Blood vessel myography: a tale of two techniques. By Dr Emma Moss
Blood vessel myography is a valuable in vitro technique for the sensitive measurement of constriction and relaxation of blood vessels in response to test drugs.
Why would you use isolated blood vessels as opposed to testing in animals?
Assessing drug responses in human blood vessels gives us a much more accurate prediction of how the compound will perform in the clinic, compared to studying the responses in animals (see figure below showing differences between canine and human arteries exposed to serotonin (5-HT)).
How is myography performed?
There are two main types of myography that are routinely performed in laboratories today. Isometric myography (constant length myography), typically conducted via wire myography, and isobaric myography (constant pressure) typically conducted via pressure myography.
What’s the difference between isometric and isobaric myography?
In isometric experiments, the tissue is held at a constant initial stretch. Changes in contraction/relexation are indicated by measurements of force from sensitive isometric force transducers. Isometric myography is a higher throughput technique than isobaric myography, and is therefore often the method of choice. The advantages of this technique are that vessels remain viable showing consistent contractility and relaxatory responses. Perivascular nerves and endothelium function also remain functional. Unfortunately with this technique the vessels acquire a flattened rather than cylindrical shape and the wires exert pressure on the end walls of the vessel rather than distributing it evenly along the wall length. There is also a risk of the endothelium being damaged by the wires in the mounting procedure. However as many vessels can be run in parallel, this potential effect can be tested for at the start of the experiment, and that specific blood vessel ring removed if necessary.
Isobaric myography allows tubular sections of vessels to be mounted on cannulae inserted into either end of the vessel. Fluid is pumped into the vessel to create a desired intraluminal pressure and the diameter of the vessel is measured using an optical video dimension analyser. As the vessel constricts the vessel diameter decreases and this can be recorded using charting software. Using this technique the vessels maintain a much more physiologically round shape and there is less potential for endothelial damage. It is also possible to mimic in vivo conditions such as blood flow and blood pressure and to apply drugs of interest to the inside of the vessel, instead of the outer wall. However it is a very challenging technique and only allows a 2-3 vessels to be run at a time, therefore it is mainly used to study specific components of vascular control, such as flow mediated dilatation or vascular compliance (pressure-diameter relationships).
Why are these techniques useful to the pharmaceutical industry?
Myography is an important tool in the pharmaceutical industry for assessing the effects of potential new drugs on the vasculature. This gives the pharmaceutical companies invaluable early data on the safety and/or efficacy of their drugs in the human cardiovascular system. Both of these techniques have helped to increase the knowledge of normal function and responses of small vessels, however there is still much to learn about vascular biology and many academic laboratories employ this method in their research as they strive to learn more about the control of blood vessel function.
Does Biopta offer myography?
Biopta has over 75 years combined experience in myography and has run countless client studies using isolated human blood vessels to assess both the safety and efficacy of drugs. We also have four specially developed pressure myographs (PM-1 instrument) which allow us to investigate the effects of drugs on flow-mediated relaxation, vascular compliance and permeability in human blood vessels.
Running several vessels in parallel allows us to assess a variety of parameters at once, and the frequency with which we receive human blood vessels allows us to offer a rapid turnaround on our client studies.
The majority of our client studies are tailor made, so whether the drug company is looking to assess safety and/or efficacy, we design each study to meet the client’s individual requirements.