V alidity of Assessing in vivo Cardiac Contractility Using A “Less‐Invasive” Approach during Mechanical Ventilation: Insights from Small and Large Animal Models

Abstract

Background and Aims End-systolic elastance (Ees) derived from sequential pressure-volume (PV) loops acquired during inferior vena cava occlusion (IVCO) is the reference for quantification of in vivo left ventricular (LV) contractile performance. Given the challenges associated with midline laparotomy surgeries in animal models and the barriers of performing such measures in clinical practice, a number of single-beat estimations of LV contractile function have been proposed. Here, we examined the agreement between two single-beat estimates of Ees obtained from basal LV and arterial hemodynamics in rats and pigs and the Ees obtained from IVCO (Ees(IVC)). We also tested whether a novel approach of leveraging the respiratory-induced oscillations in cardiac PV (i.e., changes in intrathoracic pressure) during mechanical ventilation enables a “naturally” occurring change in cardiac preload and the subsequent estimation of Ees (Ees(RES)). Methods 38 Wistar rats (300-350g; aged 10 wks) and 22 Yucatan mini-pigs (20-25 kg, aged 8-12 wks) were used. Once anesthetized and ventilated, animals were instrumented with 1) a LV PV catheter for assessments of LV Ees(IVC) during IVCO and LV hemodynamics, and 2) a femoral arterial catheter to record basal systemic hemodynamics. Basal LV and arterial indices, including end-systolic volume (ESV), end-systolic pressure (ESP), and arterial systolic blood pressure (SBP), were averaged over a 30s (rats) or 60s period (pigs). Ees(IVC) was measured as the slope of end-systolic PV relationship (ESPVR). From the basal LV and arterial data we then calculated single-beat estimation of Ees(IVC), including the ESP and ESV ratio (EesSB1), and the ESP (SBP × 0.9) and EDV ratio (EesSB2). Estimation of Ees(RES) was analogous to Ees(IVC) however, respiratory-induced oscillations in cardiac preload, rather than an IVCO, was used to calculate the slope of the ESPVR. Absolute agreement between metrics was examined using intra-class correlation coefficients (ICC). Results In rats, while we found a moderate agreement between Ees(SB1) (ICC = 0.685, P < 0.001), Ees(SB2) (ICC = 0.685, P < 0.001) and Ees(IVC), there was excellent agreement between Ees(RES) and Ees(IVC) (ICC = 0.934 P < 0.001). In pigs, although a moderate agreement was observed between Ees(RES) and Ees(IVC) (ICC = 0.572, P = 0.033), no agreements were noted between Ees(SB1) (ICC = 0.352, P = 0.101), Ees(SB2) (ICC = 0.320, P = 0.0741) and Ees(IVC). Conclusion Thesefindings demonstrate that the single-beat estimates of Ees show moderate agreement with Ees(IVC) in rats. Utilizing the respiratory-induced changes in cardiac preload during mechanical ventilation, however, may provide a better less-invasive approach for estimation of cardiac contractile performance, especially in a small animal model.