Adrenaline and Experimental Thrombosis*

Abstract

The acceleration of blood coagulation in vivo by adrenaline was first demonstrated by Vosburgh and Richards in 1903. They showed in man that adrenaline in doses of 7 μg. per kg. body weight shortened the coagulation time by about 50 per cent. Subsequent studies led to conflicting conclusions until the experiments of Cannon and Gray in 1914, who showed that small doses of adrenaline promoted coagulation, but that larger doses inhibited it. This was confirmed by later investigators (Waldron, 1951; Forwell and Ingram, 1957) but, so far as we know, the effect in normal animals of adrenaline on thrombus formation, as distinct from coagulation, has not been explored. More recently, evidence has been presented that adrenaline increases Factor‐VIII activity (Ingram, 1961), shortens platelet survival and increases platelet turnover (Adelson, Rheingold, Parker, Buenaventura and Crosby, 1961; Özge and Mustard, 1964). Recently, Mitchell and Sharp (1964) and O'Brien (1963) have shown that adrenaline promotes platelet aggregation in vitro. In the present study we have directed our attention to the effect of this drug on blood coagulation, platelets and thrombus formation. Quantitative study of thrombus formation has been made possible by the development of a standard extracorporeal circulation which allows precise measurement (Downie, Murphy, Rowsell and Mustard, 1963). In view of the findings of earlier investigators studying coagulation, it seemed important to determine how dosage levels affect the results.

Markers of Haemostatic Activation before and after Blood Donation and Plasmapheresis

“…The possible pathophysiological link between blood loss and haemostatic activation is unknown, but studies in animals and humans seem to suggest that neurohumoral, in particular adrenergic, mechanisms could be involved [34][35][36][37][38][39]. The neurohumoral response to haemorrhage is complex, however, and may depend on factors such as the species investigated, the amount of blood lost and the use of anaesthesia [40].…”

The effects of carbon disulphide exposure on brain catecholamines in rats

“…As catecholamines or drugs acting on catecholamine metabolism can influence brain functions and behaviour (Hornykiewicz, 1966 ;Brodie, Spector & Shore, 1959;Dewhurst, 1968), vasoregulation (Furchgott, 1955), thrombus formation (Rowsell, Carbon disuilphide on brain catecholamines Hegardt, Downie, Mustard & Murphy, 1966), lipid metabolism (Wirsen, 1965), the development of cardiovascular lesions (Mehes, Papp & Rajkovits, 1967;David, Hecht & Uerlings, 1968 ;Nityanand, 1967 ;Whittington-Coleman, Carrier & Clower, 1968), the effect of CS2 on catecholamine metabolism might be a common denominator for the development of carbon disulphide intoxication. This hypothesis that CS2 acts on the metabolism of catecholamines gained support by reports that disulfiram (Goldstein, Anagnoste, Lauber & McKereghan, 1964;Musacchio, Kopin & Snyder, 1964) and diethyldithiocarbamate (DDC) (Carlsson, Lindquist, Fuxe & Hokfelt, 1966;Edington, 1968) inhibit dopamine-p-hydroxylase, and disulfiram is metabolized through DDC to CS2 (Johnston & Prickett, 1952;Fischer & Brantner, 1967).…”

Diurnal variations of platelet stickiness compared with effects produced by adrenaline.

“…Mitchell and Sharp (1964) found that both amines accelerated platelet clumping. Rowsell et al (1966) and noradrenaline on platelet aggregation in vitro. He also suggested (O'Brien, 1964a) that these catecholamine effects might be due to the stimulation of an adenosine triphosphatase.…”