Effect of intermittent altitude hypoxia on the myocardium and lesser circulation in the rat

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

doi:10.1093/cvr/7.6.798

Cited by 76 publications

(37 citation statements)

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“…Early studies on animal models demonstrated that short amounts of exposure, lasting only few hours per day, to hypoxia may imitate nocturnal desaturation in COPD patients which has also resulted in the development of permanent PH [25,26]. However, the rat is a poor animal model of hypoxic pulmonary hypertension in man [27].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary haemodynamics in patients with OSAS or an overlap syndrome

Hawryłkiewicz¹,

Sliwiński²,

Górecka³

et al. 2004

Monaldi Arch Chest Dis

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Background. Alveolar hypoxia is the most important mechanism leading to pulmonary arterial vasoconstriction, remodelling and pulmonary hypertension. Patients with Obstructive Sleep Apnoea Syndrome (OSAS) experience multiple short periods of alveolar hypoxia during apnoeic episodes. However, the question as to whether these hypoxic episodes are responsible for the development of permanent pulmonary hypertension is still debatable. We aimed to investigate the relationship between the episodes of nocturnal desaturation and pulmonary haemodynamics in two distinct group patients: with pure OSAS or an overlap syndrome. Methods: We studied 67 patients with severe OSAS (means: age 45±8 years, AHI 62±22, FEV1 3.6±0.8 L = 97±16% of predicted PaO2 72±10 mmHg, PaCO2 40±4 mmHg) and 17 patients with an overlap syndrome (OS), means: age 51±5 years, AHI 64±19, FEV1 1.5±0.7 = 43±16% of predicted PaO2 57±9 mmHg). All subjects underwent pulmonary artery catheterisation with pressure and flow recordings and an overnight full sleep study. Results. On average patients with OSAS had nocturnal desaturation (mean overnight SaO2 = 87±5%) and normal PPA (15.8±4.6 mmHg). Only 11 out of 67 subjects (16%) presented with pulmonary hypertension. Patients with OS had nocturnal desaturation (mean overnight SaO2 = 80.2±8.5%) and mild pulmonary hypertension (PPA 24.2±7.4 mmHg). Only three out of 17 patients had normal pulmonary arterial pressure. Conclusions. In patients with severe OSAS, pulmonary hypertension is rare (16%) and is related best to the severity of the disease and to obesity. In OS patients diurnal pulmonary hypertension is frequent but does not correlate with the severity of nocturnal desaturation.

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Section: Discussionmentioning

confidence: 99%

Pulmonary haemodynamics in patients with OSAS or an overlap syndrome

Hawryłkiewicz¹,

Sliwiński²,

Górecka³

et al. 2004

Monaldi Arch Chest Dis

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“…In addition, the origin of right ventricular hypertrophy is most likely multifactorial and includes increased pressure load from remodeling and vasoconstriction, increased ET-1 myocardial expression, or increased myocardial protein kinases (28), or some combination of these factors. Additionally, histologic changes in the right ventricular myocardium have been reported in adult rats exposed to prolonged hypoxia (29). Consequently, treatment with TBC3711 may help to counteract some, but not all, of these mechanisms.…”

Section: Discussionmentioning

confidence: 99%

TBC3711, an ETA Receptor Antagonist, Reduces Neonatal Hypoxia-Induced Pulmonary Hypertension in Piglets

et al. 2001

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The pulmonary vasculature of newborns with persistent pulmonary hypertension is characterized by active vasoconstriction and vascular remodeling. It has been suggested that endothelin-1 (ET-1), a potent vasoconstrictor and growth promoter, may be involved in the pathogenesis of persistent pulmonary hypertension of the newborn. To determine whether treatment with an ET A receptor antagonist can reverse pulmonary hypertension in the neonate, 1-d-old piglets were exposed to hypoxia for 3 d to induce pulmonary hypertension and then treated for the remainder of the 14 d with an orally active, nonpeptidic ET A antagonist (TBC3711, 22 mg·kg). At the end of the exposure, Hb, pulmonary artery pressure, right ventricle to left ventricle plus septum weight ratio, percentage wall thickness, ET-1 circulating levels, perfusion pressure, and dilator response to the nitric oxide (NO) donor, SIN-1 (3-morpholinosydnonimine-N-ethylcarbamide) in isolated perfused lungs were determined. Exhaled NO and hemodynamic variables were also examined in an intact anesthetized animal preparation that had undergone the same treatment. By 3 d of exposure to hypoxia, piglets had already developed significant pulmonary hypertension as estimated by their pulmonary artery pressure (24.0 Ϯ 1.3 mm Hg versus 14.2 Ϯ 3.4 mm Hg) and percentage wall thickness (26.6 Ϯ 5.9% versus 18.7 Ϯ 2.4% for vessels 0-30 m). Whereas further exposure to hypoxia for 14 d did not enhance the increase in pulmonary artery pressure and percentage wall thickness, it did augment the right ventricle to left ventricle plus septum weight ratio (0.71 Ϯ 0.09 versus 0.35 Ϯ 0.01). ET-1 circulating levels were increased only when exposure to hypoxia was prolonged to 14 d (5.1 Ϯ 2.4 pg/mL versus 1.0 Ϯ 0.4 pg/mL). Treatment with TBC3711 from d 3 to d 14, once pulmonary hypertensive changes were established and while hypoxic exposure persisted, caused significant reduction in the right ventricle to left ventricle plus septum weight ratio (0.60 Ϯ 0.06), pulmonary artery pressure (20.0 Ϯ 4.8 mm Hg), and percentage wall thickness (18.5 Ϯ 3.3%) and restored the dilator response to the NO donor SIN-1. Prolonged hypoxia markedly reduced exhaled NO concentrations (0.3 Ϯ 0.6 ppb), although treatment of hypoxic animals with TBC3711 restored the concentration of exhaled NO (4.4 Ϯ 2.8 ppb) to the level of normoxic controls (4.9 Ϯ 3.0 ppb). Lastly, treatment with TBC3711 increased ET-1 circulating levels in both the normoxic (5.4 Ϯ 2.8 pg/mL) and hypoxic (13.0 Ϯ 6.3 pg/mL) groups. In conclusion, the specific ET A receptor antagonist, TBC3711, can significantly ameliorate the morphologic changes encountered in hypoxia-induced pulmonary hypertension in the newborn piglet and may improve the dilator response to NO.

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“…pulmonary microvessels; hypoxia; intact chest STRUCTURAL AND FUNCTIONAL changes of the pulmonary circulation, particularly during the pathogenesis of pulmonary arterial hypertension (PAH), remain to be fully elucidated. Specifically, the small peripheral pulmonary arteries (Ͻ500 m) are believed to be most susceptible to structural changes during, for example, chronic exposure to hypoxia (1,6,7,15,19,32).To date, most small-animal studies that have described the anatomic geometry of the pulmonary circulation have been limited to the use of in vitro or ex vivo preparations. While such data have aided our understanding concerning the pulmonary microcirculation, such invasive procedures ultimately disrupt the natural physiological milieu of the lung.…”

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confidence: 99%

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confidence: 99%

Imaging of the pulmonary circulation in the closed-chest rat using synchrotron radiation microangiography

Schwenke

Pearson²,

Umetani³

et al. 2007

Journal of Applied Physiology

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Schwenke DO, Pearson JT, Umetani K, Kangawa K, Shirai M. Imaging of the pulmonary circulation in the closed-chest rat using synchrotron radiation microangiography. J Appl Physiol 102: [787][788][789][790][791][792][793] 2007. First published October 12, 2006; doi:10.1152/japplphysiol.00596.2006.-Structural changes of the pulmonary circulation during the pathogenesis of pulmonary arterial hypertension remain to be fully elucidated. Although angiography has been used for visualizing the pulmonary circulation, conventional angiography systems have considerable limitations for visualizing small microvessels (diameters Ͻ 200 m), particularly within a closed-chest animal model. In this study we assess the effectiveness of monochromatic synchrotron radiation (SR) for microangiography of the pulmonary circulation in the intact-chest rat. Male adult Sprague-Dawley rats were anesthetized, and a catheter was positioned within the right ventricle, for administering iodinated contrast agent (Iomeron 350). Subsequently, microangiography of pulmonary arterial branches within the left lung was performed using monochromatic SR. Additionally, we assessed dynamic changes in vessel diameter during acute hypoxic (10% and 8% O 2 for 4 min each) pulmonary vasoconstriction (HPV). Using SR we were able to visualize pulmonary microvessels with a diameter of Ͻ100 m (the 4th generation of branching from the left axial artery). Acute hypoxia caused a significant decrease in the diameter of all vessels less than 500 m. The greatest degree of pulmonary vasoconstriction was observed in vessels with a diameter between 200 and 300 m. These results demonstrate the effectiveness of SR for visualizing pulmonary vessels in a closed-chest rat model and for assessing dynamic changes associated with HPV. More importantly, these observations implicate SR as an effective tool in future research for assessing gross structural changes associated with the pathogenesis of pulmonary arterial hypertension. pulmonary microvessels; hypoxia; intact chest STRUCTURAL AND FUNCTIONAL changes of the pulmonary circulation, particularly during the pathogenesis of pulmonary arterial hypertension (PAH), remain to be fully elucidated. Specifically, the small peripheral pulmonary arteries (Ͻ500 m) are believed to be most susceptible to structural changes during, for example, chronic exposure to hypoxia (1,6,7,15,19,32).To date, most small-animal studies that have described the anatomic geometry of the pulmonary circulation have been limited to the use of in vitro or ex vivo preparations. While such data have aided our understanding concerning the pulmonary microcirculation, such invasive procedures ultimately disrupt the natural physiological milieu of the lung. Ideally, a technique of visualizing the pulmonary circulation within a closed-chest model, i.e., under intact neurohumoral regulation, is required to fully understand the structural and functional properties of the microcirculation in the normal lung as well as understand the dynamic changes that occur in pathologic...

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Effect of intermittent altitude hypoxia on the myocardium and lesser circulation in the rat

Cited by 76 publications

References 0 publications

Pulmonary haemodynamics in patients with OSAS or an overlap syndrome

Pulmonary haemodynamics in patients with OSAS or an overlap syndrome

TBC3711, an ETA Receptor Antagonist, Reduces Neonatal Hypoxia-Induced Pulmonary Hypertension in Piglets

Imaging of the pulmonary circulation in the closed-chest rat using synchrotron radiation microangiography

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