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Dynamics of cardio-pulmonary response to exercise in patients affected by essential hypertension

English title Dynamics of cardio-pulmonary response to exercise in patients affected by essential hypertension
Applicant Ferretti Guido
Number 143427
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 Cardiovascular Research
Start/End 01.10.2012 - 31.03.2016
Approved amount 412'267.00
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All Disciplines (5)

Discipline
Cardiovascular Research
Pathophysiology
Neurophysiology and Brain Research
Physiology : other topics
Cardiovascular Diseases

Keywords (6)

cardiovascular system; exercise; human physiopathology; baroreflexes; neural control; essential hypertension

Lay Summary (English)

Lead
Lay summary

Essential hypertension, a disease in which elevated arterial blood pressure is  associated with normal values of cardiac output (the amount of blood pumped by the heart in one minute), has a remarkable health impact on our societies. High blood pressure is the leading risk for mortality in the world, because it increases the risk for cardiovascular diseases, causing more than 7 million deaths (some 13% of deaths globally) every year worldwide. The control of essential hypertension is thus of primary importance in medical systems’ strategy to prevent cardiovascular accidents. Current behavioural measures and pharmacological treatments have remarkably improved the clinical control of essential hypertension. Nevertheless, shedding light on the physiopathology of this disease will add much to our understanding of its causes and to the measures that could be taken. In the last ten years, huge efforts were made to understand the genetic aspects of essential hypertension, yet with poor results: although a genetic component in essential hypertension is highly probable, the genetics of hypertension is very complex and hard to disentangle yet. Recent results on the neural regulation of renal function have led to re-emphasize the role of neural mechanisms in the genesis of essential hypertension. On this basis, we postulate that patients affected by essential hypertension are characterised by a different functional organisation of the neural system controlling circulation (the forefront of blood pressure control) from that of normal heallthy individuals. If this is so, the study of the cardiovascular response to exercise in hypertensive patients would provide important information on the subject, because a re-organisation of the neural control system of cardiovascular function would translate into measurable differences in i) the steady state level of selected cardiovascular parameters during moderate intensity exercise, and ii) the characteristic parameters describing the rapid cardiovascular adjustments upon exercise onset. Thus, the aim of this project is to investigate with contemporary non-invasive techniques the steady-state and the dynamics of the cardiovascular response to exercise in patients affected by essential hypertension and compare them with those obtained in healthy control subjects of similar age, sex and physical fitness. In particular, we will perform a quantitative analysis of i) the haemodynamics of the oxygen transport system at the steady state of submaximal exercise, upright and supine (steady state study) and ii) the the kinetics of heart rate, cardiac output, mean blood pressure and pulmonary oxygen uptake at exercise onset, upright, supine and under exposure to lower body negative pressure (a tool allowing precise control of the amount of blood that at rest is displaced from the thoraxo the lower limbs). As a counterpart of hypertensive patients, we will extend the tests to patients affected by chronic orthostatic intolerance, who are situated on the opposite side of the blood pressure regulation spectrum. The results of this project will improve our view of the neural mechanisms involved in the cardiovascular regulations during exercise. But most importantly they will contribute to shedding light on the origin of essential hypertension and eventually designing novel, more targeted strategies of exercise administration as a preventive and therapeutic tool.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Collaboration

Group / person Country
Types of collaboration
Raffaello Furlan, University of Milano Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Associated projects

Number Title Start Funding scheme
127620 Dynamics of pulmonary gas exchange and systemic oxygen delivery during exercise transients in patients affected by specific cardiopulmonary diseases 01.10.2009 Project funding (Div. I-III)
61780 Dynamics of oxygen transport in humans: posture, exercise and hypoxia. 01.10.2000 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)

Abstract

With this project, we propose to take a new step in the study of neural mechanisms of cardiovascular control in patients with essential hypertension, starting from the concept that essential hypertension results from a different organisation of the overall neural regulation of the cardiovascular system, which inevitably affects the dynamics of the cardiovascular response at exercise onset and the cardiovascular steady state during moderate exercise. If this is the case, the study of the cardiovascular response to exercise with contemporary techniques would provide important information on the subject, because a re-organisation of the neural control system of cardiovascular function would translate into measurable differences in i) the steady state level of selected cardiovascular parameters during moderate intensity exercise, possibly leading to a different oxygen flow in mixed venous blood, and ii) the characteristic parameters describing the rapid cardiovascular adjustments upon exercise onset. Thus, the main aim of this project is to investigate the steady-state and the dynamics of the cardiovascular response to exercise in patients affected by essential hypertension. A study of the exercise responses of patients affected by essential hypertension would be of great importance, not only for improving our view of the neural mechanisms participating in the cardiovascular response to exercise on a systemic level, but also and most importantly for shading light on the origin of essential hypertension and eventually design novel, more targeted strategies of exercise administration as a preventive and therapeutic tool. In particular, we propose to perform a quantitative analysis of i) the haemodynamics of the oxygen transport system (systemic oxygen delivery and oxygen flow in mixed venous blood, considered as mirrors of the status of autonomic output to the cardiovascular system) at the steady state of submaximal exercise, upright and supine (steady state study) and ii) the dynamics of the cardiovascular response to exercise, namely the kinetics of heart rate, stroke volume, cardiac output, mean blood pressure and pulmonary oxygen uptake at exercise onset, upright, supine and under exposure to lower body negative pressure (dynamic study). Therefore, two separate experiments (one at exercise steady state, the other during exercise transients) will be carried out on young subjects affected by essential hypertension, and sexed- and age- matched healthy controls. Moreover, as a counterpart of hypertensive patients, we count to extend the tests to patients affected by chronic orthostatic intolerance, who are situated on the opposite side of the blood pressure regulation spectrum.
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