Point-of-care detection of myocardial injury, a pre-clinical study

Evaluation of myocardial function is critical in severe inflammations as myocarditis, COVID-19 and sepsis, since it can lead to organ failure and death. Point-of-care detection of myocardial injury may improve the treatment of these critically ill patients. The study aimed to develop point of care technology for assessing the systolic and diastolic cardiac functions in animal model of systemic inflammation. Ultrasound and ventricular pressure were continuously recorded in Langendorff perfused isolated adult rat hearts. A computer controlled system controlled the ventricle loading conditions. The preload of both ventricles swung in a sinusoidal manner between target values of 2 and 22 mmHg. Collagenase (MMP8) was added to the Krebs-Henseleit solution following baseline recordings, to emulate the release of MMPs from activated leukocytes and macrophages. Collagenase perfusion led to gradual decline in peak systolic pressure and decrease in the end-diastolic volume (EDV), that were associated with concentric myocardial wall thickening. Extracellular matrix degradation by collagenases caused sever diastolic dysfunction with overt shift of the end-diastolic volume toward lower volumes, without significant changes in the epicardial diameter. Early detection of these signs may assist in assessing the severity of the myocardial injury and prompt the adequate treatment. © 2021 IEEE.

Early mechanical signs of myocardial injury in a model of systemic inflammation

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 enddiastolic 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.