Isolated Heart Perfusion System for Small Rodents

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Anna Gallagher
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$Refractory Period Myocyte$ Engineering Phenotyping of

1 Isolated Heart Perfusion System for Small Rodents IH-SR is the Ultimate Choice for Ex-vivo Cardiovascular Research in Mouse, Rat and Guinea Pig Models! Cardiovascular Screening Contractility Studies Ischemia and Reperfusion Cardiac Mapping Refractory Period Myocyte Harvesting & Isolation Tissue Engineering Phenotyping of Transgenics Electrophysiology (ECG, MAP) Safety Pharmacology Hemodynamics Cardioplegia

Isolated Heart Perfusion System for Small Rodents Hugo Sachs Elektronik Harvard Apparatus has always provided top-notch, fully integrated physiology research systems.

For nearly two decades the Hugo Sachs Elektronik IH-series of Isolated Heart Systems has been the gold standard for cardiac physiology measurements in both Langendorff and Working Heart perfusion

What makes the IH-SR so Revolutionary? What makes the IH-SR unique is the revolutionary Perspex construction which simply cannot be matched.

2 Isolated Heart Perfusion System for Small Rodents Hugo Sachs Elektronik Harvard Apparatus has always provided top-notch, fully integrated physiology research systems. Continuing our tradition of innovation and high performance we are happy to unveil the next generation Isolated Heart Perfusion System for Small Rodent models, the new IH-SR. For nearly two decades the Hugo Sachs Elektronik IH-series of Isolated Heart Systems has been the gold standard for cardiac physiology measurements in both Langendorff and Working Heart perfusion modes. Today, the IH-SR continues to lead the way with an expanded range of measurement capabilities and ease of use which breaks new ground in ex-vivo cardiac research. What makes the IH-SR so Revolutionary? What makes the IH-SR unique is the revolutionary Perspex construction which simply cannot be matched. The use of Perspex instead of traditional glass allows our engineers to mill the perfusion pathway directly into the solid Perspex blocks. The result is what we call a Solid State Physiological Perfusion Circuit (S 2 P 2 C). This patented perfusion technology ensures a precisely repeatable non-turbulent perfusion pathway for the highest fidelity pressure and flow measurement. This combined with the naturally excellent thermal properties of Perspex, creates a system that allows control, maintenance and monitoring of circulatory parameters in a way that is more physiologically relevant than any conventional perfusion system. 2 physiology@harvardapparatus.com

IH-SR Features & Benefits The Langendorff System The IH-SR always starts as a Langendorff system. This means a configuration solely for retrograde perfusion down the aorta (toward the heart).

Perfusate drains as effluate from the coronary circulation via the coronary sinus and tends to drip from the apex making it easily available for collection.

Perfusions of several hours are typical, allowing a wealth of data to be collected from individual specimens.

3 IH-SR Features & Benefits The Langendorff System The IH-SR always starts as a Langendorff system. This means a configuration solely for retrograde perfusion down the aorta (toward the heart). In this mode, the aortic valve prevents the perfusate from entering the left ventricle, but the coronary arteries are perfused via the coronary ostia which are located just outside the valve. Perfusate drains as effluate from the coronary circulation via the coronary sinus and tends to drip from the apex making it easily available for collection. The IH-SR configured in this way provides an excellent platform for physiological monitoring using the robust Langendorff assay. Perfusions of several hours are typical, allowing a wealth of data to be collected from individual specimens. The Working Heart System The modular nature of the IH-SR allows for initial integration or later upgrade with the Working Heart perfusion pathway. This enables orthograde perfusion: entering the left atrium, flowing through the left ventricle and exiting the aorta. In this way, a more physiological assay of ventricular contractility is possible as the left ventricle is now fully-ejecting and performing pressure-volume and acceleration work. In order to fully exploit this advantage, the IH-SR includes a specialized pathway which easily allows introduction of a Pressure or Pressure-Volume catheter directly into the left ventricle via the aorta. In either configuration, the IH-SR can be outfitted as a complete Cardiac Physiology Workstation with a range of measurement devices, signal conditioning equipment and acquisition & analysis software to provide a superior solution for virtually any study. To get started, select the basic system then add specific options to suit the particular needs of your study. If any questions arise, our expert technical team of scientists and engineers is always ready to assist with system configuration, application support or custom design requests. Langendorff and Working Heart illustrations used with permission courtesy of SANOFI-AVENTIS, Germany. physiology@harvardapparatus.com 3

Langendorff serves as the starting point

Control PLUGSYS Modular Amplifier System

Electrodes Opens & Swings Completely Out

and Probes Perfusate Supply & Peripheral

4 IH-SR Langendorff: The Basis for Any Heart Perfusion Study The IH-SR Langendorff serves as the starting point for all isolated heart experiments. Advanced engineering provides ease of use and exceptional stability of measurements while maintaining the flexibility to upgrade to more advanced capabilities. Aortic Block Core of the System Very Low Flow Resistance Small Dead Space Volume Integrated Bubble Trap and Shut-Off Stopcock Highly Stable Attachment Point for the Heart, Probes and Electrodes Solid State Physiological Perfusion Circuit for Stable Pressure & Flow Control PLUGSYS Modular Amplifier System Low Noise, Analog Fidelity and Control Huge Range of Measurement Capabilities Grows to Fit Your Application Compact, Space-Saving Arrangement Can Output Signals to Virtually Any Data Acquisition System Basic Measured Parameters Perfusion Pressure Coronary Flow Isovolumetric LVP Heart Chamber Closes Fully for Superior Temperature Control Spacious Enough for a Range of Physiological Measurement Probes and Electrodes Opens & Swings Completely Out of the Way for Easy Adjustment of Heart and Probes Perfusate Supply & Peripheral Equipment Unique Double-Walled Glass Reservoir with Aeration Pathway Roller Pump with Feedback Control Thermocirculator Electrical Stimulator for Pacing Benefits Compact Design, Optimized for: Mouse, Hamster, Rat, Guinea Pig Constant Pressure or Constant Flow in One Unit Modular Design to Integrate More Applications in the Future Unique Aortic Block and Heart Chamber Allows Unsurpassed Physiological Simulation Small Flow Resistance and Low Dead Space Volume for Highly Reproducible and Accurate Results Low Volume Drug Injection Pathway is Ideal for Compound Screening A Complete, Flexible System for a Range of Applications 4 physiology@harvardapparatus.com physiology@harvardapparatus.com 5

IH-SR System Extensions: Upgrades for Maximum

Working Heart Completely integrated Left

Membrane Mimicks Resistance of Peripheral

Ventricular Catheter Allows High- Fidelity

$Measurement Cardiac Rhythm Refractory Period$ Electrical Stimulator for Pacing Multi-lead

Epicardial Monophasic Action Potentials Note:

Output Measurement Intraventricular Pressure

Pulsatile Flow Measurement Phasic Coronary

Application Continuous Real- Time Monitoring

Action Potential Epicardial Monophasic Action

5 IH-SR System Extensions: Upgrades for Maximum Capability The IH-SR is engineered for the most demanding applications. As a result, the basic system can easily be upgraded to add capability modules for virtually any Ex-Vivo cardiovascular assay. For detailed descriptions of system extensions and options, see pages Working Heart Completely integrated Left Atrial Perfusion Block Patented Afterload Membrane Mimicks Resistance of Peripheral Vasculature Integrated Pathway for Ventricular Catheter Allows High- Fidelity Pressure and Pressure- Volume Measurements Pulmonary Artery Cannulation System for Collection of Coronary Effluate Integrated Flow Probes for Real- Time Phasic Flow Measurement Cardiac Rhythm Refractory Period Electrical Stimulator for Pacing Multi-lead ECG Analysis and ECG Mapping Endo and Epicardial Monophasic Action Potentials Note: Langendorff illustration used with permission courtesy of SANOFI-AVENTIS, Germany. Hemodynamics & Contractility Direct Cardiac Output Measurement Intraventricular Pressure & Pressure-Volume Loop Meaurements Real-Time Pulsatile Flow Measurement Phasic Coronary Flow Measurement Pharmacology/ Physiology Metabolic Studies Drug Application with Precision Control Automated Dose Response Protocol Set Physiological Threshold to Control Drug Infusion Flow Controlled Drug Application Continuous Real- Time Monitoring of po2, ph and pco2 Electrophysiology/ Safety Pharmacology Single or Multi-lead ECG Analysis ECG Mapping Endocardial Monophasic Action Potential Epicardial Monophasic Action Potentials Cardioplegia Cardioplegia Solution Supply Cell Isolation Supply for Enzyme-Containing Perfusate 6 physiology@harvardapparatus.com physiology@harvardapparatus.com 7

6 IH-SR Basic: The Starting Point for your Heart Perfusion IH-SR Basic System Measured Signals and Calculated Parameters on an IH-SR Basic System: The Following Signals are Recorded as Raw Data: Isovolumetric Left Ventricular Pressure (Balloon Method) dlvp/dt Perfusion Pressure Perfusion Flow The Following Parameters are Calculated from the Raw Data: Systolic and Diastolic LVP Heart Rate dp/dt Max, dp/dt Min, Contractility Index Mean Perfusion Pressure Mean Perfusion Flow Coronary Resistance Features and Benefits Compact Design, Optimized Individually for: Mouse, Rat or Guinea Pig Constant Pressure or Constant Flow Perfusion in one unit, easily switch between the two modes Compact, doesn t require wall-installed high water columns, suitable for hearts from hypertensive rats (perfusion pressures up to 300 mmhg are possible) Unique integrated small volume Aortic Block with built-in Bubble Trap and Windkessel Large Fully-Heated Heart Chamber Natural physiological environment for the isolated heart Hearts are kept alive for hours in a very stable physiologic environment Easy-to-use with smooth open and closed operation All electrodes, catheters and probes are fully enclosed for easy access and to maintain physiological conditions while performing the experiments. Unique cannula design Cannula resistance is optimized according to Hagen-Poiseuilles physical law Different cannula sizes available, all metal, no fragile glass cannulae Proprietary Mini Holders allow easy and stress-free positioning of electrodes, catheters and probes 8 physiology@harvardapparatus.com

Aortic Block: The Single Most Important Part of System The Aortic Block really is the core of the IH-SR.

Over 20 years of experience, research and development have resulted in this system core which simply cannot be duplicated.

Pacing Electrode Full Range of Aortic Cannule Features and Benefits ECG Electrodes, LVP Balloon and Aortic Cannula Mounted to the Aortic Block Unique

simulate aortic compliance Low flow resistance and dead space volume, minimizes perfusion artifacts Integrated stopcock to control Ischemia/Reperfusion

7 Aortic Block: The Single Most Important Part of System The Aortic Block really is the core of the IH-SR. It is the attachment point for the heart and the central hub for perfusion control, physiological monitoring and drug infusion. Over 20 years of experience, research and development have resulted in this system core which simply cannot be duplicated. Flow Direction Aortic Block Base Unit Integrated Flow Probe Quick Shut-off Stopcock Bubble Trap Cannula Mount Exploded View of Aortic Block Detail of Pacing Electrode Full Range of Aortic Cannule Features and Benefits ECG Electrodes, LVP Balloon and Aortic Cannula Mounted to the Aortic Block Unique integrated small-volume Aortic Block with built-in Bubble Trap and Windkessel Bubble Trap located just above the Aortic Cannula Built-in Windkessel to simulate aortic compliance Low flow resistance and dead space volume, minimizes perfusion artifacts Integrated stopcock to control Ischemia/Reperfusion Small system volume, important if expensive drugs are used Drug injection pathway built directly into aortic perfusate stream Aortic Block with attached Cannula, LVP Ballon and Pacing Electrode 9

The IH-SR Basic Consists of the Main System & Selections Among the Following Options IH-SR Basic System APT300 Pressure Transducer PLUGSYS Modular Amplifier System Pacing and LVP

Perfusion Pressure Measurement Pressure Transducer TAM-A Transducer Amplifier Module Perfusion Controller Module, SCP PLUGSYS Basic System Case 601 Isovolumetric LVP Measurement Using

Mouse Hearts Pump Tubing (TYGON) Mini Balloon Kit for Mouse Heart Mouse Ventricular Balloon Assembly Kit 1 Liter Jacketed Buffer Resevoir Option II 73-4020 Additions to IH-SR core system

8 The IH-SR Basic Consists of the Main System & Selections Among the Following Options IH-SR Basic System APT300 Pressure Transducer PLUGSYS Modular Amplifier System Pacing and LVP Measurement Capability Full Range of Aortic Cannule Main System Basic IH-SR (Core System) Basic Unit IH-SR for Isolated Small Rodent Hearts Thermocirculator Analog Roller Pump Perfusion Pressure Measurement Pressure Transducer TAM-A Transducer Amplifier Module Perfusion Controller Module, SCP PLUGSYS Basic System Case 601 Isovolumetric LVP Measurement Using Balloon Method Pressure Transducer Holder for Pressure Transducer TAM-A Transducer Amplifier Module Option I Additions to IH-SR core system for Mouse hearts Aortic Cannula for Mouse Hearts Pump Tubing (TYGON) Mini Balloon Kit for Mouse Heart Mouse Ventricular Balloon Assembly Kit 1 Liter Jacketed Buffer Resevoir Option II Additions to IH-SR core system for Rat hearts Aortic Cannula for Rat Hearts Pump Tubing (TYGON) Balloon Kit for Rat Hearts 2 Liter Jacketed Buffer Resevoir 10 physiology@harvardapparatus.com

Data Acquisition and Analysis ISOHEART Software LabChart Pro Software Features and Benefits ISOHEART Software - Dedicated for Isolated Heart Experiments - Easy Data Reduction and Export - Can

Operation - Advanced Automated Analysis Routines - Online and Offline Analysis of ECG - Automation of Experimental Protocols - Proven Track Record A complete IH-SR System for Measurement and Analysis

Evaluates the Following Parameters: Systolic and Diastolic LVP Heart Rate dp/dt Max,dP/dt Min, Contractility Index Mean Perfusion Pressure Mean Perfusion Flow Coronary Resistance Option III 73-4039

9 Data Acquisition and Analysis ISOHEART Software LabChart Pro Software Features and Benefits ISOHEART Software - Dedicated for Isolated Heart Experiments - Easy Data Reduction and Export - Can Calculate Over 50 Parameters - Fully Pre-Configured Out of the Box for All Measurement and Analysis - Calculates Many Parameters Online PowerLab with LabChart Pro Software - Intiutive Setup and Operation - Advanced Automated Analysis Routines - Online and Offline Analysis of ECG - Automation of Experimental Protocols - Proven Track Record A complete IH-SR System for Measurement and Analysis Measured signals and calculated parameters on an IH-SR Basic system: The Following Signals are Recorded: Isovolumetric Left Ventricular Pressure dlvp/dt Perfusion Pressure Perfusion Flow The Software Evaluates the Following Parameters: Systolic and Diastolic LVP Heart Rate dp/dt Max,dP/dt Min, Contractility Index Mean Perfusion Pressure Mean Perfusion Flow Coronary Resistance Option III Data Acquisition and Evaluation System ISOHEART 16 Channels of USB Data Acquisition ISOHEART Software Option IV Data Acquisition and Evaluation System PowerLab 8 Channel Power Lab Hardware LabChart Pro 7 Software physiology@harvardapparatus.com

IH-SR Working Heart: The Heart Model for Physiological Fully-Ejecting

this model with physiological simulation that cannot be matched.

Resistance for Optimal Atrial Fill Built in Shut Off Stopcock for Rapid

Flow Measurement Phasic Aortic Flow Measurement Phasic Atrial Flow

Probes Solid State Physiological Circuit Ensures Non-Turbulent, Laminar

Control Huge Range of Measurement Capabilities Grows to Fit Your

Virually Any Data Acquisition System Benefits Physiological Starling

Range Allows Precise Control of Cardiac Afterload to Simulate Hypo,

Work Under Adjustable Load Optional Continuous Measurement of Metabolic

ers, i.e. ph, po 2, pco 2 Compact Design, Optimized for Each Species:

Applications in the Future Unsurpassed Physiological Environment Unique

Environment Low Flow Resistance and Dead Space Volume Built-in

Ischemia/Reperfusion Integrated Pathway for Insertion of a Pressure or

Afterload Control Small Flow Resistance and Low Dead Space Volume for

Pathway Solid State Physiological Circuit Mimics In-vivo Perfusion and

10 IH-SR Working Heart: The Heart Model for Physiological Fully-Ejecting Working Cardiovascular Studies The Working Heart model is the ultimate Ex-Vivo physiological model. The IH-SR Working Heart allows the researcher to take full advantage of this model with physiological simulation that cannot be matched. Left Atrial Block Integrated Constant Pressure Preload Column Low Flow Resistance for Optimal Atrial Fill Built in Shut Off Stopcock for Rapid Control of Ventricular Flow Integrated Flow and Pressure Measurement Flow Measurement Phasic Aortic Flow Measurement Phasic Atrial Flow Measurement Phasic Coronary Flow Measurement Fully Integrated Flow Probes Solid State Physiological Circuit Ensures Non-Turbulent, Laminar Flow PLUGSYS Modular Amplifier System Low Noise, Analog Fidelity and Control Huge Range of Measurement Capabilities Grows to Fit Your Application Compact, Space-Saving Arrangement Can Output Signals to Virually Any Data Acquisition System Benefits Physiological Starling Resistance Patented Membrane Afterload Control 0-300mmHg Adjustment Range Allows Precise Control of Cardiac Afterload to Simulate Hypo, Normo, or Hypertensive States Aortic Block Assessment of External Heart Work Under Adjustable Load Optional Continuous Measurement of Metabolic Parameters, i.e. ph, po 2, pco 2 Compact Design, Optimized for Each Species: Mouse, Hamster, Rat, Guinea Pig Modular Design to Integrate More Applications in the Future Unsurpassed Physiological Environment Unique Physiological Afterload System (Starling Resistor) Natural Physiological Environment Low Flow Resistance and Dead Space Volume Built-in Windkessel to Simulate Aortic Compliance Shut Off Stopcock to Control Ischemia/Reperfusion Integrated Pathway for Insertion of a Pressure or Pressure-Volume Catheter Unique Aortic Block for Precision Preload and Afterload Control Small Flow Resistance and Low Dead Space Volume for Highly Reproducible and Accurate Results Low Volume Drug Injection Pathway Solid State Physiological Circuit Mimics In-vivo Perfusion and Prevents Measurement Artifact Working Heart illustration used with permission courtesy of SANOFI-AVENTIS, Germany. 12 physiology@harvardapparatus.com physiology@harvardapparatus.com

Working Heart Left Atrial & Aortic Cannulation Points Pulmonary Artery Cannulation System for Collection of Coronary Effluent Features Allows rapid and easy switching between Working Heart and

The result is vastly improved arterial pressure evaluation without the risk of damage to heart valves.

11 Working Heart Left Atrial & Aortic Cannulation Points Pulmonary Artery Cannulation System for Collection of Coronary Effluent Features Allows rapid and easy switching between Working Heart and Langendorff Modes Patented Physiological Afterload System (Starling resistor) eliminates the conventional water column to create an afterload. The result is vastly improved arterial pressure evaluation without the risk of damage to heart valves. Integrated low volume afterload-optimized Aortic Block Compact, less space in lab is necessary, no high water column afterload (afterload pressures up to 300 mmhg are possible) Reduced line resistance, optimized to exceed species flow producing optimal atrial filling Proprietary patented afterload system to eliminate water column bouncing Laminar flow lines to improve accuracy of flow measurement Design optimized to minimize volume and reduce temperature losses Benefits Provides a valuable tool for the researcher who wants to study cardiac function and metabolism Combines the advantages of an isolated organ preparation with in situ-like perfusion features Allows a more comprehensive monitoring of functional parameters, the calculation of the external heart work and mechanical efficiency, and a considerably higher sensitivity for various experimental manipulations. Measured Signals and Calculated Parameters on an IH-SR Working Heart System: The Following Signals can be Recorded: Preload (left atrial preload / ventricular filling pressure) Afterload (determining the diastolic and systolic aortic pressure) Left Ventricular Pressure or Pressure-Volume Loops Atrial, Aortic and Coronary Flow Option V Working Heart Option Left Atrial Block and Starling Resistor Peristaltic Pump with Tubing Buffer Reservoir 2 Liter Pressure Measurement for Preload (transducer with acessories and amplifier) Option VI Working Heart Cannula for Mouse Hearts, 1.3 mm OD Option VII Working Heart Cannula for for Rat Hearts, 2.3 mm OD 14 physiology@harvardapparatus.com

Hemodynamics & Contractility Option VIII 73-4035 Measurement of Cardiac Output for Mouse Hearts Flow Probe 1.

5mm ID Adapter Block to Preload Block TTFM Flowmeter Option X 73-4037 LVP Measurement in Mouse Hearts Millar Pressure Catheter 0.

12 Hemodynamics & Contractility Option VIII Measurement of Cardiac Output for Mouse Hearts Flow Probe 1.0mm ID Adapter Block to Preload Block TTFM Flowmeter Option IX Measurement of Cardiac Output for Rat Hearts Flow Probe 2.5mm ID Adapter Block to Preload Block TTFM Flowmeter Option X LVP Measurement in Mouse Hearts Millar Pressure Catheter 0.8F Connecting Cable to Amplifier Adapter Port for MicroTip Catheter TAM-A Tranducer Amplifier Module Millar Pressure and Pressure-Volume Catheters Option XI LVP Measurement in Rat Hearts Millar Pressure Catheter 2.0F Connecting Cable to Amplifier Adapter port for MicroTip Catheter TAM-A Tranducer Amplifier Module Option XII Pressure-Volume Loop Measurement in Mouse Hearts Millar Pressure Volume Catheter 0.9F MPVS Ultra Pressure Volume Hardware and Control Software Cables and Calibration Accessories Option XIII Millar MPVS Pressure-Volume System Pressure-Volume Loop Measurement in Rat Hearts Millar Pressure Volume Catheter 1.6F MPVS Ultra Pressure Volume Hardware and Control Software Cables and Calibration Accessories Please Note: Contact Your Local Representative to Discuss Pressure-Volume Loop Analysis Options. physiology@harvardapparatus.com

Real-Time Pulsatile Flow Measurement The precision manufacture of the Aortic Block allows unparalleled accuracy and fidelity of pressure and flow

The resultant Solid State Physiological Perfusion Circuit produces a smooth laminar flow pattern which makes in-depth Cardiac IntegratedHemodynamics Flow

Features Cannula Mount Flow Probe Integrated Directly into Aortic Block Direct Real-Time Flow Measurement Unique Integrated Transit Time Flow Probe in the

line resistance, minimize volume and reduce temperature losses Benefits Real-Time Flow Measurement allows the study of Myogene Autoregulation (Reactive

13 Real-Time Pulsatile Flow Measurement The precision manufacture of the Aortic Block allows unparalleled accuracy and fidelity of pressure and flow measurements. The resultant Solid State Physiological Perfusion Circuit produces a smooth laminar flow pattern which makes in-depth Cardiac IntegratedHemodynamics Flow probe studies possible. Features Cannula Mount Flow Probe Integrated Directly into Aortic Block Direct Real-Time Flow Measurement Unique Integrated Transit Time Flow Probe in the Aortic Block Laminar Flow Lines to improve accuracy of Flow Measurement Different flow probe sizes available, depending on species Compact design to reduce line resistance, minimize volume and reduce temperature losses Benefits Real-Time Flow Measurement allows the study of Myogene Autoregulation (Reactive Hyperemia) By comparison, Indirect Flow Measurement can typically follow increasing flow rates but often lags behind or simply fails to report decreasing flow rates. Additional Recordings to an IH-SR Basic System: The Following Signal is Recorded: Phasic Coronary Perfusion Flow Option XIV Direct Flow Measurement for Mouse Hearts Flow Probe 1.0mm ID Adapter Block to Aortic Block TTFM Flowmeter Option XV Direct Flow Measurement for Rat Hearts Flow Probe 2.0mm ID Adapter Block to Aortic Block TTFM Flowmeter Please Note: In a Basic Langendorff System, Option XIV and XV are Used to Directly Measure Coronay Flow. In a Working Heart System, These Options Now Measure Aortic Flow. 16 physiology@harvardapparatus.com

Electrophysiology & Safety Pharmacology Features Complete tools for studying heart rate and ECG, as well as Repolarization and Conductance Optimized Pacing Electrode Mini ECG Electrodes with

& MAP Measurement using Micro MAP Electrode for Mouse Mini MAP Electrode for Rat Reduced stray fields from the Pacing Electrode for more accurate recordings The dedicated holders allow precise

IH-SR Basic System: The Following Signal are Recorded: Pacing ECG MAP Option XVI 73-4025 Measurement of One Epicardial Monophasic Action Potential on Mouse Hearts Micro MAP-tip Electrode Mini Holders

14 Electrophysiology & Safety Pharmacology Features Complete tools for studying heart rate and ECG, as well as Repolarization and Conductance Optimized Pacing Electrode Mini ECG Electrodes with dedicated holders Mini Monophasic Action Potential Electrodes for epicardial and endocardial recording, with dedicated holders Multi-lead ECG recording Benefits LVP & Single Lead ECG Measurement LVP & MAP Measurement using Micro MAP Electrode for Mouse Mini MAP Electrode for Rat Reduced stray fields from the Pacing Electrode for more accurate recordings The dedicated holders allow precise placement ECG and MAP Electrodes on any location around the heart Unique Multi-ECG Electrode setup Precision MAP Electrodes for long-term recording of stable MAP signals Additional Recordings to an IH-SR Basic System: The Following Signal are Recorded: Pacing ECG MAP Option XVI Measurement of One Epicardial Monophasic Action Potential on Mouse Hearts Micro MAP-tip Electrode Mini Holders Opposite Holder to Maintain the Heart in Position Connecting Cable to Amplifier BPA Biopotential Amplifier Option XVII Measurement of One Epicardial Monophasic Action Potential on Rat Hearts Mini MAP-tip Electrode Mini Holders Opposite Holder to Maintain the Heart in Position Connecting Cable to Amplifier BPA Biopotential Amplifier Option XVIII Measurement of Endocardial Monophasic Action Potential on Rat Hearts Intracardial MAP-tip Electrode with Holders Connecting Cable to Amplifier BPA Biopotential Amplifier

$Cardiac Rhythm Refractory Period Stimulator C Pacing Electrode Features Optimized Coaxial Pacing Electrode Mini ECG Electrodes with dedicated holders Mini Monophasic Action$ Flexible ECG Electrodes follow the heart beat, dedicated holders allow easy positioning on the heart Precision MAP Electrodes with dedicated holders allow easy positioning

Flexible ECG Electrodes follow the heart beat, dedicated holders allow easy positioning on the heart Precision MAP Electrodes with dedicated holders allow easy positioning

Mini Ball Joint Holders Connecting Cable to Amplifier ECGA, Amplifier for ECG Option XX 73-4024 Pacing Stimulator C Coaxial Stimulation Electrode Set, Small Please Note: If

15 Cardiac Rhythm Refractory Period Stimulator C Pacing Electrode Features Optimized Coaxial Pacing Electrode Mini ECG Electrodes with dedicated holders Mini Monophasic Action Potential Electrodes for epicardial and endocardial recording, with dedicated holders Benefits Reduced stray fields from the Pacing Electrode for more accurate recordings Flexible ECG Electrodes follow the heart beat, dedicated holders allow easy positioning on the heart Precision MAP Electrodes with dedicated holders allow easy positioning on the heart Small Electrodes allow Multiple ECG and MAP signals to be recorded even on mouse hearts Option XIX Measurement of ECG Lead II 2 Contact ECG Electrodes Mini Ball Joint Holders Connecting Cable to Amplifier ECGA, Amplifier for ECG Option XX Pacing Stimulator C Coaxial Stimulation Electrode Set, Small Please Note: If Monophasic Action Potential Recording is Required See Options XVI, XVII and XVIII for Electrophysiology. 18 physiology@harvardapparatus.com

Metabolic Studies ZABS Flow-Through Ion-Sensitive Electrodes Features Sensors for Continous Online Measurement of ph, po 2, pco 2 Large Selection of Other Ion-Sensitive Sensors Specific Sensors for

sampling of effluent Data is continuously logged for quantification and time-dependent analysis Additional Recordings to an IH-SR Basic System: The Following Signals are Recorded: Option XXI 73-4028

Shielding Case OPPM, Oxygen Partial Pressure Amplifier po 2 Zero Calibration Solution Option XXIII 73-4030 ph Measurement ph Sensor Set Shielding Case phmm, ph Amplifier Option XXIV 73-4031 pco 2

16 Metabolic Studies ZABS Flow-Through Ion-Sensitive Electrodes Features Sensors for Continous Online Measurement of ph, po 2, pco 2 Large Selection of Other Ion-Sensitive Sensors Specific Sensors for ß-D-Glucose and L-Lactate Benefits Pulmonary Artery Cannulation System for Collection of Coronary Effluent Continuous measurement capability yields improved and more meaningful data than intermittent sampling of effluent Data is continuously logged for quantification and time-dependent analysis Additional Recordings to an IH-SR Basic System: The Following Signals are Recorded: Option XXI Cannulating System for Pulmonary Artery on Rat Hearts for Metabolic Studies Cannula with Holders Peristaltic Pump Mounting Plate for Sensors Option XXII po 2 Measurement po 2 Sensor Set Shielding Case OPPM, Oxygen Partial Pressure Amplifier po 2 Zero Calibration Solution Option XXIII ph Measurement ph Sensor Set Shielding Case phmm, ph Amplifier Option XXIV pco 2 Measurement pco 2 Sensor Set Shielding Case EMM, Electrometer Amplifier Please Note: Pulmonary Cannulation Only for Rat Hearts. For Other Measurements like Na+, K+, Ca++, ß-D-Glucose or L-Lactate Contact Technical Support or your Local Representative. ph po 2 pco 2 Na+, K+, Ca++ ß-D-Glucose L-Lactate physiology@harvardapparatus.com

Special Option Multi-Mapping ECG Option XXV 73-4049 Multi-Mapping ECG, 32 Microelectrodes Electrode Array Connecting Head and Amplifier

Lightweight Miniature Headstage Low-Noise Amplifier Option XXVI 73-4050 Multi-Mapping ECG, 64 Microelectrodes Electrode Array Connecting

XXVIII 73-4042 Flow Controlled Drug Application in Constant Pressure Mode Pump PHD 2000 Connecting Tubing Controlling Software Option to

17 Special Option Multi-Mapping ECG Option XXV Multi-Mapping ECG, 32 Microelectrodes Electrode Array Connecting Head and Amplifier Evaluating Software Features 32 or 64 Microelectrodes with 300µm Distance Biocompatible Material Easy-to-Use Software Spike Detection Lightweight Miniature Headstage Low-Noise Amplifier Option XXVI Multi-Mapping ECG, 64 Microelectrodes Electrode Array Connecting Head and Amplifier Evaluating Software Drug Application Option XXVII Drug Application Syringe Pump 11 Connecting Tubing Option XXVIII Flow Controlled Drug Application in Constant Pressure Mode Pump PHD 2000 Connecting Tubing Controlling Software Option to ISOHEART Please Note: Option XXVIII Requires the Use of the ISOHEART Software

Cardioplegia and Temperature Studies Features Additional Perfusion System for Cardioplegia Solution Benefits Buffer Reservoirs Separate perfusion circuit for cardioplegia solution Allows introduction

18 Cardioplegia and Temperature Studies Features Additional Perfusion System for Cardioplegia Solution Benefits Buffer Reservoirs Separate perfusion circuit for cardioplegia solution Allows introduction of cardioplegia solution without removing the heart from the system Additional Equipment to a IH-SR Basic System: Cardioplegia Solution Perfusion System Option XXIX Additions for Cardioplegia Solution Application Reservoir for Cardioplegia Solution Additional Warming or Cooling Heat Exchanger 3-way Stopcock Option XXX Low-Temperature Thermociculator, 230V 6 Liter Thermocirculator Option XXXI Low-Temperature Thermociculator, 115VAC 6 Liter Thermocirculator Please Note: The cardioplegia Application May Require Keeping the Perfusion Solution Cool. In this Case the Second Cooling Thermocirculator is Required. physiology@harvardapparatus.com

Cell Isolation Enzyme Solution Reservoir, 100 ml Cell Collection Funnel Features Additional Perfusion System for Enzymatic Disintegration

Better Data Additional Equipment to a IH-SR Basic System: Enzyme Perfusion System Option XXXII 73-4046 Cell Isolation with IH-SR Basic System

19 Cell Isolation Enzyme Solution Reservoir, 100 ml Cell Collection Funnel Features Additional Perfusion System for Enzymatic Disintegration Cardiomyocyte isolation Benefits Low Volume Enzyme Perfusion System Controlled Flow or Pressure During Desintegration Better Control for Better Data Additional Equipment to a IH-SR Basic System: Enzyme Perfusion System Option XXXII Cell Isolation with IH-SR Basic System Protease Reservoir Magnetic Stirrer Tubing, Heat Exchanger and Bubble Trap 22 physiology@harvardapparatus.com

Other Options Option XXXIII 73-4047 Temperature Measurement Micro Thermocouple IT-18 Connecting Cable Adapter

Containing Albumin or Fatty Acids Holder for Fiber Oxygenators Mounting and Connecting Kit for Fiber

Effluate Funnel for Fraction Collection Option XXXVI Collection Funnel 73-0129 Preparation Dish for Mouse

20 Other Options Option XXXIII Temperature Measurement Micro Thermocouple IT-18 Connecting Cable Adapter Port to the Aortic Block TCAM Thermocouple Module Option XXXIV Oxygenating System for Foaming Solutions Containing Albumin or Fatty Acids Holder for Fiber Oxygenators Mounting and Connecting Kit for Fiber Oxygenators Pack of 5 Fiber Oxygenators Fiber Oxygenator mounted to top plate of IH-SR Option XXXV Effluate Funnel for Fraction Collection Option XXXVI Collection Funnel Preparation Dish for Mouse Hearts Preparation Dish for Mouse Hearts Fiber Oxygenator physiology@harvardapparatus.com

84 October Hill Road Holliston, MA 01746 phone: 508.893.8999 toll-free: 800.272.2775 fax: 508.429.5732 email: physiology@harvardapparatus.com web: www.harvardapparatus.com, www.hugo-sachs.

Physiology, Tissue Engineering, Pharmacology and Toxicology.

analysis, in-vivo monitoring and ex-vivo perfusion.

21 84 October Hill Road Holliston, MA phone: toll-free: fax: web: Customer Support Hugo Sachs Elektronik Harvard Apparatus provides complete research solutions across all life science fields including: Behavioral Neuroscience, Cardiovascular and Respiratory Physiology, Tissue Engineering, Pharmacology and Toxicology. We provide researchers with a range of tools and equipment for virtually any application including: compound screening, drug infusion, microfluidics, PK-ADMET, high fidelity data acquisition and analysis, in-vivo monitoring and ex-vivo perfusion. Hugo Sachs Elektronik Harvard Apparatus is the best single source for research systems, equipment and support to keep your research moving at the pace of science. For a system description according your requirements please use: or contact our technical experts at our sales subsidiaries or authorized distributors For a custom configuration and full system quotation: physiology@harvardapparatus.com PRSRT STD US POSTAGE PAID HOLLISTON, MA PERMIT NO physiology@harvardapparatus.com

Isolated Heart PERFUSION SYSTEMS CONTENTS SPECIALIZED APPLICATIONS & OPTIONS ADDITIONAL & REPLACEMENT COMPONENTS

Isolated Heart PERFUSION SYSTEMS For Mouse to Small Pig Animal Models Hugo Sachs Elektronik (HSE), part of the Harvard Bioscience family of companies, provides state-of-the-art, fully integrated physiology