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Pulmonary Hypertension Animal Models

A lack of validated pulmonary hypertension animal models is the reason why there aren’t enough studies exploring the pathophysiology and therapies for Pulmonary Hypertension (PH).


What is pulmonary hypertension?
Pulmonary hypertension (PH) is a condition where blood pressure is increased in the arteries of the lungs and is typically associated with left heart disease and classified as Group 2 PH .


Pre-clinical studies validating pulmonary hypertension animal models.
Dr. Dayeh’s research group from the Montreal Heart Institute1 recently addressed this issue with  novel pulmonary hypertension animal models. They induced heart failure by coronary artery ligation, which led to the development of PH in mice. The findings were particularly interesting as it was discovered that myocardial infarction (MI) has an impact on pulmonary capacity, through alveolar and vascular remodeling evidenced by collagen deposition and cellular proliferation.

Further, MI mice clearly developed a restrictive respiratory syndrome characterized by a decrease in lung compliance, measured with the flexiVent.


Pumonary Hypertenstion Animal Models - lung functions measured with the flexiVent

Read more about other Techniques & Measurements employed by the flexiVent.

Four weeks after surgery, Dr. Dayeh and her team were able to assess specific lung characteristics in their subjects such as quasi-static compliance, quasi-static elastance, and respiratory system resistance. Since the flexiVent goes beyond traditional resistance and compliance measurements, it helps captures crucial details about the mechanical properties of conducting airways, terminal airways and parenchyma, providing a unique tool to perform a comprehensive assessment of Group 2 PH models and more!


Dayeh, Nour R., et al1 study outcomes showed:
  • Myocardial infarction (MI) from coronary artery ligation is a validated mouse model of Group 2 PH
  • Wall motion score index (WMSI) is an accurate predictive marker of PH
  • Echocardiography in mice appears as a preferential method for the diagnosis and monitoring of Group 2 PH

More Publications featuring the flexiVent and other SCIREQ research systems.

Attending a training such as the Phenotyping Mice Models of Human Lung Disease organized by the Jackson Laboratory is a great way to advance skillsets or simply get started in the field of respiratory research. It represents a wonderful opportunity for researchers of all stages to learn and network in a structured yet informal environment. The uniqueness of the event lies in the roundness of the approach, which combines theoretical sessions and practical experience in all topics.
 
SCIREQ has been a partner in this event for years now and has contributed with providing hands-on experience to participants with lung function measurements using the flexiVent alongside authorities in the field. Practical exercises are designed to demonstrate a response to a particular intervention, highlight unique measurements (including partitioning the lungs between airway and tissue effects), and analyze outcomes with respect to their physiological implications.
 
JAX Experiments
As an example, participants were guided during the last workshop to utilize pressure-volume loops to confirm the effects of an intervention with implications on lung surfactant and atelectasis.
Figure 1: Pressure-volume loops from a subject before (left) and after (right) a lung lavage. The red line represents the Salazar-Knowles equation fit to the deflation limb of the pressure-volume curve.

They were also invited to examine the effect of increasing the positive end expiratory pressure (PEEP) during ventilation and lung function measurements while exploring the impact on detailed respiratory mechanics parameters before and after the intervention.

 
Airway responsiveness to a specific bronchoconstrictor agent before and after a therapeutic treatment or an assessment of various lung volumes are also typically part of the repertoire of techniques taught.  
Figure 2: Single (left) and broadband (right) forced oscillation outcomes prior to and following increasing doses of nebulised methacholine in presence or absence of a bronchodilator treatment.
Looking forward
The event runs every second year in Bar Harbor, Maine, and accepts a limited number of participants. Plan ahead to take part in the workshop, which we highly recommend to both senior researchers and students alike. 

References

Empowering Researchers

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