Pulsed Wave Doppler Assessment of Diastolic Dysfunction in the ZSF-1 Rat Model of Pulmonary Hypertension Due to Left Heart Disease

Diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) are significant contributors to pulmonary hypertension (PH) due to left heart disease. Standard in vivo evaluation of relaxation abnormalities in preclinical models includes two-dimensional (2D) echocardiography with Doppler assessment of transmitral flow and tissue relaxation, which is complex, expensive, and requires sophisticated echocardiographic equipment. Here, a valuable surrogate method to evaluate diastolic dysfunction in PH due to left heart disease is demonstrated in a well-established rodent model using pulsed wave Doppler ultrasound without 2D echocardiography. Diastolic transmitral flow pattern is identified from the apical window and is correlated with a simultaneously recorded ECG tracing. Indices of diastolic function are collected, and the identification of these indices is described in this protocol. This low-cost, readily implemented technique identifies relevant markers of diastolic dysfunction associated with PH, cardiovascular disease, and HFpEF. Moreover, it reproducibly detects its progression over time, when 2D echocardiography is not preferred or available. The primary limitations of this method are related to the absence of visualization of cardiac structures, the potential for inaccuracies due to the angle dependence of the Doppler signal, as well as the animal's body habitus, which can be mitigated by adjusting the location of the probe and optimizing its alignment with blood flow.