Anton H. M. Jageneau

A NEW SERIES OF POTENT ANALGESICS

potent analgesic and a potent atropine-like substanc615. Which sort of activity predominates seems to depend, in the first place, upon the nature of substituent R of structure 1,. Analgesics have been found among compounds of the methadone type, for example I, R = COC,H,, methadols and acylated methadols, I, R = CHOR’C,H,; sulfones, I, R = SO,C,H,; esters, I, R = COOC,H, ; ketimines and acylated ketimines, I, R = C : NR’C,H,2p5*

Chemistry and pharmacology of compounds related to 4-(4-hydroxy-4-phenyl-piperidino)-butyrophenone

SummaryHaloperidol (R 1625) is 50 to 100 times more active than chlorpromazine as an inhibitor of exploratory motor behaviour in rats. Emotional defaecation in rats is inhibited by both drugs at similar dose levels.

Stimulation of the coronary collateral circulation by lidoflazine (R 7904)

SummaryLidoflazine, a new and very longacting coronary vasodilator was given to 18 dogs with a chronically developing stenosis and occlusion of the circumflex coronary artery for 4 and 6 weeks respectively. 18 other dogs with chronically developing stenoses leading to occlusion of the circumflex artery were used as controls. Lidoflazine in a dosis of 20 mg/kg/day increased the speed of development of the collateral circulation and prohibited symptoms of permanent cardiac hypoxia. Permanent myocardial hypoxia, caused by a higher degree of physical activity in a group of “freely exercising” dogs produced the same favorable effects on the canine coronary collateral circulation.

The radioactive microsphere method for the assessment of regional myocardial blood flow after coronary artery occlusion

SummaryIn this study, we have tried to determine the magnitude of the inaccuracy of the radioactive microsphere method — due to variations in the diameter distribution of the spheres — for measuring regional myocardial blood flow after coronary artery occlusion. In 5 mongrel dogs, three types of 15 μm microsperes, labelled with125I,141Ce or85Sr, were injected simultaneously after the descending branch of the left coronary artery had been ligated. Myocardial samples were taken from the left ventricle and divided into four groups according to the number of spheres per sample. The radioactivity of the various isotopes per gram tissue was expressed as percentage of their activity per milliliter of the reference sample. The diameter distribution of microspheres, labelled with each of the isotopes, was determined light-microscopically in suspensions belonging to three different batches.The relative error, as determined from the difference in relative radioactivity of the various types of microspheres in the tissue samples, was higher than the theoretical error for each of the number of spheres per sample. It is very likely that this discrepancy is caused by the differences in diameter distribution of the various types of microspheres, resulting in non-random error. The smaller spheres tended to go to low flow areas and the larger ones to high flow areas. Because of the non-randomness, the error due to diameter variations in the spheres can be diminished by randomizing the order of injection of the various isotopes.The present study indicates that the relatively high degree of accuracy of the microsphere method for the determination of blood flow to large parts of the myocardium with an unimpeded coronary circulation, as was described in literature, cannot be extrapolated to the determination of regional myocardial blood flow after coronary artery occlusion, when the combination of small tissue samples, variations in the diameter distribution of the spheres and an unevenly distributed myocardial blood flow unfavourably affect the accuracy of the method.

Enhancement of coronary reactive hyperemia in unanaesthetized pigs by an adenosine-potentiator (Lidoflazine)

SummaryThe potentiation of coronary reactive hyperemia by oral doses of Lidoflazine after different periods of coronary artery occlusion in non-anaesthetized miniature pigs is described.Doses varying from 2.5 to 80 mg/kg of Lidoflazine were investigated and occlusion periods from 10 to 80 sec were used.Coronary blood flow was measured by an electromagnetic flowmeter and the occlusions were performed with a pneumatic occlusive device.The enhancement of the reactive hyperemic response is believed to result from potentiation of a transmitter substance, probably adenosine, by Lidoflazine.

A NEW SERIES OF POTENT ANALGESICS: Dextro 2:2‐diphenyl‐3‐methyl‐4‐morpholinobutyrylpyrrolidine and related basic amides: Part II :Comparative analgesic activity, acute toxicity and tolerance development in rats for R875, morphine, pethidine and methadone

The analgesic activity, acute toxicity and development of tolerance of R875, morphine, pethidine and methadone after subcutaneous administration in rats have been measured. In this animal, R875 is shown to be several times more active than the three other compounds. R875 has a faster onset of action, higher therapeutic ratios and a slower rate of development of tolerance.

A cardiac arrest model in rats for evaluating the antihypoxic action of flunarizine

Abstract Ventricular fibrillation was used to produce hypoxia in unanaesthetized rats. Flunarizine was given as hypoxia protectant in doses of 1 mg/kg i.v. just before fibrillation, which was induced with a small bipolar electrode catheter placed in the right ventricle. Aortic blood pressure (AoP), electrocardiogram (ECG) and the respiratory amplitude were recorded continuously. A significant lethality in the control group and the significantly enhanced recovery of ECG, AoP and respiration in the flunarizine groups make the model suitable to indicate antihypoxic actions of a drug.

A simple pneumatic cuff for occlusion of small arteries in dogs, pigs and sheep.

SummaryA description is given of a pneumatic arterial occlusion device which is simple to make and easy to install, and which permits reliable determination of zero flow for calibration of implanted flowmeters.

Analysis of the isovolumic pressure in the canine left ventricle.

SummarySome of the factors which influence the shape of left ventricular isometric pressure are discussed. Complete isometric recordings were obtained in dogs by raising the afterload (aortic pressure) with a special blood pump of own design. The effects of ventricular geometry, myocardial wall thickness and finite velocity of the depolarization wave are discussed. The relation between active state of muscle fibers and isometrically developed pressure in the left ventricle is derived analytically. The commonly used velocity of the contractile element was computed in a new way by differentiation of logarithmically transformed pressure data. This derived function is compared with the simple derivative (dp/dt) with regard to their potential value as indices of myocardial contractility. Contractile element velocity as based on a 3-component model was not found sensitive to so-called contractility changes in the intact heart.

Konstruktion und Eigenschaften neur Meßköpfe zur elektromagnetischen Registrierung der Blutströmung

ZusammenfassungDie physikalisch-elektronischen Eigenschaften von Strömungswandlern zur induktiven Messung der Blutströmungsgeschwindigkeit an uneröffneten Gefäßen werden analysiert. Ein Verfahren zur Herstellung verbesserter Strömungswandler wird beschrieben. Die entwickelten Instrumente unterscheiden sich von den in der Literatur beschriebenen und im Handel erhältlichen Typen durch folgende Vorteile:1.Starke Reduzierung der induktiven Störspannung bis auf höchstens etwa 10–20% des zu erwartenden Nutzsignals.2.Völlige Unterdrückung des kapazitiven Störsignals.3. Unterdrückung von Verlustwiderständen, verursacht durch Feuchtigkeitsaufnahme bei chronischer Implantation. Diese Verbesserungen konnten erreicht werden durch folgende Abweichungen vom Kolinschen3 Vorgehen:1.Die fast völlige Eliminierung der induktiven Störspannung ist nur möglich durch Anpassung der Spulenposition gegenüber der Lage der Elektrodenzuleitung und nicht umgekehrt, vorausgesetzt, daß es sich um magnetkernlose Strömungswandler handelt.2.Eine durch galvanische Metallisierung gewonnene Zwischenschicht zwischen Elektrodenebene und Spulenebene erwies sich als ein guter statischer Schirm, welcher kapazitives „Übersprechen“ von den Spulen auf die Elektroden verhindert.3.Der Metallschirm erwies sich gleichzeitig als eine Sperre gegen die Feuchtigkeitsaufnahme bei chronischer Implantation des Strömungswandlers.4.Die Kombination von Polycarbonaten, Silikonkautschuk und Akrylaten (als Verbindungsmittel) erwies sich bei der Konstruktion von Strömungswandlern als besonders günstig.5.Mit wenigen Lagen dünnen Eisendrahtes lassen sich besonders kleindimensionierte Magneten für kleine Blutgefäße herstellen.