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pv loops (left ventricle)

A pressure-volume (pv) loop is a plot of pressure (y-axis) against volume (x-axis) during cardiac cycles.

In relation to the left ventricle of the heart, pv loop studies enable characterization of the intact heart's performance under various situations (effect of drugs, disease, characterization of mouse strains,…)

An example of a pv loop from the left ventricle is shown below.

left ventricle pv loop in iox software

Each side of the "loop" corresponds to one of the four phases of the cardiac cycle:

• ventricular filling (D to A).
• isovolumetric contraction (A to B)
• ejection (B to C)
• isovolumetric relaxation (C to D)

pv loop studies are today widespread. Their uptake was driven by the development of techniques to obtain real-time volume signals, such as those based on conductance catheters, especially miniature models for use in rodents.

 

conductance catheter technique

In this technique, changes in ventricular volume are correlated to changes in electrical resistance of the blood pool in the left ventricle.

The conductance catheter contains several ring electrodes along its length. A high-frequency low-amplitude constant current is passed through the outer electrodes to generate an electric field. The potential difference between any pair of inner electrodes is inversely proportional to the amount of conductive material at that site.

When in place, the catheter should ideally extend along the entire long axis of the left ventricle. In catheters designed for larger subjects, there are several inner (measuring) electrodes. The division of the catheter into segments in this way improves the accuracy of the total volume signal, obtained by summing all segments. Catheters for small subjects normally have two measuring electrodes, due to size limitations.

calculating ventricular volume

The formula for ventricular volume is as follows:

V volume

α alpha factor (see below). The default value is 1.
ρ specific resistance of blood
L distance between pair of electrodes
G measured conductance
G^P parallel conductance (see below)

L is available from catheter data sheets, while ρ can be measured directly if appropriate equipment is available.

parallel conductance, G^P

The conductance measured by the catheter is actually the conductance of the blood and of the surrounding myocardial tissue; this latter conductance is called the parallel conductance (GP).

alpha factor, α

The alpha factor in fact takes into account several other factors that influence the measured signal: the fact that catheter segments do not span the entire ventricle, the non-uniformity of the electrical field inside the ventricle, the geometry of the left ventricle…

If the alpha factor is not taken into account, the calculated volume will be an underestimate of the actual volume.

calibration procedure

There is a fairly linear relationship between absolute volumes and measured conductance. The calibration involves determination of the gain and offset of this relationship.

gain

There are two approaches for determining gain:

• cuvette calibration: measuring the conductance of a known volume of blood. This method sometimes provides inaccurate results.
• direct approach: directly measuring a stroke volume (sv) or cardiac output (co), then calculating the gain as: value measured directly divided by value measured by conductance catheter

The gain factor should ideally be determined in every experiment. Unfortunately, there is no simple method for measuring volume. The gold standard is thermodilution; other possibilities include using an aortic flow probe or echocardiography.

If no method is available, use the default α proposed by iox or enter a value obtained in the same species under identical or similar experimental conditions (in published studies for example).

offset

In every case, the offset (parallel conductance) must be calculated.

In practice, the parallel conductance is usually taken into account by deducting a correction volume from the calculated total volume. To obtain the correction volume, a saline solution may be injected into the subject, to reduce the blood resistance and therefore simulate increased ventricular volume. Vmax and Vmin measurements are made over several beats. The Vmax points measured for different simulated volumes lie along a straight line, as do Vmin points. The Vmax and Vmin lines are extrapolated, and at the point where they cross, Vmax = Vmin = 0, so the conductance is parallel conductance only. The volume at this point is the correction volume.

 

setups

emka TECHNOLOGIES provides full setups for left ventricular PV loop studies for all species.

Several models of catheters are made by Millar Inc, including the Ultra-Miniature Pressure-Volume Catheters for rodents.

The pressure and volume signals travel from the catheter, to the signal conditioning unit (model MPVS-300 from Millar) then to a strain-gauge amplifier board in the amplifier mainframe.

The outputs from the amplifier mainframe go to the acquisition card of the PC via the interface box.

The PC must be running iox2 for the acquisition. The pressure-volume analyzer is an add-on module specifically designed for processing left ventricular PV loop data.

 

 

pressure-volume (PV) analyzer

The PV analyzer in iox software .

 

further reading

Baan J et al (1984) Continuous measurement of left ventricular volume in animals and humans by conductance catheter. Circulation 70: 812-823

Seminal paper that first described the conductance catheter technique (free full-text article).

Pacher P, Nagayama T, Mukhopadhyay P, Bátkai S, Kass DA (2008) Measurement of cardiac function using pressure–volume conductance catheter technique in mice and rats. Nature Protocols 3(9): 1422-34.

Supplementary information (video files) available online here