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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/H322    most recent 00790.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gujic, M. Articles by van de Borne, P. Search for Related Content PubMed PubMed Citation Articles by Gujic, M. Articles by van de Borne, P.

Effects of enoximone on peripheral and central chemoreflex responses in humans

¹Department of Cardiology, Erasme Hospital, Brussels, Belgium; and ²Department of Clinical Pharmacology, Faculty of Medicine and University Hospital, Toulouse, France

Submitted 9 July 2007 ; accepted in final form 18 October 2007

cAMP plays an important role in peripheral chemoreflex function in animals. We tested the hypothesis that the phosphodiesterase inhibitor and inotropic medication enoximone increases peripheral chemoreflex function in humans. In a single-blind, randomized, placebo-controlled crossover study of 15 men, we measured ventilatory, muscle sympathetic nerve activity, and hemodynamic responses to 5 min of isocapnic hypoxia, 5 min of hyperoxic hypercapnia, and 3 min of isometric handgrip exercise, separated by 1 wk, with enoximone and placebo administration. Enoximone increased cardiac output by 120 ± 3.7% from baseline (P < 0.001); it also increased the ventilatory response to acute hypoxia [13.6 ± 1 vs. 11.2 ± 0.7 l/min at 5 min of hypoxia, P = 0.03 vs. placebo (by ANOVA)]. Despite a larger minute ventilation and a smaller decrease in O₂ desaturation (83 ± 1 vs. 79 ± 2%, P = 0.003), the muscle sympathetic nerve response to hypoxia was similar between enoximone and placebo (123 ± 6 and 117 ± 6%, respectively, P = 0.28). In multivariate regression analyses, enoximone enhanced the ventilatory (P < 0.001) and sympathetic responses to isocapnic hypoxia. Hyperoxic hypercapnia and isometric handgrip responses were not different between enoximone and placebo (P = 0.13). Enoximone increases modestly the chemoreflex responses to isocapnic hypoxia. Moreover, this effect is specific for the peripheral chemoreflex, inasmuch as central chemoreflex and isometric handgrip responses were not altered by enoximone.

phosphodiesterase inhibitor; adenosine 3',5'-cyclic monophosphate