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Biomedical subjects

B Ostádal

Publications and source records attributed to B Ostádal.

At least 55 records · Page 3Linked to original sources

The effect of chronic hypoxia on the developing cardiopulmonary system.

The effect of chronic hypoxia (barochamber, 8 h per day, 5 days a week, stepwise up to 7000 m) on some cardiac functional and metabolic parameters was compared in rats acclimatized either from the 4th day or the 12th week of postnatal life. Pulmonary hypertension and right ventricular enlargement were found in both age group. Whereas in young hypoxic animals the weight of the right ventricle increased linearly with the right ventricular pressure, in adult high altitude exposed rats this relation could not be proved. High altitude induced significant increase of concentration of collagenous proteins: in adult animals increased collagen III only, in young also collagen I. The changes of the energy metabolism were similar in both age groups: activity of enzymes of the lactate metabolism and glucose phosphorylation increased; on the other hand, catabolism of fatty acids decreased. Chronic hypoxemia significantly influenced also the myocardial metabolism in children with congenital heart disease; the aerobic capacity was decreased both in the atrial and ventricular tissue; atrial changes were even more pronounced. The type of changes was, however, different from the rat heart.

Acclimatization↗

Intermittent high altitude--induced changes in energy metabolism in the rat myocardium and their reversibility.

Selected enzyme activities of energy metabolism were studied in the myocardium of laboratory rats exposed to intermittent altitude hypoxia (IAH, 4-8 h daily, 5 days a week, in a hypobaric chamber, stepwise up to 7,000 m). No significant differences were found between the right and the left ventricle in the control animals. Glucose-utilizing capacity (HK) and capacity for the synthesis and degradation of lactate (LDH) increased significantly in both ventricles during acclimatization. The other enzyme activities associated with anaerobic glycolysis (TPDH, GPDH) and those linked up in aerobic metabolism (MDH, CS) did not change significantly. On the other hand, the ability to break down fatty acids (HOADH) decreased significantly. All the above changes in the enzyme profile were found after only 24 4-h exposures, in both the hypertrophic right ventricle and the unenlarged left ventricle. When the length of daily exposure was raised from 4 to 8 h, the above changes were not intensified and 45 days after the last exposure to IAH, none of the given activity values differed from those estimated in the corresponding control animals.

3-Hydroxyacyl CoA Dehydrogenases↗

Effect of the administration of prostaglandins (PGE2) in the early postnatal period on closure of the ductus arteriosus in the laboratory rat.

Maintenance of a patent ductus arteriosus by means of prostaglandins enables the surgical correction of a congenital heart defect in infants to be postponed until a phase of development when the operation hazards are smaller. We investigated the pathophysiological consequences of this therapeutic measure in an experimental model in which E2 prostaglandin was administered to newborn laboratory rats. It was found that, physiologically, the ductus arteriosus (DA) closed progressively within 180 min after birth. The repeated administration of PGE2 (subcutaneously, 15 micrograms.kg-1 every 30 min from the 5th min after birth) blocked closure of the DA, which was still fully patent 300 min after birth. Histological tests showed no significant differences in the structure of the tunica media of the physiologically patent and the PGE2-treated DA. The results show that PGE2 also inhibit physiological closure of the DA in newborn rats. Long-term study of this pathophysiological process is at present impeded by the need for the continuous administration of prostaglandins.

Animals↗

Microcomputer analysis of the intraventricular pressure curve of the isolated rat heart.

The authors evolved an automatic system for the measurement and analysis of the course of pressure in the left ventricle of the isolated laboratory rat heart perfused in vitro after Langendorff. Attached to it is a microcomputer which automatically samples the course of the left ventricular pressure curve over a segment comprising five cardiac cycles and, within 30 s, evaluates the mean systolic and diastolic pressure, the maximum rate of the increase and decrease in pressure, the contractility index, the mean integral pressure and the heart rate. The apparatus shows a standard error of less than 1% for pressure and of up to 2% for derivation.

Animals↗

The effect of isoprenaline on the phospholipid content of the compact and spongious musculature of the carp ventricular myocardium.

1. After a single injection of 40 mg kg-1 of isoprenaline to the carp, lysophospholipids appear in the tissue of the heart ventricle, ethanolamine plasmalogens increase and choline plasmalogens decrease; phosphatidylinositol is lowered in the spongious layer only. 2. Daily administration of 5 mg kg-1 of the drug leads, after 5 doses, to a dramatic decrease of the diphosphatidylglycerol content; during the subsequent 5 and 10 doses a return to normal values occurs. Shifts in plasmalogens are similar to those found after a single high dose. Some other phospholipids change significantly. 3. All changes reveal that the spongious musculature is more sensitive to the drug than the compact one.

Animals↗

Effect of isoprenaline on 85Sr accumulation in the myocardium of the adult rat.

The administration of a single dose of isoprenaline to adult male rats stimulated 85Sr uptake by their blood, liver and myocardium. Whereas the 85Sr concentration in the blood and liver rose by only 36% and 42% respectively, the increase in the various compartments of the heart was 5-7 times this value. This finding is also documented by the increase in the ratio of the 85Sr concentration in the heart and blood. The increase observed in 85Sr accumulation in the myocardium is comparable to the repeatedly described changes which occur in radioactive calcium after the administration of isoprenaline.

Animals↗

Age-dependent influence of a moderate altitude (1,350 m) on the rat cardiopulmonary system.

The aim of the study was to determine whether a moderate altitude (1,350 m, Strbské Pleso, High Tatras) would act as a hypoxic stimulus on the cardiopulmonary system of young and adult rats. We used three experimental groups of animals differing in the duration of time for which they were kept at the given altitude (60 and 120 days) and the age at which they were acclimatized (from the 5th and the 60th day of life). The controls were kept at an altitude of 200 m (Prague). We found that an altitude of 1,350 m produced a significant increase in blood pressure in the lesser circulation; this response did not depend on the animals' age. Right ventricular enlargement occurred at the same time and was more pronounced in rats which had been acclimatized from infancy. The systemic blood pressure fell mildly, but significantly, only in animals exposed to altitude from adulthood; elevation of the haematocrit was likewise recorded only in this group. The results show that even a moderate altitude influences the cardiopulmonary system of the rat in a manner characteristic of the effect of chronic hypoxic hypoxia.

Acclimatization↗

Pertussis toxin inhibits negative inotropic and negative chronotropic muscarinic cholinergic effects on the heart.

We injected rats with pertussis toxin, known to cause ADP ribosylation of the Gi regulatory protein of the adenylate cyclase complex and of another closely related GTP binding protein in the heart, and after 7 days we examined several effects of muscarinic activation on the heart. The negative chronotropic effect of carbamoylcholine on spontaneously beating perfused hearts was conspicuously diminished. While 10(-5) mol/l carbamoylcholine invariably produced heart arrest in control rats, the heart rate did not decrease by more than 20% in the toxin-treated rats even when the concentration of carbamoylcholine was raised to 10(-2) mol/l. The negative inotropic effect of carbamoylcholine examined on electrically paced ventricles perfused with isoproterenol was reduced, while the maximum positive inotropic effect of isoproterenol was substantially increased after toxin treatment. The inhibitory action of carbamoylcholine on the isoproterenol-stimulated accumulation of cyclic AMP in the heart auricles was attenuated. The weakening by pertussis toxin of the negative inotropic effect of carbamoylcholine is probably mainly due to the ADP ribosylation of the Gi regulatory protein and the subsequent loss of influence of muscarinic receptors on adenylate cyclase. The blockade of the negative chronotropic action of carbamoylcholine by pertussis toxin strongly indicates, together with other recently published evidence, that the Gi or another closely related GTP binding protein in the cardiac pacemaker cells is involved in the coupling of muscarinic receptors to the K+ channels.

Adenylate Cyclase Toxin↗

Different effect of propranolol and verapamil on isoprenaline-induced changes in the chick embryonic heart.

Isoprenaline (IPRO) has been reported to cause pathological lesions of the embryonic heart. The purpose of the present study was to ascertain whether the development of IPRO-induced changes can be reduced--similarly as in adults--by beta blockade or calcium antagonists. IPRO was administered to 10-day-old chick embryos intraamnially (i.a.) in a dose of 2 X 10 mg.kg-1 per 48 h; propranolol (Inderal) and verapamil (Isoptin) were injected i.a. in a dose of 1.0 or 10.0 mg.kg-1 before each injection of IPRO. It was found that propranolol completely blocked the cardiac IPRO-induced changes, i.e. cardiomegaly, avascular areas and elevation of cAMP. On the other hand, verapamil was found to have no protective effect in any dose used. Furthermore, it increased the mortality of experimental embryos. This fact support the hypothesis that cardiac sensitivity to calcium antagonists may differ during prenatal development.

Animals↗

Increased affinity to substrate in sarcolemmal ATPases from hearts acclimatized to high altitude hypoxia.

It has been well documented that acclimatization to chronic high altitude hypoxia involves a complex of adaptation changes which are capable of protecting the myocardium in diverse situations such as in acute hypoxia, coronary occlusion-induced ischaemia or isoprenaline-induced calcium overload. Since many of the former changes concern membrane functions, namely those of the sarcolemma, the activities and kinetic properties of sarcolemmal Mg2+-, Ca2+- and (Na+ + K+)-ATPase were investigated in right heart ventricles of rats acclimatized to intermittent high altitude hypoxia simulated in a barochamber. In the course of the experiment, the ventricles were subjected to a special anoxic test in vitro. The high altitude induced increase in cardiac tolerance to anoxia was not accompanied by any preservation of the sarcolemmal ATPase activities. On the contrary, membrane preparations obtained from the right ventricles of hearts acclimatized to high altitude exhibited significantly lower ATPase activities in comparison to non-acclimatized controls. The significant diminution in Km values of ATPases established in acclimatized hearts points to an increase in the affinity of their active sites to ATP. The latter effect is in agreement with the lowered rate of both the decrease in ATPase activities and the reduction of contractility in acclimatized hearts during the anoxic test, as well as with the considerably improved postanoxic reparability of contractions as compared to the controls. It is being concluded that the sarcolemmal changes at the level of ATPases involved in ionic transport processes represent an integral part of the adaptation complex to chronic high altitude hypoxia.

Acclimatization↗

Increase and regression of the protective effect of high altitude acclimatization on the isoprenaline-induced necrotic lesions in the rat myocardium.

Cardiac resistance to the cardiotoxic effect of isoprenaline--ISO (single dose of 0.1 mg X kg-1) was studied in rats acclimatized to intermittent high altitude--IHA (barochamber, 8 h a day, 5 days a week, stepwise up to 7000 m). The extent of lesions was evaluated quantitatively by means of the increased accumulation of 203HgCl2. Five weeks' acclimatization was followed by a marked increase in the resistance of the myocardium to the necrogenic effect of ISO; this effect was more expressed in the left ventricle, so that the right to left difference generally observed under normoxic conditions disappeared. The increased resistance of the myocardium to ISO-induced damage persisted long after the animals had been returned to normoxic conditions; even six weeks after the last hypoxic exposure the sensitivity of the myocardium to damage had still not returned to the values of unacclimatized animals.

Acclimatization↗

Calcium antagonists and the developing heart.

Ontogenetic differences in cardiac sensitivity to calcium antagonists were studied in chick embryonic and postnatal immature rat heart. It has been found that verapamil exhibits no protective effect on isoprenaline-induced changes of the chick embryonic heart. Furthermore, it increased the mortality of experimental embryos. The mortality of verapamil-treated rats was age-dependent, increasing with decreasing age of animals. Similarly, the intensity of negative inotropic response of the isolated right ventricular myocardium and isolated perfused rat heart was significantly greater in the youngest age groups. These results point to the possible negative consequences of the clinical use of calcium antagonists during the early phases of ontogeny.

Age Factors↗

Ontogenetic differences in cardiac sensitivity to verapamil in rats.

The degree of a negative inotropic response of the isolated right ventricle to verapamil as well as the mortality rate were studied in rats during their postnatal development. Male Wistar rats aged 3, 15, 30, and 90 days were used. The isolated right ventricle was incubated in a glucose-free solution with a mixture of 95% O2 and 5% CO2 and electrically stimulated. The amplitude of isotonic contractions (AIC) was registered. In 90-day-old rats, AIC was 74.1 +/- 6.2% of initial amplitude 45 min after administration of verapamil; in 30-day-old, 41.1 +/- 6.4%; in 15-day-old, 38.2 +/- 4.1%; and in 3-day-old rats, only 2.6 +/- 1.5. The difference between the 3-day-old rats and all older groups was statistically highly significant. The mortality rate of verapamil-treated rats increased with decreasing age of animals. It is concluded that the sensitivity of the rat myocardium to verapamil is age dependent: the negative inotropic effect of this drug increases with decreasing age of the animal. This indicates a possible risk in the therapeutic use of verapamil when given to newborns and infants.

Aging↗

The effect of oxidized isoprenaline on the chick embryonic heart.

Intra-amnial administration of isoprenaline (IPRO) to chick embryos induces a number of myocardial lesions. The purpose of the present study was to investigate whether similar changes may also be induced after injection of spontaneously oxidized isoprenaline and commercially obtained adrenochrome. Cardiotoxicity of these substances has been demonstrated in adult animals. IPRO, oxidized IPRO, or adrenochrome were administered intra-amnially to 10-day-old chick embryos at doses of 0.1, 1.0, 10.0, and 100.0 mg X kg-1. Parallel experimental groups received propranolol at a dose of 1 mg X kg-1, 15 s before injection of IPRO or oxidized IPRO. The cAMP level in the heart was determined by radioimmunoassay 2 and 30 min after administration of IPRO, oxidized IPRO, or adrenochrome at a single dose of 10.0 mg X kg-1. It has been found that in embryos the effect of IPRO and oxidized IPRO is dose dependent. The rise in mortality and development of cardiomegaly together with increased hydration and disturbances of the development of coronary vascularization were highly significant starting from the dose of 10 mg X kg-1. Furthermore, both drugs significantly increased cAMP levels in the embryonic heart. On the other hand, the administration of adrenochrome was without any effect. The changes induced by IPRO were prevented by the administration of the beta-blocking agent propranolol; the lesions induced by spontaneously oxidized IPRO were, however, prevented only partially.

Adrenochrome↗

Transport ATPases in the erythrocytes of rats acclimatized to intermittent altitude hypoxia.

The activity of Na+/K+- and Ca2+-ATPase and some allosteric properties of Na+/K+-ATPase were studied in whole erythrocytes and their membrane preparations (ghosts) from rats exposed to intermittent altitude hypoxia (10 and 24 exposures, 8 h/day in an altitude chamber, stepwise up to an altitude of 7,000 m). Ca2+-ATPase activity was increased both in whole erythrocytes and ghosts after the first phase of acclimatization (10 exposures). In a standard incubation medium (containing 3 mmol.l-1 MgCl2 ), Na+/K+-ATPase activity in the ghosts was also increased after the initial phase of acclimatization whereas in whole erythrocytes Na+/K+-ATPase was only decreased in the regression phase. At high MgCl2 concentrations (12 mmol.l-1) changes of Na+/K+-ATPase activity both in whole erythrocytes and in the ghosts followed similar time course with a pronounced increase in the first phase of acclimatization (10 exposures) followed by an abrupt drop (24 exposures) and then by a gradual normalization in the regression phase. Sensitivity of the enzyme to mounting MgCl2 concentrations was increased in the ghosts at the end of acclimatization and was decreased in whole erythrocytes during acclimatization and especially in the regression phase. It has been suggested that chronic altitude hypoxia leads to the alteration of cooperative interaction of the Na+/K+-ATPase subunits in the erythrocyte membrane and accumulation of some factor in the cells inhibiting this enzyme.

Acclimatization↗

Ultrastructure of isoproterenol-induced myocardial damage in chick embryos.

Isoproterenol is known to cause severe myocardial lesions when given in toxic doses to adult homoiotherms. Previous studies on chick embryos revealed myocardial damage with scattered necroses in the outer layer of ventricular myocardium. The present ultrastructural study, performed on embryos 6 to 20 days old, has shown various types of cellular lesions; mainly cellular oedema, mitochondrial swelling, necroses of isolated cardiac muscle cells, fatty degeneration, accumulation of glycogen, and signs of increased proteosynthesis in the surviving muscle cells. Morphological features of the lesions differed from those which are known to be induced by isoproterenol in adult animals and seemed to depend on the stage of embryonic development.

Animals↗

Phospholipid content in the compact and spongious musculature of the carp heart (Cyprinus carpio).

The phospholipid content of the spongious and compact musculature of the heart of the carp (Cyprinus carpio) was compared. The content of phospholipids is higher in the spongious musculature, the greatest difference being in the content of diphosphatidylglycerol: 2.53 mumol P . g-1 wet weight in the spongious layer and 1.29 mumol P . g-1 wet weight in the compact one. In both tissues plasmalogens represent 20-27% of the tissue content of choline and ethanolamine phosphoglycerides.

Animals↗