Intermittent Hypoxia 2: Cardiovascular and Metabolism
Cuvinte cheie
Abstract
Descriere
There are many physiological situations in which the organism is exposed to hypoxia, such as exercise and altitude. In addition some pathological situations also involve hypoxia, such as obesity, heart failure, respiratory failure and sleep apnea syndrome.
Hypoxia associated with altitude is frequently marked by the presence of sleep during periodic breathing induces a particular pattern of hypoxia called intermittent hypoxia. Also some subjects are "intolerant altitude" and develop specific pathologies at high altitude (acute mountain evil, pulmonary edema ...).
We recently demonstrated that subjects tolerate the altitude had just intermittent hypoxia while they were sleeping during the simulated altitude. The protective role of intermittent hypoxia in the mechanisms of occurrence of intolerance to altitude remains to be understood more precisely. In fact those who were intolerant to altitude has no periodic breathing and therefore intermittent hypoxia during the oxygen-deficient atmosphere.
Conversely, the sleep apnea syndrome (SAS) also characterized by a HI. It is produced by repeated episodes of airway obstruction during sleep, producing a sequence: respiratory effort, hypoxia / re-oxygenation and sleep interruption.
The HI is associated with both a well established cardiovascular morbidity but also to cardioprotection. This relates to cardiovascular morbidity rise in blood pressure can certainly promote the development after many years of hypertension. On the other hand the presence of sleep apnea syndrome is advanced as a factor favoring the coronary collateral circulation and therefore will bring a cardioprotective effect for patients.
Understanding the mechanisms of physiological adaptations to intermittent hypoxia by passing a deleterious evolution of a protective HI is therefore critical.
Exposure to altitude or OSAS induces the activation of intermediary mechanisms such as sympathetic activation, altered vascular reactivity, systemic inflammation and low-grade oxidative stress. The direct involvement of these mechanisms is dependent mainly intermediate of intermittent hypoxia. The shift in equilibrium between activator and inhibitor factors will evolve either to a protective mode (adaptation to altitude) or pathologic (cardiovascular complication of OSA).
Sympathetic activation has been demonstrated in patients with OSAS, reversible with effective treatment. The importance of cardiovascular sympathetic activation in elevating blood pressure by intermittent hypoxia is shown in animal models of HI. We also found an increase in sympathetic activation in our reversible model of HI in healthy subjects.
The elevation of that sympathetic activity is assumed to be multifactorial. An increase in tone but also a central potentiation thereof by an increase in peripheral chemoreflex sensitivity (sensitive to hypoxia) and against a lack of regulation by the arterial baroreflex.
Moreover angiotensin system modulates the central sympathetic tone and peripheral chemoreflex sensitivity. These actions are complementary in a signaling pathway of particular interest in exposure to intermittent hypoxia.
Datele
| Ultima verificare: | 11/30/2018 |
| Primul depus: | 04/17/2012 |
| Inscriere estimată trimisă: | 02/06/2014 |
| Prima postare: | 02/09/2014 |
| Ultima actualizare trimisă: | 12/26/2018 |
| Ultima actualizare postată: | 12/30/2018 |
| Data actuală de începere a studiului: | 08/06/2013 |
| Data estimată de finalizare primară: | 07/16/2014 |
| Data estimată de finalizare a studiului: | 03/15/2017 |
Stare sau boală
Intervenție / tratament
Drug: Arm 1: Real hypoxia and ¨Placebo
Drug: Arm 2: Hypoxia placebo and Placebo
Drug: Arm 3: Hypoxia and Valsartan
Drug: Arm 4: Hypoxia and Amlodipine
Fază
Grupuri de brațe
| Braţ | Intervenție / tratament |
|---|---|
| Placebo Comparator: Arm 1: Real hypoxia and ¨Placebo This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 2. | Drug: Arm 1: Real hypoxia and ¨Placebo The subjects receive 1 oral pill of placebo each morning during the second week of the two periods, so 14 pills in all. |
| Placebo Comparator: Arm 2: Hypoxia placebo and Placebo This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the hypoxia placebo and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 1. | Drug: Arm 2: Hypoxia placebo and Placebo The subjects receive 1 oral pill of placebo each morning during the second week of the two periods, so 14 pills in all. |
| Active Comparator: Arm 3: Hypoxia and Valsartan This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the Valsartan during the first two weeks and, after the wash-out, receive the treatment of the arm 4. | Drug: Arm 3: Hypoxia and Valsartan The subjects receive 1 oral pill of Valsartan each morning during the second week of the two periods, so 14 pills in all. 1 pill equal 40 mg. |
| Active Comparator: Arm 4: Hypoxia and Amlodipine This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the amlodipine during the first two weeks and, after the wash-out, receive the treatment of the arm 3. | Drug: Arm 4: Hypoxia and Amlodipine The subjects receive 1 oral pill of Amlodipine each morning during the second week of the two periods, so 14 pills in all. 1 pill equal 6,944 mg of amlodipine besilate with 5 mg of amlodipine. |
Criterii de eligibilitate
| Vârste eligibile pentru studiu | 18 Years La 18 Years |
| Sexe eligibile pentru studiu | All |
| Acceptă voluntari sănătoși | da |
| Criterii | Inclusion Criteria: - Healthy subject - Subject aged of 18 years-old at least - Diagnostic AHI<15/h and <5% of total sleep time spent with a SaO2<90% - Free and informed consent signed - Subject covered by social security - Negative pregnancy test Exclusion Criteria: - Subject with a medical pathology (respiratory, cardiovascular, renal, metabolic, neurological...) - Tobacco consumption > 5 cigarettes/days - Alcohol consumption > 3 units/days (1 unit=1 drink) - Subject under trusteeship or guardianship - Subject unaffiliated with the social security - Person deprived of their liberty, adult protected by laws, person hospitalized - Ongoing participation in another clinical research study - Subject non-cooperative or respectful of obligations inherent in the participation in the study |
Rezultat
Măsuri de rezultate primare
1. Change in sympathetic activity [Day 1 and at Day 14]
Măsuri de rezultate secundare
1. Measure of adrenergic, inflammatory and metabolic markers in adipose tissues by chronic intermittent hypoxia versus placebo in healthy nonobese subjects. [Day 14]
2. Measure variations in parameters of inflammation in adipose tissue by chronic intermittent hypoxia versus placebo in healthy nonobese subjects. [Day 14]
3. Measure of metabolic aspects of the OGTT test. [Day 14]
4. Measure the activation of systemic inflammation by chronic HI versus placebo in healthy nonobese subjects. The systemic inflammation will be assessed in non-stress and during the OGTT. [Day 14]
5. Assessing markers implicated in the pathophysiology of chronic metabolic diseases after HI versus placebo in healthy nonobese subjects during OGTT. [Day 14]
6. Change in vascular responsivness [At day 1 and Day 14]
7. Change in Sympathetic and vascular determinant of Blood pressure [Day 1 and Day 14]
