Restored Hypoxic Pulmonary Vasoconstriction by Peripheral Chemoreceptor Agonists in Dogs

Abstract

Hypoxic stimulation of the peripheral chemoreceptors inhibits hypoxic pulmonary vasoconstriction (HPV). On the other hand, almitrine, a peripheral chemoreceptor agonist, has been reported in some studies to enhance HPV. To further explore this apparent contradiction, we investigated the effects of two different low intravenous doses of almitrine on pulmonary arterial pressure (Ppa) versus cardiac index (Q) plots in 32 pentobarbital-anesthetized dogs ventilated alternatively in hyperoxia (FIO2, 0.4) and in hypoxia (FIO2 0.1). HPV, defined as a hypoxia-induced increase in Ppa over the entire range of Q studied, from 2 to 5 L/min/m2, was elicited in 16 dogs. In the first eight of these "responders," almitrine 2 micrograms/kg/min had no vascular effect, and in the other eight, almitrine 4 micrograms/kg/min inhibited HPV. In 16 other dogs, hypoxia did not affect Ppa over the entire range of Q. In these "nonresponders," almitrine 2 micrograms/kg/min (n = 8) as well as 4 micrograms/kg/min (n = 8) restored HPV. To answer the question whether the ability to restore HPV would be specific to almitrine, we administered intravenously the structurally unrelated chemoreceptor agonist doxapram at the dose of 20 micrograms/kg/min to an additional group of eight "nonresponders," and this treatment also restored HPV. Intravenous infusion of the malic acid solution solvent of almitrine had no effect on Ppa/Q plots in a final group of eight "nonresponders". We conclude that low dose almitrine and doxapram restore HPV in dogs with a naturally absent hypoxic pulmonary pressor response, probably by a direct effect at the pulmonary vessels.