Forsøksdyr: Noninvasive pressure-volume method for improved evaluation of cardiac function

Godkjenningsdato 03.12.2020

Godkjenningsperiode 04.12.2020-03.12.2024

Pressure-volume analysis is the gold standard for assessing ventricular function of the heart. However, this analysis is not done in clinical practice as it requires invasive measurement of ventricular pressure which is associated with stroke risk as well as it is a resource demanding procedure. We have developed a noninvasive method for estimation of ventricular pressure by echocardiography. Since volume already can be measured noninvasively by echocardiography, together this provides a novel new method for noninvasive pressure-volume analysis. Hence, all patients undergoing echocardiographic examination can potentially be investigated by this method.

The main object of this project is to verify this noninvasive echocardiographic pressure-volume method. We will verify the accuracy of the noninvasive method in our animal model where the echocardiographic method will be compared with invasive gold standard measurements. Invasive and noninvasive pressure-volume measurements will be compared during several interventions mimicking relevant clinical conditions. Of particular interest is its utility in left bundle branch block (LBBB) which is a cardiac conduction abnormality where the different walls of the left ventricle are electrically stimulated and contract at different times (dyssynchrony). This condition often results in a reduction in pump function which can end up developing or worsening heart failure. This condition can be treated with cardiac resynchronization therapy (CRT), which is a medical device that resynchronizes the ventricle's contraction by sending electric impulses to the heart muscle. However, the response varies strongly among patients and approximately 30-40 percent of them do not benefit from this therapy. The pressure-volume method may help identify the patients that may respond to this treatment and help optimize CRT-settings.

Myocardial efficiency has been shown to improve after CRT. As myocardial efficiency is one parameter that can be extracted from the pressure-volume analysis, we will investigate how myocardial efficiency changes from baseline to after induction of LBBB and with CRT and changes with different CRT-settings. How well the method reflects changes in cardiac function will also be investigated during changes in loading conditions, in response to drugs and during ischemia.

Based on data from previous similar trials, a total of 20 canine experiments are planned. The trials require extensive instrumentation of the heart and they will therefore be performed as acute, terminal attempts. During experiments physiological measurements will be registered at different intervals during the interventions. Canines tolerate the prolonged instrumentation without serious complications during the experiment, as opposed to porcines that have higher mortality. Furthermore, studies have shown that canines have most similar electrical conduction system to humans and therefore represent a good experimental model for LBBB, while for example porcines have a different purkinje system so they do not exhibit the same degree of dyssynchrony. The number of animals is reduced by collecting data for multiple studies at the same time without any significant increased risk of failed attempts.

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