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Blood Flow

Overview:

Blood flow is the movement of blood through the vessels of the circulatory system. It is pulsatile in the large arteries as a result of ventricular ejection and diminishes in amplitude as it approaches the capillaries. In the veins it is non-pulsatile and is a result of a number of factors including respiratory movement, muscle compression and the small residual arterial pressure.

Blood flow is measured over time and often expressed in milliliters or liters per minute. It can be measured either invasively or non-invasively and quantitatively or qualitatively. The rate and distribution of blood flow through the circulatory system is variable and related to several factors including physical activity, cardiac output and venous return.

Applications where blood flow measurements are performed include:

Tumor monitoring and angiogenesis
Intra-cranial monitoring in stroke and brain injury
Peripheral Vascular Disease
Gastroenterology
Diabetes research
Dermatology

Method:

Blood flow can be easily recorded with a PowerLab data acquisition system and a suitable blood flow meter that can provide an analog output voltage (maximum ± 10 V) to the PowerLab unit.

Non-Invasive Techniques

Laser Doppler Flowmetry (LDF)
Laser Doppler systems use a probe containing optical fiber light guides to apply a low power laser light to a small area of tissue. With the Doppler technique, laser light from one fiber is scattered within the tissue and some is scattered back to the probe when reflected off the moving particles, i.e. red blood cells. Another optical fiber collects the backscattered light from the tissue for recording. The emitted and returned signals are then compared to extract the Doppler shift proportional to the red blood cell perfusion (or flux).

Note: The Doppler technique tells you about the velocity shift due to blood flow but cannot quantify actual blood flow. Laser Doppler signals from the tissue are recorded in BPU (Blood Perfusion Units) which is a relative unit scale defined using a carefully controlled motility standard. This motility standard calibration solution contains a suspension of latex spheres undergoing Brownian motion.

Blood flow measurements using the Laser Doppler Blood FlowMeter
The absolute strength of the signal is related to several factors including the degree of vascularization of the tissue. Therefore, the signal strength can vary markedly due to the position of the laser tip and the tissue type. The signal is often referred to as 'tissue perfusion' rather than blood flow, as it cannot be directly calibrated in units, such a mL/min. Relative changes in the signal can be related to effects such as local vasodilatation/constriction and so this method is useful for some pharmacological studies where more invasive methods are not suitable.

Note: The laser Doppler technique detects mean flow over numerous vessels and is not used for determination of flow in a single vessel. For single vessel measurements, invasive techniques, such as transit-time ultrasound, are more suitable.

Strain Gauge Plethysmography
Strain Gauge Plethysmography is a non-invasive method particularly suitable for human use and is also referred to as, venous occlusion plethysmography. It involves tying a strain gauge- in this case a stretchable tube containing a liquid metal, such as mercury or an indium-gallium alloy- around the limb (e.g. forearm). Changes in limb circumference alter the cross-sectional area of the tube and hence the electrical resistance of the liquid metal. This is monitored by a suitable meter, e.g. Hokanson EC6 meter, which can output an analog voltage signal directly to a PowerLab system.

Invasive Techniques

Thermodilution
For periodic determination of flow rates, the thermodilution method uses a small temperature probe to monitor the change in blood temperature when a bolus of cool fluid (of known volume and temperature) is injected into the circulatory system. The area under the curve produced when temperature is plotted against time is used to calculate blood flow and cardiac output. The Cardiac Output Pod is suitable for use with small animals ONLY (mice, rats, guinea pigs or rabbits) and uses T-type thermocouple probes. It is supplied with the T-type Ultra Fast Thermocouple Probe and can be directly connected to a PowerLab with Pod ports or indirectly via the Pod Expander. See the Cardiac Output application page for more information.

Transit-Time Ultrasound Flow Meter
Transonic Systems' ultrasonic transit-time technology has been the gold standard for volume flow measurement for more than two decades. With the transit-time technique, the ultrasound travels a fixed distance and is reflected off a stationary reflector plate. The difference between upstream and downstream transit times is directly proportional to volume flow, independent of the vessel diameter. Transit-time ultrasound gives a direct measurement of blood flow rate in milliliters per minute. This technique is not subject to problems with electrical interference or baseline drift and does not require direct contact with the vessel.

Flowprobes are available for use in animal blood vessels as well as laboratory tubing and include;

Perivascular Flowprobes are available for acute and chronic measurements of flow in animal blood vessels. These probes are placed around the vessel and do not interfere with flow to the target tissues. They are available in a wide range of sizes (0.5 to 35 mm) and configurations. The probes are suitable for recording in small and large vessels in a variety of species, ranging from mice, large domestic animals through to sheep and cows. Probes suitable for measuring cardiac output directly from the ascending aorta are also available.
Tubing Flowsensors are available for volume flow measurements in tubing applications such as isolated perfused organ studies. The in-line flowsensors can be easily spliced into laboratory tubing and are calibrated to measure volume flow of water, saline, buffer solutions, blood or other fluids. The four-transducer sensor design offers precision accuracy for flows of less than 1 ml/min up to 100L/min.

Software:

The LabChart Advantage:

(may require additional Modules and Extensions)

LabChart data files can be marked with events using the Comments feature
Maximum, minimum and average signal amplitudes can be calculated using the Data Pad
The Units Conversion feature can be used to convert signals into relevant units e.g. ml/min
The Cardiac Output Module for Windows provides the user with ability to easily extract and calculate cardiac output from small animals, using the thermodilution technique
Macros can automate many tedious and repetitive analysis tasks
The display of the signal can be compressed for long term trend observations
Data can be easily transferred into popular spreadsheet and graphing programs for further analysis and reporting

LabChart

LabChart software (for Windows and Macintosh) together with a PowerLab data acquisition system offers up to 32 channels of real-time data acquisition, data integrity, easy selection of hardware settings, powerful online and offline analysis, procedure automation, seamless extraction of experimental data and flexible display options. Additional acquisition and analysis functionality is provided with the use of specialized LabChart Extensions and LabChart Modules. Modules are available as part of LabChart Pro while Extensions are free for download from the website for existing LabChart users.

Human blood flow measured using ML191 Blood Flowmeter

Cardiac Output Module

The Cardiac Output Module (Windows) provides easy extraction and calculation of cardiac output from small animals recorded in LabChart, using the thermodilution technique.
It provides:

Automatic calculation of cardiac output in mL/min from a thermodilution curve
Automatic calculation of baseline temperature and baseline slope correction
Automatic calculation of the area under the curve
Automated extraction of exportable parameters in a spreadsheet format

GLP and 21 CFR Part 11

For researchers working within a laboratory requiring GLP and 21 CFR Part 11 compliance, the GLP Client and GLP Server are available for use with LabChart (Windows only) and PowerLab data acquisition systems. For more information, visit the Good Laboratory Practice application page or contact your nearest ADInstruments representative.

Hardware:

PowerLab Data Acquisition Systems

The PowerLab is a high-performance data acquisition unit capable of recording at speeds of up to 400,000 samples per second continuously to disk (aggregate). PowerLab units are compatible with instruments, signal conditioners and transducers supplied by ADInstruments, as well as many other third-party companies. In addition to standard single-ended BNC inputs, 4 differential Pod ports are also available for direct connection of Pod signal conditioners and appropriate transducers. Research PowerLab units include:

PL3504 PowerLab 4/35 - 4 Channels
PL3508 PowerLab 8/35 – 8 Channels
PL3516 PowerLab 16/35 – 16 Channels

Research Systems

Transit-Time Ultrasound Blood/Fluid Flow Systems
ADInstruments provide flow systems and probes of various sizes for implanting in blood vessels in animal models from mice through to adult pig. These probes are available for both chronic and acute applications and are calibrated to provide the user with blood flow measurements in milliliters per minute in conscious and anesthetized animals. The flow meters easily integrate with any PowerLab data acquisition systems.

These systems include:

PL3508B11 One Channel Perivascular Flow System - measuring blood flow from a single vessel
PL3508B12 One Channel Tubing Flow System - measuring flow in a single tube
PL3508B13 Two Channel Perivascular Flow System - simultaneously measuring blood flow from two vessels
PL3508B14 Two Channel Tubing Flow System - simultaneously measuring flow from two tubing setups
PL3508B15 Two Channel Perivascular/Tubing Flow System - simultaneously measuring flow from a single blood vessel and single tube

Instruments

The ADInstruments ML191 Blood Flowmeter is a single channel laser Doppler flowmeter that connects to any PowerLab data acquisition system. A variety of needle or surface probes are available.

Signal Conditioners

The ML313 Cardiac Output Pod (no thermocouple) is used with T-type thermocouples (thermodilution technique) to determine the cardiac output in small animals (mice, rats, guinea pigs or rabbits) ONLY. The Pod can be used with any appropriate T-Type thermocouples and has a 'delta' temperature mode to allow a signal offset to be applied so that small temperature variations are monitored accurately.

The ML313C Cardiac Output Pod (with thermocouple) configuration consists of the Cardiac Output Pod with additional products including:

MLT1402 T-type Ultra Fast Thermocouple Probe with a fast response time of 0.005 seconds
Cardiac Output Module (Windows) for LabChart

Transducers and Accessories

Perivascular Flowprobes
To determine the appropriate flow probe for measurement of blood flow in a specific vessel in a particular species, view the Probe Application Guide. Detailed information about the physical and operational specifications of the Flowprobes is available in the Perivascular Probe Specifications. When ordering a Perivascular Flowprobe, please consult the Flowprobe Ordering Guide.

Tubing Flowprobes
PXL-Series Flowsensors can be calibrated and programmed for up to 4 different fluid/ temperature/ tubing combinations and will work with most flexible tubing types. For a guide to the most appropriate flow sensor for measurement of tubing flow, consult the PXL Flowsensor Guide.

PXN-In-Line Flowsensors splice into laboratory tubing and measure absolute volume flow of blood and other fluids. For a guide to the most appropriate flow sensor for measurement of tubing flow, consult the PXN Flowsensor Guide.

Blood Flowmeter Probes
Several surface and invasive fiber optic probes are available from ADInstruments and include:

MSP140AR Adhesive Rings for Surface Probes
MLA191 Calibration Kit (required and for probes that are purchased separately)

Cardiac Output
The MLA313 Cardiac Output Accessory Kit helps facilitate the measurement of cardiac output from small animals. It can be used with the ML313C Cardiac Output Pod (with thermocouple) or ML313 Cardiac Output Pod (no thermocouple). It includes:

Hamilton LR (Luer tip) Glass syringe (250µl)
Repeating dispenser
Luer needle hubs
Three-way stop-cocks
Touhy Borst Adaptors
Polyethylene tubing

Dynamic fluid shifts induced by fetal bypass
Baker R S, Lam C T, Heeb E A and Eghtesady P, Journal of Thoracic and Cardiovascular Surgery, 714-722, 2009

Impaired ATP turnover and ADP supply depress cardiac mitochondrial respiration and elevate superoxide in nonfailing spontaneously hypertensive rat hearts
Hickey AJ, Chai CC, Choong SY, de Freitas Costa S, Skea GL, Phillips AR, Cooper GJ., American Journal of Physiology: Cell Physiology, C766–C774, 2009

Laser Doppler flowmetry for assessment of myocardial microperfusion in the beating rat heart
Li X-F, Wang Y-P, Vascular Pharmacology, 207–214, 2007

The material on this page is provided in good faith and believed accurate at the time of writing. No responsibility will be taken, or liability accepted, for damages arising from the use of information herein. Readers are urged to check with respective manufacturers the accuracy of all product related information.

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