A Pressure-Based Method for Estimation of Right Ventricular Ejection Fraction in a Rodent Model of Pulmonary Arterial Hypertension

Abstract

Background: Experimental studies of pulmonary hypertension (PH) in rodents commonly focus upon right ventricular systolic pressure (RVSP) and Fulton Index to quantify disease severity. While RV ejection fraction (RVEF) can also be measured in vivo with echocardiography or catheter-based measurement of intracardiac volume, widespread application is limited by cost and technical limitations. Nonetheless, in humans with PH, RVEF has prognostic significance suggesting value of the measure in experimental models. The present study was designed to test the hypothesis that a relatively simple method based entirely upon analysis of the RV pressure waveform can accurately estimate RVEF over the range evident in normal and PH animals. Methods: RV pressure and volume data sampled at 1000 Hz and acquired under IACUC-approved protocols from 15 rats (7 controls, 8 sugen/hypoxia PH) were used. Data had been recorded during isoflurane anesthesia and mechanical ventilation with a Millar Aria 1 PV System linked to an ADI Powerlab and a 1.4-F Millar conductance catheter introduced into the RV long axis via apical puncture. The volume signal was calibrated using the cuvette method and measured reference values for RVEF (EFmeas) calculated as stroke volume/end-diastolic volume. From the pressure signal, RVEF was estimated (EFest) as (Pmax-ESP)/Pmax where Pmax = the predicted RV pressure that would have been achieved if ejection did not occur, and ESP = end-systolic pressure defined from an event marker based upon the second derivative of RV pressure (figure 1A). Method comparison procedures were applied to describe correlation, accuracy (bias), and precision (limits of agreement or LOA). EFest was considered potentially interchangeable with EFmeas if the bias was <10% of the mean of all data and overall error (SD of the bias x 1.96/the mean of all EF values) was <30%. Results: Across the dataset, RVSP ranged from 22 to 96 mmHg and EFmeas from 0.19 to 0.60. Method comparison data (figure 1 B and C) demonstrate strong correlation between EFmeas and EFest (r 2 = 0.813, p< 0.0001), a bias of -0.02 (4% of mean) with LOA from -0.11 to 0.08, and an overall error of 20%. Conclusions: The study results demonstrate that when compared to RVEF directly measured by intraventricular conductance catheter in normal and PH rats, the pressure-based method provides RVEF estimates with a high degree of correlation, minimal bias, and modest error. These data suggest potential utility for RVEF estimation as an adjunct to RVSP in rat models of PH.

Defining end-systolic pressure for single-beat estimation of right ventricle–pulmonary artery coupling: simple… but not really

“…Under each condition, data were recorded at steadystate and during transient occlusion of the inferior vena cava to reduce preload. From steadystate recordings of RVP and volume, Pmax was predicted as previously described 10 , SV derived, and SB measures of Ees and Ea calculated using ESP defined by 4 different methods: a) RV pressure at the point of estimated time varying elastance (ESPtve) 10 ; b) mPAP 3 ; c) adjusted mPAP 8 ; and d) peak RVSP 7 . From MB caval occlusion data, Ees was determined as the slope of the ESPVR and Ea was calculated as ESP/SV with end-systole defined as the point of maximal pressure/volume ratio 11 .…”

“…However, in this study, the ESP for SB estimation of Ees and Ea was derived from a presumably linear end systolic pressure volume relationship (ESPVR), not as a specifically defined point in the cardiac cycle. More recently, Heerdt et al, described a method to define the point of maximal time-varying elastance for individual beats based upon the second derivative of the RVP waveform, and used this point to determine ESP for SB estimation of RV ejection fraction 10 .…”