Reversibility of Pulmonary Hypertension and Right Ventricular Hypertrophy Induced by Intermittent High Altitude Hypoxia in Rats

Ressl, J; Urbanová, D; Widimský, Jiří; Ošťádal, B; Pelouch, V.; Procházka, J

doi:10.1159/000193097

Cited by 37 publications

(24 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decrease is relatively small in NREM sleep, but there is episodic, marked hypoventilation during variable breathing in REM sleep [28]. Repetitive episodes of transient hypoxia in experimental animals can lead to many of the changes seen in chronic pulmonary hypertension [29, 30, 31, 32, 33]. …”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Endothelin-1 Elevation in Chronic Obstructive Pulmonary Disease Patients with Nocturnal Oxyhemoglobin Desaturation

Trakada

Marangos²,

Spiropoulos³

2001

Respiration

View full text Add to dashboard Cite

Background: Nonapneic, oxyhemoglobin desaturation associated with sleep has been described in patients with chronic obstructive pulmonary disease (COPD). Hypoxemia stimulates endothelin-1 (ET-1) secretion. Once released, ET-1 can act locally to elicit sustained pulmonary artery vasoconstriction, bronchoconstriction and activation of alveolar macrophages. Objective: The aim of this study was to examine a possible correlation between ET-1 levels and nocturnal, nonapneic, oxyhemoglobin desaturation during sleep, in patients with COPD. Methods: We examined 48 COPD patients with formal polysomnography (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin desaturation. Twelve of them were disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of them desaturated below a baseline sleep saturation of 90% for 5 min or more, reaching a nadir saturation of at least 85%. We collected arterial samples to measure ET-1 levels, after 5 min of the first period of desaturation, in each of the 19 patients. We also collected arterial samples in the morning, before the study, to measure baseline ET-1 levels in all patients. Results: Baseline arterial ET-1 levels during the day were very significantly higher in ‘desaturator’ COPD patients (2.058 ± 0.252 pg/ml) compared to ‘non-desaturator’ COPD patients (1.382 ± 0.159 pg/ml; p < 0.001). Also in ‘desaturator’ COPD patients ET-1, levels during the night were significantly higher (4.297 ± 1.107 pg/ml) compared to those during the day (p ≤ 0.001) and a significant negative correlation was observed between ET-1 levels and degree of desaturation (p < 0.0001, r = 0.9305). Conclusions: According to our study we can conclude that (1) ET-1 levels are significantly higher in ‘desaturator’ COPD patients both during the day and during the night, and (2) ET-1 levels correlate negatively significant with the degree of the oxyhemoglobin desaturation. These findings are consistent with the hypothesis that ET-1 plays a very important role in the pathophysiological manifestations of COPD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanisms of Endothelin-1 Elevation in Chronic Obstructive Pulmonary Disease Patients with Nocturnal Oxyhemoglobin Desaturation

Trakada

Marangos²,

Spiropoulos³

2001

Respiration

View full text Add to dashboard Cite

show abstract

“…Several investigations have been performed in rats, evaluating effects of intermittent hypoxia (IH) on pulmonary haemodynamics [27][28][29][30][31]. Severe hypoxia was applied in a hypobaric chamber for 4-8 h?day -1 , 5-7 days a week, with a total of 13-24 exposures.…”

Section: Intermittent Hypoxia In Animal Modelsmentioning

confidence: 99%

Effects of intermittent hypoxia on pulmonary haemodynamics: animal modelsversusstudies in humans

Zieliński¹

2005

Eur Respir J

View full text Add to dashboard Cite

The aim of this review was to analyse the effects of intermittent hypoxia (IH) on pulmonary haemodynamics, comparing results of animal experiments with results of clinical studies.In animal investigations even short hypoxic exposure, continuously or in short repeated episodes mimicking obstructive sleep apnoea (OSA), leads to pulmonary artery remodelling and to pulmonary hypertension (PH). Results of investigations on effects of nocturnal IH on pulmonary haemodynamics in patients with chronic obstructive pulmonary disease (COPD) are discordant. Earlier studies reported the development of mild PH in subjects desaturating during sleep, while more recent investigations did not confirm those findings.Alveolar IH developing during apnoeic episodes during sleep in OSA patients is a diseaseinduced model to study its effects on pulmonary haemodynamics. In the majority of studies in OSA patients pulmonary arterial pressure remained within normal values. PH was found in patients with OSA accompanied by COPD and/or extreme obesity.People commuting between lowland and high altitude due to their employment, are also repeatedly exposed to IH. Results of clinical investigations suggest that it did not lead to the development of permanent PH.The mechanisms of discrepancies between effects of intermittent hypoxia in animal models and in humans remain to be studied.

show abstract

“…Per haps the most apparent functional change is the pulmonary hypertension which de velops as a consequence of sustained hy poxic pulmonary vasoconstriction. Pul monary hypertension and right ventricu lar hypertrophy (RVH) have been induced by continuous exposure to hypobaric hy poxia [1][2][3][4][5][6][7][8] or normobaric hypoxia [9][10][11], and by intermittent exposures to severe hypobaric hypoxia [12][13][14] and intermitt ent normobaric hypoxia [15]. This re sponse of the pulmonary circulation is in triguing because of the marked interspe cies variability that exists [16,17], Some animals, such as cows and pigs, develop severe pulmonary hypertension, whereas other animals, such as sheep and dogs, ap pear to be hyporesponsive to hypoxia [3,16].…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Vascular Changes in Young and Aging Rats Exposed to 5,486 m Altitude

et al. 1984

View full text Add to dashboard Cite

Young (YNG) and middle-aged (MA) male rats were exposed to 5,486 m for durations ranging from 1 to 42 days to determine the effect of age on the progression of polycythemia, right ventricular hypertrophy (RVH), lung vascular muscularization, and pulmonary vascular responsiveness. Other rats were exposed for 42 days at 5,486 m and were then allowed to recover at 1,520 m for periods up to 42 days. The progression and subsequent regression of polycythemia and RVH with altitude exposure were similar for YNG and MA rats. However, YNG rats exhibited vascular muscularization during the altitude exposure, characterized by hypertrophy of smooth muscle cells, whereas MA rats exhibited little or no change in vascular morphology. Lungs from both altitude-exposed YNG and MA rats exhibited blunting of acute hypoxic pulmonary vasoconstriction upon exposure to 5,486 m, with more severe blunting apparent in MA rats. Pressor responses to angiotensin II (All) were potentiated in lungs from high altitude rats, particularly in the YNG rats, and this increased responsiveness persisted during the recovery period. A positive correlation was found in YNG rats between the degree of vascular muscularization and the pressor response to All, suggesting that increased muscle mass was partially responsible for the potentiated Allresponses. However, MA rats did not exhibit the same correlation for All, and neither YNG nor MA rats exhibited increased responsiveness to 5-hydroxytryptamine. The results indicate that age influences the morphologic responses to altitude exposure and vascular responsiveness to All, but does not affect the polycythemic response or the degree of RVH

show abstract

Reversibility of Pulmonary Hypertension and Right Ventricular Hypertrophy Induced by Intermittent High Altitude Hypoxia in Rats

Cited by 37 publications

References 1 publication

Mechanisms of Endothelin-1 Elevation in Chronic Obstructive Pulmonary Disease Patients with Nocturnal Oxyhemoglobin Desaturation

Mechanisms of Endothelin-1 Elevation in Chronic Obstructive Pulmonary Disease Patients with Nocturnal Oxyhemoglobin Desaturation

Effects of intermittent hypoxia on pulmonary haemodynamics: animal modelsversusstudies in humans

Pulmonary Vascular Changes in Young and Aging Rats Exposed to 5,486 m Altitude

Contact Info

Product

Resources

About