Name: invasive hemodynamic monitoring of aortic and pulmonary artery hemodynamics in a large animal model of ards
Uploaded: 2018-11-26T12:30:00.000+00:00
Duration: 8 min 12 s
Description: Watch this Scientific Journal Video about Invasive Hemodynamic Monitoring of Aortic and Pulmonary Artery Hemodynamics in a Large Animal Model of ARDS at JoVE.com

The authors have no acknowledgements.

This prospective experimental trial with 21 anesthetized male and female domestic pigs (German landrace) at the age of 3&#8211;6 months with a body weight between 45-55 kg was approved by the Governmental Commission on the Care and Use of Animals of the City of Hamburg (Reference-No. 18/17). According to the ARRIVE guidelines, all experiments were carried out and all animals received care in compliance with the &#39;Guide for the Care and Use of Laboratory Animals&#39; (NIH publication No. 86-23, revised 1996)11.
1. Flow Probe Two-point Calibration
<ol>
	<li>Put flow probes in deionized water and connect the probe to the transonic flow probe system by putting the plug into the perivascular flow module.</li>
	<li>Open the data analysis software (e.g., LabChart 8).</li>
	<li>For a two-point calibration, start a measurement by setting the flow probe system to Zero and after a few seconds to Scale.</li>
	<li>In the data analysis software window, go to Units Conversion and choose two-point calibration. Mark a baseline to set to zero. Then, mark an area with 10 L/min and set to 1 V as a preset value.</li>
	<li>Repeat the procedure for the other probe.</li>
</ol>
2. Millar Catheter Calibration
<ol>
	<li>Prior to the zeroing and calibration, pre-soak the tip of the catheter in sterile body temperature warm water for 30 min.</li>
	<li>Connect the Millar catheter to the bridge amplifier by putting the plug into the bridge amplifier module.</li>
	<li>Start the data analysis software.</li>
	<li>Put the tip of the catheter into the pneumatic zeroing tool, set the value to 0 mmHg and start a measurement by clicking Start in the program.</li>
	<li>Keep the measurement running and set the pneumatic zeroing tool to 100 mmHg. Stop the measurement by clicking Stop.</li>
	<li>Run the data analysis software by pressing Start and then press Stop. Click Amplify in the window of bridge and choose Units. Set the baseline of 0 and 100 mmHg, accordingly. According to the preset value for calibration that the software provides, the catheter is now calibrated for all body pressures.</li>
	<li>Repeat the procedure for the other Millar catheter.</li>
</ol>
3. Preparation of the Pig
<ol>
	<li>Medicate the pig by injecting 20 mg/kg of Ketanest, 4 mg/kg of Azaperon and 0.1 mg/kg Midazolam intramuscularly and place a 20 G IV-line into a vein of the ear.</li>
	<li>Place ECG stickers on the chest and oxygen probe on the tail.</li>
	<li>Administer pure oxygen (15&#8211;18 L/min) via the pig&#39;s nose using a mask and surgically prepare down to the trachea.</li>
	<li>Put a loop around the trachea, use a scalpel (11 blade) to make an incision into the trachea and place an 8.5 Mallinckrodt tube into it for a safe airway. Fix the tube with the preset loop and close the skin with sutures.</li>
	<li>Begin anesthesia with Sevoflurane using a MAC of 0.9 (in adolescent pigs equivalent to an endexpiratory concentration of 2.0%)&#160;&#160;and infusion of 0.01 mg/(kg&#8729;h) Fentanyl. Start mechanical ventilation with a tidal volume of 10 mL/kg, a rate of 14/min, and a positive end expiratory pressure (PEEP) of 7 mmHg. Set the inspiratory oxygen rate (fiO2) to 0.3. After 10 min depth of anesthesia is deep enough to perform surgery safely. No elevation of HR and BP should be detected.</li>
	<li>Maintain fluid balance at basal volume rate of 10 mL/(kg&#8729;h) cristalloid using an infusion pump.</li>
	<li>Gently clean the pig&#39;s skin using soap water. Use a skin disinfection solution containing povidone-iodine to decrease skin contamination.</li>
</ol>
4. Vital Parameter Measurements
<ol>
	<li>Use an ultrasound for inserting a 5 F thermistor tipped arterial catheter into the right femoral artery, an 8 F introducer sheath into the left femoral artery, a central venous catheter and an 8 F introducer sheath into the jugular vein (Figure 1).</li>
	<li>Place the catheter placement using Seldinger&#39;s technique12.
	<ol>
		<li>Place a needle into the target vessel under ultrasound vision.</li>
		<li>Put a wire through the needle into the vessel, verify the correct placement of the wire using ultrasound and keep the wire in the vessel throughout the whole procedure. Remove the needle and place a dilator onto the wire.</li>
		<li>With gentle pressure, put the dilator through the skin into the vessel using the wire as guidance. Remove the dilator, put the catheter onto the wire, make sure to the end of the wire is seen at the end of the catheter and place the catheter it into the vessel.</li>
		<li>Remove the wire by gently pulling it out of the catheter.</li>
	</ol>
	</li>
	<li>Insert a 7F pulmonary artery catheter (PAC) into the 8F introducer sheath and place it in the RV. If needed for taking mixed venous blood gas samples, insert the PAC further into the PA until a pulmonary artery curve is shown on to the monitor and pull it back after receiving the samples.</li>
	<li>Insert the first Millar-tip catheter into the 8F introducer sheath in the left femoral artery and placing it in the aorta.</li>
	<li>Perform a mini-laparotomy (approximately 5&#8211;10 cm is enough) above the symphysis by using the electrocautery for prepping down to the linea alba.
	<ol>
		<li>Open the linea alba with scissors and pull out the bladder very gently.</li>
		<li>Put a purse string suture in the bladder using a 3/0 suture and make an incision into the bladder with a scalpel (11 blade).</li>
		<li>Insert a urinary catheter into the bladder, inflate the catheter&#39;s balloon with water and fix it using the purse-string suture. Close the abdomen with a 3/0 suture.</li>
	</ol>
	</li>
</ol>
5. Surgical Preparation of the Heart
<ol>
	<li>Before opening the chest increasing the fiO2 to 1.0 and administer 0.1 mg kg(-1) pancuronium initial bolus intravenously13.</li>
	<li>Perform a median sternotomy.
	<ol>
		<li>Use the electrocautery for prepping down to the sternum. Gently dissect the sternum from the surrounding tissue before dividing the bone with an oscillating saw.</li>
		<li>Use the electrocautery to reduce bleeding and seal the sternum with bone wax. Place a sternal rib spreader between the two halves of the opened sternum and widely open the chest as much as needed for surgery by twisting the handle on the device.</li>
	</ol>
	</li>
	<li>Open the pericardium gently using scissors and forceps and fix it to the skin with a 2/0 suture.</li>
	<li>Dissect down the pulmonary and the artery ascending aorta very gently to avoid bleeding. Carefully place the ultrasound flow probes around both arteries, respectively (Figure 2).</li>
	<li>Place 2 purse string sutures in the pulmonary artery using a 5/0 suture. Use a scalpel (11 blade) to make a small stitch incision (approximately 1 mm) in the middle of the purse strings and place the Millar catheter into the pulmonary artery before fixing it (Figure 3).</li>
	<li>Carefully clamp the LAA and place 2 purse string sutures in it using a 4/0 suture. Make a small incision and place a central venous line into the left atrium before fixing it using the purse string sutures (Figure 3).</li>
	<li>Close the pericardium by suturing a sterile glove onto it, to maintain hemodynamics reliable (Figure 4). Perform the sternal closure with wires and close the skin with a 3/0 suture.</li>
</ol>
6. Assessment and Data Acquisition
<ol>
	<li>Start each measurement with 2 min of AO and PA flow measurements, as well as AO and PA pressure measurements using the data analysis software by clicking Start and Stop button in the program.</li>
	<li>Perform transcardiopulmonary thermodilution to provide cardiac output (CO) as well as pulse pressure variance (PPV) and stroke volume variance (SVV) by using the PiCCO2 system. To start the measurement, click the TD | Start.</li>
	<li>Consecutive inject 15 mL of 10 &#176;C cold saline into a thermistor at the central venous line in the jugular vein three times for thermodilution at each measurement step.</li>
	<li>Take an arterial, central venous and mixed venous blood gas sample after each transcardiopulmonary thermodilution measurement step.</li>
</ol>
7. Volume Optimizing
<ol>
	<li>After a baseline measurement M0 (steps 6.1&#8211;6.4) of all parameters, administer a volume loading step using 5 mL/kg of colloidal infusion (Voluven) using an infusion pump that is connected to the central venous line.</li>
	<li>After 5 min of equilibration, start another measurement step M1 (steps 6.1&#8211;6.4). If the newly generated cardiac output measured by thermodilution using the PICCO2 system (see step 6.2&#8211;6.3) does not increase compared to the formerly measured CO by at least 10%, start another volume loading step (step 7.1).</li>
	<li>Continue with volume loading and equilibration steps until there is no more increase in CO of more than 10%. Now, a balanced fluid status is reached.</li>
</ol>
8. Induction of ARDS with Right Ventricular Dysfunction
<ol>
	<li>Increase the fiO2 to at least 0.5 to 0.8 as required to maintain a spO2 of at least 90%.</li>
	<li>Induce an ARDS with consecutive right ventricular dysfunction by infusion of oleic acid (OA) (0.03&#8211;0.06 mL/kg for about 2 h).</li>
	<li>Use continuous administration of adrenalin using a perfusor (3 mg of adrenalin in 50 mL of saline) to keep hemodynamics stable. Increase the infusion rate as required to maintain a mean arterial pressure of 50 mmHg.</li>
	<li>Add calcium, magnesium and antiarrhythmics (1% Lidocain) as required during the infusion of OA to maintain a stable sinus rhythm.</li>
</ol>
9. Volume Optimizing
<ol>
	<li>After induction of mild to moderate ARDS, perform another measurement of all parameters (M2) by completing steps 6.1&#8211;6.4. 
	NOTE: Now, the baseline model for hemodynamic measurements in ARDS in a pig model is set. For further investigation on volume responsiveness in ARDS and right ventricular dysfunction start to reduce volume load by taking as much blood as need per protocol or increasing volume load by adding a defined amount of infusion.</li>
</ol>
10. Finalization
<ol>
	<li>After finishing the measurements euthanize the pigs while under anesthesia by injecting 1mmol/kg potassium chloride intravenously.</li>
</ol>

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Daniel A. Reuter is a member of Pulsion Medical Advisory Board. Constantin J.C. Trepte has received honorary award for lectures by Maquet. All other authors declare no conflicts of interest.

ARDS, complicated by pulmonary hypertension, is a very deadly disease. For patients suffering from this condition, further information about treating it is necessary. When working and researching with living creatures, it is very important to be as sensible as possible. In this case it is necessary to gather as much information as possible in one experiment.
There are some critical surgical steps in an open-beating heart model like this. To not use pigs unnecessarily, there must be an experien...

Right ventricular (RV) dysfunction is a major cause of morbidity and mortality in patients with heart failure1, especially if the underlying cause is pulmonary hypertension2. The RV pumps blood into the low-resistance pulmonary system, which is normally associated with high compliance. Therefore, the RV is characterized by low peak systolic pressure. It also generates one sixth the stroke work compared with the left ventricle (LV)3. Due to its thinner muscle, the RV is very vulnerable to a change in pre- and afterload4,5. The isovolumic phases of contraction and relaxation during systole and diastole in the RV are not as distinct as in the LV. The examination of left and right ventricular hemodynamic parameters is highly important in therapy of critically ill patients with acute right heart distress4,7, because RV failure increases short-term mortality significantly6.
Preload parameters like the central venous pressure (CVP) and left ventricular preload parameters like pulmonary capillary wedge pressure (PCWP) have been used for a long time to determine volume status of patients. Lately, it has been shown that these parameters alone are not suitable to detect a patient&#39;s need of fluids8,9,10. Recognizing fluid responsiveness is essential to detect and treat volume deprivation and volume overload in patients with RV dysfunction. Avoiding volume overload is essential to decrease the mortality and length of intensive care unit (ICU) stay in these patients.
With this study, we established a pig model of right ventricular dysfunction that is consistent and replicable. Due to its similarity to humans, it is necessary to establish consistent and reproducible experimental large animal models of cardiac hemodynamics and measurements for research purpose.

<table><tbody><tr><td>Animal Bio Amp</td><td>ADInstruments</td><td>FE136</td><td></td></tr><tr><td>Quad BridgeAmp</td><td>ADInstruments</td><td>FE224</td><td></td></tr><tr><td>Power Lab 16/35</td><td>ADInstruments</td><td>5761-E</td><td></td></tr><tr><td>LabChart 8.1.8 Windows</td><td>ADInstruments</td><td></td><td></td></tr><tr><td>Pulmonary artery catheter 7 F</td><td>Edwards Lifesciences Corporation</td><td>&amp;nbsp;&amp;nbsp;131F7&amp;nbsp;</td><td></td></tr><tr><td>Prelude Sheath Introducer 8 F</td><td>Merit Medical Systems, Inc.</td><td>SI-8F-11-035</td><td></td></tr><tr><td>COnfidence Cardiac Output Flowprobes</td><td>Transonic</td><td>AU-IFU-PAUProbes-EN Rev. A 4/13</td><td></td></tr><tr><td>Adrenalin</td><td>Sanofi</td><td>6053210</td><td></td></tr><tr><td>Oleic acid</td><td>Sigma Aldrich</td><td>112-80-1</td><td></td></tr><tr><td>Magnesium Verla</td><td>Verla</td><td>7244946</td><td></td></tr><tr><td>Ketamin</td><td>Richter Pharma AG</td><td>BE-V433246</td><td></td></tr><tr><td>Azaperon</td><td>Sanochemia Pharmazeutika AG</td><td>QN05AD90</td><td></td></tr><tr><td>Midazolam</td><td>Roche Pharma AG</td><td>3085793</td><td></td></tr></tbody></table>

invasive hemodynamic monitoring of aortic and pulmonary artery hemodynamics in a large animal model of ards

One of the leading causes of morbidity and mortality in patients with heart failure is right ventricular (RV) dysfunction, especially if it is due to pulmonary hypertension. For a better understanding and treatment of this disease, precise hemodynamic monitoring of left and right ventricular parameters is important. For this reason, it is essential to establish experimental pig models of cardiac hemodynamics and measurements for research purpose. 
This article shows the induction of ARDS by using oleic acid (OA) and consequent right ventricular dysfunction, as well as the instrumentation of the pigs and the data acquisition process that is needed to assess hemodynamic parameters. To achieve right ventricular dysfunction, we used oleic acid (OA) to cause ARDS and accompanied this with pulmonary artery hypertension (PAH). With this model of PAH and consecutive right ventricular dysfunction, many hemodynamic parameters can be measured, and right ventricular volume load can be detected. 
All vital parameters, including respiratory rate (RR), heart rate (HR) and body temperature were recorded throughout the whole experiment. Hemodynamic parameters including femoral artery pressure (FAP), aortic pressure (AP), right ventricular pressure (peak systolic, end systolic and end diastolic right ventricular pressure), central venous pressure (CVP), pulmonary artery pressure (PAP) and left arterial pressure (LAP) were measured as well as perfusion parameters including ascending aortic flow (AAF) and pulmonary artery flow (PAF). Hemodynamic measurements were performed using transcardiopulmonary thermodilution to provide cardiac output (CO). Furthermore, the PiCCO2 system (Pulse Contour Cardiac Output System 2) was used to receive parameters such as stroke volume variance (SVV), pulse pressure variance (PPV), as well as extravascular lung water (EVLW) and global end-diastolic volume (GEDV). Our monitoring procedure is suitable for detecting right ventricular dysfunction and monitoring hemodynamic findings before and after volume administration.

Our animal model shows a broad variety of hemodynamic parameters in pigs. Due to its similarity in size and hemodynamics, one can easily use the exact same equipment as used in humans to get similar results.&#160;However, anesthesia values are based on experience and may change based on weight/ age/ strain of pig.&#160; A veterinarian should be consulted to evaluate anesthetic plan.
Results of previous OA induced acute lung inju...

Watch this Scientific Journal Video about Invasive Hemodynamic Monitoring of Aortic and Pulmonary Artery Hemodynamics in a Large Animal Model of ARDS at JoVE.com

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

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.

One of the leading causes of morbidity and mortality in patients with heart failure is right ventricular (RV) dysfunction, especially if it is due to ...

invasive-hemodynamic-monitoring-aortic-pulmonary-artery-hemodynamics

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

10.0K Views.  Universitatsklinikum Hamburg-Eppendorf. 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.

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

Echocardiographic Assessment of the Right Heart in Mice

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential therapies. Given the expense and time involved in creating animal models of disease, it is critical that researchers have tools to accurately assess phenotypic expression of disease. Right ventricular dysfunction is the major manifestation of pulmonary hypertension. Echocardiography is the mainstay of the noninvasive assessment of right ventricular function in rodent models and has the advantage of clear translation to humans in whom the same tool is used. Published echocardiography protocols in murine models of PAH are lacking.
In this article, we describe a protocol for assessing RV and pulmonary vascular function in a mouse model of PAH with a dominant negative BMPRII mutation; however, this protocol is applicable to any diseases affecting the pulmonary vasculature or right heart. We provide a detailed description of animal preparation, image acquisition and hemodynamic calculation of stroke volume, cardiac output and an estimate of pulmonary artery pressure.

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.

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential ...

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. 
Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed.

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.

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle ...

A Large Animal Model for Pulmonary Hypertension and Right Ventricular Failure: Left Pulmonary Artery Ligation and Progressive Main Pulmonary Artery Banding in Sheep

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing novel therapeutics for PH requires a clinically relevant large animal model of increased pulmonary vascular resistance and RVF. This manuscript discusses the latest development of the previously published ovine PH-RVF model that utilizes left pulmonary artery (PA) ligation and main PA occlusion. This model of PH-RVF is a versatile platform to control not only the disease severity but also the RV&#39;s phenotypic response.
Adult sheep (60-80 kg) underwent left PA (LPA) ligation, placement of main PA cuff, and insertion of RV pressure monitor. PA cuff and RV pressure monitor were connected to subcutaneous ports. Subjects underwent progressive PA banding twice per week for 9 weeks with sequential measures of RV pressure, PA cuff pressures, and mixed venous blood gas (SvO2). At the initiation and endpoint of this model, ventricular function and dimensions were assessed using echocardiography. In a representative group of 12 animal subjects, RV mean and systolic pressure increased from 28 &#177; 5 and 57 &#177; 7 mmHg at week 1, respectively, to 44 &#177; 7 and 93 &#177; 18 mmHg (mean &#177; standard deviation) by week 9. Echocardiography demonstrated characteristic findings of PH-RVF, notably RV dilation, increased wall thickness, and septal bowing. The longitudinal trend of SvO2 and PA cuff pressure demonstrates that the rate of PA banding can be titrated to elicit varying RV phenotypes. A faster PA banding strategy led to a precipitous decline in SvO2 &#60; 65%, indicating RV decompensation, whereas a slower, more paced strategy led to the maintenance of physiologic SvO2 at 70%-80%. One animal that experienced the accelerated strategy developed several liters of pleural effusion and ascites by week 9. This chronic PH-RVF model provides a valuable tool for studying molecular mechanisms, developing diagnostic biomarkers, and enabling therapeutic innovation to manage RV adaptation and maladaptation from PH.

This manuscript describes the surgical technique and experimental approach to develop severe right ventricular pressure overload to model their adaptive and maladaptive phenotypes.

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing ...

Bioengineering

Induction and Phenotyping of Acute Right Heart Failure in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The morphological and functional phenotyping of the right ventricle is of particular importance in the context of hemodynamic compromise in patients with ARHF. Here, we describe a method to induce ARHF in a previously described large animal model of chronic PH, and to phenotype, dynamically, right ventricular function using the gold standard method (i.e., pressure-volume PV loops) and with a non-invasive clinically available method (i.e., echocardiography). Chronic PH is first induced in pigs by left pulmonary artery ligation and right lower lobe embolism with biological glue once a week for 5 weeks. After 16 weeks, ARHF is induced by successive volume loading using saline followed by iterative pulmonary embolism until the ratio of the systolic pulmonary pressure over systemic pressure reaches 0.9 or until the systolic systemic pressure decreases below 90 mmHg. Hemodynamics are restored with dobutamine infusion (from 2.5 &#181;g/kg/min to 7.5 &#181;g/kg/min). PV-loops and echocardiography are performed during each condition. Each condition requires around 40 minutes for induction, hemodynamic stabilization and data acquisition. Out of 9 animals, 2 died immediately after pulmonary embolism and 7 completed the protocol, which illustrates the learning curve of the model. The model induced a 3-fold increase in mean pulmonary artery pressure. The PV-loop analysis showed that ventriculo-arterial coupling was preserved after volume loading, decreased after acute pulmonary embolism and was restored with dobutamine. Echocardiographic acquisitions allowed to quantify right ventricular parameters of morphology and function with good quality. We identified right ventricular ischemic lesions in the model. The model can be used to compare different treatments or to validate non-invasive parameters of right ventricular morphology and function in the context of ARHF.

We present a protocol to induce and phenotype an acute right heart failure in a large animal model with chronic pulmonary hypertension. This model can be used to test therapeutic interventions, to develop right heart metrics&#160;or to improve the understanding of acute right heart failure pathophysiology.

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The ...

Simultaneous Electrocardiography Recording and Invasive Blood Pressure Measurement in Rats

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. Research focusing on cardiovascular disease models, potential cardiovascular therapeutic targets or pharmaceutical agents requires assessment of systemic arterial pressure and heart rhythm changes. In situations where radio telemetry systems are not available or affordable, the technique of femoral artery cannulation is an alternative way to obtain intra-arterial pressure waveform recordings and systemic BP measurements. This technique is economical and can be performed with standard equipment in animal facilities. However, invasive arterial pressure recording requires cannulation of small arteries, which can be a challenging surgical skill. Here, we present step-by-step protocols for femoral artery cannulation procedures. Key procedures include the calibration of the data acquisition system, tissue dissection and femoral artery cannulation, and setup of the arterial cannulation system for pressure recording. Surface electrocardiography recording procedures are also included. We also present examples of BP recordings from normotensive and hypertensive rats. This protocol allows reliable direct recordings of systemic BP with simultaneous electrocardiography.

Here, we describe a setup for simultaneous recording of electrocardiography and intra-arterial blood pressure (BP) in experimental rats, which can be done with standard equipment in animal facilities and can be applied to physiological or pharmacological studies to investigate pathogenic or therapeutic mechanisms in cardiovascular medicine.

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. ...

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.

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. ...

Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome (ARDS)

Various animal models exist to study the complex pathomechanisms of the acute respiratory distress syndrome (ARDS). These models include pulmo-arterial infusion of oleic acid, infusion of endotoxins or bacteria, cecal ligation and puncture, various pneumonia models, lung ischemia/reperfusion models and, of course, surfactant depletion models, among others. Surfactant depletion produces a rapid, reproducible deterioration of pulmonary gas exchange and hemodynamics and can be induced in anesthetized pigs using repeated lung lavages with 0.9% saline (35 mL/kg body weight, 37 &#176;C). The surfactant depletion model supports investigations with standard respiratory and hemodynamic monitoring with clinically applied devices. But the model suffers from a relatively high recruitability and ventilation with high airway pressures can immediately reduce the severity of the injury by reopening atelectatic lung areas. Thus, this model is not suitable for investigations of ventilator regimes that use high airway pressures. A combination of surfactant depletion and injurious ventilation with high tidal volume/low positive end-expiratory pressure (high Tv/low PEEP) to cause ventilator induced lung injury (VILI) will reduce the recruitability of the resulting lung injury. The advantages of a timely induction and the possibility to perform experimental research in a setting comparable to an intensive care unit are preserved.

Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome ARDS

A combination of surfactant washout using 0.9% saline (35 mL/kg body weight, 37 &#176;C) and high tidal volume ventilation with low PEEP to cause moderate ventilator induced lung injury (VILI) results in experimental acute respiratory distress syndrome (ARDS). This method provides a model of lung injury with low/limited recruitability to study the effect of various ventilation strategies for extended periods.

Various animal models exist to study the complex pathomechanisms of the acute respiratory distress syndrome (ARDS). These models include pulmo-arterial ...

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

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease, primarily affecting small pulmonary arterioles of the lung. Currently, there is no cure for PAH. It is important to discover new compounds that can be used to treat PAH. The mouse hypoxia-induced PAH model is a widely used model for PAH research. This model recapitulates human clinical manifestations of PAH Group 3 disease and is an important research tool to evaluate the effectiveness of new experimental therapies for PAH. Research using this model often requires the administration of compounds in mice. For a compound that needs to be given directly into the bloodstream, optimizing intravenous (IV) administration is a key part of the experimental procedures. Ideally, the IV injection system should permit multiple injections over a set time course. Although the mouse hypoxia-induced PAH model is very popular in many laboratories, it is technically challenging to perform multiple IV bolus dosing and invasive hemodynamic assessment in this model. In this protocol, we present step-by-step instructions on how to carry out multiple IV bolus dosing via mouse jugular vein and perform arterial and right ventricle catheterization for hemodynamic assessment in mouse hypoxia-induced PAH model.

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.

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease, primarily affecting small pulmonary arterioles of the lung. Currently, ...

Ascending Aortic Banding for Studying Pressure-Overload Induced Heart Failure

A Minimally Invasive Model of Aortic Stenosis in Swine

Large animal models of heart failure play an essential role in the development of new therapeutic interventions due to their size and physiological similarities to humans. Efforts have been dedicated to creating a model of pressure-overload induced heart failure, and ascending aortic banding while still supra-coronary and not a perfect mimic of aortic stenosis in humans, closely resembling the human condition.
The purpose of this study is to demonstrate a minimally invasive approach to induce left ventricular pressure overload by placing an aortic band, precisely calibrated with percutaneously introduced high-fidelity pressure sensors. This method represents a refinement of the surgical procedure (3Rs), resulting in homogenous trans-stenotic gradients and reduced intragroup variability. Additionally, it enables swift and uneventful animal recovery, leading to minimal mortality rates. Throughout the study, animals were followed for up to 2 months after surgery, employing transthoracic echocardiography and pressure-volume loop analysis. However, longer follow-up periods can be achieved if desired. This large animal model proves valuable for testing new drugs, particularly those targeting hypertrophy and the structural and functional alterations associated with left ventricular pressure overload.

Author Spotlight: Development of a Minimally Invasive Large-Animal Model for Reliable and Reproducible Cardiovascular Research 

This protocol describes a minimally invasive surgical procedure for ascending aortic banding in swine.

Large animal models of heart failure play an essential role in the development of new therapeutic interventions due to their size and physiological ...

Surgically Induced Cardiac Volume Overload by Aortic Regurgitation in Mouse

Aortic regurgitation (AR) is a common valvular heart disease that exerts volume overload on the heart and represents a global public health problem. Although mice are widely applied to shed light on the mechanisms of cardiovascular disease, mouse models of AR, especially those induced by surgery, are still paucity. Here, a mouse model of AR was described in detail which is surgically induced by disruption of the aortic valves under high-resolution echocardiography. In accordance with regurgitated blood flow, AR mouse hearts present a distinctive and clinically relevant volume overload phenotype, which is characterized by eccentric hypertrophy and cardiac dysfunction, as evidenced by echocardiographic and invasive hemodynamic evaluation. Our proposal, in a reliable and reproducible manner, provides a practical guide on the establishment and assessment of a mouse model of AR for future studies on molecular mechanisms and therapeutic targets of volume overload cardiomyopathy.

This protocol presents a practical guide on the surgery for creation of aortic regurgitation (AR) in the mouse. Assessment of the AR mouse by echocardiography and invasive hemodynamic measurement recapitulates its clinically relevant characteristics of volume overload-induced eccentric hypertrophy, suggesting its promising application in the study of cardiac hypertrophy.

Aortic regurgitation (AR) is a common valvular heart disease that exerts volume overload on the heart and represents a global public health problem. ...