Non‐Perfused Coronary Arteries Are Able to Maintain Structural Integrity in Developing Scar Tissue Following a Transmural Myocardial Infarction

Abstract

IntroductionWhereas considerable effort has been devoted to identify a suitable source of contractile cells to be used for replacement of a post‐myocardial infarction (MI) scar with the newly‐formed cardiac muscle tissue, an exploration for the viable routes of arterial blood supply to the sites of regenerating myocardium remained mostly neglected. However, the presence of a sustainable blood delivery system seems imperative for survival of newly‐grown myocardium.HypothesisWe hypothesize that if the vessels of the original arterial bed, remaining in post‐MI region, will be able to maintain their structural integrity for the duration of post‐MI scar formation they can potentially be suitable for use as a natural blood delivery system to support the regenerating myocardium.MethodsA large transmural MI was induced in middle‐aged, male Sprague‐Dawley rats by permanent ligation of the left coronary artery. Post‐MI rats were euthanized 3, 7 and 14 days after occlusion and their hearts were processed to paraffin for morphological evaluation. Sham‐operated rats were used as age‐matched controls. Serial sections from each heart were stained with various histological techniques or with an anti‐smooth muscle alpha‐actin antibody. Images were captured using a Leica DM 4000B microscope and analyzed by Image‐Pro Analyzer v.7.0 software. Statistical analysis was performed using Prism 6 software package.ResultsWe found that whereas most arterioles and small arteries within an infarcted region have undergone necrosis during 3 days after MI, the medium‐sized and larger arteries appeared to preserve their structural integrity up to 14 days post‐MI. Quantitative assessment showed that surviving residual arteries continued to maintain their structural parameters, such as external diameter, lumen diameter, wall thickness and wall‐to‐lumen ratio, during 7 post‐MI days. However, in 14‐day‐old scars, some non‐perfused arteries began to demonstrate the evidence of noticeable neointimal thickening, composed of activated smooth muscle cells, that narrowed the vessel lumen and led to a significant increase in wall‐to‐lumen ratio (0.35±0.02 in post‐MI rats vs. 0.11±0.01 in sham‐operated rats, P<0.0001). Moreover, the majority of remaining vessels showed a various degree of degenerative changes, including perivascular and intravascular collagen accumulation, disintegration of internal elastic lamina and patchy disappearance of smooth muscle cells from the vessel media.ConclusionOur findings reveal that a number of large and medium‐sized coronary arteries, residing in post‐infarcted region, were capable of maintaining their structural integrity during two post‐MI weeks. This observation supports a concept that these vessels can be used as a potential route for reestablished arterial blood supply that would be necessary to facilitate the replacement of scar tissue by newly‐formed cardiac muscle.Support or Funding InformationNew Jersey Health Foundation