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)<sup class=...

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M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Role+of+the+Pulmonary+Afferent+Receptors+in+Producing+Hemodynamic+Changes+during+Hyperinflation+and+Endotracheal+Suctioning+in+an+Oleic+Acid-Injured+Animal+Model+of+Acute+Respiratory+Failure.">The Role of the Pulmonary Afferent Receptors in Producing Hemodynamic Changes during Hyperinflation and Endotracheal Suctioning in an Oleic Acid-Injured Animal Model of Acute Respiratory Failure.</a> Biology Research for Nursing. 1 (3), 179-189 (2000).</li><li>Galie, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=2015+ESC/ERS+Guidelines+for+the+diagnosis+and+treatment+of+pulmonary+hypertension.">2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.</a> European Heart Journal. 37, 67-119 (2015).</li><li>Galie, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=2015+ESC/ERS+Guidelines+for+the+diagnosis+and+treatment+of+pulmonary+hypertension:+The+Joint+Task+Force+for+the+Diagnosis+and+Treatment+of+Pulmonary+Hypertension+of+the+European+Society+of+Cardiology+(ESC)+and+the+European+Respiratory+Society+(ERS),+Endorsed+by:+Association+for+European+Paediatric+and+Congenital+Cardiology+(AEPC),+International+Society+for+Heart+and+Lung+Transplantation+(ISHLT).">2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).</a> European Respiratory Journal. 46, 903-975 (2015).</li><li>Oliveira, R. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Usefulness+of+pulmonary+capillary+wedge+pressure+as+a+correlate+of+left+ventricular+filling+pressures+in+pulmonary+arterial+hypertension.">Usefulness of pulmonary capillary wedge pressure as a correlate of left ventricular filling pressures in pulmonary arterial hypertension.</a> Journal of Heart and Lung Transplantation. 33 (4), 459 (2014).</li><li>Hoeper, M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+global+view+of+pulmonary+hypertension.">A global view of pulmonary hypertension.</a> Lancet Respiratory Medicine. 4, 306-322 (2016).</li><li>Nagy, A. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+pulmonary+capillary+wedge+pressure+accurately+reflects+both+normal+and+elevated+left+atrial+pressure.">The pulmonary capillary wedge pressure accurately reflects both normal and elevated left atrial pressure.</a> American Heart Journal. 167 (6), 876-883 (2014).</li><li>Daughters, G. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+the+pericardium+on+left+ventricular+diastolic+filling+and+systolic+performance+early+after+cardiac+operations.">Effects of the pericardium on left ventricular diastolic filling and systolic performance early after cardiac operations.</a> Journal of Thoracic and Cardiovascular Surgery. 104 (4), 1084-1091 (1992).</li><li>Zimmerman, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Posttransfusion+Increase+of+Hematocrit+per+se+Does+Not+Improve+Circulatory+Oxygen+Delivery+due+to+Increased+Blood+Viscosity.">Posttransfusion Increase of Hematocrit per se Does Not Improve Circulatory Oxygen Delivery due to Increased Blood Viscosity.</a> Anesthesia &amp; Analgesia. 124 (5), 1547-1554 (2017).</li><li>Giglioli, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemodynamic+effects+in+patients+with+atrial+fibrillation+submitted+to+electrical+cardioversion.">Hemodynamic effects in patients with atrial fibrillation submitted to electrical cardioversion.</a> International Journal of Cardiology. 168 (4), 4447-4450 (2013).</li></ol>

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>&#160;&#160;131F7&#160;</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 ...

This method can help answer key questions in the field of intensive care medicine about hemodynamic monitoring, right-ventricular dysfunction, and ARDS. The main advantages of this technique are that it is simple and easy to reproduce. The implications of this technique extend toward patient volume status assessment in the critical field of ARDS.Though this method can provide insight into disease pathogenesis, monitoring and volume status in ARDS, it can also be applied to heart failure, sepsis, or respiratory failure. Generally, individuals new to this method will struggle since the success of this procedure requires skilled anesthesia, cardiac surgery, and intensive care medicine implementation. Visual demonstration of this method is critical.The bleeding that occurs during open heart surgery can impair your vision as you are learning the steps of the procedure. Using an ultrasound and Seldinger's technique, place a needle into the left femoral artery of an anesthetized pig. Then, place an eight French introducer sheath, with a combined dilator onto the wire, taking care that the end of the wire is observed at the end of the catheter.After verifying correct placement of the wire, remove the needle, and place the catheter into the vessel, using gentle pressure. Place five French thermistor-tipped arterial catheter into the right femoral artery, and a central venous catheter, and an eight French introducer sheath into the jugular vein as just demonstrated. Next, insert a seven French pulmonary artery catheter into an eight French introducer sheath, and place the pulmonary artery catheter into the right ventricle.Then insert the first Millar tip catheter into the eight French introducer sheath in the left femoral artery, and place the sheath into the aorta. Using electrocautery, make a five to 10 centimeter incision from above the symphysis down to the linea alba, and use scissors to open the linea alba. Gently exteriorize the bladder, and use a 3-0 suture to place a purse string suture in the bladder.Use a number 11 scalpel blade to make an approximately five millimeter incision in the bladder, and insert a urinary catheter into the bladder. Then inflate the catheter balloon with water, and use a purse string suture to secure the balloon, closing the abdomen with a second 3-0 suture. To prepare the heart, increase the inspiratory oxygen rate to one, and administer eight milligrams of pancuronium intravenously.Using electrocautery, make a medial incision down the sternum, and gently dissect the sternum from the surrounding tissue. Divide the bone with an oscillating saw, and use electrocautery to reduce the bleeding. Seal the sternum with bone wax, and use a sternal rib spreader to open the chest as much as necessary for the surgery.Using scissors and forceps, gently open the pericardium, and fix the tissue to the skin with a 2-0 suture. Gently dissect down the pulmonary artery and ascending aorta, and carefully place ultrasound flow probes around both arteries. Using a 5-0 suture, place two purse string sutures in the pulmonary artery, and use a number 11 scalpel blade to make an approximately one millimeter stitch incision between the purse strings.Place the Millar catheter into the pulmonary artery before fixing the catheter with the sutures, and carefully clamp the left atrial appendage. Use a 4-0 suture to place two purse string sutures in the atrium, followed by a small incision. Place a central venous line into the left atrium, before fixing the line with the purse string sutures.And suture a sterile glove over the pericardial opening. Then perform a sternal closure with wires, and close the skin with a 3-0 suture, according to standard procedures. To measure the hemodynamic parameters, use the data analysis software to obtain two minutes of aortic and pulmonary arterial flow measurements, as well as aortic and pulmonary artery pressure measurements.To perform transcardiopulminary thermodilution, click TD start in the pulse contour cardiac output system two. Then inject 15 milliliters of 10 degree Celsius saline into a thermistor at the central venous line in the jugular vein three times for thermodilution at each measurement step, and obtain an arterial, central venous, and mixed venous blood gas sample after each transcardiopulminary thermodilution measurement step. After obtaining a baseline measurement for each parameter, connect an infusion pump to the central venous line to deliver five milligrams per kilogram of colloidal infusion.After five minutes of equilibration, start another measurement step, and continue with the volume loading and equilibration steps until a balanced fluid status is reached. To induce acute respiratory distress syndrome with consecutive right-ventricular dysfunction, first increase the inspiratory oxygen rate to between 5 to 8, as necessary, to maintain a peripheral capillary oxygen saturation of at least 90%Next, infuse oleic acid into the superior vena cava using a profuser to deliver continuous adrenaline to keep the hemodynamics stable, and delivering calcium, magnesium, and antiarrythmics as necessary to maintain a stable sinus rhythm. When mild to moderate acute respiratory distress has been achieved, measure all of the same hemodynamic parameters as just demonstrated.Oleic acid infusion, as just demonstrated, induces mild to moderate acute respiratory distress, as evidenced by a robust oxygenation index decrease that is accompanied by a statistically significant increase in carboxylated blood. To measure the pulmonary vascular resistance to monitor pulmonary hypertension, a catheter can be placed in the left atrial, as a pulmonary artery catheter placed in the pulmonary artery through the pulmonary flow probe can result in incorrect flow measurements. Once mastered, this technique can be completed in five hours, if it's performed properly.While attempting this procedure, it's important to take up to two hours of time to administer the oleic acid, as a too quick delivery has severe negative effects on hemodynamics. After its development, this technique paved the way for researchers in the field of ARDS and consecutive right-ventricular dysfunction to explore the appropriate volume-load, and find a better treatment in these high morbidity and mortality diseases. Don't forget that working with living animals, such as pigs, requires ethical approval, and should only be done if absolutely necessary for the understanding of the treatment of a disease.

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

Research

JoVE Journal

Medicine

10.0K Görüntüleme.  Universitatsklinikum Hamburg-Eppendorf. Bu yöntem hemodinamik izleme, sağ ventrikül disfonksiyonu ve ARDS ile ilgili yoğun bakım tıbbı alanındaki anahtar soruların cevaplanmasına yardımcı olabilir. Bu tekniğin başlıca avantajları basit ve çoğaltılması kolay olmasıdır. Bu tekniğin etkileri ARDS'nin kritik alanında hasta hacim durum değerlendirmesine kadar uzanır.Bu yöntem ARDS'de hastalık patogenezi, izlenmesi ve hacim durumu hakkında bilgi sağlasa da kalp yetmezliği, sepsis veya solunum yetmezl...