Close relation between hypothalamic and cardiac norepinephrine during stress and its role in acute myocardial infarction disrhythmias

Summary The decrease of the norepinephrine levels in hypothalamus and heart caused by stress is prevented by pargyline and imipramine. Such a decrease in spleen and adrenals is not affected. Chlorpromazine and lithium only prevent the norepinephrine decrease in the spleen. The uptake of H³norepinephrine by isolated atria of guinea-pig increases during anoxia; the change to a normal oxygen situation decreases these norepinephrine levels by more than 50%.     

Effect of propylene glycol and ethanol on3H-noradrenaline efflux from an isolated blood vessel

Summary Propylene glycol (14 mM), but not ethanol (17 mM), enhanced the late phase of passive³H-efflux from rabbit isolated aortic rings preloaded with³H-(–)-noradrenaline. We conclude that, with regard to³H-noradrenaline release studies, propylene glycol is unsuitable for aiding the dissolution of e.g. corticosterone in physiological salt solution, while ethanol can be used for this purpose.This study was supported by the Danish Medical Research Council. The authors gratefully acknowledge the technical assistance of Miss Mariann Wolmar.     

Die Wirkung von Theophyllin auf den cellulären Ca-Stoffwechsel des Warmblüterherzens

Summary In isolated, electrically driven, left guineapig atria, theophylline (5×10^–4 g/ml) increased the rate of⁴⁵Ca uptake and release without affecting the total myocardial Ca content and the amount of exchangeable cellular Ca. In sheep and calf heart preparations, theophylline (10^–4–10^–3 g/ml) increased Ca inward current during excitation (as examined indirectly by Ca dependent changes of membrane potential in TTX-containing solutions) as well as tension development. It is concluded that the positive inotropic effect of theophylline in mammalian hearts is due to an increase in Ca influx during the excitation process.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Der Einfluss von Acetylcholin auf den Calciumumsatz ruhender und kontrahierender Vorhofmuskulaturin vitro

Summary Acetylcholine 5 × 10^–8 g/ml reduces the Ca⁴⁵ uptake of the beating left atria of guinea-pig; the tissue calcium is not altered. In resting atria, acetylcholine 5 × 10^–7 g/ml has no influence upon the calcium content and Ca⁴⁵ uptake. It is concluded that acetylcholine acts by shortening the action potential duration and thereby reduces the release of cellular calcium per excitation.

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Mit grosszügiger Unterstützung durch die Deutsche Forschungsgemeinschaft.     

The possible role of isoforms of cytochrome c oxidase subunit VIa in mammalian thermogenesis

A single cDNA of cytochrome c oxidase subunit VIa was characterised from liver, heart and the thermogenic organ of the partially endotherm tuna fish. The amino acid sequence revealed high identity with subunit VIa from carp and trout, but low identity to subunits VIaL (liver type) and VIaH (heart type) of mammalian cytochrome c oxidase. In reconstituted cytochrome c oxidase from bovine heart, the H ⁺/e⁻ stoichiometry is decreased from 1.0 to 0.5 at high intraliposomal ATP/ADP ratios via exchange of bound ADP by ATP at the matrix domain of the transmembraneous subunit VIaH. Reconstituted cytochrome c oxidase from bovine liver and kidney, containing subunit VIaL, revealed H ⁺/e⁻ ratios below 0.5, independent of the ATP/ADP ratio. The results suggest the evolution of three types of subunit VIa. Subunits VIaH and VIaL are postulated to participate in mammalian thermogenesis. Received 3 May 1999; received after revision 10 June 1999; accepted 29 June 1999     

Vitamin D receptors in heart: Effects on atrial natiuretic factor

We report that receptors for vitamin D exist in distinct regions of the heart in female and male mice, predominantly in the right atrium where most of the cardial atrial natriuretic peptide (ANF) is produced. Tritiated 1,25-dihydroxyvitamin D₃ (1,25-D₃, vitamin D, soltriol) and ANF are colocalized in nuclei and cytoplasm respectively in identical cardiomyocytes. Changes of ANF tissue and blood levels under dietary deficiency and treatment with 1,25-D₃ suggest direct genomic actions of vitamin D on myoendocrine cells of the atrium for the regulation of ANF manufacture and secretion. These results were obtained by combining thaw-mount autoradiography with immunocytochemistry using tritiated 1,25-D₃ and an antibody against rat ANF. This antibody was also used in a radioimmunoassay to determine atrial natriuretic factor in plasma, atria and ventricles of normal or vitamin D-deficient mice.     

Differences in the content and turnover of noradrenaline in rat heart atria and ventricles and circadian-phase-dependency

In light-dark-synchronized male rats the levels of noradrenaline in heart atria were about 3 times that found in heart ventricles. Noradrenaline turnover rate which were about 8-9 fold greater for the atria than for the ventricles displayed a circadian-phase-dependency with increased rates in the dark period in both parts of the rat heart.     

Sensitivity of the developing chick myocardium to the positive inotropic effects of calcium and isoproterenol

Summary The present results show that the sensitivity of the chick myocardium to the positive motropic effect of Ca⁺⁺ decreases during development and that the Ca⁺⁺ concentration of the physiological solution used must be lowered below normal to study the effects of positive inotropic agents in preparations from younger embryos. Isoproterenol elicits positive inotropic responses in 7–9-day embryonic ventricle and in newborn chick atria; however, the 4-day embryonic myocardium is unresponsive to isoproterenol.This work was supported by Grant No. HL-15995 from the National Heart Institute (USPHS).The authors would like to thank Dr.F. E. Shideman for the isolated tissue baths used in these experiments.     

Die DNS-synthese im rattenherzen als funktion des lebensalters. Autoradiographische untersuchungen mit3H-thymidin

Summary The percentage of DNA-synthesising heart muscle nuclei of white rats (³H-thymidine, autoradiography) decreases rapidly during the first month of life reaching a minimum at the fourth month. From then up to 27 months the number of labelled muscle nuclei remains rather constant. Also in nuclei of connective tissue the³H-thymidine labelling index decreases as a function of the rats age. The number of mitotic figures is always about 10 times lower than labelled nuclei. Mostly in heart muscle cells they occur as collapsed mitoses never leading to cytoplasma division¹⁴.     

The cephalopod heart: The evolution of a high-performance invertebrate pump

Cephalopods typically have high metabolic rates. They have blood in which the oxygen carrier is haemocyanin, a pigment that is found only in solution and which never seems to be present in concentrations that will transport more than 4–5 vols % of oxygen. Their hearts must in consequence have very high cardiac outputs. In this account the performance of the heart ofNautilus, the only surviving ectocochleate, is contrasted with the performance of the hearts of coleoids,Octopus which has a relatively low metabolic rate (for a coleoid) and squids which have very high oxygen uptakes by any standards. In all these animals, heartbeat frequency is temperature-dependent and the additional oxygen demand in exercise is met very largely by a 2–3-fold increase in stroke volume. With the exception ofNautilus, cephalopods tend to utilise nearly all of the oxygen transported in the blood even at rest; they show very limited factorial scopes. Specific power output has, however, increased dramatically from 2.7 mWg^–1 in an activeNautilus to 5.5 mWg^–1 inOctopus and up to 20 or 30 mWg^–1 in species ofLoligo. The increase is almost entirely due to a 10-fold increase in heartbeat frequency. It is argued that frequency cannot be used as a means of responding to extra demand in an animal that must also carry automatic compensation for changes in metabolic rate dependent upon the ambient temperature, and that the use of frequency in some squid may be associated with a reduced temperature tolerance. Cephalopod systemic hearts do not scale directly with body mass, like the hearts of fish and the higher vertebrates. Smaller cephalopods have relatively larger hearts (as Mass^0.9). A typical 100-g coleoid would have a heart mass of 0.15 g. Oegopsid squids appear to be exceptional with hearts twice as large.     

Die Abhängigkeit der Ca++-Aufnahme isolierter Mitochondrien des Herzmuskels von der Na+-und K+-Konzentration als mögliche Ursache der inotropen Digitaliswirkung

Summary In isolated mitochondria of heart muscle from rabbits and oxen there is, under suitable conditions, an accumulation of Ca⁺⁺, which is significantly enhanced by elevating the K⁺/Na⁺ quotient of the incubation medium. K-strophanthine (10^–5–10^–7) does not influence the accumulation of Ca⁺⁺ by the mitochondria of heart muscle. Therefore the intracellular increase in exchangeable Ca⁺⁺ observed after digitalis-glycosides could be explained by a decrease of the intracellular K⁺/Na⁺ quotient, which is caused by inhibition of the membrane ATPase and diminishes the capacity for Ca⁺⁺ accumulation in mitochondria.     

Development of noradrenaline uptake in the human foetal heart

Summary The development of NA-uptake mechanisms in the human foetal heart start at the same time as the adrenergic terminals were visible. The highest³H-NA values in the human foetal heart were only 25–30% of those found in the mouse heart.Acknowledgment. The technical assistance of Miss Marjo Martonen is gratefully acknowledged. This investigation was supported by a grant from the National Research Council for Medical Science, Finland.     

Prostaglandin A2 (PGA2) increases the coronary vascular resistance in the guinea-pig isolated heart preparation

Summary Prostaglandin A₂ (PGA₂) in concentrations of 1.5·10^–8 to 3·10^–6 M was found to produce concentration-dependent increase in the coronary vascular resistance of the guinea-pig isolated heart without alterations in myocardial contractile force and oxygen consumption.Supported by the Deutsche Forschungsgemeinschaft.     

Positive and negative inotropic effects of carbachol on the embryonic chick atrium

The effect of carbachol on twitch tension of atrial preparations from chick embryos of different incubation ages (3–14 days) was studied. At every age carbachol evoked negative (at low concentrations) and positive (at higher concentrations) inotropic responses. Maximal response values for both effects increased with age; in 3- and 5-day atria the positive inotropic response prevailed. The muscarinic antagonist pirenzepine inhibited the positive (on 5-day atria) and negative (on strips of 14-day atria) inotropic effects of carbachol with pA₂ values of 6.8 and 8.0, respectively, suggesting that muscarinic receptors mediating these effects belong to different receptor subtypes.     

Limited proteolysis of lactate dehydrogenase from procine heart with trypsin: Characterization and reactivation of the fragments

Summary The ternary complex formed by native lactate dehydrogenase (LDH) from porcine heart, NAD⁺ and sulfite, was digested with trypsin over a period of 12–16 h³. After removal of the ligands and residual native lactate dehydrogenase by ion exchange chromatography dimers were obtained which were almost inactive. The dimers were lacking a hexapeptide at the N-terminus; however, the secondary structure was the same as that of native lactate dehydrogenase. The circular dichroism spectra showed a dependence on temperature which suggested an equilibrium of two different structural states.The reaction of antibodies against native porcine heart LDH with the dimers restored the catalytic activity, and subsequently the dimers behaved similarly to the native enzyme. Addition of 1 M phosphate or NAD-sulfite to the dimers restored 80–90% of the catalytic activity. It could be demonstrated that the behaviour of the reactivated dimers, in contrast to that of the inactive dimers, was similar to the behaviour of native lactate dehydrogenase. For instance, ultracentrifugal analysis showed that dimers reactivated with NAD–SO₃ ^– were associated to give tetramers.The reaction of antibodies against native LDH with the dimers reactivated with NAD–SO ₃ ^– demonstrated that the native LDH and the dimers have the same surface determinants.     

Endogenous oscillatory activity and TTX-sensitive spikes of the heart muscle in early juveniles of the isopod crustaceanLigia exotica

The heart beat of early juveniles of the littoral isopodLigia exotica occurred at a frequency of 250 to 350/min, associated with rhythmic activity of the heart muscle. Each burst was composed of a slow depolarizing potential with superimposed spike potentials. The spike potential was eliminated by perfusion with TTX-containing or Na⁺-free saline. In TTX-saline, the slow potential was unchanged in frequency and amplitude. By current injection into the heart muscle, the rhythm of the slow potential was phase-shifted and its frequency was changed in a membrane potential-dependent manner. These results show that the heart ofLigia early juveniles acts as an endogenous muscle oscillator generating oscillatory slow potentials and Na⁺-dependent spikes.     

Potentiation by taurine of the inotropic effect of ouabain and the content of intracellular Ca++ and taurine in the heart

Summary Under certain conditions, taurine (3.0 mM) potentiated cardiac contractile response to ouabain in the normal medium. The potentiation by taurine was also observed in the low K⁺ medium, in which the positive inotropic effect of ouabain increased. The potentiation as seen in both media was, at least in part, due to the increase by taurine of Ca⁺⁺ content in the heart. Taurine in the heart was not directly related to this potentiation.     

Uptake of3H-GABA (γ-aminobutyric acid) and3H-leucine in the pancreatic islets and substantia nigra of the rat

Summary Isolated pancreatic islets and thin slices of substantia nigra (SN) of the rat were incubated in a medium containing³H-GABA or³H-leucine to test the activity of both tissues in the uptake of those substances. Pancreatic islets showed a low uptake of both³H-GABA and³H-leucine, but SN had a high activity in the uptake of³H-GABA, though not for³H-leucine. This suggests that GABA contained at high levels in the pancreatic islets plays some functional role other than in neurotransmission as in the central nervous system (CNS).     

Effect of dibutyryl cyclic AMP and analogs on the rate of contractions of myocytes in culture

Summary ²O,⁶N-butyryl, 3, 5-cyclic monophosphate (dibu cAMP) when added to fetal rat heart cells in culture inhibits myocyte contraction. This inhibition is 100, 84 and 51% complete when the dibu cAMP concentration used is 2, 0.2 and 0.02 mM, respectively. The potency of dibu cAMP derivatives in myocyte contraction inhibition follows the order, dibu cAMP> ⁶N-bu cAMP> ²O-bu cAMP=AMP>butyrate. The inhibition caused by the first three chemicals is greater than 70%.The author was a Moss Heart Fellow and acknowledges the technical assistance of Ms Martha Peet. This work was supported in part by the American Heart Association, National Science Foundation and American Cancer Society.