ISCHEMIA OF THE LIMB STIMULATES THROMBOXANE PRODUCTION AND MYOCARDIAL DEPRESSION

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 157  (6) , 500-504
Abstract
Thromboxane A2 is thought to be an important mediator of cardiopulmonary dysfunction, hence stimuli that effect synthesis of this prostanoid are of major interest. The thesis that ischemia of the limb is a significant stimulus to thromboxane A2 synthesis and the generation of a circulating negative inotrope was tested. Twelve healthy volunteers, taking no medications and ranging in age from 21 to 29 yr, underwent inflation of an arm cuff to either 70 or 220 mm Hg for 10 min. Immediately after deflation of the cuff from 220 mm Hg, the stable degradation product of thromboxane A2, thromboxane B2, rose from a base line plasma level of 34 .+-. 6 pg/ml (mean .+-. SEM [standard error of the mean]) to 70 .+-. 18 pg/ml. In contrast, deflation from a cuff pressure of 70 mm Hg resulted in a lower thromboxane B2 level of 26 .+-. 9 pg/ml (P < 0.05). Plasma obtained before and after inflation of the cuff to 220 mm Hg was used to bathe a rat papillary muscle. Developed tension fell from a base line of 2.80 .+-. 0.19 to 2.44 .+-. 0.17 g (P < 0.01). There was no significant change in developed tension induced by plasma harvested after the cuff was inflated to 70 mm Hg. The baseline plasma level of 6-keto-prostaglandin F1.alpha. the hydrolysis product of prostacyclin, was 46 pg/ml; the plasma serotonin, 51 ng/ml; the platelet serotonin, 1.02 .mu.g/109 platelets; platelet count, 220,000/mm2, and white blood count, 6094 mm2. These values did not change significantly with cuff inflation to either 220 or 70 mm Hg. Evidently, ischemia of the limb leads to thromboxane A2 production. Possible adverse cardiac effects related to this event are suggested by the bioassay demonstrating that circulating plasma with high levels of thromboxane B2 is associated with the depression of tension of an isolated rat papillary muscle.