During this webinar sponsored by Transonic, Dr. Tim Hacker and Dr. Filip Konecny present common hemodynamic set ups for large animal models. Using case studies from dogs and swine models, they show surgical best-practices, tips for catheter navigation and how to correctly position a PV-catheter in the left or right ventricle. In addition, they explain how researchers can verify accurate and reliable PV loop data at the bench-side. Large animal hemodynamic research models are on the rise. They are increasingly used in various preclinical studies including pharmaco-safety and drug discovery assessment, ventricular assist-device testing and models of pulmonary artery hyperthrophy and right ventricular overload. Important to these applications and all cardiovascular studies is the collection of both central and peripheral hemodynamics, with a focus on instantaneous pressure and volume measurements from the beating heart (PV Loops). Only with PV loops can scientists obtain the most comprehensive evaluation of cardiac function. It is therefore critical for cardiovascular scientists to understand how PV Loop data should be collected along with these peripheral hemodynamic measurements. This webinar aims to discuss these essential elements and how they should be applied. Key Topics: Basic and advanced set ups for large animal hemodynamic studies Essential hemodynamic equipment/technology Anaesthetic and drug considerations for large animal PV studies Surgical approaches -- which one is best for you? How to successfully navigate the PV catheter and validate correct position in the ventricle Right ventricle PV loops -- important surgical, data collection and analysis considerations Unique attributes of 'admittance' derived volume

1. Best-Practices to Achieve Quality Pressure-
Volume Loop Data in Large Animal Models
Filip Konecny, DVM PhD
Transonic
Tim Hacker, PhD
University of Wisconsin
Andy Henton
InsideScientific
Sponsored by:

2. InsideScientific is an online educational environment
designed for life science researchers. Our goal is to aid in
the sharing and distribution of scientific information
regarding innovative technologies, protocols, research
tools and laboratory services.

3. Thank you to our event sponsor

4. Best-Practices for Successful
PV Loop Data Collection in
Large Animals
Filip Konecny, DVM PhD
Applications Scientist &
Surgical Trainer
Transonic
Copyright 2015 Transonic & InsideScientific . All Rights Reserved.

5. THIS WEBINAR IS TO PRESENT A SERIES OF
“LARGE ANIMAL BEST PRACTICES” THAT WILL
EVOKE CONFIDENCE IN YOUR PV LOOP DATA
WHILE YOU ARE COLLECTING IT.
WHEN FOLLOWED, THE SANITY CHECKS PRESENTED WILL
PREVENT THE MULTIDISCIPLINARY TEAM FROM COLLECTING
INNACURATE DATA
Webinar Objectives…

6.  Permits the measurement of P-V relationships
(longitudinally) at multiple time points over a
long period of time capturing instant changes
 Allows for the determination of instantaneous
PV relationships in the ventricles; both
individually (LV or RV), or simultaneously (bi-
ventricular) application
 good data reproducibility, no use of radiation,
low initial price and maintenance
 Allows extrapolating central and peripheral
hemodynamic responses reflecting its
respective changes
Value of PV Hemodynamics in Large Animal Models

7. Value of PV Hemodynamics in Large Animal Models
For more info please see our PV Workbook, pages 2-4
Echocardio (TTE) Cardiac CT Cardiac MRI PV (admittance)
Volumetry relies on
geometric assumptions
Volumetry relies on
geometric assumptions
Volumetry relies on
geometric assumptions
PV corrects geometric
assumption live
LOAD DEPENDENT LOAD DEPENDENT LOAD DEPENDENT
LOAD DEPENDENT
LOAD INDEPENDENT
Ventricle Pressure
not measured
Ventricle Pressure
not measured
Ventricle Pressure
not measured
Ventricle Pressure
measured/correlated
with volume-live

8. Value of PV Hemodynamics in Large Animal Models
Click to
Download
the workbook

9. Control unit of PV system
with “Large Animal” license,
connects to data acquisition
system (DAQ) using supplied
analog cable.
Supplied HDMI cable
connects the PV catheter to
the control unit.
Large Animal PV Tools & Equipment

10. Large Animal PV Tools & Equipment
Hemochron Jr. Signature
Plus in-vitro whole
blood micro-coagulation
system.
Two valuable tools often
omitted by researchers
are an Arterial Blood Gas
monitor, and Whole Blood
Micro-Coagulation
System.
Arterial blood gas (ABG)
using IRMA True Point
cartridges
For more info please see
pg. 98-103 in workbook
Download modifiable
excel sheet

11. Variable Segment Length (VSL) Catheters
Excitation rings (1 and 4)
(1 and 5)
(1 and 6)
(1 and 7)
VSL
Segm. 4
VSL
Segm. 3
VSL
Segm. 2
VSL
Segm. 1

12. VSL Recording Rings to Ventricle Size
Size
(OD)
Shaft
Length
5F
45
inches
(114.3cm)
Ventricle
size
45-75mm
55-90 mm
5F -Pigtail (20, 30, 40, 50 mm) ring spacing
5F-Straight (50, 60, 70, 80 mm) ring spacing
Example of two
5F PV catheters
Pigtail-Aorta
Straight-Apex
Numbers
correspond to
recording rings
VSL ring spacing
is customizable

13. Data Accuracy Comes From Calibration
• PV systems track SV, EF and Contractility.
• Absolute Volume is mathematically calculated value.
• The calculation is based on three calibration values that
the researcher needs to be aware of:
1. Stroke Volume Calibration Factor
2. Blood Resistivity (Rho)
3. Heart Type (Muscle Electrical Property)

14. 1. Stroke Volume Calibration Factor
When a specific catheter is connected to the control ADV unit a default SV value will be populated
based on the size/ring configuration. However, it is recommended that scientists use one of the
following options to determine the most accurate reference as possible…
If no secondary SV reference can be made result to literature or use the catheter default.
Flow Probe PA catheterEchocardiography Cardiac MRI

15. 2. Blood Resistivity-BR (Rho)
Resistivity (or conductivity) is a
property of the blood being measured.
Default values for BR are entered in the
ADV500 control unit that represent healthy
non-modified mammalian blood at 37C. If
your experiments involve changing blood
properties (i.e. hemorrhagic shock models),
make measurements manually to address
both pre and post blood change states.
In large Animals (Dog, Swine, MiniPig,
Sheep and Cow), BR range is 1.4-1.6 Ωm Calibration probe touching meniscus of freshly drawn blood.
Please note the position of the probe. Do not submerge.

16. 3. Heart Type (Muscle Electrical Property)
• The ADV 500 uses the term “Muscle
Properties” to describe the ability of
the myocardium to conduct a
constant AC current signal.
• It is important to acknowledge this
calibration parameter since it will
impact how much tissue contribution
is removed from the measured
admittance signal.
• We offer tool to measure and add as
custom
For more info please
see pg. 32-34
The ADV500 offers 3 default options
for Heart Type

17. Example: 72kg Swine
Animal Phase Range Phase Amplitude Magnitude Range Magnitude Amplitude
Swine large (>65kg) 1-3 degrees 1.5 degree 15-30 mS 4-6 mS
Example of left
ventricle PV data
using 7F PV catheter
with pigtail; electrode
ring spacing:
50,60,70,80mm
Insertion: RCA/Aorta
Active Segment: VSL 3
Note: Channel 1 and 2 (ECG)

18. Suggested Reading…
Large animal models of heart failure: a critical link in
the translation of basic science to clinical practice.
Admittance-based pressure-volume loops versus gold standard cardiac
magnetic resonance imaging in a porcine model of myocardial infarction.
Right Ventricular Energetics and Power in Pulmonary Regurgitation vs.
Stenosis Using Four-Dimensional Phase-Contrast Magnetic Resonance
Invasive surgery reduces infarct size and preserves cardiac function in a
porcine model of myocardial infarction.
Admittance-based pressure-volume loop measurements in a porcine
model of chronic myocardial infarction.

19. Large Animal Left and Right
Ventricular PV Loops
Tim Hacker, PhD
Director,
Cardiovascular Physiology Core
University of Wisconsin-
Madison
Copyright 2015 T. Hacker, Transonic & InsideScientific. All Rights Reserved.

20. A bit of background…
• Developed 22 different cardiovascular animal
models in animals from mice to primates
• Measurement & imaging of structural and physiologic
parameters in all models
• Currently using PV loops:
– to measure LV function in stem cell treated infarcted swine hearts
– to measure RV function a dog model of pulmonary hypertension
• Using the ADV500 system in large animals for 3 years
and small animals for over 5

21. Our Tools & Equipment List
1. 0.035 J guide wires (several)
2. Guide catheters or long sheaths (9Fr)
3. 7 Fr VSL straight tip and pig tail catheters, 9 and 11 Fr sheaths
4. Swan-Ganz Catheter (thermodilution) to measure SV
5. Infusion pump for dobutamine
6. Patient monitor
7. Ventilator (intubate)
8. Percutaneous access kit (ultrasound)
Tip: Get the largest
balloon you can find
for occlusions (24 mm)

22. How we choose the right catheter
Approach: carotid, jugular, femoral, apical stab
Ventricle: right or Left
Heart Size: overall length and internal space
Operator Preference: over the wire vs. pig tail
What works for us:
• LV carotid = 7Fr pig tail VSL (terminal)
• LV femoral = 7Fr straight over the wire (survival)
• RV jugular = 7Fr straight over the wire (survival
or terminal) with long curved sheath.

23. Anesthesia
Pre-anesthesia:
Pigs: Xylazine 2mg/kg and Telazol 4 mg/kg IM
Dogs: Morphine Sulfate 0.5 mg/kg
and Acepromazine 0.5 mg/kg SQ
Extra anesthesia: Propofol 2-40 mg/kg IV
Procedure anesthesia: Isoflurane (2%)
Tip: learn about use of anesthetics and their reported hemodynamic
effects before PV experimentation

24. Catheter Insertion
If Terminal -- Cut down of carotid or jugular
If Survival -- Percutaneous femoral or jugular (ultrasound guidance)
• 9-11 Fr sheaths (dilate up as needed to get the large sheaths in)
• Right Ventricle, we use a 60cm long sheath with an ‘L’ shaped tip to deliver the
catheter to junction of the SVC and the RA
• We cover the catheter with a sleeve during insertion through the sheath’s diaphragm.
• Percutanous access of femoral vein for Swan Ganz and balloon
Tip: An experienced cardiologist is valuable to show you the ropes, but
ultimately once in the vessels it is not overly difficult to place the catheters.

25. Percutaneous Access
Instruments used for
femoral vascular access via
percutaneous Seldinger
technique.
• 18-gauge, 2 3/4-inch
Seldinger needle,
• introducer sheath
(cannula),
• 0.035-inch guide wire
• Heparinized saline

26. Femoral vasculature
access via percutaneous
Seldinger technique.
Needle is inserted into the
arterial lumen to advance
an 0.035-inch guide wire
before the introduction of
a 7F sheath (cannula).
Percutaneous Access
Tip: Color code your
lines (Artery = Red)

27. Catheter insertion through percutaneous sheath
Final sheath placed in vessel
is at least 2F size to allow
smooth introduction and
withdrawal. Percutaneous
methods can reduce
procedure time and improve
animal recovery.
Tip: Ultrasound can be
used to find vessels.

28. Catheter Placement
1. Swan Ganz, use pressures and fluoroscopy to guide
2. PV catheter use contrast to get road map
3. Fluoro to guide into heart -- run wire or sheath to desired location
4. Note number of segments in ventricle
5. Check PV loops and phase/pressure to refine location
6. Run occlusion balloon to above diaphragm but below heart apex
Tip: Patience and a light touch
are a key to proper placement.
Tip: Rotate catheter to get pressure
window away from cords/papillary

29. IVC Occlusion
caudal
Insert deflated Fogarty occlusion
balloon catheter into the IVC
through the percutaneous LFV
access.
The insertion port on the LFV
access has to be at least 2F size
bigger to allow smooth access of
the balloon catheter.
Tip: Place occlusion balloon
just above the diaphragm
and just below apex of heart.

30. Monitoring Physiology
Measurement Dog (10-20 kg) Swine (25-50 kg)
Temperature 99.5 - 102 F / 37.5 - 39.0 °C 100 - 102.5 F / 37.5 - 39.5 °C
Respiration Rate 12 - 18 breaths/min 12 - 20 breaths/min
Heart Rate 75 - 105 beats/min 85 - 115 beats/min
EtCO2 35 - 45 mmHg 35 - 45 mmHg
SpO2 93 - 100 % 93 - 100 %

31. Tip: vital signs monitoring is crucial
for PV repeatability
Tip: Body temp and hydration changes will affect heart
rate and SV
Tip: Check pressure & HR trends during long
procedures to confirm stability
Monitoring Physiology

32. Special Consideration – Maintaining Blood Volume
• loss of 10 % total blood volume is tolerable (for PV)
• loss of 20-25% will lead to shock (Final data not physiological)
• good PV vascular technique will minimize blood loss
• fluid loss due to dry air ventilation, fasting, etc.
Species Blood Volume Blood Loss (10%) Blood Loss (20%)
Dog (15kg) 86 ml/kg ~100ml ~200ml
Swine (30 kg) 65 ml/kg ~200 ml ~400 ml
Tip: Start IV at
beginning of
procedure
(saline, “Ringers”)

33. Load-Dependent LV Baseline Values
Measurement (units) Dog Swine
Heart Rate (bpm) 75 - 105 85 - 115
Systolic Pressure (mmHg) 90 - 110 75 - 100
Diastolic Pressure (mmHg) 3 - 5 3 - 5
Phase (degrees) 2.5 - 5.0 2.5 - 4.0
Magnitude (mS) 9 - 15 8 - 14
Ejection Fraction (%) 60 - 70 45 - 55
Note : These values are typical for control animals with isoflurane

34. PV Loops Are Position Dependent
• Get position close using x-ray
• Use contrast to define spaces if needed,
save a cine loop for later reference
• LV Placement -- Long axis from AO to apex
• Note number of segments in LV by x-ray
• RV Placement -- Outflow track axis (tip at
PA valve)
Tip: Breathing movement can make a big
difference in the quality of the loop.

35. Creating an IVC Occlusion
IVC occlusion
Admittance Catheter
Tip: Use a dobutamine
challenge (20mcg/kg/min)
to further define changes
between treatments
• Suspend respiration
• Inflate balloon quickly
• Monitor loop quality
• Deflate balloon
• Repeat at least 3 times

36. IVC Occulsion:
Pig LV

37. IVC Occulsion: Dog LV

38. IVC Occulsion: Dog RV with PAH

39. Suggested Reading…
Intravenous Followed by X-ray Fused with MRI-Guided
Transendocardial Mesenchymal Stem Cell Injection Improves
Contractility Reserve in a Swine Model of Myocardial Infarction.
View additional publications from Dr. Tim Hacker

40. Thank You!
For additional information on solutions for
large animal PV loops and hemodynamic
monitoring equipment please visit:
http://transonic.com/