Effects of Vasodilators on Hypoxic Pulmonary Vasoconstriction in Normal Man

Naeije, Robert; Mélot, Christian; Mols, Pierre; Hallemans, Roger

doi:10.1378/chest.82.4.404

Cited by 109 publications

(61 citation statements)

References 28 publications

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“…34) Inhalation of 12.5% O 2 decreases arterial oxygen pressure to below 50 mmHg, and increases pulmonary vascular resistance because of constriction of precapillary arteries. 35,36) Ghofrani, et al 37) demonstrated that sildenafil, a phosphodiesterase-5 inhibitor, inhibited hypoxic pulmonary vasoconstriction and reduced right ventricular afterload which, in turn, resulted in increased CO during exercise, and that improvement of oxygen transport to the exercising muscles increased the VO 2 max. These findings suggested that impaired right ventricular function due to hypoxiainduced pulmonary vasoconstriction might play a role in this attenuated SV and CO response during exercise.…”

Section: Discussionmentioning

confidence: 99%

Effects of Acute Hypoxia at Moderate Altitude on Stroke Volume and Cardiac Output During Exercise

et al. 2010

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SummaryIt has been unclear how acute hypoxia at moderate altitude affects stroke volume (SV), an index of cardiac function, during exercise. The present study was conducted to reveal whether acute normobaric hypoxia might alter SV during exercise.Nine healthy male subjects performed maximal exercise testing under normobaric normoxic, and normobaric hypoxic conditions (O 2 : 14.4%) in a randomized order. A novel thoracic impedance method was used to continuously measure SV and cardiac output (CO) during exercise.Acute hypoxia decreased maximal work rate (hypoxia; 247 ± 6 [SE] versus normoxia; 267 ± 8 W, P < 0.005) and VO 2 max (hypoxia; 2761 ± 99 versus normoxia; 3039 ± 133 mL/min, P < 0.005). Under hypoxic conditions, SV and CO at maximal exercise decreased (SV: hypoxia; 145 ± 11 versus normoxia; 163 ± 11 mL, P < 0.05, CO: hypoxia; 26.7 ± 2.1 versus normoxia; 30.2 ± 1.8 L/min, P < 0.05). In acute hypoxia, SV during submaximal exercise at identical work rate decreased. Furthermore, in hypoxia, 4 of 9 subjects attained their highest SV at maximal exercise, while in normoxia, 8 of 9 subjects did.Acute normobaric hypoxia attenuated the increment of SV and CO during exercise, and SV reached a plateau earlier under hypoxia than in normoxia. Cardiac function during exercise at this level of acute normobaric hypoxia might be attenuated. (Int Heart J 2010; 51: 170-175) Key words: Normobaric hypoxia, Cardiac output, Oxygen uptake, Exercise testing D uring ascent to a moderate to high altitude, individuals are exposed to progressive decreases in atmospheric pressure that lead to a reduction in inspired, alveolar, and arterial oxygen pressures. Training at moderate altitude (corresponding to 2000 -3000 m) is associated with relatively severe hypoxemia during submaximal and maximal exercise, 1) and acute hypoxia of this level decreases VO 2 max as well as exercise capacity.2-4) Thus, hypoxia at moderate altitude limits training intensity, which leads to relative deconditioning in elite athletes, although endurance athletes often use hypoxic training to improve sea-level performance. 5) Because VO 2 is the product of cardiac output (CO) and the arterio-venous oxygen content difference (C(a-v)O 2 ), a decrease in VO 2 max at maximal exercise may be due to a decrease of either factor, or both.Acute hypoxia may induce abnormalities in cardiac function and redistribution of CO not only at rest but also during exercise. In an animal study, CO at rest increased during acute severe hypoxia (FiO 2 10% and 5%), and blood flow to all organs increased except for the skin and muscle.6) In humans under acute hypoxia, heart rate (HR) and CO increase while systemic vascular resistance decreases. 7)Echocardiography also reveals altered mitral flow patterns, suggestive of mild LV diastolic dysfunction.8) Subacute hypoxia (FiO 2 12%, simulating an altitude of approximately 4000 m) induced mild diastolic dysfunction in young healthy individuals. 9)Stroke volume (SV) increases as the work rate increases at low to moderate intensity exercise, ...

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Section: Discussionmentioning

confidence: 99%

Effects of Acute Hypoxia at Moderate Altitude on Stroke Volume and Cardiac Output During Exercise

et al. 2010

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“…A reduction in Ppa, under hypoxic conditions, has been obtained by the calcium channel-blocker nifedipine in healthy humans exposed to acute normobaric hypoxia [4] or in subjects suffering from high-altitude pulmonary oedema in hypobaric hypoxia [5]. In other aetiologies of pulmonary hypertension, such as primary pulmonary hypertension [6] or secondary to obstructive pulmonary disease [7,8], nifedipine and felodipine were efficient in decreasing Ppa.…”

Section: Aamentioning

confidence: 99%

Pulmonary hypertension in high-altitude chronic hypoxia: response to nifedipine

Antezana

Antezana²,

Aparicio³

et al. 1998

Eur Respir J

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The vasoconstrictive effect of hypoxia upon pulmonary artery vessels is well known in most mammalian species, including humans. A pure form of hypoxic pulmonary artery hypertension can be seen in high-altitude residents. A loss of adaptation to chronic hypoxia, known as chronic mountain sickness (CMS), is observed in 5-10% of people sojourning above 3,000 m and is characterized by excessive polycythaemia (H-Hb), pulmonary hypertension and nonspecific neurological symptoms [1]. Ongoing pulmonary vasoconstriction leads to increased vascular resistance and pulmonary artery pressure (Ppa), which are probable maladaptive responses to high altitude since they result in minimal improvement in ventilation-perfusion matching and increased workload for the right ventricle.In addition to vasoconstriction, chronic alveolar hypoxia is associated with structural changes in the media of terminal portions of pulmonary arterioles [2], such as smooth muscle cell proliferation, thickening of the media, proliferation and turgescence of endothelial cells. Recently, this vascular remodelling has been found in only a few residents at high altitude [3], but it is admitted that sustained hypoxia is able to increase muscularization of the small pulmonary vessels and to increase even further the pulmonary vascular resistance.A reduction in Ppa, under hypoxic conditions, has been obtained by the calcium channel-blocker nifedipine in healthy humans exposed to acute normobaric hypoxia [4] or in subjects suffering from high-altitude pulmonary oedema in hypobaric hypoxia [5]. In other aetiologies of pulmonary hypertension, such as primary pulmonary hypertension [6] or secondary to obstructive pulmonary disease [7,8], nifedipine and felodipine were efficient in decreasing Ppa. Calcium antagonists have also been shown to be efficient in experimental hypoxic pulmonary vasoconstriction [9,10].Reversal of hypoxic pulmonary hypertension with calcium channel-blockers has not been evaluated in a population chronically exposed to high altitude. Venesection has been used to treat CMS, but no modification of pulmonary haemodynamics has been reported.The objectives of this study were to assess pulmonary hypertension in native residents at high-altitude by echocardiography, to analyse the relationship between Ppa and H-Hb, and to study the effect of acute administration of nifedipine on pulmonary pressure. In the presence of reversible vascular changes in altitude-induced pulmonary hypertension, a nifedipine-induced vasodilatation could be anticipated. Materials and methods SubjectsThirty males and one females, native residents of La Paz (3,500-4,100 m), Bolivia, were included in this nonrandomized study. Asymptomatic subjects were recruited Systolic pulmonary arterial pressure (Ppa) was studied by Doppler echocardiography, at rest and after sublingual nifedipine, in 31 asymptomatic residents at 3,600 m. Individuals were separated into two groups according to resting Ppa: a group with low Ppa (ð4.7 kPa, n=17) and a group with high Ppa (>4.7 kPa, n=14). Ind...

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“…Although the magnitude of the response may vary from one individual to another [1,14], ventilation with FI,O 2 0.12 in the current study resulted in a changes in Sa,O 2 , heart rate and (estimated) cardiac output compatible with previous studies using direct measurements of Ppa [1,7,31]. Studies using other techniques, performed in both experimental animals and humans, have suggested that under conditions of generalised hypoxia there is a redistribution of blood from dependent to nondependent lung regions [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

“…Previous work has shown that a fractional concentration of oxygen in inspired gas (FI,O 2 ) of 0.12-0.14 results in reproducible hypoxic pulmonary vasoconstriction [13,14]. To permit the administration of both an FI,O 2 of 0.21 and 0.12 in the ventilator circuit, the ventilator air intake was connected in the usual fashion to the wall supply, and the oxygen (O 2 ) intake to a cylinder of 12% O 2 in nitrogen (N 2 ) (BOC Special Gases, Sunningdale, UK).…”

Section: Administration Of Hypoxic Gas Mixture and Inhaled Nitric Oxidementioning

confidence: 99%

Pulmonary perfusion quantified by electron-beam computed tomography: effects of hypoxia and inhaled NO

Jones¹,

Hansell²,

Evans³

2003

Eur Respir J

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Patients with acute lung injury may benefit from the manipulation of pulmonary blood flow using inhaled nitric oxide (iNO) to optimise ventilation/perfusion matching. Current techniques for studying changes in regional pulmonary perfusion are difficult to apply clinically. This study therefore investigated the potential of electronbeam computed tomography (EBCT) to quantify the effects of hypoxia and iNO on regional pulmonary perfusion in five healthy subjects.Contrast-enhanced sections were obtained sequentially under conditions of normoxia, hypoxia (fractional concentration of oxygen in inspired gas (FI,O 2 ) 0.12) and hypoxia, with iNO (14.8 parts per million (ppm)) administered during inspiration in the supine position. Regions of interest were placed along the nondependent to dependent axis and values for relative perfusion derived.Under normoxic conditions a vertical gradient of perfusion existed, which became less apparent due to increased perfusion in nondependent regions after the induction of hypoxia (FI,O 2 0.12). Under physiological circumstances, the distribution of pulmonary blood flow is regulated by a local action of alveolar oxygen tension on precapillary pulmonary vessels. Thus, the reflex of hypoxic pulmonary vasoconstriction (HPV) ensures that blood flow is diverted away from areas of damaged lung, thereby preserving the matching of ventilation (V9) and perfusion (Q9) [1,2]. In contrast, patients with acute lung injury (ALI) demonstrate diminished HPV leading to adverse changes in V9/Q9 matching, manifesting clinically as refractory hypoxaemia [3]. The favourable manipulation of V9/Q9 therefore assumes considerable therapeutic significance. In this context, nitric oxide (NO), an endothelially derived vasodilator that modulates vascular tone in health and disease [4], has been demonstrated to be a selective pulmonary vasodilator when administered by inhalation both in experimental animals [5,6] and humans [7], improving physiological variables (specifically pulmonary artery pressure (Ppa) and arterial oxygen tension) in patients with ALI [4]. The effects of NO on HPV in terms of the modulation of changes in regional pulmonary blood flow induced by hypoxaemia are, however, unknown.Although techniques for studying regional pulmonary perfusion have been difficult to apply clinically, a gravitational distribution of pulmonary perfusion has been described in normal subjects, determined by the interrelationship between hydrostatic, alveolar and interstitial pressures [8,9]. Moreover, animal studies employing high spatial-resolution techniques suggest that the influence of gravity is less important than the structure of the pulmonary vascular tree in determining regional blood flow in the lung [10,11]. The authors have recently employed electron-beam computed tomography (EBCT) to quantify regional pulmonary perfusion in normal subjects placed in the supine and prone positions, demonstrating that a gravitational gradient of pulmonary perfusion existed in both supine and prone positions [12]....

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Effects of Vasodilators on Hypoxic Pulmonary Vasoconstriction in Normal Man

Cited by 109 publications

References 28 publications

Effects of Acute Hypoxia at Moderate Altitude on Stroke Volume and Cardiac Output During Exercise

Effects of Acute Hypoxia at Moderate Altitude on Stroke Volume and Cardiac Output During Exercise

Pulmonary hypertension in high-altitude chronic hypoxia: response to nifedipine

Pulmonary perfusion quantified by electron-beam computed tomography: effects of hypoxia and inhaled NO

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