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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

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.

Abstract

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.

Introduction

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 sim....

Protocol

The animal protocol was reviewed and approved by the Institutional Animal Care and Use Committee at Fuwai Hospital, Chinese Academy of Medical Science, Peking Union Medical College (NO.0000287). The experimental animals were housed and fed according to the guidelines of animal welfare in China.

NOTE: Eight- to 12-week-old male C57BL mice were housed in an environment with a 12 h dark/ 12 h light cycle. The PAH mice were housed for 4 weeks under an oxygen concentration of 10%, maintained by an .......

Representative Results

The pressure transducer catheter was inserted into the right ventricle (Figure 3A) through a tunnel expanded by a 25 G needle, and a typical RVP waveform (Figure 3C) was obtained. The catheter was continually adjusted and slowly advanced and kept in the same axis as the pulmonary artery while passing through the pulmonary valve (Figure 3B). When the pressure sensor was successfully .......

Discussion

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 .......

Acknowledgements

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).

....

Materials

NameCompanyCatalog NumberComments
2,2,2-TribromoethanolSigma-AldrichT48402-5GFor anesthesia
Animal temperature controllerPhysitemp Instruments, Inc.TCAT-2LVFor temperature control
Dissection forcepsFine Science Tools, Inc.11274-20For surgery
Gemini Cautery SystemGeminiGEM 5917For surgery
Intravenous catheter (22G)BD angiocath381123For intubation
LabChart 7.3ADInstrumentsFor data analysis
Light illumination systemOlympusFor surgery
Mikro-Tip catheterMillar Instruments, Houston, TXSPR-1000For pressure measurement
Millar Pressure-Volume SystemsMillar Instruments, Houston, TXMVPS-300For pressure measurement
O2 Controller and Hypoxia chamberBiospherixProOx 110For chronic hypoxia
PowerLab Data Acquisition SystemADInstrumentsPowerLab 16/30For data recording
ScissorsFine Science Tools, Inc.14084-08For surgery
Small animal ventilatorHarvard ApparatusMini-Vent 845For surgery
StereomicroscopeOlympusSZ61For surgery
Surgery tape3MFor surgery
Terg-a-zyme enzymeSigma-AldrichZ273287-1EAFor catheter cleaning

References

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