Key result
5-HT2 antagonism abolishes coronary thrombus formation, requiring a ~39-fold adrenaline increase to restore growth.
Why the study?
The study sought to quantitate the interaction between adrenaline and 5-hydroxytryptamine on the rate of platelet thrombus formation in the stenosed coronary artery with damaged endothelium.
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5-HT2 antagonism may inhibit coronary thrombosis in adrenaline-elevated states; leaves open translation to human ACS.
The interaction between adrenaline and 5-hydroxytryptamine (5-HT) has been quantitated on the rate of thrombus formation, in the stenosed coronary artery with damaged endothelium of the anaesthetized dog. 2. Changes in the plasma concentration of adrenaline were produced by varying the rate of an intravenous infusion of adrenaline and in the effects of 5-HT, by intravenous injections of the selective 5-HT2 receptor antagonist, ICI 170809. 3. Increases in the plasma concentration of adrenaline, which did not cause significant changes in blood pressure and heart rate, increased the rate of thrombus formation. 4. Antagonism of the 5-HT2 receptor by ICI 170809, in the absence of an infusion of adrenaline, abolished thrombus formation (mean ED50 0.41 microgram kg-1, i.v.). 5. The effects of adrenaline were non-competitively antagonized by ICI 170809; maximum effects were obtained in the dose-range 50-200 micrograms kg-1, i.v., when the mean dose-ratio increase in adrenaline required to restore equivalent rates of thrombus formation was 39 fold. 6. These results are consistent with a synergism between adrenaline and 5-HT and emphasize the importance of both on thrombus formation.
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McAuliffe et al. (1993) studied Stenosed coronary artery with damaged endothelium and platelet thrombus formation. Intravenous adrenaline infusion and selective 5-HT2 receptor antagonist ICI 170809 vs. Absence of adrenaline infusion or baseline was evaluated on Rate of platelet thrombus formation in the stenosed coronary artery. 5-HT2 receptor antagonism by ICI 170809 abolished coronary thrombus formation (ED50 0.41 mcg/kg) and required a 39-fold adrenaline dose increase to restore thrombus growth.
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