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J Moravec

Publications and source records attributed to J Moravec.

At least 19 recordsLinked to original sources

Noradrenaline synchronizes evoked quantal release at frog neuromuscular junctions.

1. Noradrenaline (NA) increases synaptic efficacy at the frog neuromuscular junction. To test the hypothesis that one of the actions of NA is to shorten the period over which evoked quanta are released, we measured the latencies of focally recorded uniquantal endplate currents (EPCs). 2. NA shortened the release period for evoked quantal release. The interval between the time when responses with minimal delay appeared and the point at which 90 % of all latencies had occurred was shortened in the presence of 1 x 10-5 M NA by about 35 % at 20 C and by about 45 % at 8 C. Inhibitor and agonist experiments showed that NA acts on a beta-adrenoreceptor. 3. The better synchronization of release significantly increased the size of reconstructed multi- quantal EPCs. This suggests that NA facilitates synaptic transmission by making the release of quanta more synchronous. 4. The synchronizing action of NA might potentiate neuromuscular transmission during nerve regeneration, transmitter exhaustion and other extreme physiological states where the quantal content is reduced, such as survival in cold and hibernation.

Adrenergic alpha-Agonists↗

3-D characterization of ganglion cells of the terminal nerve plexus of rat atrioventricular junction.

Three-dimensional (3-D) morphology of neurons of the terminal nerve plexus of the atrioventricular junction was examined in a scanning electron microscope. Distributions of different cell types encountered as well as their relations to different structures of the atrioventricular specialized tissue were also studied. Most neurons were found disseminated in a thin connective tissue layer separating different segments of the atrioventricular conductive tissue from the interventricular septum. Sometimes, they formed small pluricellular ganglia (up to 5 neurons) but, frequently, they occurred isolated in the terminal ramifications of the intramural nerve plexus of specialized tissue. Some intranodal neurons could also be identified. According to their 3-D morphology, nerve cells of the perinodal ganglionated plexus could be divided into three categories: (1) Large unipolar neurons were scattered throughout the atrioventricular junction. Their long and thin axonal projections were often directed towards the interventricular septum. (2) Large pseudounipolar or bipolar neurons were located at a few specific loci, namely all along the bundle of His and its bifurcation into the right and left bundle branches. Frequently, they occurred solitary and immersed amongst strands of surrounding muscle cells. Only occasional synaptic impacts could be identified on the surface of neuronal bodies of these bipolar neurons. On the other hand, their dendritic varicosities were richly innervated. Due to their irregular shape, intimate association with muscular elements and their topographical superposition with occasional spindle-like structures, these nerve cells recall prospective sensory neurons involved in integration of mechanical and neural stimuli to the heart. (3) Small multipolar interneurons could be identified in the retronodal ganglion and within right and left bundle branches. The present description of morphological heterogeneity of intramural nerve cells agrees with recent morphological and functional classifications of autonomic neurons and supports the idea that, at the level of the atrioventricular junction, a self-governed neuronal network may be operating.

Animals↗

Palmitate oxidation by the mitochondria from volume-overloaded rat hearts.

In this work, an attempt was made to identify the reasons of impaired long-chain fatty acid utilization that was previously described in volume-overloaded rat hearts. The most significant data are the following: (1) The slowing down of long-chain fatty acid oxidation in severely hypertrophied hearts cannot be related to a feedback inhibition of carnitine palmitoyltransferase I from an excessive stimulation of glucose oxidation since, because of decreased tissue levels of L-carnitine, glucose oxidation also declines in volume-overloaded hearts. (2) While, in control hearts, the estimated intracellular concentrations of free carnitine are in the range of the respective Km of mitochondrial CPT I, a kinetic limitation of this enzyme could occur in hypertrophied hearts due to a 40% decrease in free carnitine. (3) The impaired palmitate oxidation persists upon the isolation of the mitochondria from these hearts even in presence of saturating concentrations of L-carnitine. In contrast, the rates of the conversion of both palmitoyl-CoA and palmitoylcarnitine into acetyl-CoA are unchanged. (4) The kinetic analyses of palmitoyl-CoA synthase and carnitine palmitoyltransferase I reactions do not reveal any differences between the two mitochondrial populations studied. On the other hand, the conversion of palmitate into palmitoylcarnitine proves to be substrate inhibited already at physiological concentrations of exogenous palmitate. The data presented in this work demonstrate that, during the development of severe cardiac hypertrophy, a fragilization of the mitochondrial outer membrane may occur. The functional integrity of this membrane seems to be further deteriorated by increasing concentrations of free fatty acids which gives rise to an impaired cooperation between palmitoyl-CoA synthase and carnitine palmitoyltransferase I. In intact myocardium, the utilization of the in situ generated palmitoyl-CoA can be further slowed down by decreased intracellular concentrations of free carnitine.

Adenosine Triphosphate↗

Control of oxidative metabolism in volume-overloaded rat hearts: effect of propionyl-L-carnitine.

The objective of the present work was the assessment of metabolic events responsible for the improvement of hemodynamic function of volume-overloaded hearts from rats receiving propionyl-L-carnitine. A severe cardiac hypertrophy was induced in 2-mo-old rats by surgical opening of an aortocaval communication. Three months later, during in vitro perfusions with 1.2 mM palmitate, 11 mM glucose, and 10 IU/l insulin, the mechanical performance and overall energy turnover (myocardial O2 consumption) of hypertrophied rat hearts were significantly decreased under conditions of moderate and high workloads. These changes in cardiac energetics paralleled the decrease in total tissue carnitine content and alterations in exogenous palmitate oxidation. The oxidative utilization of glucose was also slightly depressed in volume-overloaded hearts while steady-state glycolysis rates increased, especially in hearts subjected to high mechanical loads. This slowing of metabolic pathways involved in acetyl-CoA generation resulted in decreased NADH availability and in an apparent substrate limitation of oxidative phosphorylation suggested by a failure of cytosolic unbound ADP to drive respiration. Long-term administration of propionyl-L-carnitine normalized the degree of reduction of mitochondrial pyridine nucleotides and improved the kinetics of mitochondrial ATP production in volume-overloaded hearts. The resulting acceleration of energy turnover was essentially related to improved oxidative utilization of glucose, but steady-state palmitate oxidation rates also increased in severely hypertrophied hearts. This concomitant acceleration of glucose and palmitate oxidation may be related to the particular experimental conditions (high exogenous palmitate concentrations, elevated workloads) used in this study. We assume that the increase in intracellular carnitine, together with a stimulation of acetyl-CoA demands related to high workloads, creates conditions that are compatible with the simultaneous relief of pyruvate dehydrogenase and carnitine palmitoyltransferase I. The resulting increase in the rate of steady-state ATP production improves, in turn, the mechanical activity of volume-overloaded hearts.

Adenosine Diphosphate↗

A resistance of head lice (Pediculus capitis) to permethrin in Czech Republic.

An outbreak of pediculosis at primary schools was recorded in the Czech Republic in 1992. Almost 20% of children in some schools were infested. This outbreak can be attributed to the resistance of head lice to permethrin, which has not been mentioned in literature yet. The resistance factors established in three towns range between 2 and 385 and between 5 and 557 for LC50 and LC90 values, respectively. This resistance has developed after exclusive use of pyrethroids lotion and shampoo in the Czech Republic since 1978, and it was accompanied by a cross-resistance to d-phenothrin and bioalethrin. But the susceptibility of head lice to malathion and pirimiphos-methyl in 1992 was very similar to that found in 1981. The lotion containing 0.3% of malathion (Diffusil H92 M) has been fully effective against the resistant lice. When introduced into the practice, it quickly reduced the infestation of children in primary schools. The other lotion and shampoo containing 0.3% and 0.7% of pirimiphos-methyl respectively were found to be effective as well.

Adolescent↗

Control of oxidative metabolism in volume-overloaded rat hearts: effects of different lipid substrates.

The relationship between intracellular energy parameters and myocardial O2 consumption (VO2) was studied in control and volume-overloaded hearts perfused with different lipid substrates and over a range of left ventricular work loads. In control hearts, a unique linear relationship between log of cytosolic [ATP]/[ADPf].[Pi] (where [ADPf] is concentration of free ADP) and myocardial VO2 was observed between low and high work loads for both fatty acids studied. In volume-overloaded hearts perfused in the presence of exogenous palmitate, the slope of the relationship between log [ATP]/[ADPf].[Pi] and myocardial VO2 was considerably depressed. It would seem that, under these conditions, much of the thermodynamic control of respiratory chain function has been lost. When myocardial VO2 was expressed as a function of cytosolic ADPf, the cytosolic ADPf was not regulatory. This may be related to a substrate limitation of the respiratory chain, as suggested by an excessive oxidation of pyridine nucleotides. When octanoate, instead of palmitate, was used, most of the above limitation of the respiration disappeared. With this substrate, the reduction of mitochondrial pyridine nucleotides in volume-overloaded hearts was similar to that in controls, and the linear relationship between log [ATP]/[ADPf].[Pi] and myocardial VO2 reappeared over the range of work loads studied. The above failure of cytosolic phosphate potential and ADPf to drive respiration when mitochondrial NADH is low fits well with the integrated model of kinetic regulation, as proposed by recent nuclear magnetic resonance studies. our results also indicate that, even at high respiratory rates, free-energy change of ATP synthesis of volume-overloaded hearts can be protected by use of an appropriate substrate. This, in turn, prevents contractile failure.

Adenosine Diphosphate↗

Assessment of the cardiostimulant action of propionyl-L-carnitine on chronically volume-overloaded rat hearts.

Chronic volume overload was induced in young rats of Wistar strain by surgical opening of the aorto-caval fistula. Three months later, during in vitro perfusion with exogenous palmitate, left ventricular function and energy turnover (QO2) of hypertrophied hearts were severely depressed. This seemed to be related to impaired long-chain fatty acid utilization, as reflected by decreased 14CO2 production from U-14C-palmitate and decreased tissue levels of L-carnitine. Another group of rats exposed to chronic volume overload was pretreated for 2 weeks before sacrifice with propionyl-L-carnitine (250 mg/kg/day), and the hearts were perfused with 1.2 mM palmitate and 10 mM propionyl-L-carnitine. In this group, both mechanical performance and the oxygen consumption rate were quite comparable to those of untreated controls. On the other hand, tissue levels of L-carnitine were only slightly increased, and the rate of 14CO2 production from U-14C-palmitate was insignificantly improved. This suggests that propionyl-L-carnitine administration promotes the mechanical performance of normoxic volume-overloaded hearts via a mechanism other than improved palmitate utilization. The possibility that propionyl moieties themselves replenish with mitochondrial intermediates of the tricarboxylic cycle (malate, acetyl-CoA) is not excluded.

Animals↗

Fatty acid oxidation and mechanical performance of volume-overloaded rat hearts.

Chronic volume overload was induced in 2-mo-old rats by surgical opening of the aortocaval fistula. Rats were killed 3 mo later and their hearts were atrially perfused. During the perfusions with 1.2 mM palmitate, mechanical performance of volume-overloaded hearts was significantly decreased both under conditions of a moderate work load and, mainly, after the clamp of the aortic outflow line. Respective O2 consumption rates as well as the rates of 14CO2 production from [U-14C]palmitate were decreased to the same extent. When 2.4 mM octanoate was used as the exogenous substrate, both the O2 consumption rates and the rates of CO2 production of volume-overloaded hearts became comparable to those of control hearts perfused with same substrate. Mechanical activity of volume-overloaded hearts returned to control values and remained stable during the entire perfusion period tested. Total tissue L-carnitine was decreased by approximately 30% in volume-overloaded hearts, which may suggest that palmitate oxidation has been limited at the level of carnitine-acylcarnitine translocase. However, our polarographic studies of the respiratory activity of isolated mitochondria indicated that the palmitoylcarnitine translocation proceeds normally. On the other hand, state 3 respiration of the mitochondria from volume-overloaded hearts supplemented with either palmitate or palmitate and L-carnitine was significantly lower than that of control ones. This may suggest that an alteration of the enzymes involved in long-chain fatty acid activation and/or long-chain fatty acyl transfer to L-carnitine has developed under conditions of chronic mechanical overloading of the heart.

Animals↗

Catecholaminergic and peptidergic nerve components of intramural ganglia in the rat heart. An immunohistochemical study.

Immunohistochemical properties of the terminal nerve network in the rat heart were assessed by use of the elution-restaining method. The colocalization of the enzymes involved in catecholamine synthesis (tyrosine hydroxylase--TH. dopamine-beta-hydroxylase--DBH) as well as the respective distributions of the neuropeptides associated with the adrenergic nervous system (neuropeptide tyrosine--NPY, C-terminal flanking peptide of neuropeptide Y--C-PON) were studied in series of serial sections throughout the interatrial septum and the atrioventricular junction. Our data suggest that ganglion cells of sulcus terminalis as well as the epicardial ganglia enclosed between the superior vena cava and ascending aorta are VIP- and TH-negative, but neuropeptide Y- and DBH-immunoreactive. They give rise to three intraseptal nerves directed towards the specialised structures of the atrioventricular junction. These nerve fascicles contain abundant, thick TH-immunoreactive nerve fibres and scarce, thin NPY- and DBH-immunoreactive fibres. The cell bodies of the intramural ganglion cells localized between the right and left branches of the bundle of His (Moravec and Moravec 1984) are strongly TH- and DBH-immunoreactive. They are innervated by thick nerve fibres having the same immunohistochemical properties (NPY- and DBH-immunoreactivities) as those of a subpopulation of the epicardial ganglion cells and seem to supply some of the TH-immunoreactive nerve fibres directed via the intraseptal nerves to the epicardial ganglia. The existence of a multicomponent nerve network, characterized by a reciprocal innervation of the sinus node and atrioventricular node areas, is suggested by our immunohistochemical data.

Animals↗

Catecholamine-synthesizing enzymes and neuropeptides in rat heart epicardial ganglia; an immunohistochemical study.

The subepicardial atrial ganglia of rat hearts were examined using immunohistochemical techniques and antibodies against the catecholamine-synthetic enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), and the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and met-5-enkephalin (ENK). Some of the ganglion cells present in the ganglia exhibited DBH-like immunoreactivity (LI) and NPY-LI, whilst these cells never exhibited TH-, VIP-, CGRP-, SP- or ENK-LI. Groups of small cells exhibiting an intense TH-LI, corresponding to cells referred to as catecholamine-containing cells and sometimes small intensely fluorescent cells in the literature, were observed in the ganglia. A subpopulation of these cells exhibited immunoreactivity to one of the neuropeptides tested, namelyu SP. Only a few of the cells showing TH-LI displayed DBH-LI. Nerve fibres showing SP-, CGRP-, DBH- and TH-LI were present in the ganglia; some of these fibres being closely associated with the ganglion cells or with the cells showing TH-LI. The observation provide new information on the catecholamine-synthetic enzyme/neuropeptide expression of the ganglion and catecholamine-containing cells and of the associated nerve fibres of rat heart subepicardial ganglia.

Animals↗

Carnitine transport and exogenous palmitate oxidation in chronically volume-overloaded rat hearts.

L-Carnitine transport and free fatty acid oxidation have been studied in hearts of rats with 3-month-old aorto-caval fistula. For carnitine transport experiments, the hearts were perfused via the ascending aorta with a bicarbonate buffer containing 11 mM glucose and variable concentrations L-[14C]carnitine (10-200 microM). In some experiments, the active component of carnitine transport was suppressed by the adjunction of 0.05 mM mersalyl acid. The subtraction of passive from total transport allowed reconstruction of the saturation curves of the carrier-mediated transport of L-carnitine. Our data suggest that at a physiological carnitine concentration (50 microM), the rate of [14C]carnitine accumulation was significantly depressed in mechanically overloaded hearts. In addition, according to Lineweaver-Burk analysis, the affinity of the membrane carrier for L-carnitine was considerably diminished (Km carnitine 125 instead of 83 microM, Vmax unchanged). The above alterations of L-carnitine transport did not result from a decrease of the transmembrane gradient of sodium, since the intracellular Na+ content of the hypertrophied hearts was quite similar to that of control hearts. The ability of atrially perfused, working hearts to oxidize the exogenous free fatty acids was assessed from 14CO2 production obtained in the presence of [U-14C]palmitate or [1-14C]octanoate. The total 14CO2 production, expressed per min per g dry weight, was significantly diminished in hearts from rats with the aorto-caval fistula if 1.2 mM palmitate was used. On the other hand, in the presence of 2.4 mM octanoate, a substrate which circumvents the carnitine-acylcarnitine translocase, no such reduction of the 14CO2 production could be detected. Our results suggest that the decrease of L-carnitine transport, resulting in a significant depression of tissue carnitine, may impair long-chain fatty acid activation and/or translocation into mitochondria. In contrast, the oxidation of short-chain fatty acids, the activation of which takes place directly in mitochondrial matrix, is not limited in volume-overloaded hearts.

Animals↗

Adrenergic neurons and short proprioceptive feedback loops involved in the integration of cardiac function in the rat.

Serial cryostat and paraffin-embedded sections through the atrioventricular junction of the rat heart were studied at the light-microscopic level after indirect immunohistochemical staining (tyrosine hydroxylase, neuropeptide Y, C-terminal flanking peptide of neuropeptide Y immunoreactivities) or silver impregnation. The distribution of these immunoreactivities in the Hissian ganglion (Moravec and Moravec 1984) as well as the relationships of the Hissian ganglion cells with the surrounding structures have been studied to assess its function. The results suggest that the Hissian ganglion is composed of large multipolar neurons displaying both tyrosine hydroxylase (TH) and related peptide (neuropeptide Y. C-terminal flanking peptide of neuropeptide Y) immunoreactivities. The dendritic projections of these adrenergic cells penetrate the reticular portion of the atrioventricular node and the upper segments of the interventricular septum where they constitute sensory-like corpuscles. The hypothesis that the adrenergic neurons of the atrioventricular junction are involved in short proprioceptive feedback loops necessary for beat-to-beat modulation of cardiac excitability and intracardiac conduction can thus be suggested.

Adrenergic Fibers↗

Decreased L-carnitine transport in mechanically overloaded rat hearts.

The transport of L[14C] carnitine was studied in rat hearts with a three-month-old aorto-caval fistula. Tissue TG content was determined in order to assess the state of FFA utilization. The hearts were perfused with a bicarbonate buffer containing 11 mM glucose and variable concentrations (10-200 microM) of L[14C] carnitine. In some experiments, the active component of carnitine transport was suppressed by the adjunction of 0.05 mM mersalyl acid. The subtraction of passive from total transport allowed us to reconstruct the saturation curves of the net active transport of L-carnitine. Our results suggest that at physiological carnitine concentration (50 microM) the uptake of L-carnitine is significantly depressed in mechanically overloaded hearts. These changes are not related to alterations of coronary perfusion, since coronary flow rates (ml/min/g dry wt) are quite comparable in both groups tested. According to the Lineweaver-Burk analysis of the kinetics of saturable transport, the affinity of the membrane carrier for L-carnitine is considerably diminished in the overloaded hearts (Km[carnitine] 125 instead of 83 microM). The alterations of the kinetics of carnitine transport do not seems to be related to the decrease of the transmembrane gradient of sodium: the intracellular sodium content of the hypertrophied, but non-failing, hearts is quite similar to that of control hearts. In addition, carnitine deficiency does not lead to TG accumulation, at least under in situ conditions.

Animals↗

Intrinsic neurosecretory neurons of the rat heart atrioventricular junction: possibility of local neuromuscular feed back loops.

The microanatomy and ultrastructure of rat heart atrioventricular junction were studied on serial sections of both paraffin and epoxy embedded samples. The animals were pretreated with 5-hydroxy-dopamine in order to differentiate the adrenergic component of the terminal nerve plexus. Two kinds of ganglia could be identified throughout the interatrial septum by the optical microscope. The first was composed of large pale cells with voluminous nuclei. The other resembled acini-like clusters of osmophilic cells. Another small ganglion was invariably present between right and left branches of the bundle of His. The electron microscopic examination of this structure revealed, apart from small pale neurons (10 microns in diameter), several large 5-hydroxy-dopamine contrasted neurosecretory cells (up to 30 microns) with abundant electron dense vesicles typical for sympathetic neurons. Numerous glomeruli with dendrodendritic and axodendritic connections, some of which exhibit the same 5-hydroxy-dopamine loaded vesicles, could be found in the vicinity of the specialized conducting tissue. The functional implications of the above morphological data are not clear. However, the intrinsic neurosecretory component can be expected to modulate both specialized cells and neighbouring neurons. The heterogeneity of neuro-neuronal and neuro-muscular relations, such as perinodal mechanoreceptors, may suggest that the terminal nerve plexus not only distributes the efferent stimuli, but that it also has an integrative function which is the necessary prerequisite for a local feed back autoregulation.

Animals↗