René Bourgain

The effect of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (paf-acether) on the arterial wall.

The effect of a topical paf-acether superfusion over an injured arterial segment was assessed in the guinea-pig, using an opto-electronic in vivo thrombosis model allowing on-line quantification of small platelet thrombus dynamics. As compared to control, ADP-induced, thromboformation and behaviour, exogenous paf-acether causes a large, dense platelet thrombus, invaded and surrounded by numerous leukocytes, spreading widely over the adjoining, vacuolized, endothelium. Its embolization has to be forced with prostanoids, mepacrine, EDTA, or with a specific paf-acether antagonist (BN 52021). A few minutes after such forced embolization, a new thrombus starts growing at the same site, without renewal of the paf-acether superfusion. This phenomenon of spontaneous reappearance after forced embolization can be followed during several hours. Experiments with labelled paf-acether and the paf-acether antagonist indicate a possible endogenous paf-acether (or paf-acether-like) production triggered by superfusion with exogenous paf-acether.

Anti-Anaphylactic Properties of BN 52021: A Potent Platelet Activating Factor Antagonist

PAF-acether is a potential mediator of anaphylaxis and inflammatory reactions (Benveniste, Henson and Cochrane, 1972). It is released by various immune and chemical stimuli from inflammatory cells (basophils, neutrophils, eosinophils, macrophages, platelets) as well as from vascular endothelium; PAF-acether increases vascular permeability and causes sustained hypotension and thrombosis (reviewed by Braquet et al., 1986; Vargaftig and Braquet, 1987). It may also participate in various hypersensitivity reactions including bronchial asthma which cannot be fully accounted for by the known inflammatory mediators, including peptido-leukotrienes (reviewed by Vargaftig et al., 1985).

Properties of the Spontaneous Fluctuations in Cortical Oxygen Pressure

In previous publications (Manil et al., 1978; 1981; Bourgain et al., 1980) the spontaneous fluctuations of the cortical tissue pressure in oxygen (Po2) in the awake rabbit were described in detail. The mean amplitude of these irregular oscillations was 5% of the normal local Po2 where 100% is defined as the value recorded in normal control conditions and 0% as the value recorded when death occurred after sustained pure nitrogen breathing. Analysis of the frequency domain demonstrates that in control conditions the power of the spectrum decreased from 0.06 to 0.5 Hz.

Modulation of prostacycline synthetase by cicletanine and drugs which affect ion transport

Cicletanine, a drug which affects membrane ion transport, induces a marked increase of the liberation of PGI2 as demonstrated by the increase of the stable metabolites in the plasma following intravenous administration of arachidonic acid. Furthermore, the inhibiting effect of tranylcypromine on prostacyclin synthetase is completely removed by this pharmacon. These observations are suggestive that this drug presents a scope for treatment of thrombotic disorders as well as hypertension.

Thrombus induction by endogenic PAF-acether and its inhibition by Ginkgo Biloba extracts in the guinea pig

The anti-thrombotic effects of specific paf-acether antagonist BN 52021 were compared to the effects of Ginkgo Biloba extracts A, B, (A + B), and C. Local superfusion of BN 52021 over an experimentally injured arterial segment embolizes an existent paf-acether induced platelet thrombus. When applied before paf-acether, BN 52021 prevents local thromboformation in this model. Applied intravenously, BN 52021 reduces local thromboformation in a significant way. As compared to this BN 52021 standard, only Ginkgo Biloba B and the (A + B)-mixture present major thromboreductive activity.

Modifications of Somatosensory Evoked Cortical Potentials during Hypoxia in the Awake Rabbit

Bicher et al. (1971, 1973) evidenced that the decrease of tissue pO2 in the cortex of the cat under nitrogen breathing was followed by an increase of this pO2. The phenomenon is accompanied by an increase in cerebral blood flow and a blocking of the action potentials registered at the prefrontal level of the cortex. Bicher (1974) postulated that the increase in tissue pO2 is due to two compensatory autoregulatory mechanisms; firstly local vasodilation and secondly an active inhibition of the neuronal discharge which decreases the oxygen consumption by limiting the sodium influx into the cell and thus reducing the sodium/ potassium pump energy expenditure, although it is generally admitted that oxygen deficiency causes a decrease of the activity of the pump with progressive cell membrane depolarization. It is well Known indeed that the activity of the nervous system is rapidly abolished by anoxia. Lack of oxygen suppresses both the unitary discharge of the cells and even to a greater extent the synaptic transmission. In the present investigation the modifications of the somatosensory evoked potentials in the unrestrained awake rabbit were studied during hypoxia of the moderate (12 %) and severe (6.5 %) type.

Role of the Prostaglandin Biochemical Pathway in Platelet-Vessel Wall Interaction and Local Thrombosis

Prostaglandins play an important role in the platelet-vessel wall interaction. The inhibition of PGI2 synthetase results in an increase of platelet thrombosis induced by adenosine diphosphate. Addition of exogenous arachidonic acid further increases the phenomenon. The ratio of cyclic endoperoxides (PGG2 and PGH2) to prostacyclin (PGI2) could well be the determining trigger in platelet-vessel wall interaction and local thrombosis.

Antagonism by suloctidil of arterial thrombus formation in rats

Abstract Suloctidil, a new vascular antispasmodic agent, was tested for its antithrombotic activities on thrombosis induced in rats by ADP application on mesenteric arteries previously submitted to a standardized electrical D.C. current. Thrombus formation was significantly reduced (by 80%) by the drug (1 mg/kg i.v.), latency for appearance of the thrombus was lengthened and rate of formation was slowed. The protecting effect afforded by suloctidil lasted one hour. Using the filter loop technique it was shown that, at the same dose, suloctidil inhibited ADP induced platelet aggregation by 70% and was about 10 times more potent than dipyridamole.

Endogenic PAF-acether production by Guinea pig endothelial cells in experimental arterial thrombosis

Superfusion of PAF-acether over a branch of the mesenteric artery in the guinea pig invariably results in local endothelial injury and thrombus formation within 3-10 minutes. The thrombotic phenomena do not disappear when PAF-acether superfusion is discontinued, and even when forced embolization is induced. Within a very short interval renewal of thrombosis occurs at the same site. Several data point to a mechanism involving generation and release of endogenic PAF-acether. Recents findings on PAF-acether release by cultured endothelial cells indicate that in the in vivo situation this phenomenon could well be responsible for maintaining the thrombotic status as demonstrated by ultrastructural analysis. In a later stadium polymorphonuclear leukocytes are also involved in total thromboformation.

Endothelial Injury and Platelet Thrombosis in Mesenteric Arteries of Rats: A Scanning Electron Microscopy Study

For several years, an in vivo model for the induction and on-line quantification of arterial platelet thrombosis in mesenteric arteries of a small laboratory animal species has been developed in our laboratory. In the present paper, we further document the intimal lesions and the ADP superfusion-induced local platelet thrombus as seen in the scanning electron microscope. The surface morphology of the intimal lesion, induced by electric current, shows a circular or slightly oval denuded area, affecting about 15-20 endothelial cells. The edge of this lesion is often occupied by partially disrupted and detached endothelial cells. The successive embolizations of several ADP thrombi clean this edge and augment the denuded area. The final lesion never exceeds the area of 30-40 endothelial cells. ADP-induced platelet thrombi in invariably appear as loose, sponge-like platelet aggregates, very bloodstream-lined, anchored on the denuded subendothelium. There is an excellent correlation between the in vivo light microscopic observations and the actual ultrastructure of this platelet mass.