Reyes Liliana Jelú, Alfaro Maria Emilia, Kireta Janet Akoth, Joyner Michele Lynn, Ullas Soumya, LaViolette Brianna, Hirenallur-Shanthappa Dinesh, Tania Nessy
Translational Clinical Sciences, Pfizer Research and Development, Cambridge, MA, 02139, USA.
Department of Mathematics and Statistics, East Tennessee State University, Johnson City, 37614, USA.
Sci Rep. 2025 May 25;15(1):18216. doi: 10.1038/s41598-025-00691-2.
Left ventricular pressure-volume (PV) loop measurement provides insights into cardiac function by mapping the relationship between left ventricular pressure and volume throughout the cardiac cycle. PV loops are used extensively in pre-clinical studies, but they are obtained through invasive and often terminal procedures. In prior studies utilizing data from large mammals (e.g., pigs and humans), quantitative models have been utilized to estimate PV loops utilizing non-invasive measurements. These studies rely on three key assumptions: constant normalized elastance (ratio of pressure over volume) across individuals, accurate non-invasive estimation of left ventricular systolic and diastolic pressure, and non-invasive estimation of left ventricular volume data. Here we assessed the application and suitability of these approaches to mice, a smaller pre-clinical animal. We found limitations of this approach due to variability in elastance among mice, suggesting that the constancy observed in larger animals might not generally extend to rodents. Additionally, while non-invasive estimates of end systolic pressures were close to invasively obtained measurements, they were not reliable for determining maximum elastance. Moreover, although individual correlations between invasive and non-invasive volume measurements were strong, creating a generalized predictive model of pressure-volume loop proved challenging due to variability across sample data set.
左心室压力-容积(PV)环测量通过描绘心动周期中左心室压力与容积之间的关系,为心脏功能提供了深入见解。PV环在临床前研究中被广泛应用,但它们是通过侵入性且通常是终末期的程序获得的。在先前利用大型哺乳动物(如猪和人类)数据的研究中,已使用定量模型通过非侵入性测量来估计PV环。这些研究依赖于三个关键假设:个体间归一化弹性(压力与容积之比)恒定、左心室收缩压和舒张压的准确非侵入性估计以及左心室容积数据的非侵入性估计。在此,我们评估了这些方法在小鼠(一种较小的临床前动物)中的应用和适用性。我们发现由于小鼠之间弹性的变异性,这种方法存在局限性,这表明在较大动物中观察到的恒定性可能一般不适用于啮齿动物。此外,虽然收缩末期压力的非侵入性估计接近通过侵入性获得的测量值,但它们对于确定最大弹性并不可靠。而且,尽管侵入性和非侵入性容积测量之间的个体相关性很强,但由于样本数据集的变异性,创建压力-容积环的广义预测模型被证明具有挑战性。