In this webinar sponsored by ADInstruments, Tom Smith, Professor of Orthopaedic Surgery at Wake Forest School of Medicine, and expert in microsurgery and vascular pressure measurement techniques discusses the fundamental properties of pressure measurements in the vascular system, including the history and physics behind solid-state manometry. In addition, he explains the importance and impact of high fidelity solid-state catheters as it relates to accuracy, consistency and research outcomes.

1. Invasive Blood Pressure: fundamentals and
best-practices for preclinical research
Tweet #LifeScienceWebinar #ISCxADI
Tom Smith presents the fundamentals of invasive blood pressure
measurements for preclinical research, including technical
considerations, experimental design, and best-practices that lead to
accurate and consistent results.

2. Invasive Blood Pressure: fundamentals and
best-practices for preclinical research
Thomas L. Smith, PhD
Professor, Orthopaedic Surgery
Physiology & Pharmacology,
Institute for Regenerative Medicine,
Biomedical Engineering,
Wake Forest School of Medicine
Tweet #LifeScienceWebinar #ISCxADI

3. 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

4. To access webinar content, Q&A reports, FAQ document, and
information on lab workshops, we invite you to join our community at
www.insidescientific.com/register

5. Goals of blood pressure measurement1.
Methods2. – Indirect v. Direct
Advantages/Disadvantages3.
Applications and Choices4.
Today’s Lecture…

6. Blood Pressure Measurement
Systemic Arterial Pressure
Reflects the activity of the heart as•
well as the vascular tree
Can be assessed directly or•
indirectly
Plethysmography•
Directly•
manometric1.
Solid2. -state
combination3.

7. Indirect Measures
Plethysmography
1. Tail cuff/sensor
2. Restraint
3. Conscious
Campden Instruments Ltd.
Blood Pressure Measurement

8. Plethysmography
Blood Pressure Measurement
Advantages of process
✓ repeated measurements under similar conditions
✓ non-invasive
✓ trends over time
Disadvantages of process
tail is thermoregulatory×
relationship between tail artery pressure and aortic pressure×
observational error (psychogenic)×
Training×
one size× does not fit all rodents

9. Invasive Measurements of Arterial Pressure
Goals•
Challenges•
Fidelity•
Methods•
Blood Pressure Measurement

10. Goals
Provide an accurate•
measurement of
the blood pressure
wave form over
time
Invasive Measurements of Arterial Pressure

11. Invasive Measurements of Arterial Pressure
Deranged Physiology
Commons wikimedia.org

12. Invasive Measurements of Arterial Pressure
Challenges
Invasive• – vessel size (animal)
recording requirements•
anesthetized v. conscious1.
restrained v. free ranging2.
acute/subacute v. chronic3.

13. Invasive Measurements of Arterial Pressure
Challenges
Invasive – vessel size (animal)
• mouse carotid artery diameter = 500 microns
• femoral artery = 400 microns
• PE-10
– outside diameter = 610 microns
– inside diameter = 280 microns
• length of catheter
http://www.informatics.jax.org/cookbook/imageindex.shtml
The Anatomy of the Laboratory Mouse. Margaret J. Cook

14. Invasive Measurements of Arterial Pressure
Challenges
Invasive – vessel size (animal)
mouse carotid artery diameter =• 500 microns
femoral artery =• 400 microns
PE• -10
outside diameter =– 610 microns
inside diameter =– 280 microns
length of catheter•
http://www.informatics.jax.org/cookbook/imageindex.shtml
The Anatomy of the Laboratory Mouse. Margaret J. Cook

15. Invasive Measurements of Arterial Pressure
Methods
1. Catheter/Manometric
2. Solid State
3. Telemetery
(manometric v. solid state)

16. Catheter/Manometric
Techniques
• components
• requirements
• limitations
Invasive Measurements of Arterial Pressure

17. Required components to
assemble a fluid filled catheter
connected to a pressure
transducer…
✓ semi-rigid catheter inside vessel
✓ fluid filled system without air
bubbles
✓ pressure transducer
✓ recording device
Catheter/Manometric Techniques

18. Limitations:
1. Catheter Size and
Composition
2. Frequency response
as part of Fidelity
Catheter/Manometric Techniques
Ability of the device to
accurately measure the
pressure waveform as the
fundamental (heart rate)
increases

19. Heart rate of 60
[Fundamental of 1Hz]
10-15X the fundamental
should yield an accurate
reflection of the waveform
components.
 10-15Hz frequency response
Limitations of Fidelity – Frequency Response
Rat Heart rate of 300
[Fundamental of 5Hz]
 50-75Hz frequency response
Mouse Heart rate of 600
[Fundamental of 10Hz]
 100-150Hz frequency response

20. Limitations of Fidelity – Frequency Response
5Hz 10Hz 25Hz
Fluid Filled
Solid State

21. Phase Shift
measurement of the pulsatile
event can be shifted in time
compared to the actual event
• events of the cardiac cycle
Limitations of Fidelity – Phase Shift
Two sinusoidal waves offset from each other by a phase shift theta. Source: Wikimedia Commons
https://commons.wikimedia.org/wiki/File:Phase_shift.svg

22. Limitations
catheter size and composition•
frequency response as part of fidelity•
fidelity impacted by:•
length1.
diameter2.
transducer/recorder3.
Catheter/Manometric Techniques
✓ Length:
shorter the better
✓ Diameter:
larger the better
✓ Transducer:
high fidelity
not affected by temperature or light

23. Limitations
• for subacute and repeated chronic recordings of animal in
its own cage, requires tethering
• acclimation following tethering may take up to 2 hours
• for continuous long term monitoring, requires a hydraulic
swivel and continuous perfusion
Catheter/Manometric Techniques

24. Limitations
Transducer/Recorder:
Based upon Wheatstone
bridge circuit…
Catheter/Manometric Techniques

25. Solid State Transducers
Technology
Components:
Silicon chip with•
resistive elements
Temperature•
compensation
Ambient air reference•
Millar Mikro-Cath® pressure sensor cut-away view

26. Solid State Transducers
Technology
Because the resistive
elements are etched on a
silicon chip, the frequency
response is in the kilohertz
range…
This results in higher fidelity
Millar Mikro-Cath® pressure sensor cut-away view

27. Solid State Transducers
Requirements:
ability to be used•
intravascularly
Limitations:
• Size  available from 1-7
French (3 French/mm)

28. Solid State Transducers
Technology
Limitation:
wire connection from the test
subject to balancing circuit and
amplifier  Acute recordings
…This brings us to Telemetry

29. Implantable BP
Sensor Types:
Telemetry Limited discussion… separate webinars on this
Fluid filled (gel cap) with1.
transducer and transmitter
Solid state with transmitter2.

30. Things to consider…
Telemetry Limited discussion… separate webinars on this
Fidelity• is good
• metabolic price associated
with carrying
weight of implanted telemetry
effectively everything that was•
previously covered still applies!
Cost•
Animal is free• -ranging

31. 1. What do you need to measure for
your experiment
2. What to use
3. When to use it
Invasive Blood Pressure Measurement

32. 1. What to use
- What do you need to measure for your experiment
2. When to use it
- Start with catheter/manometric
- Evolve to solid-state
Invasive Blood Pressure Measurement

33. Model Number Material Subject Length Tip French # Sensors Tip Pressure Connector
MPR-500 Polyurethane Pig, Sheep, Other Large Animal 70 cm 5F 1 Straight Low Profile
SPR-1000 Polyimide Mouse 20 cm 1F 1 Straight Low Profile
SPR-249A Nylon Rabbit, Other Small Animal 60 cm 3F 1 Straight Low Profile
SPR-320 Polyurethane Rat 140 cm 2F 1 Straight Low Profile
SPR-330A Nylon Rabbit, Other Small Animal 130 cm 3F 1 Straight Low Profile
SPR-350
Polyurethane -
Woven Dacron
Pig, Sheep, Other Large Animal 120 cm 5F 1 Curved Low Profile
SPR-350S
Polyurethane -
Woven Dacron
Pig, Sheep, Other Large Animal 120 cm 5F 1 Straight Low Profile
SPR-407 Nylon Rat 140 cm 2F 1 Straight Low Profile
SPR-513 Nylon Rat 140 cm 2F 1 Curved Low Profile
SPR-524 Nylon Rabbit, Other Small Animal 100 cm 3.5F 1 Straight Low Profile
SPR-595 Nylon Rabbit, Other Small Animal 60 cm 3F 1 Curved Low Profile
SPR-671 Nylon Mouse 15 cm 1.4F 1 Straight Low Profile
SPR-882 Nylon Rat 140 cm 3.5F 1 Straight Low Profile

34. Summary
Invasive v. non-invasive
Solid state v. manometric
Drug screening• - non-invasive, can screen large numbers
Drug characterization•
What• are the requirements to answer the scientific question?
e.g.• - cardiac drug v. blood pressure drug

35. Thomas L. Smith, PhD
Professor, Orthopaedic Surgery
Physiology & Pharmacology,
Institute for Regenerative Medicine,
Biomedical Engineering,
Wake Forest School of Medicine
Thank You
Tweet #LifeScienceWebinar #ISCxADI
For additional information on the products and applications
presented during this webinar please visit www.adinstruments.com
tsmith@wakehealth.edu