Abstract 19523: Dismantling the Extracellular Matrix by Metalloproteinase Deteriorates Cardiac Diastolic Function Without Affecting the Maximal Elastance: Implications for Cardiac Inflammatory Diseases
Introduction: Sepsis and myocarditis are associated with significant diastolic dysfunction. The functional effects of changes in extra-cellular matrix (ECM) are not well defined.
Hypothesis: Dismantling of the collagenous ECM decreases the energy stored in the elastic elements during contraction and the restoring forces during early diastole. The associated interstitial edema also contributes to diastolic dysfunction.
Methods: Hearts of healthy rats (n=29) were excised and perfused with modified Krebs-Henseleit solution in a unique vertical Langendorff setup, with computer controlled preload and afterload. Filling pressure varied between 2 to 16 mmHg in a sinusoidal mode. The myocardium was dismantled by adding metalloproteinase 8 (neutrophil collagenase) to the perfusate while monitoring the pressure volume loops. Cardiac dimensions were measured by echocardiography and implanted sonocrystals.
Results: Peak isovolumic systolic pressure gradually decreased with associated decrease in the left ventricular (LV) volume (-30±2.8%, p<0.01) at the same end diastolic filling pressure. LV wall width increased at the expense of LV cavity (from 2.9±0.1 to 3.7±0.2 mm). There were no significant changes in the slopes of end-systolic pressure area relationship (maximal elastance) and end diastolic pressure area relationship (EDPVR). However, EDPAR shifted towards lower volumes (the intercept decreased from 28.0±3.1 to 17.3±3.1 mm2, p<0.01). Hysteresis evolved in diastolic pressure volume relationship, revealing a development of significant increase in viscosity due to ECM swelling. The decrease in LV cavity and the ensuing decline in systolic pressures were secondary to a decrease in ECM elastic recoil to original volume and increase in ECM viscosity. No changes were observed in myocyte size or morphology, but the extracellular volume increased from 3.0±0.7% to 20.4±4.7% of the cross-section area. Isolated cardiac fiber showed preserved normal fractional shortening.
Conclusions: ECM elasticity is crucial for proper systolic and diastolic functions. Dismantling the perimysium decreases the diastolic restoring forces and may play a key role in the development of diastolic dysfunction in various cardiac inflammatory diseases.
Author Disclosures: A. Landesberg: None. G. Ankri-Eliahu: None. G. Landesberg: None.
- © 2014 by American Heart Association, Inc.