Key result
Continuous 3-week hypoxia induces pulmonary hypertension in rats, with longer daily exposure worsening hemodynamics.
Why the study?
Existing hypoxia-induced pulmonary hypertension rat models are time-consuming, costly, complicated, and lack a uniform international standard.
A 3-week continuous hypoxia protocol is an efficient method to establish a rat model of hypoxia-induced pulmonary hypertension, reducing the time needed to induce significant disease phenotypes.
Background and aim: Pulmonary hypertension (PH) is a serious and even fatal disorder with limited treatment strategies. The hypoxia-induced pulmonary hypertension (HPH) rat model is commonly used in this field. While the HPH rat model has strong predictability and repeatability, the model is a chronic model, making it time-consuming, costly, and complicated and limiting the progress of the experiments. Currently, there is no uniform international standard for the HPH model. Our study aimed to find a relatively effective and efficient HPH modeling protocol. Methods: We established HPH rat models with different total hypoxia periods and different daily hypoxia times, and assessed different hypoxia modeling modes in multiple dimensions, such as haemodynamics, right ventricular (RV) hypertrophy, pulmonary arterial remodeling, muscularization, inflammation, and collagen deposition. Results: Longer daily hypoxia time resulted in higher mean pulmonary arterial pressure (mPAP)/right ventricular systolic pressure (RVSP) and more obvious RV hypertrophy, as well as more severe pulmonary arterial remodeling and muscularization, regardless of the total period of hypoxia (3- or 4-week). Moreover, pulmonary perivascular macrophages and collagen deposition showed daily hypoxia time-dependent increases, both in 3- and 4-week hypoxia groups. Conclusion: Our findings showed that the 3-week continuous hypoxia mode was a relatively efficient way to reduce the time needed to induce significant disease phenotypes, which offered methodological evidence for future studies in building HPH models.
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Cai et al. (2022) studied Hypoxia-induced pulmonary hypertension. Different hypoxia protocols vs. Different daily hypoxia times and total periods was evaluated on Haemodynamics, right ventricular hypertrophy, pulmonary arterial remodeling, muscularization, inflammation, and collagen deposition. A 3-week continuous hypoxia protocol efficiently induced significant disease phenotypes of pulmonary hypertension in rat models, with longer daily hypoxia time worsening hemodynamics and remodeling.
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