The beneficial effects of a thromboxane receptor antagonist on spinal cord perfusion following experimental cord injury.
The eicosanoids thromboxane A2 and prostacyclin have opposing actions causing vasoconstriction and vasodilation respectively. The ratio of these two eicosanoids is thus an important determinant of circulatory homeostasis. An increase in this ratio occurs in certain inflammatory conditions with dramatic consequences in organ perfusion. In spinal cord trauma, in addition to direct physical perturbation of the spinal cord, it is likely that further structural and functional loss occurs as a result of decreased tissue perfusion precipitated by an increase in the thromboxane/prostacyclin ratio. This study evaluated hemodynamics and organ perfusion, 3 h following 24 g-cm spinal cord trauma in the rat. The role of thromboxane was investigated with an inhibitor of thromboxane synthesis (Dazoxiben) and with a receptor antagonist (13-APT). Cardiac output and blood pressure were unaffected by Dazoxiben, 13-APT, or spinal cord trauma. Injury effected approximately a 40% decrease in spinal cord perfusion from 0.41 to 0.25 ml/min/g which was not improved by the thromboxane synthase inhibitor, Dazoxiben. 13-ATP completely abrogated the decline in spinal cord blood flow flowing injury. Perfusion of other selected organs demonstrated little change as a result of the spinal trauma. Brain flow remained constant at 0.78 ml/min/g brain. Coronary blood flow, however, declined from 3.2 to 2.0 ml/min/g heart tissue. The data suggest consideration of the importance of thromboxane in therapeutic attempts to reduce secondary injury arising in spinal cord trauma.
Tempel
G E
GE
Department of Physiology, Medical University of South Carolina, Charleston 29425.
Martin
H F
HF
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D007093:Imidazoles; D010627:Phenethylamines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C029166:dazoxiben; C045021:7-(2-(4-hydroxyphenethylamino)cyclopentyl)heptanoic acid; D013930:Thromboxane-A Synthase