Thromboxane ischaemia

Hall and Wolf [217] have proposed a hypothesis, concerning the pathogenesis of post-traumatic central nervous system ischaemia, which integrates an injury-induced rise in intracellular Ca2+, the increased synthesis of vasoactive prostanoids and progressive microvascular lipid peroxidation. The model used anaesthetised cats with a contusion injury to the lumbar spinal cord. Antioxidants, vitamin E and selenium, were compared with various Ca2 + antagonists, cyclo-oxygenase inhibitors, a thromboxane synthetase inhibitor and the stable prostacyclin analogue. The most impressive preservation of post-traumatic spinal cord blood flow was provided by the antioxidants. 

Figure 6.6 Urinary 2,3-dinor-thromboxane (Tx) B2 and 2,3-dinor-6-keto-prostaglandin (PG) and plasma II-dehydro-TxB2 (inset) before and following exercise-induced myocardial ischaemia in patients with stable coronary artery disease...

Two clinical studies have demonstrated that aspirin reduces the incidence of myocardial infarction and death by up to 50% in patients with unstable angina, suggesting an important role for thromboxane A2 in their occur-rence . Whether platelet activation and thromboxane A2 also play a role in the episodic ischaemia of unstable angina is unknown. Evidence of platelet activation " in patients with unstable angina based on plasma levels of platelet granule proteins, such as j8-thromboglobulin and platelet factor 4, is difficult to interpret since such measurements are highly sensitive to ex vivo platelet activation . Similarly, studies of thromboxane A2 biosynthesis have been... 

Despite the increase in thromboxane A2 biosynthesis during episodes of ischaemia, aspirin does not appear to alter the frequency of chest pain in patients with unstable angina . This might suggest that platelet activation does not play a role in the pathogenesis of these spontaneous ischaemic... 

Coker, S.J. and Parratt, J.R. (1985). AH23848, a thromboxane antagonist, suppresses ischaemia and reperfusion-induced arrhythmias in anaesthetized greyhounds. Br. ]. Pharmacol, 86, 259-264... 

Fredriksson, K., Rosen, L, Johansson, B., Wieloch, T., 1983 The thromboxane synthetase inhibitor OKY-1581 prevents cerebral ischaemia and neural transmission failure induced by sodium arachidonate platelet aggregation. J. Cereb. Blood Flow Metab. (Suppl. 1) i, S293-S294. 

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