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Disease Model | Emphasizing Chronic Mountain Sickness! Hypoxic Pulmonary Hypertension (HPH) Poses Numerous Risks

Introduction:

The plateau environment is far from ideal for survival, with numerous adverse factors, among which hypoxia poses the most severe challenge.

Although individuals living at high altitudes have adapted to the hypoxic environment, over time they undergo a series of compensatory responses; in some cases, this can lead to severe pathological changes in vital organs—what we commonly refer to as “chronic diseases.”

 

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What is HPH?

Hypoxic pulmonary hypertension (HPH) is a key physiological adaptation to high altitude and a common manifestation of chronic mountain sickness. Its hallmark features include hypoxic pulmonary vasoconstriction (HPV) and hypoxic pulmonary vessel remodeling (HPVR). During pulmonary vascular remodeling, pulmonary artery smooth muscle cells (PASMCs) undergo proliferation and hypertrophy, extracellular matrix synthesis increases, non‑muscular arteries differentiate into muscular ones, and adventitial fibroblasts proliferate. These processes lead to thickening of the small pulmonary arterial walls and narrowing of the luminal diameter, ultimately resulting in sustained elevation of pulmonary vascular resistance and persistent increases in pulmonary arterial pressure.

 

Significant pulmonary arterial hypertension is one of the key pathophysiological changes underlying chronic cor pulmonale and various forms of high-altitude illness—such as high-altitude pulmonary edema, polycythemia, and high-altitude heart disease—and represents a latent early stage of high-altitude disease; moreover, the more severe the condition, the more pronounced the pulmonary arterial hypertension.

 

If chronic pulmonary arterial hypertension remains uncontrolled, it can readily lead to compensatory right ventricular hypertrophy; in severe cases, this may progress to heart failure. However, the pathogenesis of pulmonary arterial hypertension is still under investigation; therefore, elucidating its underlying mechanisms is of great importance for the prevention and management of related cardiopulmonary diseases.

 

Establishing an HPH animal model is an important approach for studying this disease. The Aniphe BioLab Laboratory can provide you with a hypoxic pulmonary hypertension animal model.

 

Animal Model Construction

Model construction method: An SD rat model was established.

SD rats were divided into two main groups: a normal control group and a hypoxia group, with each group further subdivided into three subgroups: the 1-week group, the 2-week group, and the 3-week group.

SD rats in the hypoxia group were placed in a hypobaric chamber (simulating an altitude of 5,000 m), and tissue samples were collected at weeks 1, 2, and 3 of hypoxia for assessment of various physiological parameters.

The normal control group was housed under normoxic conditions outside the hypobaric oxygen chamber, with the same timing for parameter measurements and tissue collection as the hypoxia group.

 

Measurement Data: Determination of Physiological and Hemodynamic Parameters

At weeks 1, 2, and 3 of hypoxia exposure, anesthetized rats were injected intraperitoneally. Following antisepsis of the anterior neck skin with 75% ethanol, the right external jugular vein was incised and carefully dissected free. A 7-French Swan–Ganz catheter was then inserted through the right external jugular vein and gently advanced into the right ventricle, after which it was further advanced into the pulmonary artery to measure mean pulmonary arterial pressure.

The other end of the catheter is connected to a pressure transducer to monitor changes in pulmonary arterial pressure in the experimental animals.

 

Sample collection and measurement data: heart weight and ratios

After measuring the physiological parameters, the rats were euthanized and their hearts were excised and weighed. The weights of the right ventricular free wall (RV) and the left ventricle plus interventricular septum (LV+S) were determined separately, and the RV/(LV+S) weight ratio was calculated as an index of right ventricular hypertrophy.

Left lung tissue was harvested from rats and fixed in 4% paraformaldehyde for morphological analysis; the right lung tissue was excised, minced into small pieces, and promptly stored in liquid nitrogen for molecular biology studies.

 

Criteria for successful modeling:

As the duration of hypoxic exposure is prolonged, the mean pulmonary arterial pressure (mPAP) in rats increases significantly, and the ratio of the right ventricle to the total heart (Rv/(Lv+S)) also rises markedly. Pulmonary arterial pressure in rats gradually elevates, accompanied by evidence of right ventricular hypertrophy.

The walls of the pulmonary arterioles in rats will gradually thicken, with marked proliferation of the medial smooth muscle cells.

Upon the occurrence of the aforementioned phenomena, it indicates that the animal model of hypoxic pulmonary hypertension, established by housing animals in a low-pressure oxygen chamber to simulate an altitude of 5,000 meters, has been successfully constructed.

 

Partial Data Report (Example)

Reference: Chinese Journal of Plateau Medicine and Biology, Vol. 39, No. 1, 2018—“Establishment of a Rat Model of Hypoxic Pulmonary Hypertension with Pulmonary Vascular Remodeling and Expression of miR‑34a in Lung Tissue”

 

Ailinfei Laboratory can provide you with an animal model of hypoxic pulmonary hypertension. The Vevo 2100 ultra-high-resolution small-animal ultrasound real-time molecular imaging system was used to quantify physiological and circulatory parameters as well as molecular data. A hypoxic chamber was used to establish the model, with two ultrasound examinations conducted.

Parameter configuration: Equipped with three ultrasonic transducers, suitable for rabbits, rats, and mice; provides real-time, synchronized animal physiological data (electrocardiogram, body temperature, respiration, etc.);

A variety of measurement toolkits provide parameters for abdominal organs, the eye, embryos, and vascular structures; includes a 2D B‑mode ultrasound module, a high‑resolution continuous‑wave Doppler module (M‑mode), a pulsed‑wave Doppler module (PW), a color Doppler module, and a 3D module; offers ultrasound‑guided injections. Equipped with bone morphometric analysis and bone density assessment capabilities.

 

 

 

 

Organizer  |  Aniphe BioLab Marketing Department

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Editor-in-chief  |  Lemon

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Editor-in-chief  |  Swallows, little boats

Editor  |  Lemon

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