Abstract |
The effects of R-68070 were studied in a well-characterized model of drum-induced traumatic shock in rats. R-68070 is a combination thromboxane A2 (TxA2) synthetase inhibitor-TxA2 receptor antagonist. Pentobarbital-anesthetized (50 mg/kg) rats subjected to Noble-Collip drum trauma developed a lethal circulatory shock state characterized by a marked decrease in mean arterial blood pressure (MABP) to about 75 mmHg, resulting in a survival time of 1.58 +/- 0.18 h. This compares with MABP of 120 +/- 4 mmHg 5 h after anesthetization in rats subjected to a sham traumatic shock protocol. Administration of R-68070 (1.5 mg/kg) significantly attenuated the plasma accumulation of the lysosomal protease, cathepsin D (p less than 0.05), as well as free amino- nitrogen concentration (p less than 0.05) and myocardial depressant factor activity (p less than 0.02). Additionally, R-68070 significantly prolonged survival time to 2.85 +/- 0.48 h (p less than 0.015) compared with traumatized rats given only the vehicle. These results suggest that TxA2 may be an important mediator in traumatic shock, and that R-68070 may prove to be a useful therapeutic agent in this situation if given early in the course of the shock state.
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Authors | N Aoki, G Johnson 3rd, M R Siegfried, A M Lefer |
Journal | Eicosanoids
(Eicosanoids)
Vol. 2
Issue 3
Pg. 169-74
( 1989)
ISSN: 0934-9820 [Print] Germany |
PMID | 2534278
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Myocardial Depressant Factor
- Pentanoic Acids
- Pyridines
- Receptors, Prostaglandin
- Receptors, Thromboxane
- Valerates
- Thromboxane A2
- Cathepsin D
- Thromboxane-A Synthase
- ridogrel
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Topics |
- Animals
- Cathepsin D
(blood)
- Male
- Myocardial Depressant Factor
(blood)
- Pentanoic Acids
(therapeutic use)
- Pyridines
(therapeutic use)
- Rats
- Rats, Inbred Strains
- Receptors, Prostaglandin
(drug effects, physiology)
- Receptors, Thromboxane
- Shock, Traumatic
(drug therapy, physiopathology)
- Thromboxane A2
(physiology)
- Thromboxane-A Synthase
(antagonists & inhibitors, physiology)
- Valerates
(therapeutic use)
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