Name: Saline Calibration and Aortic Flow Calibration in a Murine Heart Failure Model
Uploaded: 2023-07-21T14:55:00
Description: Watch this Scientific Journal Video about Saline Calibration and Aortic Flow Calibration in a Murine Heart Failure Model at JoVE.com

saline calibration and aortic flow calibration in a murine heart failure model

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 Saline Calibration and Aortic Flow Calibration in a Murine Heart Failure Model at JoVE.com

Saline Calibration and Aortic Flow Calibration in a Murine Heart Failure Model  

To begin, place the anesthetized animal in the surgical area, ensuring that the surgical site is adequately shaved and disinfected. Catheterize the animal through standard surgical procedures. Next, hold the ventilator and administer 5 to 10 microliters of hypertonic saline solution intravenously through the central venous catheter.During the saline injection, record the changes in pressure and volume, and utilize power lab to calculate the VP value. To avoid disrupting the volume signal, position the mouse on its left side, then make a lateral thoracotomy towards the spine between the third and fifth thoracic vertebrae. Gently dissect a small part of the descending aorta using forceps, then place a vascular flow probe over the aorta to measure the cardiac output.