Excretion of thromboxane A2 and prostacyclin metabolites during treadmill exercise in patients with intermittent claudication

Platelet activation, with subsequent formation of thromboxane A₂ (TxA₂), is thought to play a role in the development of arterial occlusion. In patients with severe atherosclerosis of the lower limbs, characterized by leg ulcers and rest pain, the basal formation of TxA₂ and prostacyclin (PGI₂) is increased. Corresponding data in patients with more moderate atherosclerosis of the lower limbs have not been reported. Since the capacity to physical exercise is not blunted in such patients proper evaluation of their TxA₂-PGI₂ synthesis should comprise not only assessment of the basal formation, but also TxA₂/PGI₂ biosynthesis during conditions of elevated cardiovascular activity. To address this, we analysed these eicosanoids in patients with a history of intermittent claudication. Urinary dinormetabolites of TxB₂ and PGI₂ (Tx-M and PGI-M, respectively) were estimated by gas chromatography/negative ion-chemical ionization mass spectrometry in samples collected prior to, during and immediately after 20 min of severe treadmill exertion. The basal excretion of Tx-M was 105 ± 26 pg/mg creatinine. It was not changed during exercise, but increased to 176 ± 48 pg/mg creatinine (P<0·05) during the recovery. The basal excretion of PGI-M was 142 ± 25 pg/mg creatinine. The PGI-M response to exercise varied from no change at all to a 30-fold increase, without any obvious correlation to experienced leg pain, walking distance or other recorded variables. During the recovery period the outflow of PGI-M was significantly higher than at rest (482 ± 145 pg/mg creatinine; P<0·01). We conclude that in patients with intermittent claudication due to atherosclerosis (1) platelet activation does not occur during the course of the exercise, and (2) vascular prostacyclin formation can be dissociated from of TxA₂ synthesis. The observed increase in PGI-M in some of the patients is suggested to reflect tissue ischaemia induced by the lack of adequate hyperaemia during exercise.