Synergies in the Lab – PV Loops Finally Playing Nice with Other Modalities
When I started out in the industry, I had a Medical Science/Physiology double major undergraduate degree from the University of Western Ontario, which included some basic animal research into pulmonary surfactant. Like many students with a medical focus, I strongly believed in the scientific process, but likely was guilty of idealizing the process and underappreciating the techniques used in the pursuit of knowledge. Even so, I wanted to be part of the research community, so in 2009 I applied for a job at a company called at that time Scisense – specializing primarily in the collection of ventricular pressure-volume loop data. Since then, I have gained a much appreciation for the variables at play in a life science lab. In today’s blog I would like to review the importance of synergistic technologies, using our ADV500 PV loop technology as the test case.
For anyone reading this blog, you are likely aware that we manufacture the world-leading PV loop technology called “Admittance” (see our other blogs, webinars and technical notes if this is the first time you've heard about Admittance). However, what is not immediately obvious to most people is how a pressure-volume system actually calculates volume and what it means for other technologies being used in the lab. Although, the topic of PV technologies has been covered previously, below is a reminder to ensure that we are all on the same page:
A catheter is inserted into a ventricle of an anesthetized animal, a constant current is emitted from distal and proximal electrodes on the catheter tip. This current goes through the ventricle blood and heart muscle. The signal the catheter receives back, in units of voltage, is a mixture of blood and muscle conductance and needs to be converted into an absolute volume before analysis.
As we all know, research is not conducted in a vacuum and many different technologies are deployed when investigating cardiovascular function; some of these technologies will also report volume data from the heart, just like a PV system. The challenge with older, conductance based, PV systems has been the volume conversion steps that are required to come to volume data. Scientifically, it is a problem when data collected with one technique does not match another techniques data; for example, echocardiography’s ejection fraction not matching that derived from a conductance PV system. What does a researcher do when one technology does not match another? Do you discard the PV data? Use the measurements for relative change? Abandon the volume data entirely? With our ADV500, these considerations are largely a relic of the past. Let’s look at 3 common volume technologies in the lab – echo, flowprobes and MRI – and how our system is used in each.
An echocardiography machine, or “echo” machine, uses ultrasound technology to non-invasively take an image of the heart throughout its cardiac cycle. The equipment uses algorithms that assess the shape of the inner wall of the heart to determine measurements like end-systole, end-diastole, stroke volume, ejection fraction, and more. Its ability to provide serialized measurements, relatively quickly, is very attractive and the data echo machines provide are well-regarded when the operator is properly trained.
However, echo machines cannot provide critical load-independent measurements of contractility and as a result, PV loop technologies are deployed as a terminal end-point to the serialized measurements from echo. As mentioned, conductance based PV loop technologies can at times be guilting of providing data that differs dramatically from echo derived data and this is due to the volume calibration steps. The good news is that our ADV500 Admittance based PV technology is far less susceptible to these issues, as shown by Porterfield JE, et al in 2009. As you can see below:
Sample of PV loops from mice with catheter positioned off-center. Admittance technique with Wei’s equation consistently produced values closer to those determined by echo. Using SV to determine alpha gives better results than assuming a value of 1, however it is highly dependent on the success of the hypertonic saline injection and is prone to overestimating volume.
What this means is that echo can be used more reliably in conjunction with the ADV500 than other PV technologies.
At Transonic, we are best known for our innovation of vascular blood flow measurement with the introduction of Transit-Time Technology into miniaturized blood flow probes. This allowed for the calculation of volume flow through vessels, instead of Doppler-based velocity measurements. Since launching this technology, we have been included in thousands of publications, with many citing data from the pulmonary artery or aorta. These probes report, among other parameters, cardiac output and stroke volume – the same data types that a PV-loop system provides.
In this setting, our Admittance catheter again shines and even works synergistically with the flow probe. Unlike echo or MRI, the measurement of vascular flow can be done concurrently with PV loop data collection throughout the entire experiment, beat by beat. Using the ADV500, a researcher can input the live stroke volume calculations from the flow probe into the PV system’s hardware, allowing for an even tighter data collection process. Because the ADV500 calculates volume live, a researcher can correlate the two technologies together during the protocol, ensuring that the data corresponds.
Magnetic Resonance Imaging (MRI)
Finally, a less common but highly accurate measurement tool for cardiovascular function is MRI. Hoefer et al., showed that the admittance based ADV500 PV system correlated very well with MRI data and as a result, determined the technology to be a useful tool for the measurement of cardiac function – either in conjunction or separately from MRI.
At Transonic, we understand what it takes to collect meaningful data in your lab and the challenges of using different instrumentation modalities. It is a fine balance between design and execution while attempting to maximize the potential of any given experiment. Close work with our customers over decades combined with the extensive lab experience of our team of research applications specialist team has given us unique insight into countless protocols. Please be sure to reach out to our team and also check out our webinar series. Our webinars cover best practices for data collection with our technologies as well as interesting new surgical approaches and models. Cheers!