Non-Invasive Blood Pressure Waveform Monitoring in Mice

By

Andrew McClellan

Laura Miller

The Need for Blood Pressure Measurements• Baseline levels

• Effects of pharmacological drug administration

• Exercise or Food Studies

• Behavioral Response Studies

• Effects of genetic alterations

Need for Continuous Waveform Measurements vs. Single Measurements

• Single measurements only give max and min (systolic / diastolic)

• Continuous waveforms needed for frequency analysis– autonomic nervous system responses– blood pressure variability– baroreceptor function

• Examining blood pressure changes over time, like during behavioral tests

What Currently Exists

Mouse Human

Beat-to-beat Tail Cuff Arm Cuff

Continuous • Arterial Line• Implanted Catheter/

Transmitter

• Finger Cuff (Finapres)

Beat to beat BP measurements: Korotkoff Method

Mouse: inflatable tail cuff

www.TSE-systems.com

Human: inflatable arm cuff

http://www.geocities.com/lorijean_2002/academia/sphygmomanometer.jpg

What Currently Exists

Mouse Human

Beat-to-beat Tail Cuff Arm Cuff

Continuous • Arterial Line•Implanted Catheter/

Transmitter

Finger Cuff (Finapres)

What Currently Exists for Mice: Implantable transmitters•Catheter pressure transducers (Data Sciences International)

•Continuous waveform

•Require surgical implantation into carotid artery

•Mice need at least 3 weeks post-surgery recovery time for stabilization of BP/HR

•Transmitters are expensive and require corresponding receiver hardware and analysis software ($600/transmitter + $100/each battery exchange + $1000s in receivers and software)

Mills P, et al. The design and performance of an implantable device for monitoring blood pressure, heart rate, and movement activity from conscious freely moving laboratory mice. 2nd International Conference on Methods and Techniques in Behavioral Research, 1998.

Mills PA, et al A new method for measurement of blood pressure, heart rate, and activity in the mouse by radiotelemetry. J Appl Physiol. 2000 May;88(5):1537-44

What Currently Exists

Mouse Human

Beat-to-beat Tail Cuff Arm Cuff

Continuous • Arterial Line• Implanted Catheter/

Transmitter

• Finger Cuff (Finapres)

What Currently Exists: finger cuff measurements

Finapres

• Non-invasive

• Continuous waveform

• Finger cuff

Bogert LW, et al. Non-invasive pulsatile arterial pressure and stroke volume changes from the human finger. Exp. Physiol 90.4 pp 437-446. 2005

What Currently Exists

Mouse Human

Beat-to-beat Tail Cuff Arm Cuff

Continuous • Arterial Line• Implanted Catheter/

Transmitter

• Finger Cuff (Finapres)

Problem: There are no blood pressure devices that non-invasively measure a continuous waveform in mice

Our project goal

Non-invasive, continuous blood pressure waveform measurement in mice

Challenges From Adapting a Human Device

• Size – mice are much smaller

• Physiological Parameters –

HR = 500-700bpm, BP = 100-250mmHg

• Cuff – must work for above pressures

• System response – high frequency

Peňáz Method

• Dynamic pulsatile unloading of the arterial walls

• Volume clamp method

• Pressure needed to maintain mean arterial volume equals the blood pressure waveform

Plethysmographic Signal

• Obtained through measuring optical impedance through blood vessel in tail

• Optical impedance corresponds to volume of blood in artery

How it Works

• Blood volume α blood pressure

• Blood volume α optical impedance (plethysmographic signal)

• Use optical impedance to determine necessary pressure to maintain mean arterial volume

Transduction

Blood Volume = Blood Pressure

P-signal (voltage)

(photosensor)

Pressure Wave

invert & offset

(speaker)

(tail cuff)

Tail Cuff with Photosensor

www.TSE-systems.com

Peňáz Method1. Obtain plethysmographic signal2. Ramp up cuff-pressure until Vp-p of plethymographic signal is

max (offset)3. Invert plethysmographic signal4. Convert electrical signal to a pressure waveform in the tail cuff5. Increase gain until p-signal fluctuations in plethysmographic

signal are minimal

max

ramp-up

increase gain

ramp-up

Peňáz Method

max

ramp-up

increase gain

ramp-up

Circuit

buffer gain offset audio amp

Schematic

tail cuff

Harvard plethysmogram / pressure monitor

computer

pump

speaker

amplify offset

plethysmographic signal

pressure signal

analog circuit

Lab Setup

Economic AnalysisDevice:• Tail Cuff with Photosensor $400• Circuit components $10• Speaker $5• Power Source $100• Air pump $50• Pressure Sensor $100

$665Acquisition software/hardware• Windaq $2000

Plan of Attack• Use existing tail cuff• Obtain a plethysmographic signal• Build an analog circuit to amplify and

offset the signal• Use speaker to transduce voltage to

pressure• Obtain blood pressure waveform• Check waveform against catheter

transducer