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Biomedical subjects

B Ostádal

Publications and source records attributed to B Ostádal.

At least 37 records · Page 2Linked to original sources

Effect of prenatal hypoxia on contractile performance and responsiveness to Ca2+ in the isolated perinatal rat heart.

The effect of prenatal hypoxic stress on the cardiac contractile function and responsiveness to calcium was studied in rats during the perinatal period. Pregnant rats were exposed to intermittent high altitude hypoxia from day 14 to 18 of pregnancy. Foetal hearts (prenatal day 22) and the hearts of offsprings (days 1, 4 and 7) were isolated and perfused in the Langendorff mode. Developed force of contraction (DF) as well as the rate of force development and fall were measured a) at the Ca2+ concentration of 1.25 mmol.l-1, b) under increasing Ca2+ concentration (from 0.6 to 10.0 mmol.l-1). Body and heart weights were significantly smaller in hypoxic than in matched control rats starting from day 1. The contractile performance of hypoxic hearts did not differ from controls. Their inotropic response to increasing Ca2+ concentrations was, however, significantly reduced on prenatal day 22 and postnatal day 7. Our results suggest that prenatal maternal hypoxia affects the cardiac inotropic responsiveness to Ca2+ even postnatally.

Animals↗

Protein profiling of the myocardium exposed to pressure overload from birth.

Aortic banding induced in 2-day-old (A2) and 6-day-old (A6) male rats increased the left ventricular (LV) weight after 60 days; right ventricular (RV) enlargement occurred in the A2 group only. The concentration of collagenous proteins in the LV was elevated in both experimental groups (more in the A2 rats) at the expenses of sarcoplasmic proteins. Aortic banding also affected the proportion of collagen types (lower collagen I, higher collagen III, V) and myosin light chains (higher LC1/LC2) in the LV. Similar changes of proteins in the RV were less pronounced.

Animals↗

Early postnatal development of contractile performance and responsiveness to Ca2+, verapamil and ryanodine in the isolated rat heart.

Contractile performance of the isolated perfused rat heart and its inotropic response to Ca2+, verapamil and ryanodine was studied in 1-, 2-, 4-, 7- and 12-day-old animals. Values of the developed force revealed two different phases: a slow decrease from day 1 to day 4 followed by a steep increase up to day 12. A similar biphasic time course was observed in the magnitude of the inotropic effect of Ca2+ (0.6-10.0 mmol.l-1): decrease from day 1 to day 4 followed by an increase up to day 7. The sensitivity to Ca2+ was, however, not changed. An analogous biphasic response was also observed during perfusion with the calcium antagonist verapamil (10(-9) to 3.3 x 10(-7) mol.l-1): the sensitivity to negative inotropic effect rose from day 1 to day 4 and then decreased at day 7 (values of IC50 were 170 +/- 61, 17 +/- 6 and 171 +/- 60 10(-9) mol.l-1 S.E.M. on day 1, 4 and 7, respectively). The contractile response to the inhibitor of calcium release from sarcoplasmic reticulum (SR)--ryanodine (10(-6) mol.l-1)--was surprisingly high already in 1-day-old animals (inhibition of contraction by more than 50%) indicating the presence of functionally active SR in the rat heart just after birth. Our data clearly shows that the early development of contractile function and inotropic responsiveness of the rat heart is not linear and changes dramatically during the first week of life.

Aging↗

Protein profiling of human atrial and ventricular musculature: the effect of normoxaemia and hypoxaemia in congenital heart diseases.

Samples of myocardial tissue were obtained during surgical intervention from children operated for different types of congenital heart disease (tetralogy of Fallot, ventricular and atrial septal defect). Sarcoplasmic, contractile and collagenous proteins were isolated by stepwise extraction from the both right ventricular and atrial musculature. It has been found that: a) the concentration of contractile proteins is significantly higher in the ventricles, b) the concentration of collagenous proteins is significantly higher in the atrium, c) the concentration of sarcoplasmic proteins was not different, d) in children with chronic hypoxia the above atrio-ventricular differences persisted. Moreover, the proportion of the soluble collagenous fraction in the atria was significantly increased.

Adolescent↗

Differences between atrial and ventricular energy-supplying enzymes in five mammalian species.

The purpose of this study was to compare a pattern of 7 enzymes of energy-supplying metabolism in atrial and ventricular myocardium in some mammalian species. Tissue samples of right and left atria and ventricles were obtained from adult male rats, guinea-pigs, rabbits, dogs and pigs. The results clearly demonstrate significant differences in enzyme activities between the atria and ventricles in all these species. In the atria the activity of enzymes connected with aerobic and lactate metabolism (hydroxyacyl-CoA-dehydrogenase, citrate synthase, malate dehydrogenase and lactate dehydrogenase) was markedly lower than in ventricles. On the other hand, in rats, dogs and pigs glucose phosphorylation capacity (hexokinase) was approximately the same in atrial tissue as in ventricles. Right-to-left metabolic differences were much less expressed; conspicuous was only the higher activity of hydroxyacyl-CoA-dehydrogenase in the left atria and ventricles of guinea-pigs and rabbits indicating higher fatty acid utilization capacity in the left heart.

Animals↗

Thyroid control of contractile function and calcium handling in neonatal rat heart.

Newborn rats were rendered hyperthyroid (daily subcutaneous injections of L-triiodothyronine, 10 micrograms 100 g-1 body weight) or hypothyroid (0.05% 6-n-propyl-2-thiouracil in drinking water to nursing mothers) during the first 3 weeks of postnatal life. Compared with the euthyroid group, hyperthyroidism resulted in: (1) cardiac enlargement with right ventricular preponderance, (2) increased cardiac contractile function, (3) increased Ca2+ uptake by the sarcoplasmic reticulum (SR), (4) decreased sensitivity to the negative inotropic effect of verapamil and (5) greater inhibition of contractile function by ryanodine. Hypothyroidism generally resulted in opposite changes. The data suggest that the development of the heart and its contractile function during early postnatal life depends on the plasma level of thyroid hormones. In particular, the relative contribution of the SR and sarcolemmal Ca2+ transport to the control of cardiac contractility seems to be markedly affected by altered thyroid states. The postnatal maturation of the SR function is accelerated in hyperthyroidism but retarded in hypothyroidism. Consequently, hyperthyroid hearts appear to be less dependent and hypothyroid ones more dependent on trans-sarcolemmal Ca2+ fluxes when compared with age-matched euthyroid animals.

Animals↗

Functional changes in the right and left ventricle during development of cardiac hypertrophy and after its regression.

OBJECTIVE: The aim was to determine left and right ventricular functional reserves and collagen concentration during the development of cardiac hypertrophy and after its regression. METHODS: Two experimental models of cardiac hypertrophy (chronic thyroxine or isoprenaline treatment of adult rats) were compared 24 h and five weeks after the agent was last given. Pressure changes in the left (right) ventricle before and after acute aortic (pulmonary artery) ligation were recorded in open chest anaesthetised animals. The difference in dP/dtmax after and before ligation was regarded as the functional reserve. The total collagen concentration was determined in both ventricles separately by means of hydroxyproline. RESULTS: Left and right ventricular weight increased by 20% and 30% respectively in the two models employed. In the thyroxine treated group, the functional reserve of the left ventricle rose very noticeably, whereas in the isoprenaline treated group it decreased. The right ventricular functional reserve did not differ from that in the controls in either of the two groups. The collagen concentration rose in the left ventricle in the isoprenaline group only. Five weeks after the last administration of the agent, cardiac mass and ventricular function did not differ from the control values in either of the models studied; the only exception was the incomplete regression of left ventricular hypertrophy and persistent structural and functional impairment of the left ventricle in the isoprenaline treated group. CONCLUSIONS: Our results indicate that hearts undergoing a comparable degree of experimental hypertrophy may have different functional and structural properties; significant differences were found between the right and left ventricular response. Regression of hypertrophy together with a reversal of ventricular function usually occurs unless the myocardium has received severe structural damage.

Animals↗

Effect of prostaglandin E2 on the ductus arteriosus in the newborn rat. An ultrastructural study.

A patent ductus arteriosus (DA) was maintained in newborn rats (Wistar strain) by administering prostaglandin E2 (PG E2) in doses of 15 micrograms.kg-1 at 30 min intervals up to 300 min after birth. In the control animals, the DA was functionally closed 300 min after birth. The lumen was blocked by clustered endothelial cells at various stages of degeneration. Elastic membranes of the media had disintegrated into irregular fragments and the smooth muscle cells were contracted. Cytoplasm excrescences formed on their surface as a result of contraction protruded as hernias into adjacent muscle cells and into endothelial cells. The smooth muscle cells degenerated. The administration of PG E2 inhibited contraction of the smooth muscle cells and so also the development of degenerative changes; 300 min after birth the DA was fully patent, the elastic membranes were structurally intact, regularly organized and continuous. The smooth muscle cells had the character of synthesizing cells with richly developed granular endoplasmic reticulum. The intima and its endothelial lining were likewise free from structural changes. The ultrastructural image of the wall of the DA correspondent to the state 10 min after birth, when the DA was fully patent. The administration of PG E2 did not induce any ultrastructural changes indicative of injury to the wall of the DA.

Animals↗

Effect of isoproterenol on 85Sr accumulation in the myocardium of the rat during postnatal ontogeny.

The aim of this study was to establish whether administration of toxic doses of isoproterenol (IPRO) increases the accumulation of strontium--a homologue element of calcium--in the rat heart during postnatal development. It has been shown that in 14-day-old animals 85Sr uptake was not increased; starting from the 30th day of postnatal life this parameter increases significantly up to adulthood.

Animals↗

85Sr uptake by the chick embryonic heart: effect of high doses of isoproterenol.

The aim of the present study was to establish whether intraamnial administration of toxic doses of isoproterenol to chick embryos increases cardiac accumulation of strontium, the homologue element of calcium. It has been shown that the ability of embryonic tissues (blood, heart, and liver) to accumulate 85Sr decreases significantly during ontogeny. Administration of isoproterenol to chick embryos did not elevate the concentration of 85Sr in the heart. It seems, therefore, that isoproterenol-induced developmental changes in the chick embryonic myocardium are not necessarily due to intracellular calcium (as measured by 85Sr) overload.

Animals↗

Right ventricular function in rats with hypoxic pulmonary hypertension.

The function of the hypertrophic right ventricle (RV) was studied in adult rats with hypoxic pulmonary hypertension induced by intermittent high-altitude (IHA) exposure. The isolated RV working heart preparation that was employed enabled us to estimate ventricular contractile and pump performance under controlled loading conditions. In rats exposed to IHA hypoxia the elevated RV systolic pressure and maximum rate of pressure development were observed at various levels of preload or afterload. The peak indices of mechanical performance were almost doubled in these animals when compared with the normoxic group, while the index of contractility remained unchanged. Maximum ventricular performance was found to be a linear function of the relative RV weight. No evidence of RV pump dysfunction was detected in rats exposed to IHA; moreover, the ability of the ventricle to maintain cardiac output against increased pulmonary resistance was markedly improved. The prevention of tricuspid regurgitation by using an artificial valve did not influence the functional curves and the peak ventricular performance. The regression of hypertrophy was accompanied by a reversal of ventricular function to control values, except for the persisting slight increase of peak RV pressure. It may be concluded that the increase of the RV mass in IHA-exposed rats serves to improve maximum ventricular performance, which aids in overcoming and elevated pulmonary resistance without disturbing the pump function.

Altitude Sickness↗

Different activities of energy metabolism enzymes in children's cardiac atria and ventricles.

Tissue samples from the right atrium and ventricle of the same heart were obtained during surgery on 45 children operated on for congenital heart disease (tetralogy of Fallot, ventricular septal defect). Significant enzyme activity differences were found between atrial and ventricular muscle. Aerobic metabolism enzymes (citrate synthase, malate dehydrogenase), with lactate metabolism (lactate dehydrogenase) and fatty acid oxidation (hydroxyacyl-SoA dehydrogenase) showed significantly higher activities in ventricular muscle tissue. In contrast, hexokinase, the enzyme responsible for glucose phosphorylation was significantly higher in the atria. Hence, the right ventricle can utilize and oxidize to the full all the main nutrients (fatty acids, glucose and lactate) while the right atrium utilizes primarily glucose. These atrio-ventricular differences are independent of the type of congenital heart disease and their existence can be presumed in healthy persons, too.

3-Hydroxyacyl CoA Dehydrogenases↗

[Adaptation of cardiac energy metabolism in children with congenital heart defects].

Metabolic differences of the cardiac muscle in children with normoxaemic and hypoxaemic congenital heart disease were analyzed by means of representative enzymes of the energy metabolism in 95 specimens in 80 children with congenital heart disease. Tissue specimens from the right atria and ventricles were obtained during surgical operations. It was revealed that the myocardial metabolism of patients with congenital heart disease was markedly influenced by hypoxaemia: the aerobic capacity was significantly reduced in the atria as well as in the ventricles. Changes in the atrial musculature were, however, more marked: in addition to citrate synthase - similarly as in the ventricles - in the atria also activities of enzymes associated with lactate metabolism (LDH) and with glycolysis (TPDH, GPDH) were reduced. Patients with an atrial septal defect had a significantly lower activity of the enzyme involved in the fatty acid breakdown (HOADH) than patients with a ventricular septal defect. The described new adaptive mechanism is of practical importance for the treatment of congenital heart disease and other conditions associated with prolonged hypoxaemia.

Adaptation, Physiological↗

[Differences in the activity of enzymes associated with energy metabolism in the heart atria and ventricles in children].

Tissue specimens from the right atrium and ventricle of the same heart were obtained during surgery in 45 children operated on account of congenital heart disease (tetralogy of Fallot and ventricular septal defect). Significant differences were found in the enzyme activities between the atrial and ventricular musculature. The activities of enzymes associated with aerobic metabolism (citrate synthase, malate dehydrogenase, with lactate metabolism) lactate dehydrogenase (and the fatty acid oxidation) hydroxyacyl-SoA-dehydrogenase) were significantly higher in the ventricular musculature. Hexokinase, the enzyme responsible for glucose phosphorylation was on the other hand, significantly higher in the atria. From this ensues that the right ventricle can utilize and oxidize to a full extent all main nutrients (fatty acids, glucose and lactate), while the right atrium utilizes above all glucose. These atrio-ventricular differences do not depend on the type of the congenital heart disease and it may be assumed that they exist also in healthy subjects.

Adolescent↗

[Energy-supplying metabolism of the volume overloaded and hypoxia stressed heart in children].

This study summarizes results obtained with regard to atrial and ventricular enzymes of energy supplying metabolism in children with different types of congenital heart disease. In all groups of patients - normoxemic as well as hypoxemic - significant atrio - ventricular differences were observed: the right ventricle is amply equipped for utilization and oxidation of all major nutrients, while the right atrium utilizes glucose predominantly. Myocardial metabolism in children with congenital heart disease was significantly influenced by hypoxemia: the capacity of aerobic enzymes in cyanotic patients was significantly lower, both in atrial and ventricular tissue, whereby the atrial changes were even more striking. No marked differences were found between atrial and ventricular septal defects in normoxemic patients; the only difference was a lower capacity of fatty acid catabolism in children with atrial septal defect.

Adolescent↗

The physiological closure of ductus arteriosus in the rat. An ultrastructural study.

The evolution of morphological changes in the wall of the ductus arteriosus during its physiological closure in newborn rats was examined by electron microscopy. The contraction of smooth muscle cells in the tunica media seems to be the primary mechanism which leads to the physiological closure of the ductus arteriosus. For this reason our attention was centred mainly on the morphology of the tunica media. No important changes in the ultrastructure of smooth muscle cells can be observed in the early phases of the closure. Most of them exhibit ultrastructural features of cells with enhanced synthetic activity during all phases of the closure. The permanent contraction of smooth muscle cells results in their morphological changes. The most striking is the herniation of smooth muscle cell cytoplasm into the endothelial and later into adjoining muscle cells. These changes together with signs of degeneration of the smooth muscle cells are already clearly discernible 120 min after birth. The elastic component of the tunica media exhibits surprisingly fast changes. As soon as 60 min after birth, the fragmentation of elastic membranes and their structural changes provided evidence about the degradation of elastic material. The matrix vesicles, probably derived from the lysosomal apparatus of the muscle cells, may play an essential role in this process.

Animals↗

Effect of hypoxaemia on enzymes supplying myocardial energy in children with congenital heart disease.

The differences in energy metabolism of the myocardium in children with congenital cardiac malformations producing hypoxaemia (arterial oxygen saturation 77 +/- 2%) or normoxaemia (arterial oxygen saturation 94 +/- 2%) were analysed by measuring the activity of the representative energy-supplying enzymes. Right atrial and ventricular tissue samples were obtained during surgical interventions. We demonstrated that myocardial metabolism was significantly influenced by hypoxaemia: the aerobic capacity of the energetic metabolism was reduced both in the atriums and ventricles. Atrial myocardium was more affected: in addition to citrate synthase, the activity of enzymes connected with lactate uptake and carbohydrate catabolism was also significantly decreased. These results demonstrate that the human heart is able to adapt to hypoxaemia by changing its energetic metabolism.

Adolescent↗

Comparison of cardiopulmonary response to intermittent high-altitude hypoxia in young and adult rats.

Haemodynamic and heart weight parameters were compared in male rats exposed to intermittent high-altitude (IHA) hypoxia (barochamber, 8 h/day, 5 days/week, total of 24 exposures stepwise up to 7,000 m) starting either from the 4th day or the 12th week of postnatal life. Systemic arterial pressure and heart rate increased in adult IHA acclimatized animals only. Marked chronic pulmonary hypertension and right ventricular enlargement were found in both age groups. Right ventricular weight increased linearly with a rise of pulmonary blood pressure in animals exposed to IHA from the 4th day of life (r = 0.72); no significant relation was found in adult rats (r = 0.16). The close correlation between both variables in young hypoxic rats may be due to the ability of the developing heart to respond to chronic hypoxia by both hypertrophy and hyperplasia of myocytes.

Adaptation, Physiological↗