Name: Determining the End-Systolic and End-Diastolic Pressure-Volume Relationships in a Murine Heart Failure Model and Transesophageal Pacing
Uploaded: 2023-07-21T14:55:00
Description: Watch this Scientific Journal Video about Determining the End-Systolic and End-Diastolic Pressure-Volume Relationships in a Murine Heart Failure Model and Transesophageal Pacing at JoVE.com

determining the end-systolic and end-diastolic pressure-volume relationships in a murine heart failure model and transesophageal pacing

Exploring HR-Dependent Cardiac Performance Using an Atrial-Pacing Protocol

Heart failure represents a leading cause of hospitalization and death across the globe, and heart failure with preserved ejection fraction (HFpEF) accounts for around 50% of all heart failure diagnoses. HFpEF is characterized by diastolic dysfunction and impaired exercise tolerance, and the associated hemodynamic abnormalities, such as diastolic dysfunction, can be clearly detected through exercise-stressed hemodynamic testing or MRI scans1,2.
In experimental models, however, available modalities for assessing the physiological abnormalities related to HFpEF are limited3,4. Treadmill exercise testing (TMT) is used to determine running time and distance, which might reflect exercise-stress cardiac hemodynamics; however, this method is susceptible to interference from extraneous variables such as the body weight, skeletal muscle strength, and mental status.
To circumvent these limitations, we have devised an atrial-pacing protocol that detects subtle but crucial changes in diastolic performance based on the heart rate (HR) and have validated its usefulness in a mouse model of HFpEF5. Several physiological factors contribute to exercise-related cardiac function, including the sympathetic nerve and catecholamine response, peripheral vasodilation, the endothelial response, and the heart rate6. Among these, however, the HR-pressure relationship (also called the Bowditch effect) is known as a critical determinant of cardiac physiological features7,8,9.
The protocol involves performing a conventional pressure-volume analysis at baseline to assess the systolic and diastolic function, including parameters such as the rate of pressure development (dp/dt), the end-systolic pressure-volume relationship (ESPVR), and the end-diastolic pressure-volume relationship (EDPVR). However, it should be noted that these parameters are influenced by the HR, which can vary between animals due to differences in their intrinsic heart rate. Additionally, the effects of anesthesia on the HR should also be considered. To address this, the HR was standardized by administering atrial pacing concomitantly with ivabradine, and cardiac parameter measurements were performed at incremental heart rates. Notably, the HR-dependent cardiac response distinguished HFpEF mice from the control group mice, while no significant differences were observed in the baseline PV loop measurements (using the intrinsic heart rate)5.
While this pacing protocol may seem relatively complicated, its success rate exceeds 90% when it is well understood. This protocol would provide a useful way to study the underlying mechanisms of diastolic dysfunction in HFpEF mouse models and help in the development of new treatments for this condition.

Author Spotlight: Investigating HR-Dependent Cardiac Function in Mouse Models Through a Novel Atrial-Pacing Approach 

A Pacing-Controlled Procedure for the Assessment of Heart Rate-Dependent Diastolic Functions in Murine Heart Failure Models

The heart rate-related relationship is important for determining cardiac characteristics, particularly, in HFpEF. This protocol aims to assess heart rate-dependent cardiac function. Any experimental models, available modalities for assessing heart rate-related cardiac function, are limited to treadmill exercise testing.The treadmill test, however, is influenced by variables such as body weight. To overcome these limitations, we have developed around atrial-pacing protocol to detect subtle, yet significant changes in the later performance that are linked to heart rate. Our protocol offers a variable tool for identifying cardiac dysfunction, manifested by heart rate changes.It also presents a number approach to studying diastolic dysfunction in mirroring heart failure models, particularly in HFpEF.

Watch this Scientific Journal Video about Determining the End-Systolic and End-Diastolic Pressure-Volume Relationships in a Murine Heart Failure Model and Transesophageal Pacing at JoVE.com

Determining the End-Systolic and End-Diastolic Pressure-Volume Relationships in a Murine Heart Failure Model and Transesophageal Pacing

To begin, place the anesthetized animal in the surgical area, ensuring that the surgical site is adequately shaved and disinfected. Next, properly place the conductance catheter through standard surgical procedures. To record and analyze the baseline pressure volume or PV loop, in the lab chart software, select the baseline parameters, then click the Analyze Now button.Select the baseline option. Open the hemodynamic table and select the average data. Perform inferior vena cava or IVC occlusion by compressing the IVC using forceps.In the software, manually select the point of occlusion of IVC where both left ventricular pressure and volume decrease. Then record the PV loop for at least 20 cardiac cycles while the IVC remains occluded by selecting the occlusion option and then clicking the Analyze Now button. To perform transesophageal pacing, insert a 2-French tetrapolar electrode catheter into the esophagus.Connect the catheter to a pulse stimulator, then proceed to determine the atrial capture threshold. To slow the heart rate below 400 beats per minute, administer 20 milligrams per kilogram of ivabradine intraperitoneally. Following stabilization, acquire 20 continuous cardiac cycles of PV loops while pacing the heart at different rates from 400 to 700 beats per minute.The baseline PV loop data showed no significant differences in diastolic parameters, such as the relaxation time constant, the minimum rate of pressure change, and the end diastolic pressure volume relationship, or EDPVR, between the control and HFpEF mice. However, the HFpEF mice exhibited higher blood pressure and arterial elastins, demonstrating a typical mountain-shaped PV loop during ventricular systole. This PV loop was distinguishable from a spike caused by direct contact of the ventricular muscle on the pressure transducer.Notably, using atrial pacing, the diastolic function could be clearly distinguished between the control and HFpEF mice. In the control group, both the relaxation time constant and EDPVR improved as the pacing rate increased. Whereas in the HFpEF group, both the relaxation time constant and EDPVR worsened as the heart rate increased with atrial pacing.