Here, we present a protocol to perform an invasive hemodynamic assessment of the right ventricle and pulmonary artery in mice using an open-chest surgery approach.
Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. However, the evaluation of right ventricular pressure (RVP) and pulmonary artery pressure (PAP) remains technically challenging in mice. RVP and PAP are more difficult to measure than left ventricular pressure because of the anatomical differences between the left and right heart systems. In this paper, we describe a stable right heart hemodynamic measurement method and its validation using healthy and PAH mice. This method is based on open-chest surgery and mechanical ventilation support. It is a complicated procedure compared to closed chest procedures. While a well-trained surgeon is required for this surgery, the advantage of this procedure is that it can generate both RVP and PAP parameters at the same time, so it is a preferable procedure for the evaluation of PAH models.
Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder with elevation in pulmonary artery pressure (PAP) and right ventricular pressure (RVP) that is caused by cellular proliferation and fibrosis of small pulmonary arteries1. Pulmonary artery catheters, also called Swan-Ganz catheters2, are commonly used in the clinical monitoring of RVP and PAP. Furthermore, a wireless PAP monitoring system has been used clinically3,4,5. To mimic the disease for study in mice, a hypoxic environment is used to simulate human clinical manifestations of PAH6. In the evaluation of PAP in animals, large animals are relatively easy to monitor through pulmonary artery catheters using the same technique as for human subjects, but small animals such as rats and mice are difficult to assess because of their small body size. Hemodynamic measurement of the right ventricular system in mice is possible with an ultrasmall size 1 Fr catheter7. A method for measuring RVP and PAP in mice has been reported in the literature8,9, but the methodology lacks a detailed description. RVP and PAP are more challenging to measure than left ventricular pressure because of the anatomical differences between the left and right heart systems.
To get both PAP and RVP parameters in the same mouse, we describe an open-chest surgery-based approach for right heart hemodynamic measurements, its validation with healthy and PAH mice, and how to avoid generating artificial data during the complicated open-chest surgery. Although this technique is best performed by a well-trained surgeon, it has the advantage of being able to assess PAP and RVP in the same mouse.
Tracheal intubation is the first important step for open-chest surgeries. The classic method of tracheal intubation for small animals, such as rats or mice, involves making a T-shaped incision on the trachea and directly inserting Y-type tracheal tubing into the trachea. In practice, we find that this method is not easy during operation. The Y-type tracheal tubing is too large for small animals and forms an angle with the trachea. Thus, it is difficult to fix the tubing in place. Additionally, once the intubation tubing …
The authors have nothing to disclose.
This research is supported by the Postgraduate Education and Teaching Reform Project of Peking Union Medical College (10023-2016-002-03), the Fuwai Hospital Youth Fund (2018-F09), and the Director Fund of Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials (2018-PT2-ZR05).
2,2,2-Tribromoethanol | Sigma-Aldrich | T48402-5G | For anesthesia |
Animal temperature controller | Physitemp Instruments, Inc. | TCAT-2LV | For temperature control |
Dissection forceps | Fine Science Tools, Inc. | 11274-20 | For surgery |
Gemini Cautery System | Gemini | GEM 5917 | For surgery |
Intravenous catheter (22G) | BD angiocath | 381123 | For intubation |
LabChart 7.3 | ADInstruments | For data analysis | |
Light illumination system | Olympus | For surgery | |
Mikro-Tip catheter | Millar Instruments, Houston, TX | SPR-1000 | For pressure measurement |
Millar Pressure-Volume Systems | Millar Instruments, Houston, TX | MVPS-300 | For pressure measurement |
O2 Controller and Hypoxia chamber | Biospherix | ProOx 110 | For chronic hypoxia |
PowerLab Data Acquisition System | ADInstruments | PowerLab 16/30 | For data recording |
Scissors | Fine Science Tools, Inc. | 14084-08 | For surgery |
Small animal ventilator | Harvard Apparatus | Mini-Vent 845 | For surgery |
Stereomicroscope | Olympus | SZ61 | For surgery |
Surgery tape | 3M | For surgery | |
Terg-a-zyme enzyme | Sigma-Aldrich | Z273287-1EA | For catheter cleaning |