Abstract |
We investigated the effects of TCV-309, a novel platelet activating factor (PAF) antagonist, on circulatory dysfunction and hematological abnormalities in experimental canine endotoxin (ET) shock. ET caused biphasic hypotension with a decrease in cardiac output (CO), left ventricular systolic pressure (LVP) and its dp/dt(max). The first hypotensive phase occurred within 15 min, and the second phase between 90 and 180 min following the injection of ET. Pulmonary vascular resistance (PVR) abruptly increased at 15 min with a partial recovery, and was then sustained at twice the basal value throughout the experiment. TCV-309 attenuated the hypotension, the decrease in CO, LVP and its dp/dt(max), and the increase in PVR. TCV-309 had no significant effect on the increase in TPR. The decrease in plasma fibrinogen and the increase in hematocrit and plasma lactate were significantly attenuated by TCV-309. These data suggest that PAF may be a key mediator leading to shock in sepsis.
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Authors | M Kawamura, T Kitayoshi, Z Terashita, S Fujiwara, M Takatani, K Nishikawa |
Journal | Journal of lipid mediators and cell signalling
(J Lipid Mediat Cell Signal)
Vol. 9
Issue 3
Pg. 255-65
(May 1994)
ISSN: 0929-7855 [Print] Netherlands |
PMID | 7921785
(Publication Type: Journal Article)
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Chemical References |
- Isoquinolines
- Platelet Activating Factor
- Pyridinium Compounds
- Tetrahydroisoquinolines
- TCV 309
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Topics |
- Animals
- Blood Circulation
(drug effects)
- Blood Pressure
(drug effects)
- Disease Models, Animal
- Dogs
- Heart
(drug effects, physiopathology)
- Hematologic Diseases
(drug therapy, etiology)
- Hemodynamics
(drug effects)
- Isoquinolines
(pharmacology)
- Male
- Platelet Activating Factor
(antagonists & inhibitors, physiology)
- Platelet Count
(drug effects)
- Pyridinium Compounds
(pharmacology)
- Shock, Septic
(blood, drug therapy, etiology)
- Tetrahydroisoquinolines
- Time Factors
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