Beneficial effects of a novel anti-hypoxemic agent, TEI-7322, on bleomycin-induced experimental hypoxemia in rats.

Abstract

Almitrine bismesylate is known to be an anti-hypoxemic agent that acts via the enhancement of hypoxic pulmonary vasoconstriction. However, screening for this class of compounds has been minimal, owing, in part, to a lack of convenient hypoxemic models in small animals. The present study was designed to establish a convenient model of hypoxemia induced by bleomycin and to evaluate anti-hypoxemic agents including a newly synthesized compound. TEI-7322, 2-allylamino-4-tert-butyl-amino-7-methyl-7H-pyrrolo[2,3- d]pyrimidine hydrochloride by using this model. Bleomycin was intratracheally instilled into rats. After 3 weeks, the arterial blood gas pressures were monitored in the animals in the conscious state. Then, prednisolone, doxapram, almitrine or TEI-7322 was administered to the bleomycin-treated rats to monitor changes in arterial blood gas pressures. Bleomycin-treated rats showed a decrease in the arterial blood O2 pressure (PaO2). The blood CO2 pressure (PaCO2) increased, along with an increase in the alveolar-arterial oxygen difference (AaDO2). These blood gas pressures in bleomycin-treated rats were not affected by treatment with prednisolone. Doxapram decreased the PaCO2 but did not change the PaO2. However, administration of almitrine or TEI-7322 significantly improved the PaO2 of bleomycin-treated rats with a decrease in the PaCO2. In conclusion, (1) bleomycin-induced lung injury causes hypoxemia in rats, probably resulting from ventilation-perfusion inequality; thus this model may be useful for evaluating anti-hypoxemic agents; and (2) TEI-7322, as well as almitrine, showed anti-hypoxemic effects in this model with different properties from those of doxapram, possibly due to improvement of ventilation-perfusion inequality, indicating that TEI-7322 may be a potent candidate for the treatment of hypoxemia.

• Authors: H Horiuchi, Y Uejima, Y Sakuma, T Kadota, N Okada, K Taniguchi, K Takenouchi, Y Yamanaka, H Uno, K Komoriya
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 287 Issue 1 Pg. 27-34 (Dec 04 1995) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8666022 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• Pyrimidines
• Respiratory System Agents
• TEI 7322
• Bleomycin
• Almitrine
• Oxygen

Topics

• Almitrine (pharmacology)
• Animals
• Antibiotics, Antineoplastic (adverse effects)
• Bleomycin (adverse effects)
• Blood Gas Analysis
• Hypoxia (blood, chemically induced, drug therapy)
• Lung (drug effects)
• Male
• Oxygen (blood)
• Pyrimidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Respiratory System Agents (pharmacology)