Myocardial microvascular permeability, interstitial oedema, and compromised cardiac function

Abstract

The heart, perhaps more than any other organ, is exquisitely sensitive to increases in microvascular permeability and the accumulation of myocardial interstitial oedema fluid. Whereas some organs can cope with profound increases in the interstitial fluid volume or oedema formation without a compromise in function, heart function is significantly compromised with only a few percent increase in the interstitial fluid volume. This would be of little consequence if myocardial oedema were an uncommon pathology. On the contrary, myocardial oedema forms in response to many disease states as well as clinical interventions such as cardiopulmonary bypass and cardioplegic arrest common to many cardiothoracic surgical procedures. The heart's inability to function effectively in the presence of myocardial oedema is further confounded by the perplexing fact that the resolution of myocardial oedema does not restore normal cardiac function. We will attempt to provide some insight as to how microvascular permeability and myocardial oedema formation compromise cardiac function and discuss the acute changes that might take place in the myocardium to perpetuate compromised cardiac function following oedema resolution. We will also discuss compensatory changes in the interstitial matrix of the heart in response to chronic myocardial oedema and the role they play to optimize myocardial function during chronic oedemagenic disease.

Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

“…Indeed, an increase in cardiac water content by as little as 2.5% leads to a 30% to 40% reduction in cardiac output. 42,43 Furthermore, the remarkable improvement of cardiac function seen with our lymphangiogenic therapy is likely attributable to a combination of both direct (interstitial fluid pressure normalization) and indirect (cardiac fibrosis) effects of limiting myocardial edema. Different from lymphatic networks in other organs, 44,45 notably the essential absence of smooth muscle cells on cardiac precollectors, and only sparse muscular cells on its collecting ducts, 30 the heart largely depends on extrinsic factors for regulation of its lymphatic drainage.…”

Targeting of Extracellular RNA Reduces Edema Formation and Infarct Size and Improves Survival After Myocardial Infarction in Mice

“…Importantly, cardiac function is already significantly compromised once the interstitial fluid volume is moderately increased 2. Myocardial edema formation represents a major clinical problem and leads to vessel collapse, stunning of the myocardium, induction of arrhythmias, and impaired cardiac function.…”

“…Edema occurs in response to ischemia/reperfusion, inflammation, organ transplant rejection, or cardioplegic arrest during surgical interventions such as coronary artery bypass grafting 3. Following myocardial infarction (MI), vascular permeability (VP) across the microvascular endothelium is increased, resulting in persistent postischemic vasogenic edema 2, 4. Myocardial tissue in the border zone of the MI is partially perfused by collateral vessels, preventing necrosis of these acutely undersupplied myocardial regions.…”

A non-canonical Notch complex regulates adherens junctions and vascular barrier function

“…While a host of soluble factors including growth factors, circulating lipids, and reactive oxygen species chemically signal to endothelial cells, hemodynamic forces locally and acutely regulate vascular permeability by remodeling endothelial cell-cell junctions and the cytoskeleton 6 . The shear stress of steady, laminar flow improves barrier integrity through stabilization of cell-cell junctions, while perfusion defects increase vascular permeability and contribute to pathogenesis of cardiovascular diseases including atherosclerosis 7 , stroke 8 , and myocardial infarction 9 . While in vitro studies have identified putative shear stress-responsive signaling pathways that mediate endothelial junction and cytoskeletal remodeling 7 , the mechanisms that link hemodynamic shear stress to the regulation of endothelial cell-cell junctions and vascular permeability remain unknown.…”