We will determine the contributions of the lung and the chest wall muscles to three key determinants of systemic oxygen transport during exercise, namely, cardiac output, locomotor muscle blood flow and arterial O2 content. First, we will test the hypothesis that the work of breathing (Wv) during exercise is an important determinant of the vascular resistance (VRL), blood flow (QL) and therefore the VO2 of the working limb locomotor muscles (VO2L) - especially at maximum exercise intensity in health and in patients with chronic heart failure. We will also determine the effects of exercise intensity, of hypoxia and of respiratory muscle training on the influence of Wv on QL. Microneurography will be used to assess if increased Wv affects limb muscle blood flow via reflexly triggered augmentation of muscle sympathetic nerve activity.
A second aim concerned with cardiopulmonary interactions during exercise will address if respiratory-induced negative intrathoracic pressure during exercise compromises stroke volume and cardiac output in the healthy heart as well as the heart in failure. Thirdly, we will determine if the healthy female - of widely varying VO2max and age - has an increased susceptibility to exercise-induced diffusion limitation causing arterial hypoxemia (EIH), and also to expiratory flow limitation and to increased Wv. Our preliminary data support these proposals of a significant compromising effect of Wv on locomotor muscle blood flow at max exercise and of a strong influence of gender on exercise-induced arterial hypoxemia via diffusion limitation. Finally, we will quantify the relative contributions of Wv (via effects on QL) and diffusion limitation (via EIH) to the limitation of VO2max and exercise endurance performance with special emphasis on the highly fit, the female, healthy aging and the patient with chronic heart failure.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Respiratory and Applied Physiology Study Section (RAP)
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University of Wisconsin Madison
Public Health & Prev Medicine
Schools of Medicine
United States
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Smith, Curtis A; Blain, Grégory M; Henderson, Kathleen S et al. (2015) Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2 : role of carotid body CO2. J Physiol 593:4225-43
Dempsey, Jerome A; Xie, Ailiang; Patz, David S et al. (2014) Physiology in medicine: obstructive sleep apnea pathogenesis and treatment--considerations beyond airway anatomy. J Appl Physiol (1985) 116:3-12
Dempsey, Jerome A; Smith, Curtis A (2014) Pathophysiology of human ventilatory control. Eur Respir J 44:495-512
Xie, Ailiang; Teodorescu, Mihaela; Pegelow, David F et al. (2013) Effects of stabilizing or increasing respiratory motor outputs on obstructive sleep apnea. J Appl Physiol (1985) 115:22-33
Limberg, Jacqueline K; Morgan, Barbara J; Schrage, William G et al. (2013) Respiratory influences on muscle sympathetic nerve activity and vascular conductance in the steady state. Am J Physiol Heart Circ Physiol 304:H1615-23
Amann, Markus (2011) Central and peripheral fatigue: interaction during cycling exercise in humans. Med Sci Sports Exerc 43:2039-45
Amann, Markus; Blain, Gregory M; Proctor, Lester T et al. (2011) Implications of group III and IV muscle afferents for high-intensity endurance exercise performance in humans. J Physiol 589:5299-309
Lovering, Andrew T; Elliott, Jonathan E; Beasley, Kara M et al. (2010) Pulmonary pathways and mechanisms regulating transpulmonary shunting into the general circulation: an update. Injury 41 Suppl 2:S16-23
Amann, Markus; Blain, Gregory M; Proctor, Lester T et al. (2010) Group III and IV muscle afferents contribute to ventilatory and cardiovascular response to rhythmic exercise in humans. J Appl Physiol 109:966-76
Dempsey, Jerome A; Veasey, Sigrid C; Morgan, Barbara J et al. (2010) Pathophysiology of sleep apnea. Physiol Rev 90:47-112

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