ORIGINAL ARTICLE Kinetics of skeletal muscle O 2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension Priscila B. Barbosa • Eloara M. V. Ferreira • Jaquelina S. O. Arakaki • Luciana S. Takara • Juliana Moura • Ru ´bia B. Nascimento • Luiz E. Nery • J. Alberto Neder Received: 19 August 2010 / Accepted: 20 December 2010 / Published online: 12 January 2011 Ó Springer-Verlag 2011 Abstract Impaired O 2 delivery relative to O 2 demands at the onset of exercise might influence the response profile of muscle fractional O 2 extraction (%D[deoxy-Hb/Mb] by near-infrared spectroscopy) either by accelerating its rate of increase or creating an ‘‘overshoot’’ (OS) in patients with pulmonary arterial hypertension (PAH). We therefore assessed the kinetics of O 2 uptake _ V O 2   ; D[deoxy-Hb/ Mb] in the vastus lateralis, and heart rate (HR) at the onset of heavy-intensity exercise in 14 females with PAH (con- nective tissue disease, IPAH, portal hypertension, and acquired immunodeficiency syndrome) and 11 age- and gender-matched controls. Patients had slower _ V O 2 and HR dynamics than controls (s _ V O 2 = 62.7 ± 15.2 s vs. 41.0 ± 13.8 s and t 1/2 -HR = 61.3 ± 16.6 s vs. 43.4 ± 8.8 s, respectively; p \ 0.01). No study participant had a signif- icant reduction in oxyhemoglobin saturation. In OS(-) subjects (6 patients and 7 controls), the kinetics of D[deoxy-Hb/Mb] relative to _ V O 2 were faster in patients (p = 0.05). Larger area under the OS and slower kinetics (MRT) of the ‘‘downward’’ component indicated greater O 2 delivery-to-utilization mismatch in OS(?) patients versus OS(?) controls (477.4 ± 330.0 vs. 78.1 ± 65.6 a.u. and 74.6 ± 18.8 vs. 46.0 ± 17.0 s, respectively; p \ 0.05). Resting pulmonary vascular resistance was higher in OS(?) than OS(-) patients (23.1 ± 12.0 vs. 10.7 ± 4.0 Woods, respectively; p \ 0.05). We conclude that microvascular O 2 delivery-to-utilization inequalities slo- wed the rate of adaptation of aerobic metabolism at the start of heavy-intensity exercise in women with PAH. Keywords Blood flow  Pulmonary hypertension  Hemodynamics  Near-infrared spectroscopy  Oxygen consumption  Kinetics Introduction Derangements in the diffusive and convective transport of O 2 to skeletal muscle mitochondria and intramyocyte metabolic machinery could explain the slowness of oxygen uptake _ V O 2   kinetics at the transition to exercise in patient populations (Sietsema 1992; Zhang et al. 1993; Forte et al. 1999; Riley et al. 2000; Chiappa et al. 2008; Sperandio et al. 2009). The slowed _ V O 2 dynamics lead to greater reliance on O 2 -independent pathways for ATP regeneration and accumulation of by-products related to increased muscle fatigability thereby contributing to reduced exercise tolerance in these subjects (Poole et al. 2008; Jones and Burnley 2009). In this context, we recently showed that mismatching between O 2 delivery and utilization at the microcirculatory level was related to slower cardiac output (QT) and _ V O 2 kinetics in patients with chronic heart failure (CHF) (Sperandio et al. 2009). Although these findings indicate a prominent role of O 2 delivery in limiting _ V O 2 kinetics in patients with impaired ‘‘central’’ hemodynamics, they should not be immediately extrapolated to other chronic cardiovascular disorders. Pulmonary arterial hypertension Communicated by Susan A. Ward. P. B. Barbosa  E. M. V. Ferreira  J. S. O. Arakaki  L. S. Takara  J. Moura  R. B. Nascimento  L. E. Nery  J. A. Neder (&) Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE), Respiratory Division, Department of Medicine, Federal University of Sa ˜o Paulo, Paulista School of Medicine (UNIFESP-EPM), Rua Professor Francisco de Castro 54, Vila Clementino, Sa ˜o Paulo CEP 04020-050, Brazil e-mail: albneder@pneumo.epm.br 123 Eur J Appl Physiol (2011) 111:1851–1861 DOI 10.1007/s00421-010-1799-6