Welcome to “Biotelemetry For The Life Sciences”, Session 1:

The Evolution of Wireless Monitoring in The Life Sciences and Review of Industry Standards in Drug-discovery and Safety Pharmacology and Toxicology Guest Speakers:

Brian Brockway

President, VivaQuant, LLC

Robert Hamlin, PhD DVM, DACVIM, DSPS QTest Labs and The

Ohio State University

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.

Implantable Telemetry: Past, Present, and Future

Brian Brockway

President,

VivaQuant, LLC

Copyright InsideScientific & VivaQuant, LLC. All Rights Reserved.

Why Use Implantable Telemetry?

1. Reduce impact of stress as a confounding factor1

2. Percutaneous infections eliminated1

3. Improve safety of lab personnel1

4. Enables longitudinal studies that are otherwise1 impossible

5. Improves animal welfare2

6. Fewer animals3

1. Brian Brockway and Craig Hassler 1993 2. Klaas Kramer 2000 3. Lew Kinter 1994

0

100

200

300

400

500

600

1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010

Discovery

Home-made

Commercialization

Validation

Mainstream

Publication Growth Every 5 Years

Adoption Phases of Implantable Telemetry

… increase in publications follows availability of commercial product

(EST)

*

Significant Events Impacting Development

We’ve Come A Long Way!

Enabling Innovation – Packaging 1. Impervious to

moisture

2. Radio Frequency transparent

3. Cost effective, reliable and scalable

From: Brockway and Hassler 1993

Enabling Innovation – Sensors 1. Sensor Stability

-- Stanford & NOVASensor

2. Long-term pressure sensor patency

3. Size -- small sensors for small spaces

From: Brockway and Hassler 1993

Key Contributors to Mainstream Commercialization

1. Stuart Mackay, UCSF

2. Wen Ko, Case Western

3. Thomas Fryer, NASA

4. James Meindl, Stanford

5. Dave Osgood, MiniMitter

6. Bill Barrows, NASA

Early Data Supporting Implantable Telemetry • Lappe et. al instrument six rats and measure MAP before and after placing rats in tail-cuff restraints

• Early BP implant seeking validation proves not only viable, but uncovers SHR mystery…

• Strain of rats thought to be hypertensive proven to be hypertensive only when subjected to stress

From: Brockway and Hassler 1993

• Combined Pressure and Blood Flow

• Glucose

• Chemical Entities

• O2/CO2 Saturation

• Advanced ECG

Continuing Challenges…

• More reliable devices

– Electrical interference

– Failure due to moisture penetration

• Small devices with longer sending range

– Lower infection risk

– Easier/faster surgical procedure

• Improved processing of signals and mining of data

What do we know? What next?...

• Its come a long way since the first implant in 1960

• Now commonly used for EEG, ECG, pressure, temperature

• New suppliers will bring more options & innovation

• However, there’s still a long way to go to reach full potential

References

• Proceedings of the interdisciplinary conference on the use of telemetry in animal behavior and physiology in relation to ecological problems. Ed. Slater Pergamon Press 1963.

• R. Stuart Mackay, Biomedical Telemetry, 2nd edition. John Wiley 1968

• Thomas Fryer, Implantable Biotelemetry systems. NASA. 1970

• Biotelemetry III, ed. By T. Fryer, H. Miller, and H. Sandler 1976

• Klaas Kramer, Applications and Evaluation of Radio-telemetry in Small Laboratory Animals. PhD Thesis Vrije University 1990

• Brian Brockway and Craig Hassler, Application of radiotelemetry to cardiovascular measurements in pharmacology and toxicology. In New Technologies and concepts for reducing drug toxicity. Pp 109-132. CRC Press 1993.

Predicting the Liability and Safety of Test Articles By Implantable Telemetry

Robert Hamlin, PhD

DVM, DACVIM, DSPS

QTest Labs and The Ohio State University

Copyright InsideScientific & QTest Labs. All Rights Reserved.

Presumptive Knowledge…

1. What are the parameters to be investigated?

2. What difference in them translates to benefit or risk?

3. How can they be measured with the precision

required and safety assured, without distorting them?

Parameters, which if affected, are known to translate to morbidity or mortality…

1. Chronotrope

2. Inotrope

3. Lusitrope

4. Energetic balance

5. Opposition to Ejection: impedance and resistance

6. Venous Capacity

7. Baroreceptor function: high and low pressure

8. Cardiac output and fractionation

9. Dromotrope

10. Irritability

SA Node

How Can They Be Measured?

1. ECG (PQ, QRS, QT)

2. Pressure (AoP, LVP, dP/dt)

3. Blood Flow (CO, SV, Vp)

4. PV Loops (inotrope, lusitropy, SV, Ea, ESPVR, PRSW, VO2)

5. Imaging (Echo, MRI, CT)

6. ???

Aortic Pressure

Left Ventricular Pressure

Left Atrial Pressure

Left Ventricular Wall Thickness

Left Ventricular Volume

Left Ventricular Wall Tension

Coronary Blood Flow

1 2 3 4 5 6 7 8

ventricular diastolic suction

EDV

ESV

EDWT

Peak=AL

ESWT

ventricular diastolic suction

ventricular systolic suction

After Wiggers

Left Ventricular Pressure

Coronary Blood Flow

Left Ventricular Pressure

Left Ventricular Volume

Left Ventricular Wall Thickness

Left Ventricular Wall Tension

3 2 1 6 5 4 3

curve

s

EDV EDV ESV

mitral

valve

aortic

valve

A-V

ring is

“pulled”

down

ESV

Phonocardiogram S4 S1 S2 S3

Electrocardiogram

P Ta QRS

T

QT

J-Point

ST-T

SV = stroke volume (EDV-ESV) time = time between heart beats=1/heart rate w = wave r = reflected

i = initial t = total f = function of svr = systemic vascular resistance

f(SV,εAo)

f(svr, εAo, time)

atrial “kick” Isovolumetric contraction

mean pressure=DP+(PS-DP)/3

Peak Systolic Pressure (PS)

“Diastolic” Pressure (DP)

Late systolic augmentation

Pu

lse p

ressu

re

• Pulse Pressure is a predictor of morbidity and mortality

• Peak Systolic Pressure is a predictor of stroke

• Diastolic Pressure is a predictor of heart failure

-3000

-1000

1000

3000

5000

7000

9000

11000

13000

0

20

40

60

80

100

120

140

ECG PAo

dLVP/dt LVP

Pulse

Systolic LV Mean Diastolic

EDV = (EDP - PPL) / LV

ESV

1

2

1

2

V

ADH/VP

AII

ANF

NO

ET1

Adenosine

Rx’s

SAP

CO

Ao,svr arterial smooth muscle

SV

HR SAN

Ao, svr

vmax

BV = (waterin - urineout)

Cv

“a kick”

●

●

-

lung Affectors

After Rushmer

SV

HR SAN

EDV = (EDP - PPL) / LV

ESV

1

2

1

2

V

ADH/VP

AII

ANF

NO

ET1

Adenosine

Rx’s

SAP

CO

Ao,svr arterial smooth muscle

Ao, svr

vmax

BV = (waterin - urineout)

Cv

“a kick”

●

●

-

lung Affectors

After Rushmer

EDV = (EDP - PPL) / LV

ESV

1

2

1

2

V

ADH/VP

AII

ANF

NO

ET1

Adenosine

Rx’s

SAP

CO

Ao,svr arterial smooth muscle

SV

HR SAN

Ao, svr

vmax

BV = (waterin - urineout)

Cv

“a kick”

●

●

-

lung Affectors

After Rushmer

So, we know what to measure, and how to measure it precisely and safely. Unfortunately nobody will tell us — for anything but QTc — what difference makes a difference! Therefore, how do we know with what precision a measurement should be made, or even if it should be made?

Thank You!

SESSION 2: Freedom: The Promise of Telemetry Revisited - “The Freedom To Move Anywhere At Anytime And Still Collect Quality Data”

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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.