This work was supported by the Laerdal Foundation for Acute Medicine (3374), Holger and Ruth Hesse&#39;s Memorial Foundation, S&#248;ster and Verner Lippert&#39;s Foundation, Novo Nordisk Foundation (NNF16OC0023244, NFF17CO0024868), and Alfred Benzon&#39;s Foundation.

<ol>
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None of the authors has any conflicts of interest to declare.

This paper describes a reproducible minimally invasive closed chest approach for bi-ventricular pressure-volume loop recordings.
Advancement of the PV catheter from the RA into the RV is the most critical step in this protocol. The complex composition of the RV and the stiffness of the catheter complicate insertion into the easily distended and geometrically challenging RV. This difficulty may explain why open chest instrumentation is often preferred. During pilot studies, numerous accesses an...

Pressure-volume (PV) loops contain a large number of hemodynamic information, including end-systolic and end-diastolic pressures and volumes, ejection fraction, stroke volume, and stroke work1. Furthermore, transient preload reduction creates a family of loops from which load-independent variables can be derived2,3. This load-independent evaluation of ventricular function makes PV loop recordings state-of-the-art in hemodynamic evaluation. PV loop recording can be performed in humans but is primarily used and recommended in preclinical research4,5,6.
Pressure-volume loops can be obtained from both the right ventricle (RV) and the left ventricle (LV). Most research hypotheses are focused on a single ventricle, resulting in only univentricular PV loops being recorded7,8,9,10. However, the right and left ventricles exert systolic and diastolic interdependence due to their serial and parallel connections within the tight pericardium11. Changes in the output or the size of one ventricle will affect the size, loading conditions, or perfusion of the other ventricle. Thus, bi-ventricular PV loop recordings provide a more comprehensive evaluation of the total cardiac performance. Pharmacological interventions may also affect the two ventricles and their loading conditions differently, further emphasizing the importance of bi-ventricular evaluation.
PV catheters can be advanced into either ventricle by several approaches, including open chest approach with access from the apex of the heart or through the RV outflow tract7,10,12,13,14. However, the opening of the thorax will affect the physiological conditions and may introduce bias.
Based on our experience from previous studies15,16,17,18, we aim to present our closed chest approach to bi-ventricular PV loop recordings in a large animal model of acute RV failure having minimal influence on cardiopulmonary physiology (Figure 1).

<table><tbody><tr><td>12L-RS</td><td>GE Healthcare Japan</td><td>5141337</td><td>Ultrasound probe</td></tr><tr><td>12L-RS</td><td>GE Healthcare Japan</td><td>5141337</td><td>Ultrasound probe</td></tr><tr><td>Adhesive Aperature Drape (OneMed)</td><td>evercare</td><td>1515-01</td><td>75 x 90 cm (hole: 6 x 8 cm)</td></tr><tr><td>Adhesive Aperature Drape (OneMed)</td><td>evercare</td><td>1515-01</td><td>75 x 90 cm (hole: 6 x 8 cm)</td></tr><tr><td>Alaris GP Guardrails plus</td><td>CareFusion</td><td>9002TIG01-G</td><td>Infusion pump</td></tr><tr><td>Alaris GP Guardrails plus</td><td>CareFusion</td><td>9002TIG01-G</td><td>Infusion pump</td></tr><tr><td>Alaris Infusion set</td><td>BD Plastipak</td><td>60593</td><td></td></tr><tr><td>Alaris Infusion set</td><td>BD Plastipak</td><td>60593</td><td></td></tr><tr><td>Alkoholswap</td><td>MEDIQ Danmark</td><td>3340012</td><td>82% ethanol, 0,5% chlorhexidin, skin disinfection</td></tr><tr><td>Alkoholswap</td><td>MEDIQ Danmark</td><td>3340012</td><td>82% ethanol, 0,5% chlorhexidin, skin disinfection</td></tr><tr><td>Amplatz Support Wire Guide Extra-Stiff</td><td>Cook Medical</td><td>THSF-25-260-AES</td><td>diameter: 0.025 inches, length: 260 cm</td></tr><tr><td>Amplatz Support Wire Guide Extra-Stiff</td><td>Cook Medical</td><td>THSF-25-260-AES</td><td>diameter: 0.025 inches, length: 260 cm</td></tr><tr><td>BD Connecta</td><td>BD</td><td>394601</td><td>Luer-Lock</td></tr><tr><td>BD Connecta</td><td>BD</td><td>394601</td><td>Luer-Lock</td></tr><tr><td>BD Emerald</td><td>BD</td><td>307736</td><td>10 mL syringe</td></tr><tr><td>BD Emerald</td><td>BD</td><td>307736</td><td>10 mL syringe</td></tr><tr><td>BD Luer-Lock</td><td>BD Plastipak</td><td>300865</td><td>BD = Becton Dickinson, 50 mL syringe</td></tr><tr><td>BD Luer-Lock</td><td>BD Plastipak</td><td>300865</td><td>BD = Becton Dickinson, 50 mL syringe</td></tr><tr><td>BD Platipak</td><td>BD</td><td>300613</td><td>20 mL syringe</td></tr><tr><td>BD Platipak</td><td>BD</td><td>300613</td><td>20 mL syringe</td></tr><tr><td>BD Venflon Pro</td><td>Becton Dickinson Infusion Therapy</td><td>393204</td><td>20G</td></tr><tr><td>BD Venflon Pro</td><td>Becton Dickinson Infusion Therapy</td><td>393204</td><td>20G</td></tr><tr><td>BD Venflon Pro</td><td>Becton Dickinson Infusion Therapy</td><td>393208</td><td>17G</td></tr><tr><td>BD Venflon Pro</td><td>Becton Dickinson Infusion Therapy</td><td>393208</td><td>17G</td></tr><tr><td>Butomidor Vet</td><td>Richter Pharma AG</td><td>531943</td><td>10 mg/mL</td></tr><tr><td>Butomidor Vet</td><td>Richter Pharma AG</td><td>531943</td><td>10 mg/mL</td></tr><tr><td>Check-Flo Performer Introducer</td><td>Cook Medical</td><td>RCFW-16.0P-38-30-RB</td><td>16 F sheath, 30 cm long</td></tr><tr><td>Check-Flo Performer Introducer</td><td>Cook Medical</td><td>RCFW-16.0P-38-30-RB</td><td>16 F sheath, 30 cm long</td></tr><tr><td>Cios Connect S/N 20015</td><td>Siemens Healthineers</td><td></td><td>C-arm</td></tr><tr><td>Cios Connect S/N 20015</td><td>Siemens Healthineers</td><td></td><td>C-arm</td></tr><tr><td>D-LCC12A-01</td><td>GE Healthcare Finland</td><td></td><td>Pressure measurement monitor</td></tr><tr><td>D-LCC12A-01</td><td>GE Healthcare Finland</td><td></td><td>Pressure measurement monitor</td></tr><tr><td>Durapore</td><td>3M</td><td>-</td><td>Adhesive tape</td></tr><tr><td>Durapore</td><td>3M</td><td>-</td><td>Adhesive tape</td></tr><tr><td>E-PRESTIN-00</td><td>GE Healthcare Finland</td><td>6152932</td><td>Respirator tubes</td></tr><tr><td>E-PRESTIN-00</td><td>GE Healthcare Finland</td><td>6152932</td><td>Respirator tubes</td></tr><tr><td>Exagon vet</td><td>Richter Pharma AG</td><td>427931</td><td>400 mg/mL</td></tr><tr><td>Exagon vet</td><td>Richter Pharma AG</td><td>427931</td><td>400 mg/mL</td></tr><tr><td>Fast-Cath Hemostasis Introducer 12F</td><td>St. Jude Medical</td><td>406128</td><td>L: 12 cm</td></tr><tr><td>Fast-Cath Hemostasis Introducer 12F</td><td>St. Jude Medical</td><td>406128</td><td>L: 12 cm</td></tr><tr><td>Favorita II</td><td>Aesculap</td><td></td><td>Type: GT104</td></tr><tr><td>Favorita II</td><td>Aesculap</td><td></td><td>Type: GT104</td></tr><tr><td>Fentanyl</td><td>B. Braun</td><td>71036</td><td>50 mikrogram/mL</td></tr><tr><td>Fentanyl</td><td>B. Braun</td><td>71036</td><td>50 mikrogram/mL</td></tr><tr><td>Ketaminol Vet</td><td>MSD/Intervet International B.V.</td><td>511519</td><td>100 mg/mL</td></tr><tr><td>Ketaminol Vet</td><td>MSD/Intervet International B.V.</td><td>511519</td><td>100 mg/mL</td></tr><tr><td>LabChart</td><td>ADInstruments</td><td></td><td>Data aquisition software</td></tr><tr><td>LabChart</td><td>ADInstruments</td><td></td><td>Data aquisition software</td></tr><tr><td>Lawton 85-0010 ZK1</td><td>Lawton</td><td></td><td>Laryngoscope</td></tr><tr><td>Lawton 85-0010 ZK1</td><td>Lawton</td><td></td><td>Laryngoscope</td></tr><tr><td>Lectospiral</td><td>VYGON</td><td>1159.90</td><td>400 cm (Luer-LOCK)</td></tr><tr><td>Lectospiral</td><td>VYGON</td><td>1159.90</td><td>400 cm (Luer-LOCK)</td></tr><tr><td>Lubrithal eye gel</td><td>Dechra, Great Britain</td><td></td><td></td></tr><tr><td>Lubrithal eye gel</td><td>Dechra, Great Britain</td><td></td><td></td></tr><tr><td>MBH qufora</td><td>MBH-International A/S</td><td>13853401</td><td>Urine bag</td></tr><tr><td>MBH qufora</td><td>MBH-International A/S</td><td>13853401</td><td>Urine bag</td></tr><tr><td>Natriumklorid</td><td>Fresenius Kabi</td><td>7340022100528</td><td>9 mg/ml Isotonic saline</td></tr><tr><td>Natriumklorid</td><td>Fresenius Kabi</td><td>7340022100528</td><td>9 mg/ml Isotonic saline</td></tr><tr><td>PICO50 Aterial Blood Sampler</td><td>Radiometer</td><td>956-552</td><td>2 mL</td></tr><tr><td>PICO50 Aterial Blood Sampler</td><td>Radiometer</td><td>956-552</td><td>2 mL</td></tr><tr><td>Portex Tracheal Tube</td><td>Smiths Medical</td><td>100/150/075</td><td>&quot;Cuffed Clear Oral/Nasal Murphy Eye&quot;</td></tr><tr><td>Portex Tracheal Tube</td><td>Smiths Medical</td><td>100/150/075</td><td>&quot;Cuffed Clear Oral/Nasal Murphy Eye&quot;</td></tr><tr><td>PowerLab 16/35</td><td>ADInstruments</td><td>PL3516</td><td>Serial number: 3516-1841</td></tr><tr><td>PowerLab 16/35</td><td>ADInstruments</td><td>PL3516</td><td>Serial number: 3516-1841</td></tr><tr><td>Pressure Extension set</td><td>CODAN</td><td>7,14,020</td><td>Tube for anesthetics, 150 cm long, inner diameter 0.9 mm</td></tr><tr><td>Pressure Extension set</td><td>CODAN</td><td>7,14,020</td><td>Tube for anesthetics, 150 cm long, inner diameter 0.9 mm</td></tr><tr><td>Propolipid</td><td>Fresenius Kabi</td><td>21636</td><td>Propofol, 10 mg/mL</td></tr><tr><td>Propolipid</td><td>Fresenius Kabi</td><td>21636</td><td>Propofol, 10 mg/mL</td></tr><tr><td>PTS-X</td><td>NuMED Canada Inc.</td><td>PTSX253</td><td>Inferior vena cava balloon</td></tr><tr><td>PTS-X</td><td>NuMED Canada Inc.</td><td>PTSX253</td><td>Inferior vena cava balloon</td></tr><tr><td>Radiofocus Introducer II</td><td>Radiofocus/Terumo</td><td>RS+B80N10MQ</td><td>6+7+8F sheaths</td></tr><tr><td>Radiofocus Introducer II</td><td>Radiofocus/Terumo</td><td>RS+B80N10MQ</td><td>6+7+8F sheaths</td></tr><tr><td>Rompun Vet</td><td>Beyer</td><td>86450917</td><td>Xylazin, 20 mg/mL</td></tr><tr><td>Rompun Vet</td><td>Beyer</td><td>86450917</td><td>Xylazin, 20 mg/mL</td></tr><tr><td>R&amp;uuml;sch Brilliant AquaFlate Glycerine</td><td>Teleflex</td><td>178000</td><td>Bladder catheter, size 14</td></tr><tr><td>R&amp;uuml;sch Brilliant AquaFlate Glycerine</td><td>Teleflex</td><td>178000</td><td>Bladder catheter, size 14</td></tr><tr><td>S/5 Avance</td><td>Datex-Ohmeda</td><td>-</td><td>Mechanical ventilator</td></tr><tr><td>S/5 Avance</td><td>Datex-Ohmeda</td><td>-</td><td>Mechanical ventilator</td></tr><tr><td>Safersonic Conti Plus &amp;amp; Safergel</td><td>SECMA medical innovation</td><td>SAF.612.18120.WG.SEC</td><td>18 x 120 cm (Safersonic Sterile Transducer Cover with Adhesive Area and Safergel)</td></tr><tr><td>Safersonic Conti Plus &amp;amp; Safergel</td><td>SECMA medical innovation</td><td>SAF.612.18120.WG.SEC</td><td>18 x 120 cm (Safersonic Sterile Transducer Cover with Adhesive Area and Safergel)</td></tr><tr><td>Scisense Catheter</td><td>Transonic Scisense</td><td>FDH-5018B-E245B</td><td>Serial number: 50-533. Pressure-volume catheter</td></tr><tr><td>Scisense Catheter</td><td>Transonic Scisense</td><td>FDH-5018B-E245B</td><td>Serial number: 50-533. Pressure-volume catheter</td></tr><tr><td>Scisense Pressure-Volume Measurement System</td><td>Transonic Scisense</td><td>ADV500</td><td>Model: FY097B. Pressure-volume box</td></tr><tr><td>Scisense Pressure-Volume Measurement System</td><td>Transonic Scisense</td><td>ADV500</td><td>Model: FY097B. Pressure-volume box</td></tr><tr><td>Swan-Ganz CCOmbo</td><td>Edwards Lifesciences</td><td>744F75</td><td>110 cm</td></tr><tr><td>Swan-Ganz CCOmbo</td><td>Edwards Lifesciences</td><td>744F75</td><td>110 cm</td></tr><tr><td>TruWave Pressure Monitoring Set</td><td>Edwards Lifesciences</td><td>T434303A</td><td>210 cm</td></tr><tr><td>TruWave Pressure Monitoring Set</td><td>Edwards Lifesciences</td><td>T434303A</td><td>210 cm</td></tr><tr><td>Vivid iq</td><td>GE Medical Systems China</td><td>Vivid iq</td><td></td></tr><tr><td>Vivid iq</td><td>GE Medical Systems China</td><td>Vivid iq</td><td></td></tr><tr><td>Zoletil 50 Vet (tiletamin 125 mg and zolazepam 125 mg)</td><td>Virbac</td><td>83046805</td><td>Zoletil Mix for pigs: 1 vial of Zoletil 50 Vet (dry matter); add 6.25 mL Xylozin (20 mg/mL), 1.25 mL ketamin (100 mg/mL) and 2.5 mL Butorphanol (10 mg/mL). Dose for pre-anesthesia: 10 mL/10 kg as intramuscular injection</td></tr><tr><td>Zoletil 50 Vet (tiletamin 125 mg and zolazepam 125 mg)</td><td>Virbac</td><td>83046805</td><td>Zoletil Mix for pigs: 1 vial of Zoletil 50 Vet (dry matter); add 6.25 mL Xylozin (20 mg/mL), 1.25 mL ketamin (100 mg/mL) and 2.5 mL Butorphanol (10 mg/mL). Dose for pre-anesthesia: 10 mL/10 kg as intramuscular injection</td></tr></tbody></table>

closed chest biventricular pressure-volume loop recordings with admittance catheters in a porcine model

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular evaluation is often performed in preclinical research. However, the right and left ventricles exert functional interdependence due to their parallel and serial connections, encouraging simultaneous evaluation of both ventricles. Furthermore, various pharmacological interventions may affect the ventricles and their preloads and afterloads differently. 
We describe our closed chest approach to admittance-based bi-ventricular PV loop recordings in a porcine model of acute right ventricular (RV) overload. We utilize minimally invasive techniques with all vascular accesses guided by ultrasound. PV catheters are positioned, under fluoroscopic guidance, to avoid thoracotomy in animals, as the closed chest approach maintains the relevant cardiopulmonary physiology. The admittance technology provides real-time PV loop recordings without the need for post-hoc processing. Furthermore, we explain some essential troubleshooting steps during critical timepoints of the presented procedure. 
The presented protocol is a reproducible and physiologically relevant approach to obtain a bi-ventricular cardiac PV loop recording in a large animal model. This can be applied to a large variety of cardiovascular animal research.

The present instructions describe an approach to achieve admittance-based PV recordings from both the RV and the LV in a large animal.
To compare our simultaneous PV recordings in the RV and LV, we performed a linear regression of the bi-ventricular CO measurements from our largest study18 with the highest number of simultaneous RV CO and LV CO measurements (n=379 recordings from 12 animals). We found that the slope was 1.03 (95%CI 0.90-1.15) with a Y-intercept of 695 (...

Watch this Scientific Journal Video about Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model at JoVE.com

Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model

Here we present a closed chest approach to admittance-based bi-ventricular pressure-volume loop recordings in pigs with acute right ventricular dysfunction.

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular ...

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JoVE Journal

Medicine

3.6K Views.  Aarhus University Hospital. Here we present a closed chest approach to admittance-based bi-ventricular pressure-volume loop recordings in pigs with acute right ventricular dysfunction.

Video: Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model

An Isolated Working Heart System for Large Animal Models

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart model, have been invaluable tools for studying cardiovascular function and disease1-15. Although the Langendorff heart preparation can be used for any mammalian heart, most studies involving this apparatus use small animal models (e.g., mouse, rat, and rabbit) due to the increased complexity of systems for larger mammals1,3,11. One major difficulty is ensuring a constant coronary perfusion pressure over a range of different heart sizes &#8211; a key component of any experiment utilizing this device1,11. By replacing the classic hydrostatic afterload column with a centrifugal pump, the Langendorff working heart apparatus described below allows for easy adjustment and tight regulation of perfusion pressures, meaning the same set-up can be used for various species or heart sizes. Furthermore, this configuration can also seamlessly switch between constant pressure or constant flow during reperfusion, depending on the user&#8217;s preferences. The open nature of this setup, despite making temperature regulation more difficult than other designs, allows for easy collection of effluent and ventricular pressure-volume data.

Most studies involving the Langendorff apparatus use small animal models due to the increased complexity of systems for larger mammals. We describe a Langendorff system for large animal models that allows for use across a range of species, including humans, and relatively easy data acquisition.

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart ...

Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect

Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these strategies is to examine their effects on heart function. There are several techniques to measure in vivo cardiac mechanics (e.g., echocardiography, pressure/volume relations, etc.). Compared to echocardiography, real-time left ventricular (LV) pressure/volume analysis via catheterization is more precise and insightful in assessing LV function. Additionally, LV pressure/volume analysis provides the ability to instantaneously record changes during manipulations of contractility (e.g., &#946;-adrenergic stimulation) and pathological insults (e.g., ischemia/reperfusion injury). In addition to the maximum (+dP/dt) and minimum (-dP/dt) rate of pressure change in the LV, an accurate assessment of LV function via several load-independent indexes (e.g., end systolic pressure volume relationship and preload recruitable stroke work) can be attained. Heart rate has a significant effect on LV contractility such that an increase in the heart rate is the primary mechanism to increase cardiac output (i.e., Bowditch effect). Thus, when comparing hemodynamics between experimental groups, it is necessary to have similar heart rates. Furthermore, a hallmark of many cardiomyopathy models is a decrease in contractile reserve (i.e., decreased Bowditch effect). Consequently, vital information can be obtained by determining the effects of increasing heart rate on contractility. Our and others data has demonstrated that the neuronal nitric oxide synthase (NOS1) knockout mouse has decreased contractility. Here we describe the procedure of measuring LV pressure/volume with increasing heart rates using the NOS1 knockout mouse model.

This article describes the measurement of murine left ventricular function via pressure/volume analysis at different heart rates.

Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these ...

Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. Pulmonary Hypertension (PH) was induced in 3-week-old piglets by a progressive obstruction of the pulmonary vascular bed. A ligation of the left Pulmonary Artery (PA) was performed first through a mini-thoracotomy. Second, weekly embolizations of the right lower pulmonary lobe were done under fluoroscopic guidance with n-butyl-2-cyanoacrylate during 5 weeks. Mean Pulmonary Arterial Pressure (mPAP) measured by ritght heart catheterism, increased progressively, as well as Right Atrial pressure and Pulmonary Vascular Resistances (PVR) after 5 weeks compared to sham animals. Right Ventricular (RV) structural and functional remodeling were assessed by transthoracic echocardiography (RV diameters, RV wall thickness, RV systolic function). RV elastance and RV-pulmonary coupling were assessed by Pressure-Volume Loops (PVL) analysis with conductance method. Histologic study of the lung and the right ventricle were also performed. Molecular analyses on RV fresh tissues could be performed through repeated transcutaneous endomyocardial biopsies. Pulmonary microvascular disease in obstructed and unobstructed territories was studied from lung biopsies using molecular analyses and pathology. Furthermore, the reliability and the reproducibility was associated with a range of PH severity in animals. Most aspects of the human CTEPH disease were reproduced in this model, which allows new perspectives for the understanding of the underlying mechanisms (mitochondria, inflammation) and new therapeutic approaches (targeted, cellular or gene therapies) of the overloaded right ventricle but also pulmonary microvascular disease.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Right Ventricular (RV) dysfunction were induced in piglets by progressive obstruction of the pulmonary arteries. Consequences were remarkably similar to those observed in CTEPH patients. This animal model would be a very useful tool for pathophysiology and therapeutic experiments on CTEPH and RV failure.

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. ...

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are therefore required to confine cardiac damage, promote survival and reduce the disease burden of heart failure. Large animal experiments are an essential part in the translational process from experimental to clinical therapies. To optimize clinical translation, robust and representative outcome measures are mandatory. The present manuscript aims to address this need by describing the assessment of three clinically relevant outcome modalities in a pig acute myocardial infarction (AMI) model: infarct size in relation to area at risk (IS/AAR) staining, 3-dimensional transesophageal echocardiography (TEE) and admittance-based pressure-volume (PV) loops. Infarct size is the main determinant driving the transition from AMI to heart failure and can be quantified by IS/AAR staining. Echocardiography is a reliable and robust tool in the assessment of global and regional cardiac function in clinical cardiology. Here, a method for three-dimensional transesophageal echocardiography (3D-TEE) in pigs is provided. Extensive insight into cardiac performance can be obtained by admittance-based pressure-volume (PV) loops, including intrinsic parameters of myocardial function that are pre- and afterload independent. Combined with a clinically feasible experimental study protocol, these outcome measures provide researchers with essential information to determine whether novel therapeutic strategies could yield promising targets for future testing in clinical studies.

Reliable and accurate outcome assessment is the key for translation of preclinical therapies into clinical treatment. The current paper describes how to assess three clinically relevant primary outcome parameters of cardiac performance and damage in a pig acute myocardial infarction model.

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are ...

Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) generated by recording both pressure and volume during cardiac catheterization are vital when assessing both systolic and diastolic cardiac function. Left and right heart function are closely related, reflected in ventricular interdependence. Thus, recording biventricular function in the same animal is important to get a complete assessment of cardiac function. In this protocol, a closed chest approach to cardiac catheterization consistent with the way catheterization is performed in patients is adopted in mice. While challenging, the closed chest strategy is a more physiological approach, because opening the chest results in major changes in preload and afterload that create artifacts, most notably a fall in systemic blood pressure. While high-resolution echocardiography is used to assess rodents, cardiac catheterization is invaluable, particularly when assessing diastolic pressures in both ventricles.
Described here is a procedure to perform invasive, closed chest, sequential left and right ventricular pressure-volume (PV) loops in the same animal. PV loops are acquired using&#160;admittance technology with a mouse pressure-volume catheter and pressure-volume system acquisition. The procedure is described, beginning with the neck dissection, which is required to access the right jugular vein and the right carotid artery, to the insertion and positioning of the catheter, and finally the data acquisition. Then, the criteria required to ensure the acquisition of high-quality PV loops are discussed. Finally, the analysis of the left and right ventricular PV loops and the different hemodynamic parameters available to quantify systolic and diastolic ventricular function are briefly described.

Presented here is a protocol to assess biventricular heart function in mice by generating pressure-volume (PV) loops from the right and left ventricle in the same animal using closed chest catheterization. The focus is on the technical aspect of surgery and data acquisition.

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) ...

Cardiac Response to &#946;-Adrenergic Stimulation Determined by Pressure-Volume Loop Analysis

Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of specific treatments on the heart. Due to the feasibility of genetic manipulations the mouse has become the most common mammalian animal model to study cardiac function and to search for new potential therapeutic targets. Here we describe a protocol to determine cardiac function&#160;in vivo using pressure-volume loop measurements and analysis during basal conditions and under &#946;-adrenergic stimulation by intravenous infusion of increasing concentrations of isoproterenol. We provide a refined protocol including ventilation support taking into account the positive end-expiratory pressure to ameliorate negative effects during open-chest measurements, and potent analgesia (Buprenorphine) to avoid uncontrollable myocardial stress evoked by pain during the procedure. All together the detailed description of the procedure and discussion about possible pitfalls enables highly standardized and reproducible pressure-volume loop analysis, reducing the exclusion of animals from the experimental cohort by preventing possible methodological bias.

Here we describe a cardiac pressure-volume loop analysis under increasing doses of intravenously infused isoproterenol to determine the intrinsic cardiac function and the &#946;-adrenergic reserve in mice. We use a modified open-chest approach for the pressure-volume loop measurements, in which we include ventilation with positive end-expiratory pressure.

Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of ...

Measuring Cardiac Output in a Swine Model

Swine are frequently used in medical research given their similar cardiac physiology to that of humans. Measuring cardiac parameters such as stroke volume and cardiac output are essential in this type of research. Contrast ventriculography, thermodilution, and pressure-volume loop (PV-loop) catheters can be used to accurately obtain cardiac performance data depending on which resources and expertise are available. For this study,five Yorkshire swine were anesthetized and intubated. Central venous and arterial access was obtained to place the necessary measurement instruments.A temperature probe was placed in the aortic root. A cold saline bolus was delivered to the right atrium and temperature deflection curve was recorded. Integration of the area under the curve allowed for the calculation of the current cardiac output.A pigtail catheter was percutaneously placed in the left ventricle and 30 mL of iodinated contrast was power injected over 2 seconds. Digital subtraction angiography images were uploaded to volumetric analysis software to calculate the stroke volume and cardiac output. A pressure volume-loop catheter was placed into the left ventricle (LV) and provided continuous pressure and volume data of the LV, which allowed the calculation of both stroke volume and cardiac output.All three methods demonstrated good correlation with each other. The PV-loop catheter and thermodilution exhibited the best correlation with a 3% error and a Pearson coefficient of 0.99, with 95% CI=0.97 to 1.1, (p=0.002). The PV-loop catheter against ventriculography also showed good correlation with a 6% error and a Pearson coefficient of 0.95, 95% CI=0.96 to 1.1 (p=0.01). Finally, thermodilution against ventriculography had a 2% error with r=0.95, 95% CI=0.93 to 1.11, (p=0.01). In conclusion, we state that the PV-loop catheter, contrast ventriculography, and thermodilution each offer certain advantages depending on the researcher's requirements. Each method is reliable and accurate for measuring various cardiac parameters in swine such as the stroke volume and cardiac output.

Thermodilution, pressure-volume loop catheters, and contrast ventriculography are reliable and accurate methods for determining cardiac physiology such as stroke volume and cardiac output in a laboratory setting in swine.

Swine are frequently used in medical research given their similar cardiac physiology to that of humans. Measuring cardiac parameters such as stroke volume ...

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice

Cardiac pressure-volume loop analysis is the &#8220;gold-standard&#8221; in the assessment of load-dependent and load-independent measures of ventricular systolic and diastolic function. Measures of ventricular contractility and compliance are obtained through examination of cardiac response to changes in afterload and preload. These techniques were originally developed nearly three decades ago to measure cardiac function in large mammals and humans. The application of these analyses to small mammals, such as mice, has been accomplished through the optimization of microsurgical techniques and creation of conductance catheters. Conductance catheters allow for estimation of the blood pool by exploiting the relationship between electrical conductance and volume. When properly performed, these techniques allow for testing of cardiac function in genetic mutant mouse models or in drug treatment studies. The accuracy and precision of these studies are dependent on careful attention to the calibration of instruments, systematic conduct of hemodynamic measurements and data analyses. We will review the methods of conducting pressure-volume loop experiments using a conductance catheter in mice.

Cardiac pressure-volume loop analysis is the most comprehensive way to measure cardiac function in the intact heart. We describe a technique to perform and analyze cardiac pressure volume loops, using conductance catheters.

Cardiac pressure-volume loop analysis is the &#8220;gold-standard&#8221; in the assessment of load-dependent and load-independent measures of ventricular ...

Biology

Measuring Pressure Volume Loops in the Mouse

Understanding the causes and progression of heart disease presents a significant challenge to the biomedical community. The genetic flexibility of the mouse provides great potential to explore cardiac function at the molecular level. The mouse&#39;s small size does present some challenges in regards to performing detailed cardiac phenotyping. Miniaturization and other advancements in technology have made many methods of cardiac assessment possible in the mouse. Of these, the simultaneous collection of pressure and volume data provides a detailed picture of cardiac function that is not available through any other modality. Here a detailed procedure for the collection of pressure-volume loop data is described. Included is a discussion of the principles underlying the measurements and the potential sources of error. Anesthetic management and surgical approaches are discussed in great detail as they are both critical to obtaining high quality hemodynamic measurements. The principles of hemodynamic protocol development and relevant aspects of data analysis are also addressed.

This manuscript describes a detailed protocol for the collection of pressure-volume data from the mouse.

Understanding the causes and progression of heart disease presents a significant challenge to the biomedical community. The genetic flexibility of the ...

Investigating Physiological Responses to Acute Volume Overload in Porcine Models

Adult and Pediatric Porcine Model of Acute Volume Overload

This protocol describes an acute volume overload porcine model for adult Yorkshire pigs and piglets. Both swine ages undergo general anesthesia, endotracheal intubation, and mechanical ventilation. A central venous catheter and an arterial catheter are placed via surgical cutdown in the external jugular vein and carotid artery, respectively. A pulmonary artery catheter is placed through an introducer sheath of the central venous catheter. PlasmaLyte crystalloid solution is then administered at a rate of 100 mL/min in adult pigs and at 20 mL/kg boluses over 10 min in piglets. Hypervolemia is achieved either at 15% decrease in cardiac output or at 5 L in adult pigs and at 500 mL in piglets. Hemodynamic data, such as heart rate, respiratory rate, end-tidal carbon dioxide, fraction of oxygen-saturated hemoglobin, arterial blood pressure, central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, partial arterial oxygen pressure, lactate, pH, base excess, and pulmonary artery fraction of oxygen-saturated hemoglobin, are monitored during experimentation. Preliminary data observed with this model has demonstrated statistically significant changes and strong linear regressions between central hemodynamic parameters and acute volume overload in adult pigs. Only pulmonary capillary wedge pressure demonstrated both a linear regression and a statistical significance to acute volume overload in piglets. These models can aid scientists in the discovery of age-appropriate therapeutic and monitoring strategies to understand and prevent acute volume overload.

Author Spotlight: Exploring Venous Waveforms in Porcine Models to Tackle Volume Overload in Medicine

The protocol here shows how continuous administration of crystalloids into the central veins of a euvolemic pig/piglet allows for the appropriate investigation of the physiological effects of acute volume overload.