Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast medium in rats.
The effects of carbazochrome sodium sulfonate (AC-17), a capillary stabilizer, on pulmonary edema and dysfunction induced by ioxaglate, an ionic radiographic contrast medium, were evaluated in rats. The pulmonary edema was evaluated by the extravasation of intravenously injected Evans blue into lung tissues, while pulmonary dysfunction was determined by monitoring blood gasses including pO(2). Ioxaglate (4 g I/kg, i.v.) caused a marked increase in vascular permeability and a decrease in arterial pO(2). AC-17 reversed the ioxaglate-induced vascular hyperpermeability in a dose-dependent manner. In addition, AC-17 (10 mg/kg) significantly inhibited the decrease in arterial pO(2). In isolated rat pulmonary mast cells, ioxaglate markedly enhanced the histamine release, which was not affected by AC-17. On the other hand, AC-17 did significantly blocked the hyperpermeability induced in cultured bovine endothelial cells by tryptase, thrombin and proteinase-activated receptor-2 agonist peptide (SLIGKV-NH(2)). These findings suggest that AC-17 blocks radiographic contrast medium-induced pulmonary dysfunction by maintaining the endothelial barrier function. Thus, the compound is potentially useful for the prophylaxis of contrast media-induced acute pulmonary adverse events during angiography.
Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. sendou@st.hosp.kyushu-u.ac.jp
Toshiaki
T
Sendo
Takeshi
T
Goromaru
Keisei
K
Aki
Naoko
N
Sakai
Yoshinori
Y
Itoh
Ryozo
R
Oishi
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D003287:Contrast Media / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects; D007485:Ioxaglic Acid / Q000633:toxicity*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D010100:Oxygen; D007485:Ioxaglic Acid