Platelet-derived thromboxane A2 decreases microvascular perfusion after arterial repair.
Previous work suggests that cod liver oil helps to protect the microcirculation from the consequence of thromboembolic events. The possibility that altered synthesis of thromboxane A2 accounts for the protective effects seen with cod liver oil was investigated in the present study. This was done using the combined thromboxane A2 synthetase inhibitor and thromboxane A2-prostaglandin H2 receptor blocker R68070 (Ridogrel). A standardized microvascular injury was inflicted on the right iliac artery of the rat to generate emboli. The downstream cremaster muscle was used to visualize the passage of the ensuing emboli and to assess the effects of this arterial injury on capillary perfusion and arteriole diameters. The number of visible emboli was not changed by either cod liver oil diet or Ridogrel administration. However, capillary perfusion was preserved by using cod liver oil (n = 7) and was significantly increased by using Ridogrel (n = 7) in comparison with untreated controls (n = 7) in which capillary perfusion was decreased because of the emboli. The administration of Ridogrel to cod liver oil-treated animals (n = 7) provided no additive benefit. The percentage change in A-2 vessel diameters in cod liver oil-treated (n = 7) animals was no different from the control group (n = 7). Ridogrel (n = 7), on the other hand, produced a significant increase in A-3 vessel (n = 21) diameters, but its effects were comparatively less in the cod liver oil-treated animals (n = 7). The formation of platelet aggregates (emboli) appears relatively independent of thromboxane A2 in the rat. Ridogrel is very effective in protecting the microcirculation, and these effects appear to be mediated by A-3 vasodilatation, which, therefore, is at least partially thromboxane A2-dependent. The positive effects of cod liver oil may be mediated by a mechanism that reduces thromboxane A2 synthesis, but further studies are necessary.
O'Shaughnessy
M
M
Division of Plastic and Reconstructive Surgery, Cork University Hospital, Ireland.
Anderson
G L
GL
Acland
R D
RD
Barker
J H
JH
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D003060:Cod Liver Oil / Q000627:therapeutic use*; D004617:Embolism / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007083:Iliac Artery / Q000293:injuries; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply*; D010421:Pentanoic Acids / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D010421:Pentanoic Acids; D011725:Pyridines; D013928:Thromboxane A2; D003060:Cod Liver Oil; D013930:Thromboxane-A Synthase; C060219:ridogrel