Improving Rodent Cardiovascular Research Outcomes with Integrated Surgical Monitoring

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Improving Rodent Cardiovascular Research Outcomes with Integrated Surgical Monitoring

1. Attaining ‘Normal’ Cardiac Function for PV Analysis (Dr. James Clark)

• Parameters to Monitor & How

• The importance of Fluid-Support

• Effects of Anaesthesia and Cooling

• How Temperature can Effect Infarct Size

2. Demonstration: Integrated Monitoring with the MouseMonitor™ S (Graham Sattler)

• System Operation, File Recording and Playback

• Screenshots for Collaboration

• System Integration Components and Configuration

• Presets and Flexibility

Sponsored by:

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Attaining ‘Normal’ Cardiac Function For PV Analysis

Dr. James E. Clark Senior Lecturer in Applied Physiology

British Heart Foundation Centre of Excellence, Cardiovascular Division,

Faculty of Life Sciences and Medicine, King’s College London

0 10 20 30 40 50

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Volume (µl)

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mH

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Complicated Surgery occupies the surgeon

Myocardial infarction Abdominal aortic

banding PV Loop acquisition

Myocardial infarction Abdominal aortic

banding PV Loop acquisition

Complicated Surgery occupies the surgeon

EFFECTIVE MONITORING IS KEY!

Parameters to Monitor

• Temperature

• ECG

• Respiration

• Oxygen Saturation

• Blood Pressure

• Respiratory Gasses (ETO2 and ETCO2)

• Blood Flow (peripheral)

ESSENTIA

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• Operating table and microscope

• Homeothermic platform

• Physiological Monitoring

• PV Catheter and data acquisition system

• Suitable anaesthetic

• Ventilation

• Surgical instruments

Essentials for Murine PV Surgery

Effective Surgical Monitoring

Data Acquisition Temperature Control Electrocardiogram

Isolated Carotid Artery PV Catheter Insertion

Blood-free Surgical Field & Fluid Support

• Maintain ‘normal blood volume’ during any measurement

– Proper hydration

– Fluid support

• Fluid support can be administered I.V. or I.P.

– Saline

– 1-3% BSA

– Hydroxyethyl starch

• Care should be taken not to over-hydrate

From Zuurbier et al, AJP (282), 2002

The Importance of Fluid Support

Haes (0.2ml/10g/hr)

Saline (0.5ml/10g/hr)

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ssure

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Abdominal IVC occlusion

Fluid Support Maintains Blood Pressure

Resulting PV Loop measures

Procedure Room at BHF Centre

Purpose-built Operating Table

Integrated heat mat and rectal (T-type) rectal thermister

Yang X et al. Am J Physiol Heart Circ Physiol 1999;277:H1967-H1974

K e t /M e d 2 % IS O 2 % IS O

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(%) &

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HR E F % S P (m m H g )

In tu b a te d

*

*

*

**

Clark et al. (unpublished data)

Anaesthetics and Cardiac Function

Picard et al, F1000Research (3), 2014

Effect of the Depth of Anaesthesia

There are considerable differences between INDUCTION and MAINTENANCE-levels of anaesthesia on function.

Even small changes in temperature can effect function

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mm

hg)

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Baseline Cooling Re-warmed

Clark et al. (unpublished data)

Affect of Cooling on Developed Pressure

Baseline Heater Turned Off (7.5 minutes) Re-warmed (200 ul 42°C saline I.P.)

Temperature Monitoring DURING Procedures P

ress

ure

(m

mh

g)

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Unless homeostasis is maintained data will ‘drift’

Clark et al. (unpublished data)

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Core Temperature (°C)

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mm

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Core Temperature (°C)

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oke

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l)

The Importance of Temperature Monitoring

C57bl/6j mice subjected to cooling/re-warming protocol Clark et al. (unpublished data)

(N=5) (N=5)

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100 37˚C 32˚C 24˚C 20˚C

RVU

LV

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mm

Hg)

Clark et al. (unpublished data)

Core Temperature

The Importance of Temperature Monitoring

Apical PV Access 0 200 400 600 800

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ture

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Thoracotomy

39-40°C saline-soaked gauze to avoid evaporative heat loss

Clark et al. (unpublished data)

Maintenance of temperature throughout protocol

Clark & Marber Exp.Physiol. (2013)

Murine Myocardial Ischaemia-Reperfusion

Suture snare system

Clark et al. Journal of Pharmacological and Toxicological Methods, Vol. 59, No. 2, 03.2009, p. 94 - 99.

Murine Myocardial Ischaemia-Reperfusion

Hanging weight system

Murine Myocardial Ischaemia-Reperfusion

Balloon in place

Balloon inflated

Clark & Marber Exp.Physiol. (2013)

Eckle et al. Am J Physiol Heart Circ Physiol 291: H2533–H2540, 2006

Infarct size is dependent on temperature

Sutherland et al. Clin and Exp. Pharmacol. and Physiol. (2003) 30, 867–878

Tissier R et al. Cardiovasc Res. (2012) 94(2):217-25

Infarct size is dependent on temperature

Cardiac temperature (°C) during a 30 min CAO in rabbits Cardiac temperature (°C) during a 60 min CAO in sheep

Surgically-mediated Changes in ECG

• ECG -- limb lead and augmented leads

• HR

• Breathing rate

• Core temperature

• Blood oxygenation (with SpO2 module)

• Data recording

– On tablet and/or

– Analogue output

MouseMonitor™ S

Preliminary Results

Stable monitoring platform

No electrical interference with PV acquisition

Reliable ECG and data recording using built-in pads or needle electrodes

Temperature control 0 10 20 30 40 50

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Volume (µl)

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A Demonstration: Integrated Surgical Monitoring with the MouseMonitor™ S

Graham Sattler

Product Development Manager,

Indus Instruments

1. PV Loop Theory

2. PV Loop Applications

3. PV Loop System Setup Tips & Best Practices

4. PV Loop Surgical Preparation Overview

5. PV Loop Signal Optimization Tips & Best Practices

6. PV Loop Procedure Documentation

PV Loop Webinar Series so far…

1. PV Loop Theory

2. PV Loop Applications

3. PV Loop System Setup Tips & Best Practices

4. PV Loop Surgical Preparation Overview

5. PV Loop Signal Optimization Tips & Best Practices

6. PV Loop Procedure Documentation

7. Surgical Procedure Outcome Evaluation

PV Loop Webinar Series so far…

Capability

• Responsive Heating

• Surgical Monitoring

– Heart Rate

– Core Temperature

– ECG (6-Lead)

– Mouse & Rat Electrodes

• Easy Documentation

View the following demonstration videos online…

1. System Operation

2. Standalone File Recording & Playback

3. Capturing Screenshots for Collaboration

Example Screenshot #1

Example Screenshot #2

Low Latency Sync BNC Cable

External Grounding Cable

System Integration Components

View the following demonstration videos online…

1. System Integration

Configuration

2. Presets & Flexibility

Thank You! For additional information on Surgical Monitoring best-practices and solutions for preclinical research please visit:

http://www.indusinstruments.com

NEXT WEBINAR: Dr. Navin Kapur, Assistant Professor and Assistant Director of the MCRI at Tufts, will discuss how PV loop data can translate from mouse to man and provide a confident approach to evaluating drug studies, device validation and treatments outcomes.

WORKSHOP: