Abstract Introduction The commonly used Pressure-Volume loops focus on the cavity volume and quantify the cardiac systolic work. We focused on changes in wall geometry and have hypothesized that pressure-wall area relationships, in short-axis, relate to the intra-myocardial work (IMW) that is stored during systole and released during early diastole. Purpose The study aims to validate the novel IMW concept and to test its ability to quantify the severity of diastolic dysfunction in a model of myocardial injury during inflammation. Materials and Methods Short-axis ultrasound cines were continuously acquired (12MHz, 40-70 fps) in Langendorff perfused isolated rat hearts (N=7), with unique preload and afterload control of both ventricles. Dedicated artificial intelligence segmentation model was developed for fast and accurate quantification of both Pressure-Volume loops and IMWs. Inflammatory myocardial injury was emulated by adding MMP8 (secreted by activated macrophages and neutrophils) to the perfusion. Results 120,000 echocardiographic images of isolated rat hearts (n=7) were analyzed. The wall dynamics generated counterclockwise loops on the pressure-wall area plane that consisted of three phases: (1) Initial fast and large wall thickening, with 74±15% of the total wall area increase and only 7.79±6.44% of the total systolic pressure development. (2) The main (94.71±8.01%) systolic pressure upstroke, with only minor further changes in wall area. (3) Closure of the IMW loop during the diastolic isovolumic relaxation. This phase describes the fast energy release, when moving over the hypotenuse of the triangle-like loop, from end-systole to the end of the isovolumic relaxation. The IWM generated during the two systolic phases and released during diastole was of the same order as the systolic external work. MMP perfusion led to progressive shift of the end-diastolic pressure cavity-volume relationship to lower volumes, with marked decrease in end-diastolic volume (-20.0±17.2%, p=0.04) at the same filling pressure. There were insignificant changes in the systolic maximal elastance, hence, the progressive decline in myocardial recoil was associated with decrease in the external work. In parallel, there was conspicuous drop in the IMW (-60.82±19.44%, p=0.03). While the e` tracks the motion of a single point on the mitral annulus, the suggested IWM is based on monitoring a large myocardial mass and is easier to be acquired. The major fast changes in the IMW loops occurred at the isovolumic contraction and relaxation phases, and they relate to myocardial twist and recoil and to fast changes in myocardial shape. Conclusions The novel IMW is easily derived from short-axis echocardiographic images, and describes the systolic-to-diastolic energy conversion. The matrix plays a key role as the main energy storage element for myocardial recoil. IMW may play important roles in cardiac recoil and in assessment of diastolic dysfunction.Intra-myocardial work - MMP8 perfusion
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