Abstract 12259: Early Mechanical Signs of Myocardial Injury in a Model of Systemic Inflammation

Abstract

Introduction: Early detection of myocardial dysfunction in severe inflammations, as myocarditis COVID-19 and sepsis, is of great merit. We hypothesized that metalloproteinases (MMPs) discharge from activated macrophages and leukocytes dismantles the extracellular matrix (ECM), leading to diastolic and systolic dysfunctions. Methods: The right and left ventricle functions were studies in a unique Langendorff setup, with computer controlled preloads and afterloads, utilizing rat hearts (n=7). Collagenase (MMP8) was added to the Krebs-Henseleit solution after the baseline recording. Pressure-Area loops and changes in the cardiac geometry were continuously recorded by short-axis ultrasound cines (15MHz, 20 fps) of both ventricles. Results: ECM dismantling caused immediate systolic and diastolic dysfunctions, especially in the LV. Significant decreases in the LV systolic pressure and EDV developed with overt shift of the end-diastolic pressure-volume relationship toward lower volumes. The decrease in the EDV was associated with myocardial wall thickening. After collagenase perfusion yielded 10% drop in systolic pressure, LV EDV at EDP of 12 mmHg dropped by 20.0±17.2 % (p=0.04) and LV wall volume increased by 3.39±3.68 % (p=0.04), without significant changes in the epicardial diameter. Consequently, both diastolic stiffness to volume ratio (S2V) of the diastolic elastance to EDV, and myocardial wall thickness to cavity area ratio (W2C) significantly increased. S2V and W2C increased by 1.48±0.51 and 1.32±0.34 folds relative to baseline, respectively (p=0.03, p =0.03). S2V and W2C increased by 1.82±0.71 and 1.52±0.46 folds, respectively, after 20% drop in systolic pressure (p= 0.02, p=0.02). An intact ECM is essential for the diastolic recoil. Dismantling the ECM diminishes the diastolic recoil and increases diastolic stiffness. Interestingly, the right ventricle presented similar trends, but the changes were insignificant, and the RV was less vulnerable to damage. Conclusion: ECM degradation causes severe systolic and diastolic dysfunctions. Novel indices (S2V and W2C) for early detection of myocardial involvement in severe inflammatory diseases were developed.