[Oleic acid-induced PaO2 decrease model for primary screening of drugs for hypoxemia: effects of tranexamic acid and procaterol hydrochloride on the decrease in PaO2].
We constructed an oleic acid (OA)-induced PaO2 decrease model in guinea pigs. We then examined several basic conditions to establish the primary screening model to determine useful drugs for hypoxemia. Hartley strain guinea pigs were anesthetized with pentobarbital (25 mg/kg) and catheterized into the subclavian artery for blood sampling and for measuring blood pressure; they were also catheterized into the subclavian vein for drug administration. Then the animal was immobilized with pancuronium (0.1 mg/kg) and ventilated by a ventilator with room air. The following results were obtained: 1) there were no significant fluctuations of PaO2, PaCO2 and pH throughout the 11 sampling over a 2-hr period. Airway pressure and blood pressure also remained relatively constant. 2) Percentage of decrease in PaO2 by OA (15 microliters/kg) in the hyperventilated group was greater than that in the normally-ventilated group. 3) Increasing doses of 10, 15, 30 and 60 microliters/kg of OA resulted in dose-dependently lower values of PaO2. 4) Tranexamic acid (2 g/kg, i.p.) significantly prevented the decrease in PaO2 at 10 and 15 min after OA (15 microliters/kg) injection. 5) Procaterol hydrochloride (0.1 microgram/kg, i.v.) failed to inhibit the decrease in PaO2 by OA (15 microliters/kg). These results suggest that by using a suitable ventilation and OA dose, this model could be used as a primary screening model of drugs for hypoxemia and that tranexamic acid might be an effective drug for hypoxemia caused by a mechanism by which OA decreases PaO2.
Moriuchi
H
H
Department of Pathopharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Yuizono
T
T
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D000860:Hypoxia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids; D010313:Partial Pressure; D017265:Procaterol / Q000627:therapeutic use*; D014148:Tranexamic Acid / Q000627:therapeutic use*
D009829:Oleic Acids; D019301:Oleic Acid; D014148:Tranexamic Acid; D017265:Procaterol