We propose to determine the physiological and clinical importance of metaboreflexes originating in the inspiratory and expiratory respiratory muscles in regulating blood flow and its distribution at rest and exercise. The rationale for this proposal is based on findings in humans which show that: a) mechanical unloading of the respiratory muscles in heavy exercise causes a reduction in stroke volume and cardiac output and vasodilation and increased blood flow in locomotor muscles; b) that fatiguing the diaphragm causes a time-dependent increases in muscle sympathetic nerve activity (MSNA) in the resulting limb; and c) that central inspiratory motor output has no influence on MSNA in the intact human.
Aim 1 : We will voluntarily increase inspiratory and expiratory muscle effort in healthy humans at rest, during plantar flexion exercise and in hypoxia to determine the threshold and sensitivity of the respiratory muscle metaboreflex in response to progressive increases in respiratory muscle force output and fatigue. We will also determine the combined effects - additive or multiplicative - of combinations of forearm and diaphragm submaximal and fatiguing exercise. Outcome measures include: a) MSNA (via peroneal nerve microneurography); b) femoral arterial blood flow and vascular conductance (measured beat-by-beat with a Doppler ultrasound imaging technique).
Aim 2 : We will use local infusions of metabolites into the diaphragm and abdominal expiratory muscles in a chronically instrumented dog model in order to quantify the sensitivity and compensatory capabilities of the respiratory muscle metaboreflex and its effect on blood flow distribution at rest and exercise. This animal model will also be used to address the effects of the limb locomotor muscle metaboreflex on distribution of blood flow to the respiratory muscles during exercise.
Aim 3 : In patients with chronic heart failure of varying etiology, we will apply ventilatory assist in the form of pressure support or proportional assist mechanical ventilation to determine the influence of respiratory muscle work and intra-thoracic pressure on exercise performance, on stroke volume and cardiac output and on limb locomotor muscle blood flow and vascular resistance at rest and exercise.
|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; 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|
|Amann, Markus (2011) Central and peripheral fatigue: interaction during cycling exercise in humans. Med Sci Sports Exerc 43:2039-45|
|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|
Showing the most recent 10 out of 80 publications