Name: invasive hemodynamic monitoring of aortic and pulmonary artery hemodynamics in a large animal model of ards
Uploaded: 2018-11-26T12:30:00
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)<sup class=...

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B., Quintel, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relationship+among+cardiac+index,+inspiration/expiration+ratio,+and+perfluorocarbon+dose+during+partial+liquid+ventilation+in+an+oleic+acid+model+of+acute+lung+injury+in+sheep.">Relationship among cardiac index, inspiration/expiration ratio, and perfluorocarbon dose during partial liquid ventilation in an oleic acid model of acute lung injury in sheep.</a> Journal of Pediatric Surgery. 40 (9), 1395-1403 (2005).</li><li>Zhu, Y. B., 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=Atrial+natriuretic+peptide+attenuates+inflammatory+responses+on+oleic+acid-induced+acute+lung+injury+model+in+rats.">Atrial natriuretic peptide attenuates inflammatory responses on oleic acid-induced acute lung injury model in rats.</a> Chinese Medical Journal (English. 126 (4), 747-750 (2013).</li><li>Gould, D. A., Baun, M. 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>

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.

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Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health.
Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases.
Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult 1,2, because oxygen consumption and delivery reach equilibrium after acute transients 3. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i) 4,5.
With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

We combined frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation with diffuse correlation spectroscopy measures of cerebral blood flow index to estimate an index of oxygen metabolism. We tested the utility of this measure as a bedside screening tool to evaluate the health and development of the newborn brain.

Perinatal brain injury remains a significant cause of infant mortality  and morbidity, but there is not yet an effective bedside tool that can  accurately ...

Assessment of Plasma Coagulation on Liver Tissue in a Large Animal Model In Vivo

Plasma coagulation as a form of electrocautery is used in liver surgery for decades to seal the large liver cut surface after major hepatectomy to prevent hemorrhages at a later stage. The exact effects of plasma coagulation on liver tissue are only poorly examined. In our porcine model, the coagulation effects can be examined close to the clinical application. A combined laser Doppler flowmeter and spectrophotometer documents microcirculation changes during coagulation at 8 mm tissue depth noninvasively, providing quantifiable information about hemostasis beyond the subjective clinical impression. The temperature at coagulation site is assessed with an infrared thermometer prior and post coagulation and with a thermographic camera during coagulation, a measurement of the gas beam temperature is not possible due to the upper threshold of the devices. The depth of coagulation is measured microscopically on hematoxylin/eosin stained sections after calibration with an object micrometer and gives an exact information about the power setting-coagulation depth-relation. The sealing effect is examined on the bile ducts as it is not possible for a plasma coagulator to seal larger blood vessels. Burst pressure experiments are carried out on explanted organs to rule out blood pressure related effects.

Assessment of Plasma Coagulation on Liver Tissue in a Large Animal Model In Vivo

Here we present a protocol to experimentally assess plasma coagulation in liver tissue in vivo. In a porcine model, microcirculation is examined by laser Doppler, coagulation depth is measured histologically, temperature at coagulation site by infrared thermometer and thermographic camera, and duct sealing effect is documented by burst pressure experiments.

Plasma coagulation as a form of electrocautery is used in liver surgery for decades to seal the large liver cut surface after major hepatectomy to prevent ...

Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, we have translated a vascular injury model from a small animal into a large animal (canine), with slight modifications that can be used for pre-clinical screening of prophylactic and thrombolytic agents. In addition to the surgical methods, the modified protocol describes the step-by-step methods to assess carotid artery canalization by angiography, detailed instructions to process both the brain and carotid artery for histological analysis to verify carotid canalization and cerebral hemorrhage, and specific parameters to complete an assessment of downstream thromboembolic events by utilizing magnetic resonance imaging (MRI). In addition, specific procedural changes from the previously well-established small animal model necessary to translate into a large animal (canine) vascular injury are discussed.

Here, we present the modifications necessary to a well characterized and commonly used small animal ferric chloride-induced (FeCl3) carotid artery injury model for use in a large animal vascular injury model. The resulting model can be utilized for pre-clinical trial assessment of both prophylactic and thrombolytic pharmacological and mechanical interventions.

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, ...

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 ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

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. ...

A Pre-clinical Rat Model for the Study of Ischemia-reperfusion Injury in Reconstructive Microsurgery

Ischemia-reperfusion injury is the main cause of flap failure in reconstructive microsurgery. The rat is the preferred preclinical animal model in many areas of biomedical research due to its cost-effectiveness and its translation to humans. This protocol describes a method to create a preclinical free skin flap model in rats with ischemia-reperfusion injury. The described 3 cm x 6 cm rat free skin flap model is easily obtained after the placement of several vascular ligatures and the section of the vascular pedicle. Then, 8 h after the ischemic insult and completion of the microsurgical anastomosis, the free skin flap develops the tissue damage. These ischemia-reperfusion injury-related damages can be studied in this model, making it a suitable model for evaluating therapeutic agents to address this pathophysiological process. Furthermore, two main monitoring techniques are described in the protocol for the assessment of this animal model: transit-time ultrasound technology and laser speckle contrast analysis.

Here, we describe a pre-clinical animal model for studying the pathophysiology of ischemia-reperfusion injury in reconstructive microsurgery. This free skin flap model based on the superficial caudal epigastric vessels in the rat may also allow for the evaluation of different therapies and compounds to counteract ischemia-reperfusion injury-related damage.

Ischemia-reperfusion injury is the main cause of flap failure in reconstructive microsurgery. The rat is the preferred preclinical animal model in many ...

Evaluation of Capnography Sampling Line Compatibility and Accuracy when Used with a Portable Capnography Monitor

Capnography is commonly used to monitor patient&#8217;s ventilatory status. While sidestream capnography has been shown to provide a reliable assessment of end-tidal CO2 (ETCO2), its accuracy is commonly validated using commercial kits composed of a capnography monitor and its matching disposable nasal cannula sampling lines. The purpose of this study was to assess the compatibility and accuracy of cross-paired capnography sampling lines with a single portable bedside capnography monitor. A series of 4 bench tests were performed to evaluate the tensile strength, rise time, ETCO2 accuracy as a function of respiratory rate, and ETCO2 accuracy in the presence of supplemental O2. Each bench test was performed using specialized, validated equipment to allow for a full evaluation of sampling line performance. The 4 bench tests successfully differentiated between sampling lines from different commercial sources and suggested that due to increased rise time and decreased ETCO2 accuracy, not all nasal cannula sampling lines provide reliable clinical data when cross-paired with a commercial capnography monitor. Care should be taken to ensure that any cross-pairing of capnography monitors and disposable sampling lines is fully validated for use across respiratory rates and supplemental O2 flow rates commonly encountered in clinical settings.

The goal of this study was to evaluate the accuracy of capnography sampling lines used in conjunction with a portable bedside capnography monitor. Sampling lines from 7 manufacturers were evaluated for tensile strength, rise time, and ETCO2 accuracy as a function of respiratory rate or supplemental oxygen flow rate.

Capnography is commonly used to monitor patient&#8217;s ventilatory status. While sidestream capnography has been shown to provide a reliable assessment ...

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion

Acute kidney injury (AKI) is associated with higher risk for morbidity and mortality post-operatively. Ischemia-reperfusion injury (IRI) is the most common cause of AKI. To mimic this clinical scenario, this study presents a highly reproducible large animal model of renal IRI in swine using temporary percutaneous bilateral balloon-catheter occlusion of the renal arteries. The renal arteries are occluded for 60 min by introducing the balloon-catheters through the femoral and carotid artery and advancing them into the proximal portion of the arteries. Iodinated contrast is injected in the aorta to assess any opacification of the kidney vessels and confirm the success of the artery occlusion. This is furtherly confirmed by the flattening of the pulse waveform at the tip of the balloon catheters. The balloons are deflated and removed after 60 min of bilateral renal artery occlusion, and the animals are allowed to recover for 24 h. At the end of the study, plasma creatinine and blood urea nitrogen significantly increase, while eGFR and urine output significantly decrease. The need for iodinated contrast is minimal and does not affect renal function. Bilateral renal artery occlusion better mimics the clinical scenario of perioperative renal hypoperfusion, and the percutaneous approach minimizes the impact of the inflammatory response and the risk of infection seen with an open approach, such as a laparotomy. The ability to create and reproduce this clinically relevant swine model eases the clinical translation to humans.

This study presents a highly reproducible large animal model of renal ischemia-reperfusion injury in swine using temporary percutaneous bilateral balloon-catheter occlusion of the renal arteries for 60 min and reperfusion for 24 h.

Acute kidney injury (AKI) is associated with higher risk for morbidity and mortality post-operatively. Ischemia-reperfusion injury (IRI) is the most ...

The Miniature Pig: A Large Animal Model for Cochlear Implant Research

Cochlear implants (CI) are the most effective method to treat people with severe-to-profound sensorineural hearing loss. Although CIs are used worldwide, no standard model exists for investigating the electrophysiology and histopathology in patients or animal models with a CI or for evaluating new models of electrode arrays. A large animal model with cochlea characteristics similar to those of humans may provide a research and evaluation platform for advanced and modified arrays before their use in humans. 
To this end, we established standard CI methods with Bama mini-pigs, whose inner ear anatomy is highly similar to that of humans. Arrays designed for human use were implanted into the mini pig cochlea through a round window membrane, and a surgical approach followed that was similar to that used for human CI recipients. Array insertion was followed by evoked compound action potential (ECAP) measurements to evaluate the function of the auditory nerve. This study describes the preparation of the animal, surgical steps, array insertion, and intraoperative electrophysiological measurements. 
The results indicated that the same CI used for humans could be easily implanted in mini-pigs via a standardized surgical approach and yielded similar electrophysiological outcomes as measured in human CI recipients. Mini-pigs could be a valuable animal model to provide initial evidence of the safety and potential performance of novel electrode arrays and surgical approaches before applying them to human beings.

Miniature pigs (mini-pigs) are an ideal large animal model for research into cochlear implants. Cochlear implantation surgery in mini-pigs can be utilized to provide initial evidence of the safety and potential performance of novel electrode arrays and surgical approaches in a living system similar to human beings.

Cochlear implants (CI) are the most effective method to treat people with severe-to-profound sensorineural hearing loss. Although CIs are used worldwide, ...