Myography is the go-to methodology of choice for assessing blood vessel function and cardiovascular dysfunction in safety pharmacology. The idea behind this principle is that small or large blood vessel ring preparations are mounted using wires or pins secured unto two supports. The first support is connected to a micrometer to vary the vessel diameter, and the other support is attached to a force transducer. This setup allows the vessel to generate a standardized basal tone on all experimental ring preparations in a process called normalization. For large conduit arteries, this is less applicable.
Why is normalization important for all myography studies in small resistance arteries?
Normalization imparts a measured optimal passive tension on the vessel before experimentation. This is a pre-condition to generating maximum vessel contraction. To understand this principle, we need to revisit the sliding filament mechanism of actin-myosin cross-bridge in smooth muscle contraction. In brief, thin actin filaments interact optimum with thick myosin filaments to form cross-bridges. At the ideal level, the vessel is not overstretched nor under-stretched. This ideal condition generates maximum vascular contraction. Perfecting and replicating this optimum tension on each vessel for experimentation is the holy grail of vascular function in resistance arteries. This is critical for reliable, consistent, and reproducible results for better data interpretation.
The Wire Myograph is the gold standard for investigators for over 40 years in assessing small resistance artery function ex vivo. The LabChart data acquisition software has a built-in DMT Normalization Module to manually generate a vessel length-tension curve to facilitate the normalization procedure. This mathematically incorporates the vessel wall tension, vessel length, vessel circumference, and accurate micrometer reading. The result is the accurate micrometer reading position the vessel will be set at to conduct all experiments. This setpoint is the optimum basal tone at which the vessel will generate maximum contraction in response to an agonist. The limitation here is that this procedure is time-consuming and requires accurate micrometer reading. There is the Automated Wire Myograph to provide an option to automate this process of normalizing resistance arteries.
The Automated Wire Myograph is a significant upgrade from the standard wire myograph, not in cost but value. It is attractive because it has built-in motors that incorporate robotics and automate the normalization process for small resistance arteries. I cannot emphasize enough the significance of this feature since it is essential for the rest of the experiment to be carried out. Briefly, all parameters are entered into the DMT Normalization Menu, and the rotating motors automatically determine the length-tension curve. Following this process, the motors generate the optimum resting tension and corresponding micrometer reading setpoint. The motors revert to this optimum position, and experimentation begins. This robust and efficient automatic normalization mechanism eliminates bias, micrometer reading mistakes, and generates reproducible data, a hallmark of rigorous scientific experiments.
In conclusion, what more is needed for investigators who already use the wire myograph?
If the technical staff is well trained and can perform normalization manually and reliably, it is sufficient. For investigators open to new technology in advancing reliable myography studies in small resistance arteries, the Automated Wire Myograph is the choice. This system facilitates the generation of reproducible data, thereby saving time and, more importantly, reduces sample size to reach statistical significance. From my 15-year experience using wire myography, I never used the automated myograph for normalization and completely missed out on its value. This technology is a huge advancement and is important as it will save time and resources, produce consistent results, all hallmarks of DMT Myograph Systems.
For questions related to wire myography and normalization, please contact one of our Scientific Product Specialists.
By Dr. Larry Agbor
Scientific Product Specialist