Biomedical subjects
Publications and source records attributed to R Bourgain.
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Aiming at continuous polarographic measurement of the mean pO2 in the rabbit brain cortex before, during and after photochemically induced infarction, we designed and constructed monopolar platinum oxygen electrodes of the open type for chronical implantation. The measuring tip (length 1 mm, diameter 0.1 mm) is covered with a homogenous membrane of cellulose acetate. The electrode currents are measured by a four-channel amplifier of proper design; the device permits accurate and stable polarisation, identical for each channel. Moreover, a calibration device has been constructed. It consists of a Buchner funnel filled with Ringer solution and mounted in a temperature-controlled bath. In order to create a specific partial pressure of oxygen in the calibration chamber, predetermined gasmixtures are bubbled through the solution using computer controlled mass flow regulators. The calibration device thus permits the determination of primary and secondary electrode parameters, i.e. linearity, oxygen sensitivity and residual current, and polarisation dependency, temperature dependency, sensitivity to CO2, electrode stability, dynamic behaviour and oxygen consumption. Three groups, each of them containing ten electrodes, have been tested with regard to electrode parameters: the first group contains bare electrodes, the second and the third group contain membrane covered electrodes, with a membrane thickness of 10 and 20 microns respectively. In order to evaluate acute and long-term effects of implantation on the brain cortical tissue and on the sensors' measuring qualities, electrodes have been implanted for different time periods (51 days, 30 days, 9 days, 5 min). pO2 was recorded regularly and polarograms have been registered. The effects on cortical tissue have been studied with the aid of light microscopy.
Continuous recording of changes in local pO2 during and after brain infarction in surviving animals which can be followed for months or years, may provide interesting information concerning pathophysiology and treatment of stroke and thrombosis. We performed such measurements before, during and till 4 weeks after photochemical induction of a cerebrocortical infarction in three rabbits. Rose bengal--a photosensitive dye which sticks to endothelial cells and gives rise to endothelial damage and thrombosis when illuminated--was injected intravenously. After injection, a circular area (diameter 3 mm) of the brain cortex was illuminated using an optic fiber conducting light from a halogen lamp, whether or not filtered by heat and colour filters. In order to enable pO2 measurement in and near the infarct zone, we constructed a transparent plastic frame in which pO2 electrodes were fixed beneath and 1 mm besides a shaft permitting mounting of the optic fiber. A black adhesive ring (inner diameter 3 mm) was attached to the bottom of the frame providing a perfectly demarcated illumination area. After fixation the electrodes were calibrated and the frame was implanted in the rabbit's skull. Ten days later an infarction was induced; pO2 was monitored continuously before, during and till 4 hours after this induction. Furthermore, pO2 was recorded 24 hours, 48 hours, 5 days, 14 days and 4 weeks after infarction. Parameters describing the time course of pO2 were determined. In the illuminated area pO2 decreased after a certain latency time to reach a very low level, probably zero level, where it remained for at least 24 hours. Gradually, recovery was observed during the following days, and four weeks after infarction both level and pattern of electrode current appeared to be normal again. In the border zone pO2 decreased but did not reach zero level. Recovery was observed earlier than in the illuminated area.
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It is becoming clear that PAF plays an important role in a variety of life-threatening pathologies including shock, asthma, graft rejection and ischemia-induced damage. Pierre Braquet and colleagues analyse recent reports on PAF and ischemia and propose a hypothesis based on the catastrophe theory to explain why PAF antagonists are effective in countering ischemic injury and many other disorders. PAF antagonists, perhaps in combination with other agents, may consequently prove to have extensive therapeutic potential.
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Inflammation is usually a tightly controlled process which confines tissue damage, prevents infection, and assists in cellular regeneration. However, if the inflammatory response becomes unregulated, this normally beneficial local event may escalate into a wider malignant activity, characterized by endothelial injury, excessive cell infiltration, and vascular leakage. Due to the ability of platelet-activating factor and tumor necrosis factor to elicit the release of each other, 'prime' cell responses, and influence the activity of other cytokines, we propose that these two mediators play a pivotal role in the formation of deleterious feedback cycles leading to the above endothelial damage which may underlie pathologies such as shock, sepsis, ischemia, and asthma. Platelet-activating factor antagonists such as BN 52021 inhibit the priming and other effects induced by platelet-activating factor and thus may be of therapeutic value in such conditions.
An animal model was developed, permitting the study of thromboxane A2 and prostacyclin neoformation, after arachidonic acid (AA) injection. Two types of physiopathological responses were observed, according to the rabbit strains. In the first type, prostacyclin neoformation was predominant, AA injection inducing only reversible hypotension. In the second type, thromboxane A2 neoformation was prevalent, AA injection inducing irreversible hypotension, marked myocardial troubles, shock, and death. In both types, injection of cicletanine (5 x 10(-5) mole/kg) significantly enhanced prostacyclin neoformation. After cicletanine, a new hypertensive drug, rabbits of the second type responded like those of the first type, without severe physiopathological responses to AA injections.
BN 50341, a new benzazepine derivative, which has been shown to possess a mild anticalcic activity decreased (oral or i.v. administration) and also totally reversed (local superfusion) the in vivo electrically induced thrombus formation in rat or guinea-pig artery. These effects of BN 50341 were correlated with an inhibition of PAF-acether- and thrombin-induced platelet activation since it decreased free cytoplasmic calcium mobilization measured on cells loaded with the fluorescent probe Quin 2. Taking into account the beneficial effects of BN 50341 on vascular spasm as well as on the early stage of the process of white thrombus formation, this drug could be of therapeutic interest.
Two different families of diuretic drugs--(i) (aryloxy)acetic acid diuretics (ethacrynic acid, tienilic acid and (--)-indacrinone) and (ii) furopyridines [(+/-)-BN 50157 and (+/-)-cycletanide]--stimulate K+ movements across human red cell membranes. The kinetic properties of this effect (K+-specificity, saturability, optical isomerism, antagonism by structural analogues, etc.) strongly suggest that it is mediated by a K+-transport system with a specific binding site for some diuretic drugs. The stimulated K+ fluxes are resistant to ouabain, bumetanide and quinine, thus suggesting that they are not mediated by the Na+,K+-pump, Na+,K+-cotransport or by the Ca2+-dependent K+-permeability ('Gardos effect'). The replacement of Cl- by NO3- ions can either decrease, increase or have no effect on the stimulated K+ fluxes, depending on the diuretic drug. Although not conclusive, these observations suggest that the K+ fluxes are not mediated by stimulation of a chloride-dependent K+ carrier. The study of structural analogues showed that the intensity of the stimulation of K+ fluxes is strongly correlated with the magnitude of the natriuretic effect. Curiously, some antiallergic furopyridines are able to inhibit K+ fluxes.
A method for the recording of mass transport velocity in tissue, related to the relative local mass flow, has been developed. It is based on the heat clearance principle, applied in the continuous mode. Thermistors are used as temperature sensors; heating is performed by a high frequency square wave, thus avoiding an additional heating coil. The cooling of the heated thermistor, with as a reference a non-heated one, is related to the local mass transport velocity. A test equipment has been built for the calibration of the device and a set of results have been obtained in test fluids with a thermal conductivity approaching the one of brain tissue (glycerin and water). A mathematical model has been set up which gave results consistent with the recorded data. From this model significant parameters could be derived which, introduced in a compensation circuit, may be used in order to linearize the relation between the measuring value and the velocity variable. In vivo results in the brain cortex of the rabbit have been obtained.
For several years, the formation and evolution of thrombi in small arteries of rats has been quantitatively studied at the laboratory of PHYSIOLOGY and PHYSIOPATHOLOGY at the V.U.B. Global size parameters can be determined by projecting the image of a small arterial segment onto photosensitive cells. The transmitted light intensity is a measure for the thrombotic phenomenon. This unique method permitted extensive in vivo study of the platelet-vessel wall interaction and local thrombosis. We actually attempt to refine the spatial resolution of these measurements in order to get information on texture and form of the thrombotic mass at any stage of its evolution. Therefore a thorough understanding of how light propagates through non hemolyzed blood is essential. Application of results from Twersky's multiple scattering theory, combined with appropriate border conditions and parameter values was attempted. It is well known that the erythrocytes are mostly aligned in the direction of the blood flow. In order to explain the measured intensity profiles, we had to postulate alignment in the plane perpendicular to the flow as well. The theoretical predictions are in good agreement with the experimental values if we assume almost perfect alignment of the erythrocytes such that their short axes are pointing in the direction of the center of the artery. Conclusive evidence of the interaction between local flow properties and light transmission could be found by observing arteries with perturbated flow.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.