the heart in NO-deficient hypertension: the effect of captopril.

Long-term administration of NG-nitro-L-arginine methyl ester (L-NAME) induces development of NO-deficient hypertension. The aim of the present study was to determine whether treatment with the angiotensin-converting enzyme (ACE) inhibitor captopril can prevent hypertension, left ventricular (LV) hypertrophy, changes in nucleic acid concentration, protein synthesis and protein profile of the left ventricle. Four groups of rats were investigated: control, L-NAME 40 mg/kg/day, captopril 100 mg/kg/day, L-NAME 40 mg/kg/day along with captopril 100 mg/kg/day. NO-synthase activity in the left ventricle was found to be decreased by 69% in the L-NAME group. Captopril did not influence this inhibition of NO-synthase activity. However, it completely prevented hypertension and left ventricular hypertrophy development. The increase in left ventricular RNA and DNA concentration and -14C-leucine incorporation observed in the L-NAME group was completely prevented by simultaneous captopril treatment. The protein profile of the left ventricle in the L-NAME group was characterized by higher concentration of metabolic proteins (MP), soluble collagenous proteins (SCP) and of hydroxyproline in insoluble collagenous proteins (ICP). The concentration of hydroxyproline in ICP was significantly decreased by simultaneous captopril treatment. We conclude that captopril prevented the development of hypertension, left ventricular hypertrophy, increase in nucleic acid concentration and diminished collagen concentration by mechanisms different from affecting NO-synthase activity.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Effect of the preweaning nutritional state on the cardiac protein profile and functional performance of the rat heart.

The aim of the study was to find out whether the changes in nutritional status induced by different litter size during early postnatal development can influence quantitative and qualitative protein remodeling and contractile performance of the myocardium. Male Wistar rats born at the same day were pooled together at 2 days postbirth and assigned by random selection to dams in groups of 4, 8 or 16 rats/litter. The animals were investigated at the age of 4 and 16 weeks. The results revealed that the early postnatal nutritional modification altered weight parameters: whereas lower heart weight persisted in slow-growing rats until 16 weeks, higher body weight of fast-growing rats returned to the control level at the age of 16 weeks. Altered nutritional status influenced also protein remodeling of the myocardium: the concentration of all noncollagenous proteins (fractions of metabolic and contractile proteins) significantly increased in slow-growing rats, on the other hand, the concentration of collagenous proteins (pepsin-soluble and -insoluble fractions) was higher in fast-growing animals. The changes were, however, only transitional: three months after the end of the weaning period most protein changes returned to the control level. However, higher concentration of total blood lipids and triglycerides in fast-growing rats persisted until adulthood. Nutritional changes had, however, only minor effect on ventricular performance. No differences among groups were observed in basal values of the left ventricular pressure, while the maximum pressure attained after an acute ventricular loading and the contractile reserve were significantly decreased in slow-growing 4 week old rats. The functional consequence of altered nutritional status during weaning was only transitional, in agreement with the transient character of most structural and biochemical markers of myocardial remodeling.

Animal Nutritional Physiological Phenomena↗

PubMed1997

Regression of chronic hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and fibrosis: effect of enalapril.

Chronic hypoxia induces pulmonary hypertension and right ventricular hypertrophy. These changes are completely reversible, except for persistent myocardial fibrosis. The aim of the present study was to determine whether treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can reduce the ventricular collagen content in animals recovering from chronic hypoxia. Adult male Wistar rats were exposed to intermittent high-altitude hypoxia simulated in a barochamber (7000 m, 8 hr/day, 5 days a week, 24 exposures), then transferred to normoxia and divided into two groups: (a) treated with enalapril (0.1 g/kg/day for 60 days) and (b) without treatment. The corresponding control groups were kept under normoxic conditions. Enalapril significantly decreased the heart rate, systemic arterial pressure, and absolute left and right ventricular weights in both hypoxic and control rats; on the other hand, the pulmonary blood pressure was unchanged. The content and concentration of collagen was reduced in both ventricles of enalapril-treated hypoxic and control animals by 10-26% compared with the corresponding untreated groups. These data suggest that the partial regression of cardiac fibrosis due to enalapril may be independent of the pressure load.

Altitude Sickness↗

PubMed1996

Phospholipid composition in the rat heart exposed to pressure overload from birth.

A pressure overload was induced in 2-day-old male rats by abdominal aortic constriction, and the phospholipid composition of the left ventricle (LV) and the right ventricle (RV) were determined. Sixty days after the surgery, body weights was lower and LV weight were higher in aorta-constricted (AC) rats in comparison with shamoperated animals. Increased ventricular/body weight ratios indicated a significant degree of hypertrophy of LV and smaller hypertrophy of RV. The concentrations of total phospholipids (PL), choline phosphoglycerides (PC), ethanolamine phosphoglycerides (PE), diphosphatidylglycerol (DPG) and phosphatidylinositol (PI) were decreased in both ventricles of AC rats. The concentrations of sphingomyelin (SM) and plasmalogen PE (PLPE) increased in LV only. The changes in phospholipid composition in the developing pressure-overloaded myocardium may contribute to altered membrane functions connected with heart hypertrophy.

Animals↗

PubMed1996

The inhibition of angiotensin converting enzyme attenuates the effects of chronic hypoxia on pulmonary blood vessels in the rat.

The effect of chronic administration of angiotensin converting enzyme inhibitor on the development of hypoxic pulmonary hypertension was studied in rats. Male Wistar rats were-exposed for 3 weeks to isobaric hypoxia (10% O2) and treated with 10 mg/kg b.w. of Ramipril daily. The haemodynamic properties of the pulmonary vasculature were then measured in isolated blood-perfused lung preparation. Ramipril administration during the sojourn in hypoxia resulted in lower baseline perfusion pressure and lower slope of perfusion pressure-flow relationship compared to non-treated hypoxic rats. Partitioning of the distribution of pulmonary vascular resistance across the vascular bed by the occlusion technique showed that it was mainly due to a decrease of arterial and venous vascular resistances to blood flow. It is suggested that Ramipril attenuates the process of morphological reconstruction of pulmonary vasculature by chronic hypoxia rather than the level of vascular smooth muscle tone.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Ontogenetic differences in cardiopulmonary adaptation to chronic hypoxia.

Cardiopulmonary adaptation to chronic hypoxia was compared in rats exposed to simulated high altitude (barochamber, 8 h per day, 5 days a week, stepwise up to 7000 m, a total of 24 exposures) either from the 4th day or the 12th week of postnatal life. Pulmonary hypertension and right ventricular (RV) enlargement were comparable in both age groups. Whereas in young hypoxic animals the individual values of RV weight increased linearly with a rise of RV pressure (r = 0.72), no significant correlation was found in adult rats. Chronic hypoxia increased the concentration of cardiac collagenous proteins; this effect was more pronounced in adult animals. On the other hand, the collagen VIII ratio was markedly lower in young rats suggesting increased synthesis of collagen III in this age group. A protective effect of adaptation, i.e. increased cardiac resistance to acute hypoxic injury, was similar in both age groups and persisted even 4 months after removal of animals from the hypoxic atmosphere.

Adaptation, Physiological↗