The response of Ca-mediated action potentials and contractile activity in mammalian ventricular myocardium towards alkalosis.

Alkalosis (pH 7.8) produced by reduction of CO2 concentration augmented both upstroke velocity of Ca action potentials and isometric contractile force of mammalian heart muscle. If the increase of pH to 7.8 was achieved by a raise of HCO3 concentration (with simultaneous reduction of CO2 concentration), the positive inotropic response was not accompanied by an augmented Ca current. Obviously, the well-known positive inotropic effect of alkalosis does not only depend upon the enhancement of transmembrane Ca influx during excitation, but can be mediated alone by affecting intracellular Ca movements as well.     

Über die Wirkung von Prostaglandin E1 auf den Ca-Haushalt isolierter Meerschweinchenherzen

Summary The stimulatory effect of PGE₁ on different functions of isolated guinea-pig hearts (Langendorff method, Tyrode solution) was coupled with an increase in the rate of⁴⁵Ca uptake from the perfusion medium. The total myocardial Ca content and the amount of exchangeable cellular Ca were not affected. This action of PGE₁ on the myocardial Ca metabolism seems to be related to the positive inotropic action of PGE₁ and can most probably be explained by an increase in the membrane permeability to Ca ions (similar to the action of epinephrine).     

The influence of prostacyclin (PGI2) on contractile properties of isolated right ventricle of rat heart

The mechanism of the positive inotropic effect of prostacyclin (PGI₂) (2.6×10^?6 mol/l) on the isolated right ventricle of rat heart was studied. Our results show that the positive inotropic effect of prostacyclin is produced indirectly through beta adrenoceptors and slow Ca²⁺ channels, because blockade of slow Ca²⁺ channels with verapamil (10^?6 mol/l) and beta adrenoceptors with propranolol (10^?6 mol/l) abolishes this effect. Alpha adrenoceptors do not mediate the action of PGI₂.     

Acid-base equilibrium in the blood of sheep

Summary The acid-base equilibrium in the blood of sheep is different from that of human blood mainly because of a lower concentration of 2,3-DPG. A nomogram relating pH, pCO₂, total CO₂ content and base excess has been developed.     

The mechanics of breathing in respiratory acidosis

Zusammenfassung Nachweis, dass Inhalation von Luftgemisch mit 10% CO₂ bei wachen Kaninchen eine bronchiale Konstriktion verursacht, wenn die Lungendehnung selbst von niedrigem Blut pH begleitet ist. Erhöhung von CO₂ allein erschlafft die Bronchien und unterdrückt teilweise die Bronchienkontraktion, was mit dem niedrigen Blut pH zusammenhängt.     

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.     

Lack of effect ofTris-(hydroxymethyl)aminomethane upon myocardial contractility

Résumé Pour étudier l'action du THAM sur la contractilité, dans une préparation de myocarde isolé, on a réalisé des expériences, où l'on compare l'effet de remplacer une solution de Ringer contenant 30 mM/l de CO₃HNa, équilibrée avec une pCO₂ de 40 mm Hg (pH 7,40), par une solution de THAM ayant le même pH avec le même pCO₂. Les résultats ont permis de conclure que le THAM n'a aucune influence inotrope positive sur la contractilité, lorsque le pH extracellulaire et le pCO₂ restent invariables.     

Antihypertensive and cardiac effects of two novelβ-adrenoceptor blocking drugs

Summary Two new-adrenoceptor blocking drugs with acute antihypertensive and positive inotropic effects are described: Compound A (2-[4-(3-tert. butylamino-2-hydroxypropoxy)phenyl]-4-trifluoromethylimidazole) and MK-761 (2-(3-tert. butylamino-2-hydroxypropoxy)-3-cyanopyridine hydrochloride). In SH rats both compounds, given orally, lowered arterial pressure and were more potent than hydralazine. The antihypertensive effect of compound A but not of MK-761 was antagonized by timolol. Both compounds had positive inotropic activity on cat heart papillary muscles; these effects were antagonized by timolol. The pretreatment of animals with reserpine greatly reduced the positive inotropic effect of MK-761 but not of compound A. The acute antihypertensive and positive inotropic effects of compound A are likely to be at least partially due to stimulation of-adrenoceptors, e.g. intrinsic sympathomimetic activity. The effects of MK-761 on the same parameters appear to be mediated by different mechanisms.     

Modification des équilibres acido-basiques par le jéjunum de rat,in vitro

Summary Everted sacs of rat jejunum are able to adjust to near 6.5 any solution whose pH is situated between 5.5 and 9.5. Beyond these limits the adjustment becomes incomplete. Changes in PCO₂ and total CO₂ associated with changes in mucosal pH-values suggest that bicarbonate or CO₂-movements toward the jejunal lumen involved in this adjustment process are predominant.     

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.     

Die Wirkung von Herzglykosiden und Kalzium auf den Kaliumtransport im Herzmuskel

Summary In isolated perfused guinea pig hearts, both strophanthin and calcium produced positive inotropic effects and contracture increasing with the concentration of the drugs. Strophanthin caused a net loss of potassium from the heart to the perfusing fluid whereas calcium did not interfer in the same way with potassium exchange. The data are consistent with the view that the positive inotropic effect of cardiac glycosides depends mainly on the increased intracellular calcium concentration, perhaps due to inhibition of the active potassium and sodium transport.     

Über die Wirkung von Sr-Ionen auf den Ca2+-Austausch am Meerschweinchenvorhof

Summary When CaCl₂ in Tyrode solution was replaced by SrCl₂,⁴⁵Ca efflux from guinea-pig auricles did not change significantly. In Na-free solution, however,⁴⁵Ca influx was reduced when, in addition to CaCl₂, SrCl₂ was present in the solution, suggesting an equivalent replacement of Ca by Sr at membrane sites.     

Isoprenaline-like effects of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine on mechanical,biochemical and electrophysiological parameters in the mammalian heart

Summary The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effects of isoprenaline on the force of contraction, the cAMP content and the slow Ca⁺⁺ inward current (I_si) in isolated guinea pig papillary muscles. The results support the hypothesis that phosphodiesterase inhibitors and -adrenoceptor agonists exert their positive inotropic effects by increasing I_si via the common mediator cAMP.Acknowledgment. This work was supported by the Deutsche Forschungsgemeinschaft.     

Effect of blood pH on anionic ferritin transport through rat aortic endothelium

Summary Acute lowering of blood pH between 7.4 and 6.9 in rats by ventilation with 10 or 20% CO₂ does not increase the passage of ferritin molecules across the aortic endothelium. These results do not rule out alteration of endothelial permeability to anionic macromolecules in local circulatory disturbances when blood pH drops to levels much lower than 6.9.Supported by The Medical Research Council of Canada grant No. MA-5958.Dr J.R. Fraser was a recipient of a Summer Research Scholarship from McGill University during the completion of this study.The authors thank Colin Bier for the statistical analysis.     

Cerebrovascular reactivity to CO2: Modulation by arterial pressure

Summary Cerebrovascular reactivity to CO₂ (CO₂R), measured in halothane-anesthetized rabbits, decreased as arterial pressure was increased either pharmacologically or mechanically. On the other hand, hypotension, induced by bleeding, led to an increase in CO₂R. These responses were unaffected by denervation of baroreceptors.This work was supported by grants from NIH (HL 17903) and American Heart Association — Greater Los Angeles Affiliate (437IG). To whom requests for reprints should be sent.     

Mesodermal and endodermal differentiation of the presumptive ectoderm ofTriturus gastrula through influence of lithium ion

Zusammenfassung Stücke des präsumptiven Ektoderms der jungen Gastrula vonTriturus pyrrhogaster wurden nach 4stündiger Behandlung mit 0,06M LiCl-Lösung explantiert. Das pH wurde durch Zusatz von Li₂CO₃ auf 7.0 bis 9.8 eingestellt. Die Explantate, die bei pH 9,2 oder 9,8 behandelt wurden, differenzierten sich in zunehmender Häufigkeit neben Neuralgewebe zu Chorda und Muskulatur. Bei Behandlung mit LiCl-Lösungen von pH 7,0 und 8,0 wurden nur Blutzellen, Vornierenkanälchen oder Muskulatur in geringem Prozentsatz produziert, jedoch weder Neuralgewebe noch Chorda. Diese Explantate ergaben aber Differenzierungen von Chorda und Neuralgewebe, wenn sie nach der Li-Behandlung kurz einer Ammoniak-Lösung von pH 12,0 ausgesetzt wurden.

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This work was supported by a scientific grant of the Ministry of Education of Japan.     

Inhibition de la décarboxylation in vitro de la phosphatidylsérine par l'acide 2-aminoéthylphosphonique

Summary Diminution of in vitro phosphatidylserine decarboxylation by adding 2 aminoethylphosphonic acid to a mitochondrial suspension of rat liver was observed. When³²P-phosphatidylserine is used as the labelled substrate, there is a noticeable decrease in the specific activity of³²P-phosphatidyl-ethanolamine formed; when the labelled substrate is¹⁴C-phosphatidylserine there is a similar reduction of the amount of¹⁴CO₂ recovered.     

Der Einfluss von 2-Deoxy-D-glucose auf die Substratoxydation in Ascites-Tumorzellen

Summary The effect of the glycolytic inhibitor 2-deoxy-D-glucose on the oxidation of¹⁴C-labelled substrates of the tricarboxylic acid cycle was investigated in ascites carcinoma cells of the mouse. In the presence of high concentrations of glucose, deoxyglucose stimulates the oxidation of pyruvate C-2 and C-3 to CO₂, but not the oxidation of succinate C-1,4 to CO₂. While deoxyglucose causes, in the absence of glucose, an inhibition of the oxidation of exogenous palmitate C-1 to CO₂, it causes, in the presence of glucose, a stimulation of the palmitate oxidation. There is a possible correlation between the effect of deoxyglucose on the intracellular ATP metabolism and the effect of deoxyglucose on the palmitate oxidation.     

Ventilatory responses to CO2 at different body temperatures in the snake,Coluber constrictor

Summary Ventilatory responses to CO₂ were examined at different temperatures in the snake,Coluber constrictor. CO₂ sensitivity increased between 15 and 25°C but not between 25 and 35°C. A rapidly occurring off-CO₂ transient hyperpnea suggested the presence of an intrapulmonary chemoreceptor.     

La voie du pentose phosphate dans le métabolisme du glucose et son interaction avec la glutathion-réductase dans les noyaux de foie de rat

Summary Rat liver nuclei, isolated in sucrose medium, convert carbon-1 of glucose-6-phosphate to CO₂ via the 6-phosphogluconic acid oxidative pathway. Conversion of glucose-1-¹⁴C to¹⁴CO₂ by the cytoplasmic fraction is greatly inhibited by nuclei. In the presence of low concentrations of NADP, the CO₂ formed by nuclei is markedly increased by the addition of GSSG.