Experimental Studies on Pulmonary Vascular Response to Alveolar Hypoxia during Almitrine Infusion in Anesthetized Dogs

Almitrine bismesylate, a peripheral chemoreceptor stimulant has been shown to increase arterial oxygen tension in patients with chronic airflow obstruction. This effect is thought to be partly attributable to the enhancement of hypoxic pulmonary vasoconstriction (HPV). However, regarding this point the results of various clinical and animal studies on almitrine are inconclusive.
The aim of this study was to investigate the effect of almitrine on HPV in anesthetized, open chested dogs. HPV was expressed in terms of flow diversion associated with hypoxic challenge to the left lower lobe (LLL) where LLL and the rest of the lung were separately ventilated. Results showed that the HPV was enhanced by relatively lower doses of almitrine infusion while attenuated by higher doses. Stimulus-response curves (relationship between end-tidal oxygen pressure and LLL blood flow) showed shift to the right, indicating that almitrine induced the pulmonary vasoconstriction dose-dependently at progressively higher end-tidal oxygen tensions during LLL hypoxic challenges. This suggested that almitrine, also enhanced the response of pulmonary vessels to hypoxia. These changes were not found during almitrine vehicle infusion.
Plasma level of 6-keto-PGF1α, the stable metabolite of PGI2 did not show any significant changes after infusion of almitrine. Besides this, following denervation of peripheral chemoreceptors, some dogs showed the same effects as observed in those without chemoreceptor denervation i,e HPV was enhanced by low doses of almitrine and attenuated by higher doses where stimulus-response curves also shifted towards the right. Doxapram, another chemoreceptor stimulant drug did not enhance or attenuate HPV. The effect of almitrine was not influenced by blocking the Ca++ entry through the voltage dependent channel.
It was therefore concluded that vasoconstriction induced by almitrine may be attributed to a direct effect on pulmonary vessels rather than being mediated via the peripheral chemoreceptors.