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Effects of TCV-309, a novel PAF antagonist, on circulatory shock and hematological abnormality induced by endotoxin in dogs. 1994

M Kawamura, and T Kitayoshi, and Z Terashita, and S Fujiwara, and M Takatani, and K Nishikawa
Pharmaceutical Research Division, Takeda Chemical Industries Ltd, Osaka, Japan.

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.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008297 Male Males
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D010976 Platelet Count The number of PLATELETS per unit volume in a sample of venous BLOOD. Blood Platelet Count,Blood Platelet Number,Platelet Number,Blood Platelet Counts,Blood Platelet Numbers,Count, Blood Platelet,Count, Platelet,Counts, Blood Platelet,Counts, Platelet,Number, Blood Platelet,Number, Platelet,Numbers, Blood Platelet,Numbers, Platelet,Platelet Count, Blood,Platelet Counts,Platelet Counts, Blood,Platelet Number, Blood,Platelet Numbers,Platelet Numbers, Blood
D011726 Pyridinium Compounds Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N. Compounds, Pyridinium
D001775 Blood Circulation The movement of the BLOOD as it is pumped through the CARDIOVASCULAR SYSTEM. Blood Flow,Circulation, Blood,Blood Flows,Flow, Blood
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts

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