Name: Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice (Video) | JoVE Journal
Uploaded: 2019-10-24T13:30:00.000+00:00
Duration: 4 min 54 s
Description: Learn invasive hemodynamic assessment for right ventricular and pulmonary artery pressure evaluation in mice using open-chest surgery. This method enables simultaneous measurement of RVP and PAP parameters for PAH research.

ai_agent_IP

ai_agent

maintenance

instantTrialDurationMinutes

isBiopharma

enableNewMyJoveSectionDesign

educationFeatures

seoMetaApi

ai_copilot_institution_blacklist

ai_chat_institution_blacklist

freeAccessWindow

ssoRoleCapture

scheduledMaintenanceBanner

joveLabsFeatures

disable_autoplay_for_bots

extended_trial_duration

5 minutes

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).

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 oxygen-controlled hypoxia chamber to induce pulmonary hypertension, and control mice were housed in room air (21% oxygen) under identical conditions. RVP and PAP measurements were performed at the end of the 4 weeks of hypoxia challenge.
1. Preoperative preparation
<ol>
	<li>Soak the pressure transducer catheter (size: 1 Fr) in 0.9% saline at room temperature for at least 30 min before the hemodynamic experiment.</li>
	<li>Filter 2,2,2-Tribromoethanol solution with 0.22 &#956;m filter and store in 4-degree refrigerator.</li>
	<li>Prepare cleaned surgery tools and supplies such as gloves for surgery.</li>
	<li>Prepare 10 mL of 1.0% digestive enzyme solution for catheter cleaning.</li>
	<li>Connect the pressure transducer catheter to a pressure-volume system.</li>
	<li>Calibrate the pressure transducer prior to obtaining pressure measurements for each mouse.
	<ol>
		<li>Turn the calibration knob to 0 mmHg and 25 mmHg to send a verification pressure signal to the data acquisition software and configure the calibration setting in the software.</li>
		<li>Turn the knob to Transducer and adjust the Balance knob to zero baseline.</li>
	</ol>
	</li>
	<li>Set up a standard stereomicroscope and a temperature-controlled small animal surgical table for body temperature maintenance during the surgery.</li>
	<li>Set up a light illumination system for microsurgery to provide enough light over the surgical area.</li>
</ol>
2. Open-Chest surgery and hemodynamic measurement
<ol>
	<li>Anesthetize mice with 250 mg/kg of 2,2,2-Tribromoethanol via intraperitoneal (i.p.) injection. If needed, repeat supplemental doses at 1/3 to 1/2 of the original dose during the procedure.</li>
	<li>Remove chest and neck fur using a shaver and hair removal lotion (Figure 1A, 2A).</li>
	<li>Secure each mouse in the supine position on a temperature-controlled small animal surgical table to help maintain body temperature (37 &#176;C) during surgery.</li>
	<li>Clean the surgical site with 70% ethanal.</li>
	<li>Once anesthesia is in effect, confirm adequate anesthesia induction using a toe pinch.</li>
	<li>Make a midline incision on the neck skin (Figure 1A).</li>
	<li>Dissect the skeletal muscle using curved forceps and expose the trachea (Figure 1B, 1C).</li>
	<li>Perform intubation through the mouth using a modified 22 G intravenous sheath catheter. Confirm that the tubing is in the trachea using forceps (Figure 1D).</li>
	<li>Connect the tubing to a small animal ventilator. Calculate and set respiration rate and tidal volume based on body weight according to the ventilator user manual10. For example, set respiration rate to 133/min and tidal volume to 180 &#956;L for a 30 g mouse based on the described calculation.</li>
	<li>Secure the tubing for ventilation using tape.</li>
	<li>Confirm adequate anesthesia induction using a toe pinch.</li>
	<li>Make a midline incision on the chest skin and carefully dissect the chest muscles using a cautery tool (Figure 2B, 2C).</li>
	<li>Cut the sternum using scissors across the middle and expose the thoracic cavity (Figure 2D).</li>
	<li>Prevent any bleeding using the cautery tool during the open-chest surgery procedure.</li>
	<li>Expose the right ventricle with retractors (Figure 2E).</li>
	<li>Insert the saline-soaked pressure transducer catheter through a small tunnel created with a 25 G needle into the right ventricle to measure RVP (Figure 2F and Figure 3A, 3C).</li>
	<li>Hold the catheter cable and cross the pulmonary valve in a coaxial manner with the pulmonary artery. Observe the pressure waveform and obtain a stable PAP signal (Figure 3B, 3D).</li>
	<li>Record hemodynamic data using the data acquisition system and software.</li>
	<li>After the final measurements, euthanize mice humanely through i.p. injection of an excess dose of 2,2,2-Tribromoethanol solution.</li>
	<li>Carefully remove catheter from the right heart system and place into a 1 mL syringe containing 1% digestive enzyme solution.</li>
	<li>Use distilled water to continuously flush the catheter carefully and store it in the original box.</li>
</ol>
3. Data analysis for hemodynamics
NOTE: The hemodynamic data were recorded and analyzed using analysis software11&#160;(Table of Materials).
<ol>
	<li>For each mouse, select at least 10 continuous and stable heartbeat cycles without noise to obtain the average data of RVP or PAP data for each parameter.</li>
	<li>Use Student&#8217;s t-test to compare the normal air control and hypoxia groups. NOTE: p &#60; 0.05 was considered statistically significant. Data are presented as the mean &#177; SD.</li>
</ol>

<ol><li>Humbert, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Advances+in+therapeutic+interventions+for+patients+with+pulmonary+arterial+hypertension%5BTitle%5D)+AND+%22Circulation%22%5BJournal%5D)">Advances in therapeutic interventions for patients with pulmonary arterial hypertension.</a> Circulation. 130 (24), 2189-2208 (2014).</li>
<li>Chatterjee, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+Swan-Ganz+catheters%3A+past%2C+present%2C+and+future%3A+a+viewpoint%5BTitle%5D)+AND+%22Circulation%22%5BJournal%5D)">The Swan-Ganz catheters: past, present, and future: a viewpoint.</a> Circulation. 119 (1), 147-152 (2009).</li>
<li>Adamson, P. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((CHAMPION+trial+rationale+and+design%3A+the+long-term+safety+and+clinical+efficacy+of+a+wireless+pulmonary+artery+pressure+monitoring+system%5BTitle%5D)+AND+%22Journal+of+Cardiac+Failure%22%5BJournal%5D)">CHAMPION trial rationale and design: the long-term safety and clinical efficacy of a wireless pulmonary artery pressure monitoring system.</a> Journal of Cardiac Failure. 17 (1), 3-10 (2011).</li>
<li>Abraham, W. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Wireless+pulmonary+artery+haemodynamic+monitoring+in+chronic+heart+failure%3A+a+randomised+controlled+trial%5BTitle%5D)+AND+%22The+Lancet%22%5BJournal%5D)">Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial.</a> The Lancet. 377 (9766), 658-666 (2011).</li>
<li>Adamson, P. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Wireless+pulmonary+artery+pressure+monitoring+guides+management+to+reduce+decompensation+in+heart+failure+with+preserved+ejection+fraction%5BTitle%5D)+AND+%22Circulation%3A+Heart+Failure%22%5BJournal%5D)">Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction.</a> Circulation: Heart Failure. 7 (6), 935-944 (2014).</li>
<li>Shatat, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Endothelial+Kruppel-like+Factor+4+modulates+pulmonary+arterial+hypertension%5BTitle%5D)+AND+%22American+Journal+of+Respiratory+Cell+and+Molecular+Biology%22%5BJournal%5D)">Endothelial Kruppel-like Factor 4 modulates pulmonary arterial hypertension.</a> American Journal of Respiratory Cell and Molecular Biology. 50 (3), 647-653 (2014).</li>
<li>SPR-1000 Mouse Pressure Catheter. , Available from: 
 <a target="_blank" href="https://millar.com/products/research/pressure/single-pressure-no-lumen/spr-1000">https://millar.com/products/research/pressure/single-pressure-no-lumen/spr-1000</a> (2019).</li>
<li>Tabima, D. M., Hacker, T. A., Chesler, N. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Measuring+right+ventricular+function+in+the+normal+and+hypertensive+mouse+hearts+using+admittance-derived+pressure-volume+loops%5BTitle%5D)+AND+%22American+Journal+of+Physiology+Heart+and+Circulatory+Physiology%22%5BJournal%5D)">Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops.</a> American Journal of Physiology Heart and Circulatory Physiology. 299 (6), 2069-2075 (2010).</li>
<li>Skuli, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Endothelial+deletion+of+hypoxia-inducible+factor-2alpha+%28HIF-2alpha%29+alters+vascular+function+and+tumor+angiogenesis%5BTitle%5D)+AND+%22Blood%22%5BJournal%5D)">Endothelial deletion of hypoxia-inducible factor-2alpha (HIF-2alpha) alters vascular function and tumor angiogenesis.</a> Blood. 114 (2), 469-477 (2009).</li>
<li>Harvard Inspira Advanced Safety Ventilator User's Manual. , Available from: 
 <a target="_blank" href="http://www.harvardapparatus.com/media/harvard/pdf/Inspira_557058_9.pdf.">http://www.harvardapparatus.com/media/harvard/pdf/Inspira_557058_9.pdf.</a> (2019).</li>
<li>LabChart. , Available from: 
 <a target="_blank" href="https://www.adinstruments.com/products/labchart?creative=290739105773_keyword=labchart_matchtype=e_network=g_device=_gclid=CjwKCAjwxrzoBRBBEiwAbtX1n42I2S06KmccVncUHkmExU8KKOXXREyzx8bvTrxYMSze-ooE0atcbRoCliwQAvD_BwE">https://www.adinstruments.com/products/labchart?creative=290739105773_keyword=labchart_matchtype=e_network=g_device=_gclid=CjwKCAjwxrzoBRBBEiwAbtX1n42I2S06KmccVncUHkmExU8KKOXXREyzx8bvTrxYMSze-ooE0atcbRoCliwQAvD_BwE</a> (2019).</li>
<li>Marius, M. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Definitions+and+diagnosis+of+pulmonary+hypertension%5BTitle%5D)+AND+%22Journal+of+the+American+College+of+Cardiology%22%5BJournal%5D)">Definitions and diagnosis of pulmonary hypertension.</a> Journal of the American College of Cardiology. 62 (25), 42-50 (2013).</li>
<li>Ciuclan, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+novel+murine+model+of+severe+pulmonary+arterial+hypertension%5BTitle%5D)+AND+%22American+Journal+of+Respiratory+and+Critical+Care+Medicine%22%5BJournal%5D)">A novel murine model of severe pulmonary arterial hypertension.</a> American Journal of Respiratory and Critical Care Medicine. 184 (10), 1171-1182 (2011).</li>
<li>Brown, R. H., Walters, D. M., Greenberg, R. S., Mitzner, W. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+method+of+endotracheal+intubation+and+pulmonary+functional+assessment+for+repeated+studies+in+mice%5BTitle%5D)+AND+%22Journal+of+Applied+Physiology%22%5BJournal%5D)">A method of endotracheal intubation and pulmonary functional assessment for repeated studies in mice.</a> Journal of Applied Physiology. 87 (6), 2362-2365 (1999).</li>
<li>Chen, W. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Right+ventricular+systolic+pressure+measurements+in+combination+with+harvest+of+lung+and+immune+tissue+samples+in+mice%5BTitle%5D)+AND+%22Journal+of+Visualized+Experiments%22%5BJournal%5D)">Right ventricular systolic pressure measurements in combination with harvest of lung and immune tissue samples in mice.</a> Journal of Visualized Experiments. (71), 50023(2013).</li>
<li>Ma, Z., Mao, L., Rajagopal, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Hemodynamic+characterization+of+rodent+models+of+pulmonary+arterial+hypertension%5BTitle%5D)+AND+%22Journal+of+Visualized+Experiments%22%5BJournal%5D)">Hemodynamic characterization of rodent models of pulmonary arterial hypertension.</a> Journal of Visualized Experiments. (110), 53335(2016).</li>
<li>Chen, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Berberine+attenuates+hypoxia-induced+pulmonary+arterial+hypertension+via+bone+morphogenetic+protein+and+transforming+growth+factor-%CE%B2+signaling%5BTitle%5D)+AND+%22Journal+of+Cellular+Physiology%22%5BJournal%5D)">Berberine attenuates hypoxia-induced pulmonary arterial hypertension via bone morphogenetic protein and transforming growth factor-β signaling.</a> Journal of Cellular Physiology. , (2019).</li>
<li>Bueno-Beti, C., Hadri, L., Hajjar, R. J., Sassi, Y. The Sugen 5416/Hypoxia mouse model of pulmonary arterial hypertension. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aBueno-Beti%2C+C+%22Experimental+Models+of+Cardiovascular+Diseases.+Methods+in+Molecular+Biology.+vol+1816%22">Experimental Models of Cardiovascular Diseases. Methods in Molecular Biology. vol 1816</a>. Ishikawa, K. , Humana Press. New York, NY. (2018).</li>
</ol>

The authors have nothing to disclose.

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 ...

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.

<table><tbody><tr><td>2,2,2-Tribromoethanol</td><td>Sigma-Aldrich</td><td>T48402-5G</td><td>For anesthesia</td></tr><tr><td>Animal temperature controller</td><td>Physitemp Instruments, Inc.</td><td>TCAT-2LV</td><td>For temperature control</td></tr><tr><td>Dissection forceps</td><td>Fine Science Tools, Inc.</td><td>11274-20</td><td>For surgery</td></tr><tr><td>Gemini Cautery System</td><td>Gemini</td><td>GEM 5917</td><td>For surgery</td></tr><tr><td>Intravenous catheter (22G)</td><td>BD angiocath</td><td>381123</td><td>For intubation</td></tr><tr><td>LabChart 7.3</td><td>ADInstruments</td><td></td><td>For data analysis</td></tr><tr><td>Light illumination system</td><td>Olympus</td><td></td><td>For surgery</td></tr><tr><td>Mikro-Tip catheter</td><td>Millar Instruments, Houston, TX</td><td>SPR-1000</td><td>For pressure measurement</td></tr><tr><td>Millar Pressure-Volume Systems</td><td>Millar Instruments, Houston, TX</td><td>MVPS-300</td><td>For pressure measurement</td></tr><tr><td>O2 Controller and Hypoxia chamber</td><td>Biospherix</td><td>ProOx 110</td><td>For chronic hypoxia</td></tr><tr><td>PowerLab Data Acquisition System</td><td>ADInstruments</td><td>PowerLab 16/30</td><td>For data recording</td></tr><tr><td>Scissors</td><td>Fine Science Tools, Inc.</td><td>14084-08</td><td>For surgery</td></tr><tr><td>Small animal ventilator</td><td>Harvard Apparatus</td><td>Mini-Vent 845</td><td>For surgery</td></tr><tr><td>Stereomicroscope</td><td>Olympus</td><td>SZ61</td><td>For surgery</td></tr><tr><td>Surgery tape</td><td>3M</td><td></td><td>For surgery</td></tr><tr><td>Terg-a-zyme enzyme</td><td>Sigma-Aldrich</td><td>Z273287-1EA</td><td>For catheter cleaning</td></tr></tbody></table>

invasive hemodynamic assessment for the right ventricular system and hypoxia-induced pulmonary arterial hypertension in mice

Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

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.

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 ...

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. ...

invasive-hemodynamic-assessment-for-right-ventricular-system-hypoxia

Research

JoVE Journal

Medicine

A specific and rapid protocol to simultaneously investigate right heart function, lung inflammation, and the immune response is described as a learning tool.  Video and figures describe physiology and microdissection techniques in an organized team-approach that is adaptable to be used for small to large sized studies.

Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice

This article provides a protocol for the echocardiographic assessment of right ventricular size and pulmonary hypertension in mice.  Applications include phenotype determination and serial assessment in transgenic and toxin-induced mouse models of cardiomyopathy and pulmonary vascular disease.

Echocardiographic Assessment of the Right Heart in Mice

Right ventricle (RV) dysfunction is critical to the pathogenesis of cardiovascular disease, yet limited methodologies are available for its evaluation. Recent advances in ultrasound imaging provide a noninvasive and accurate option for longitudinal RV study. Herein, we detail a step-by-step echocardiographic method using a murine model of RV pressure overload.

Assessment of Right Ventricular Structure and Function in Mouse Model of Pulmonary Artery Constriction by Transthoracic Echocardiography

Pulmonary arterial hypertension (PAH) is a disease of pulmonary arterioles that leads to their obliteration and the development of right ventricular failure. Rodent models of PAH are critical in understanding the pathophysiology of PAH. Here we demonstrate hemodynamic characterization, with right heart catheterization and echocardiography, in the mouse and rat.

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

We present a protocol of creating right ventricular dysfunction in a pig model by inducing ARDS. We demonstrate invasive monitoring of left and right ventricular cardiac output using flow probes around the aorta and the pulmonary artery, as well as blood pressure measurements in the aorta and pulmonary artery.

Invasive Hemodynamic Monitoring of Aortic and Pulmonary Artery Hemodynamics in a Large Animal Model of ARDS

This protocol describes the induction of pulmonary hypertension (PH) in mice based on the exposure to hypoxia and the injection of a VEGF receptor antagonist. The animals develop PH and right ventricular (RV) hypertrophy 3 weeks after the initiation of the protocol. The functional and morphometrical characterization of the model is also presented.

Induction and Characterization of Pulmonary Hypertension in Mice using the Hypoxia/SU5416 Model

Here, we provide a useful approach for studying the mechanism of right ventricular failure. A more convenient and efficient approach to pulmonary artery constriction is established using surgical instruments made inhouse. In addition, methods to evaluate the quality of this approach by echocardiography and catheterization are provided.

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice

The present protocol describes the echocardiographic characterization of right ventricular morphology and function in a rat model of pulmonary arterial hypertension.

Comprehensive Echocardiographic Assessment of Right Ventricle Function in a Rat Model of Pulmonary Arterial Hypertension

This protocol provides a step-by-step procedure for executing multiple intravenous bolus dose administration and invasive hemodynamic monitoring in mice. Investigators can use this protocol for future therapeutic compound screening for pulmonary artery hypertension.

Multiple Intravenous Bolus Dosing and Invasive Hemodynamic Assessment in a Hypoxia-Induced Mouse Pulmonary Artery Hypertension Model

The presentation of detailed methods for the evaluation of right ventricle function will enhance the quality and reliability of pulmonary hypertension research, offering a robust framework for future studies and enhancing reproducibility across different laboratories.

Evaluation of Right Ventricular Function in Experimental Models of Pulmonary Arterial Hypertension

Learn invasive hemodynamic assessment for right ventricular and pulmonary artery pressure evaluation in mice using open-chest surgery. This method enables simultaneous measurement of RVP and PAP parameters for PAH research.

Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

Explore More Videos