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Method Article
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 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.
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).
This protocol was developed and utilized for studies conducted in compliance with the Danish and Institutional guidelines on animal welfare and ethics. The Danish Animal Research Inspectorate approved the study (license no. 2016-15-0201-00840). A Danish, female slaughter pig (crossbreed of Landrace, Yorkshire, and Duroc) of approximately 60 kg was used.
1. Anesthesia and ventilation
2. Intravascular accesses
NOTE: Intravascular accesses are to be established in the right external jugular vein, the left external jugular vein, left carotid artery, left femoral artery, and right femoral vein. In the pig, the external jugular vein is much larger than the internal jugular vein and, therefore, easier to access. All materials required for this section are shown in Figure 2A.
3. Right heart catherization
4. Right ventricular pressure-volume catheter insertion (Figure 4)
5. Left ventricular pressure-volume catheter insertion (Figure 5)
6. Inferior vena cava balloon insertion
7. Pressure-volume catheter calibration
8. Baseline evaluation
NOTE: Experiment can be paused at this level for the stabilization of hemodynamics before the research protocol begins.
9. Post Protocol
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 (...
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...
None of the authors has any conflicts of interest to declare.
This work was supported by the Laerdal Foundation for Acute Medicine (3374), Holger and Ruth Hesse's Memorial Foundation, Søster and Verner Lippert's Foundation, Novo Nordisk Foundation (NNF16OC0023244, NFF17CO0024868), and Alfred Benzon's Foundation.
Name | Company | Catalog Number | Comments |
12L-RS | GE Healthcare Japan | 5141337 | Ultrasound probe |
12L-RS | GE Healthcare Japan | 5141337 | Ultrasound probe |
Adhesive Aperature Drape (OneMed) | evercare | 1515-01 | 75 x 90 cm (hole: 6 x 8 cm) |
Adhesive Aperature Drape (OneMed) | evercare | 1515-01 | 75 x 90 cm (hole: 6 x 8 cm) |
Alaris GP Guardrails plus | CareFusion | 9002TIG01-G | Infusion pump |
Alaris GP Guardrails plus | CareFusion | 9002TIG01-G | Infusion pump |
Alaris Infusion set | BD Plastipak | 60593 | |
Alaris Infusion set | BD Plastipak | 60593 | |
Alkoholswap | MEDIQ Danmark | 3340012 | 82% ethanol, 0,5% chlorhexidin, skin disinfection |
Alkoholswap | MEDIQ Danmark | 3340012 | 82% ethanol, 0,5% chlorhexidin, skin disinfection |
Amplatz Support Wire Guide Extra-Stiff | Cook Medical | THSF-25-260-AES | diameter: 0.025 inches, length: 260 cm |
Amplatz Support Wire Guide Extra-Stiff | Cook Medical | THSF-25-260-AES | diameter: 0.025 inches, length: 260 cm |
BD Connecta | BD | 394601 | Luer-Lock |
BD Connecta | BD | 394601 | Luer-Lock |
BD Emerald | BD | 307736 | 10 mL syringe |
BD Emerald | BD | 307736 | 10 mL syringe |
BD Luer-Lock | BD Plastipak | 300865 | BD = Becton Dickinson, 50 mL syringe |
BD Luer-Lock | BD Plastipak | 300865 | BD = Becton Dickinson, 50 mL syringe |
BD Platipak | BD | 300613 | 20 mL syringe |
BD Platipak | BD | 300613 | 20 mL syringe |
BD Venflon Pro | Becton Dickinson Infusion Therapy | 393204 | 20G |
BD Venflon Pro | Becton Dickinson Infusion Therapy | 393204 | 20G |
BD Venflon Pro | Becton Dickinson Infusion Therapy | 393208 | 17G |
BD Venflon Pro | Becton Dickinson Infusion Therapy | 393208 | 17G |
Butomidor Vet | Richter Pharma AG | 531943 | 10 mg/mL |
Butomidor Vet | Richter Pharma AG | 531943 | 10 mg/mL |
Check-Flo Performer Introducer | Cook Medical | RCFW-16.0P-38-30-RB | 16 F sheath, 30 cm long |
Check-Flo Performer Introducer | Cook Medical | RCFW-16.0P-38-30-RB | 16 F sheath, 30 cm long |
Cios Connect S/N 20015 | Siemens Healthineers | C-arm | |
Cios Connect S/N 20015 | Siemens Healthineers | C-arm | |
D-LCC12A-01 | GE Healthcare Finland | Pressure measurement monitor | |
D-LCC12A-01 | GE Healthcare Finland | Pressure measurement monitor | |
Durapore | 3M | - | Adhesive tape |
Durapore | 3M | - | Adhesive tape |
E-PRESTIN-00 | GE Healthcare Finland | 6152932 | Respirator tubes |
E-PRESTIN-00 | GE Healthcare Finland | 6152932 | Respirator tubes |
Exagon vet | Richter Pharma AG | 427931 | 400 mg/mL |
Exagon vet | Richter Pharma AG | 427931 | 400 mg/mL |
Fast-Cath Hemostasis Introducer 12F | St. Jude Medical | 406128 | L: 12 cm |
Fast-Cath Hemostasis Introducer 12F | St. Jude Medical | 406128 | L: 12 cm |
Favorita II | Aesculap | Type: GT104 | |
Favorita II | Aesculap | Type: GT104 | |
Fentanyl | B. Braun | 71036 | 50 mikrogram/mL |
Fentanyl | B. Braun | 71036 | 50 mikrogram/mL |
Ketaminol Vet | MSD/Intervet International B.V. | 511519 | 100 mg/mL |
Ketaminol Vet | MSD/Intervet International B.V. | 511519 | 100 mg/mL |
LabChart | ADInstruments | Data aquisition software | |
LabChart | ADInstruments | Data aquisition software | |
Lawton 85-0010 ZK1 | Lawton | Laryngoscope | |
Lawton 85-0010 ZK1 | Lawton | Laryngoscope | |
Lectospiral | VYGON | 1159.90 | 400 cm (Luer-LOCK) |
Lectospiral | VYGON | 1159.90 | 400 cm (Luer-LOCK) |
Lubrithal eye gel | Dechra, Great Britain | ||
Lubrithal eye gel | Dechra, Great Britain | ||
MBH qufora | MBH-International A/S | 13853401 | Urine bag |
MBH qufora | MBH-International A/S | 13853401 | Urine bag |
Natriumklorid | Fresenius Kabi | 7340022100528 | 9 mg/ml Isotonic saline |
Natriumklorid | Fresenius Kabi | 7340022100528 | 9 mg/ml Isotonic saline |
PICO50 Aterial Blood Sampler | Radiometer | 956-552 | 2 mL |
PICO50 Aterial Blood Sampler | Radiometer | 956-552 | 2 mL |
Portex Tracheal Tube | Smiths Medical | 100/150/075 | "Cuffed Clear Oral/Nasal Murphy Eye" |
Portex Tracheal Tube | Smiths Medical | 100/150/075 | "Cuffed Clear Oral/Nasal Murphy Eye" |
PowerLab 16/35 | ADInstruments | PL3516 | Serial number: 3516-1841 |
PowerLab 16/35 | ADInstruments | PL3516 | Serial number: 3516-1841 |
Pressure Extension set | CODAN | 7,14,020 | Tube for anesthetics, 150 cm long, inner diameter 0.9 mm |
Pressure Extension set | CODAN | 7,14,020 | Tube for anesthetics, 150 cm long, inner diameter 0.9 mm |
Propolipid | Fresenius Kabi | 21636 | Propofol, 10 mg/mL |
Propolipid | Fresenius Kabi | 21636 | Propofol, 10 mg/mL |
PTS-X | NuMED Canada Inc. | PTSX253 | Inferior vena cava balloon |
PTS-X | NuMED Canada Inc. | PTSX253 | Inferior vena cava balloon |
Radiofocus Introducer II | Radiofocus/Terumo | RS+B80N10MQ | 6+7+8F sheaths |
Radiofocus Introducer II | Radiofocus/Terumo | RS+B80N10MQ | 6+7+8F sheaths |
Rompun Vet | Beyer | 86450917 | Xylazin, 20 mg/mL |
Rompun Vet | Beyer | 86450917 | Xylazin, 20 mg/mL |
Rüsch Brilliant AquaFlate Glycerine | Teleflex | 178000 | Bladder catheter, size 14 |
Rüsch Brilliant AquaFlate Glycerine | Teleflex | 178000 | Bladder catheter, size 14 |
S/5 Avance | Datex-Ohmeda | - | Mechanical ventilator |
S/5 Avance | Datex-Ohmeda | - | Mechanical ventilator |
Safersonic Conti Plus & Safergel | SECMA medical innovation | SAF.612.18120.WG.SEC | 18 x 120 cm (Safersonic Sterile Transducer Cover with Adhesive Area and Safergel) |
Safersonic Conti Plus & Safergel | SECMA medical innovation | SAF.612.18120.WG.SEC | 18 x 120 cm (Safersonic Sterile Transducer Cover with Adhesive Area and Safergel) |
Scisense Catheter | Transonic Scisense | FDH-5018B-E245B | Serial number: 50-533. Pressure-volume catheter |
Scisense Catheter | Transonic Scisense | FDH-5018B-E245B | Serial number: 50-533. Pressure-volume catheter |
Scisense Pressure-Volume Measurement System | Transonic Scisense | ADV500 | Model: FY097B. Pressure-volume box |
Scisense Pressure-Volume Measurement System | Transonic Scisense | ADV500 | Model: FY097B. Pressure-volume box |
Swan-Ganz CCOmbo | Edwards Lifesciences | 744F75 | 110 cm |
Swan-Ganz CCOmbo | Edwards Lifesciences | 744F75 | 110 cm |
TruWave Pressure Monitoring Set | Edwards Lifesciences | T434303A | 210 cm |
TruWave Pressure Monitoring Set | Edwards Lifesciences | T434303A | 210 cm |
Vivid iq | GE Medical Systems China | Vivid iq | |
Vivid iq | GE Medical Systems China | Vivid iq | |
Zoletil 50 Vet (tiletamin 125 mg and zolazepam 125 mg) | Virbac | 83046805 | 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 |
Zoletil 50 Vet (tiletamin 125 mg and zolazepam 125 mg) | Virbac | 83046805 | 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 |
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