PLATELET-DERIVED THROMBOXANE A(2) DECREASES MICROVASCULAR PERFUSION AFTER ARTERIAL REPAIR

Previous work suggests that cod liver oil helps to protect the microci rculation from the consequence of thromboembolic events. The possibili ty that altered synthesis of thromboxane A(2) accounts for the protect ive effects seen with cod liver oil was investigated in the present st udy. This was done using the combined thromboxane A(2) synthetase inhi bitor and thromboxane A(2)-prostaglandin H-2 receptor blocker R68070 ( Ridogrel). A standardized microvascular injury was inflicted on the ri ght iliac artery of the rat to generate emboli. The downstream cremast er muscle was used to visualize the passage of the ensuing emboli and to assess the effects of this arterial injury on capillary perfusion a nd arteriole diameters. The number of visible emboli was not changed b y either cod liver oil diet or Ridogrel administration. However, capil lary perfusion was preserved by using cod liver oil (n = 7) and was si gnificantly increased by using Ridogrel (n = 7) in comparison with unt reated controls (n = 7) in which capillary perfusion was decreased bec ause of the emboli. The administration of Ridogrel to cod liver oil-tr eated animals (n = 7) provided no additive benefit. The percentage cha nge in A-2 vessel diameters in cod liver oil-treated (n = 7) animals w as no different from the control group (n = 7). Ridogrel (n = 7), on t he other hand, produced a significant increase in A-3 vessel (n = 21) diameters, but its effects were comparatively less in the cod liver oi l-treated animals (n = 7). The formation of platelet aggregates (embol i) appears relatively independent of thromboxane A(2) in the rat. Rido grel is very effective in protecting the microcirculation, and these e ffects appear to be mediated by A-3 vasodilatation, which, therefore, is at least partially thromboxane A(2)-dependent. The positive effects of cod liver oil may be mediated by a mechanism that reduces thrombox ane A(2) synthesis, but further studies are necessary.