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Dynamics of pulmonary gas exchange and systemic oxygen delivery during exercise transients in patients affected by specific cardiopulmonary diseases

English title Dynamics of pulmonary gas exchange and systemic oxygen delivery during exercise transients in patients affected by specific cardiopulmonary diseases
Applicant Ferretti Guido
Number 127620
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2009 - 30.09.2012
Approved amount 375'000.00
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All Disciplines (4)

Discipline
Neurophysiology and Brain Research
Clinical Cardiovascular Research
Cardiovascular Research
Neurology, Psychiatry

Keywords (8)

human physiopathology; exercise; neural control; cardiovascular system; lung transplant recipients; chronic orthostatic intolerance; Circulation; Patients

Lay Summary (English)

Lead
Lay summary
The neural control of circulation at exercise start and its interactions with respiration are poorly understood. Yet its knowledge is important for our understanding of several pathological states. The neurovegetative system is characterized by two parallel branches, one excitatory (the sympathetic system), the other inhibitory (the vagal system). The latter is rapidly inactivated at exercise onset. However, when the vagal system is blocked pharmacologically, the rapid response to exercise is abolished for heart rate, but only reduced for cardiac output, because the amount of blood that the heart pumps at each stroke (stroke volume) is maintained. These results suggest multifactorial origin of the rapid response of the heart to exercise. The aim of this project is to investigate the quantitative relations between the factors determining the rapid response of the heart to exercise in humans. To this aim, we plan to investigate the changes of heart rate, cardiac output and stroke volume i) in healthy young subjects under simultaneous blockade of the vagal system and of the sympathetic system, in order to extract the non-neural components of the response, and ii) in patients affected by chronic orthostatic intolerance (COI), whose neurovegetative system is altered. In fact the cardiovascular alterations of COI should modify the dynamics of the cardiovascular response to exercise, because of reduced baroreflex function. These concepts are important bricks for the construction of our understanding of the origin of essential hypertension. Thus, as a first step toward the study of essential hypertension, we also plan to investigate the effects of ageing, by performing simultaneous determinations of the rapid response of heart rate, cardiac output and stroke volume in healthy aged subjects, in supine and upright posture. With ageing in fact, due to increased rigidity of arterial walls, an increase in arterial blood pressure takes place without associated bradycardia, as in essential hypertension. Cardiac reflex alterations similar to those occurring in hypertensive patients take place. In sum, aged humans may be viewed as a group of "healthy" subjects, undergoing no pharmacological treatment, mimicking, from the cardiovascular viewpoint, the condition of essential hypertension.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Effects of gravity acceleration on human cardiovascular responses to exercise
Bonjour Julien, Bringard Aurélien, Antonutto Guglielmo, Capelli Carlo, Linnarsson Dag, Pendergast David R., Ferretti Guido (2011), Effects of gravity acceleration on human cardiovascular responses to exercise, in European Journal of Applied Physiology, 111, 2907-2917.
Cardiovascular re-adjustments and baroreflex response during clinical reambulation procedure at the end of 35-day bed rest in humans
Adami Alessandra, Pizzinelli Paolo, Bringard Aurélien, Capelli Carlo, Malacarne Mara, Lucini Daniela, Simunic Bostian, Pisot Rado, Cardiovascular re-adjustments and baroreflex response during clinical reambulation procedure at the end of 35-day bed rest in humans, in Ferretti, Guido, 1-6.

Collaboration

Group / person Country
Types of collaboration
Hôpitaux Universitaires de Genève Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Karolinska Institute Sweden (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Université de Verona Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Unniversité de Brescia Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Université de Milan Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Annual Congress of the Italian Physiological Society Poster Cardiovascular responses to standing at the end of 35-day bed rest in humans 12.09.2012 Varese, Italy Adami Alessandra; Ferretti Guido;


Awards

Title Year
Prix pour meilleur poster, Annual Congress of the Italian Physiological Society 2012

Associated projects

Number Title Start Funding scheme
114033 Dynamics of pulmonary gas exchange and systemic oxygen delivery during exercise transcients in humans 01.10.2006 Project funding (Div. I-III)
114033 Dynamics of pulmonary gas exchange and systemic oxygen delivery during exercise transcients in humans 01.10.2006 Project funding (Div. I-III)
143427 Dynamics of cardio-pulmonary response to exercise in patients affected by essential hypertension 01.10.2012 Project funding (Div. I-III)
179448 Arterial baroreflexes in dynamic conditions in humans: a closed-loop study 01.08.2018 Project funding (Div. I-III)
61780 Dynamics of oxygen transport in humans: posture, exercise and hypoxia. 01.10.2000 Project funding (Div. I-III)

Abstract

The neural control of circulation at exercise start and its interactions with respiration are poorly understood. The changes in cardiac output at exercise onset have two components: one, very fast (phase I), was attributed to withdrawal of vagal stimulation (the inhibitory branch of vegetative innervation); the other, delayed and slower (phase II), might parallel sympathetic drive stimulation (the excitatory branch of vegetative innervation). However, when the changes in cardiac output and lung oxygen uptake at exercise onset are assessed in supine posture, the rapid component disappears, although vagal activation is greater in supine than in upright posture at rest. Moreover, in acute hypoxia, a condition of reduced vagal activity and increased sympathetic activity at rest, phase I is not completely suppressed for heart rate, arterial baroreflex resetting continues to be very rapid, and stroke volume changes are the same as in normoxia, so that phase I is still present for cardiac output. Furthermore, during exposure to lower body negative pressure (LBNP), the phase I of cardiac output is unchanged, as a result of decreased phase I amplitude for heart rate and increased phase I amplitude for stroke volume. Finally, during vagal blockade, phase I was abolished for heart rate, and the smaller phase I amplitude for cardiac output was entirely due to the increase in stroke volume. These results contradict the notion that vagal withdrawal is responsible for the rapid component of the kinetics of cardiac output and lung oxygen uptake. They rather suggest multifactorial origin of the phase I kinetics of cardiac output. Concomitant clear roles appear for neural (vagal withdrawal) and mechanical (muscle pump action) factors in determining the amplitude of the response, with associated baroreflex resetting. The quantitative relations between these factors should vary, depending on the degree of vagal tone and the amount of blood displaced in the lower limbs before exercise start, but their respective extent is not understood yet. The aim of this project is to investigate the quantitative relations between the factors determining the phase I of the cardiopulmonary response to exercise in humans. To this aim, we plan to perform simultaneous determinations of the phase I kinetics of heart rate, cardiac output and lung oxygen uptake upon exercise onset in normoxia i) in healthy young subjects under simultaneous blockade of the vagal system with atropine and of the sympathetic system with metoprolol, and ii) in patients affected by chronic orthostatic intolerance (COI). In fact the former experiment will allow suppression of the entire neural control of the heart, with consequent extraction of the “pure” effects of mechanical factors exclusively. Concerning the latter experiment, the cardiovascular alterations of COI are such as to modify the dynamics of the cardiovascular response to exercise, especially during phase I, because of blunted baroreflex function. We expect lesser baroreflex resetting at exercise start, a clear identification of the vagal component of phase I, and a clarification, through the use of LBNP, of the mechanism of increased stroke volume in phase I, whether mediated or not through baroreflex stimulation. Moreover, as a first step toward the study of essential hypertension, we propose to investigate the effects of ageing, by performing simultaneous determinations of the phase I kinetics of heart rate, cardiac output and lung oxygen uptake upon exercise onset in normoxia in healthy aged subjects, in supine and upright posture. With ageing in fact, due to increased rigidity of arterial walls, an increase in arterial blood pressure takes place without associated bradycardia, as in essential hypertension. A baroreflex curve displacement, with reduced sensitivity, similar to that occurring in hypertensive patients takes place. In sum, aged humans may be viewed as a group of “healthy” subjects, undergoing no pharmacological treatment, mimicking, from the cardiovascular viewpoint, the condition of essential hypertension.
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