The Meaning of Different Forms of Structural Myocardial Injury, Immune Response and Timing of Infarct Necrosis and Cardiac Repair

Abstract

Although a decline in the all-cause and cardiac mortality rates following myocardial infarction (MI) during the past 3 decades has been reported, MI is a major cause of death and disability worldwide. From a pathological point of view MI consists in a particular myocardial cell death due to prolonged ischemia. After the onset of myocardial ischemia, cell death is not immediate, but takes a finite period of time to develop. Once complete myocytes' necrosis has occurred, a process leading to a healed infarction takes place. In fact, MI is a dynamic process that begins with the transition from reversible to irreversible ischemic injury and culminates in the replacement of dead myocardium by a fibrous scar. The pathobiological mechanisms underlying this process are very complex, involving an inflammatory response by several pathways, and pose a major challenge to ability to improve our knowledge. An improved understanding of the pathobiology of cardiac repair after MI and further studies of its underlying mechanisms provide avenues for the development of future strategies directed toward the identification of novel therapies. The chronologic dating of MI is of great importance both to clinical and forensic investigation, that is, the ability to create a theoretical timeline upon which either clinicians or forensic pathologists may increase their ability to estimate the time of MI. Aging of MI has very important practical implications in clinical practice since, based on the chronological dating of MI, attractive alternatives to solve therapeutic strategies in the various phases of MI are developing.

A theoretical timeline for myocardial infarction: immunohistochemical evaluation and western blot quantification for Interleukin-15 and Monocyte chemotactic protein-1 as very early markers

“…The finding of IL-15, MCP-1 expressions in the cardiac specimens of early infarction confirm a considerable amount of existing data that show the role of humoral (cytokines and inducible chemokines, complement, and toll-like receptors) and cellular (monocytes, macrophages, dendritic cells, T cells, mast cells, platelets, endothelial cells) mediators in the initial healing phases following cardiomyocytes death [ 4 , 6 , 17 , 24 - 31 ]. Activation of cytokine cascades in the infarcted myocardium was established in numerous studies.…”

“…Activation of cytokine cascades in the infarcted myocardium was established in numerous studies. In experimental models of myocardial infarction, the induction and release of the pro-inflammatory cytokines are regularly described [ 16 , 17 ]. The multifunctional, overlapping and often contradictory effects of the cytokines have hindered understanding of their functional role in cardiac injury and repair.…”

“…They may trigger catecholamine myotoxicity linked with ventricular fibrillation and acting through free radical mediated lipid peroxidation with intramyocellular Ca2+ influx. Contrary to the general opinion that excess catecholamines produce cardiotoxicity mainly through binding to adrenoceptors, there is increasing evidence that catecholamine-induced deleterious actions may also occur through oxidative mechanisms [ 37 , 38 ], which undoubtedly occur during myocardial reperfusion after ischemia [ 17 ]. Interstitial edema and wavy fibers have been also described [ 39 ] in very early infarct but these findings are very unspecific [ 21 ].…”

Diagnosis of myocardial infarction at autopsy: AECVP reappraisal in the light of the current clinical classification

“…Other protein markers have been shown to undergo early changes in their phosphorylation state, as is demonstrated for connexin 43 [54,55]. Markers/mediators of early inflammation (CD15, IL-6, TNF-α, IL-15, IL-8, CD18 and tryptase) have also been proposed [56]. Some of them are promising in terms of early expression and specificity (dephosphorylated connexin 43), but they have been mainly investigated in experimental models [55].…”

Caffeoylquinic Acid Derivatives Extract ofErigeron multiradiatusAlleviated Acute Myocardial Ischemia Reperfusion Injury in Rats through Inhibiting NF-KappaB and JNK Activations

“…Injury was more dominant from reperfusion than that from ischemia and release of inflammatory substance was thought to be the main cause of reperfusion-associated pathologies, such as cardiomyocyte death, contraction band necrosis, no reflow, and ventricular arrhythmia [ 4 – 6 ]. MI triggers a reparative response in which 3 overlapping phases (inflammatory, proliferative, and remodeling phase) are well described by Turillazzi et al [ 7 ]. Following cardiomyocyte death, an intense inflammatory response is detectable in the infarcted myocardium.…”