Bringing PV Loop Technology into the 21st Century with Admittance
Since 1984, Transonic has been dedicated to advancing meaningful measurements in the research setting. To achieve this goal, we have focused on developing technologies that disrupt the status quo, starting with the application of Transit-Time Ultrasound technology to measure vascular blood flow. When launched, most researchers were working with Doppler technologies that provided only relative velocity measurements, or electromagnetic technology that had inherent issues maintaining stable zero baselines. Since this time – and in the true spirit of science – we have translated our success in life science research into trusted measurement technologies that serve to improve patient outcomes.
In 2012, we onboarded another disruptive technology with the acquisition of Scisense, a company that specializes in catheter-based pressure, pressure-volume loop and electrophysiology catheters for pre-clinical applications. At the time, Scisense had recently launched a new technology into the Pressure-Volume Loop space called “Admittance” that solved several important shortcomings present in the other PV technologies. Here I will offer a brief history of Admittance; how it compares to its predecessor “Conductance” and importantly, what benefits it offers users in the lab.
To understand the technology, it first helps to understand the measurement goals. All pressure-volume technologies are trying to discern the same data – the ventricular blood pressure and blood volume within the heart during a single cardiac cycle. When mapped on an XY plot over time, the relationship of pressure to volume creates a loop shaped graph that can be tracked in real time over tens of thousands of cycles within a single data collection period. The shape and size of these loops provide information about the function of the ventricle with data types such as cardiac output, stroke volume, ejection fraction, dp/dt, and many others able to be extracted. The objective is to compare heart function between cohorts when analyzing these data sets. From this we can evaluate disease states, drug discoveries and interventions that strive to improve heart function.
Though all PV loop technologies are after the same data types, they achieve their goals in different ways, with different levels of convenience and overall success. In a pre-clinical research setting, two technologies exist – Conductance and Admittance. Both technologies work off the same general guiding principles:
- Blood pressure can be tracked with the highest level of accuracy using a solid-state pressure sensor
- Blood itself conducts electricity
- A catheter with a solid-state pressure sensor and electrodes can record blood pressure in a ventricle and voltage from the blood and heart tissue
- Conversion of the collected voltage data into absolute blood volume requires correcting for the portion of the voltage signal that is contributed by the muscle tissue.
Figure 2: Pressure-Volume Catheter in Left Ventricle. Blue dotted lines show emitted signal from distal and proximal electrodes. The Pressure sensor is circled in red.
As you can see in the figure above, the outer electrode pairs input a current while the inner electrode pairs are responsible for recording the resulting voltage measured from within the ventricle. From this approach, there are two main challenges that need to be overcome before data can be reported in units of volume:
- The muscle itself conducts electricity. Called parallel conductance or simply the “muscle contribution,” this parameter can be thought of as exogenous signal caused by the fact that muscle comes into the presence of the emitted electric current coming from the catheter. To make matters worse, this signal varies dramatically throughout the cardiac cycle as the heart gets closer to the catheter at end-systole and further away at end-diastole. The most dramatic changes in muscle contribution however result from changes in catheter position and varying loading conditions such as inferior vena cava occlusions (more on this shortly). For accurate volume to be calculated, you need to remove the muscle’s contribution from the total received signal See figure #3.
- The electric field is non-homogenous. Because the electric field is being generated from two point-source electrodes, the field itself gets weaker as it moves away from the catheter. This non-linear relationship in turn requires a non-linear conversion equation.. See figure #3.
Figure 3. The blue dotted lines show the total emitted signal from the catheter, green dotted lines show the intersection where the emitted signal contacts the muscle tissue and the yellow arrows highlight the non-linear electric field given off by the catheter. Both parameters present a problem for data correction – conductance and admittance address each differently.
These two challenges are at the “heart” of what makes Admittance so revolutionary. Using conductance technology, a user is required to manually account for the muscle contribution and non-homogenous electric field with a saline bolus injection and cuvette calibration, respectively. Both approaches are challenging and variable, and as a result many users do not perform these calibrations on each animal, even though catheter position between animals will never be equivalent. With Admittance, not only does the user eliminate the need to perform these interventions, they can also monitor catheter position throughout the experiment, all while collecting true volume live.
In the early 2000s, a new approach to PV loop data collection was proposed where electrical properties of the myocardium itself are exploited to monitor and remove their contribution to the measured signal. At the same time, a new conversion equation was developed called Wei’s equation – this equation accounts for the non-homogenous electric field and therefore more accurately tracks the non-linear nature of the relationship. Taken together, these advancements finally allowed for the monitoring of ventricular volume during the study, something that is essential for data qualification in the lab.
Monitoring of baseline data parameters such as stroke volume and ejection fraction are only part of the story however, since a key insight from PV loops is the ability to change loading conditions and from this, interrogate load-independent contractility changes. These manipulations – classically known as “occlusions” – dramatically reduce ventricular blood volume and in so doing, dramatically change the muscle’s contribution to the total signal. As such, the removal of the muscle contribution becomes even more imperative – Admittance is the only technology that can monitor and adjust for these changes. The resulting data therefore is more physiological and accurate.
Since its launch in 2009, we have continued to push the Admittance technology forward both in and out of the lab. Inside of the lab, our clients find that the live monitoring of catheter position allows for more accurate data review between animals, necessitating smaller groups sizes. The lack of calibration streamlines training and minimizes disruptions due to turn-over in the lab, while investigators can advance new studies with confidence. Outside of the lab, we continue to provide support, training and education through our application experts, who have lengthy experience with Admittance technology. As we can’t always be in the lab to support your research in person at the moment, we have also built our comprehensive library of support material. And in the true spirit of Transonic, we continue to advance more meaningful measurements in the lab with technology that is on the cutting edge of science.