Inflammation in the course of early myocardial ischemia

Abstract

Experimental models of acute ischemic myocardial injury indicate that the inflammatory response after the ischemic event contributes to tissue damage. This is especially apparent with reperfusion of the ischemic tissue. In such models some therapeutic strategies designed to reduce neutrophil accumulation or function have resulted in apparently beneficial effects. Although such findings are encouraging, interventions into these pathological processes using specific molecular targets will require greater understanding of specific mechanisms. Current evidence indicates that potential sites of therapeutic intervention will be found in pathways leading to complement activation, generation of lipid-derived mediators, adhesion of neutrophils to endothelial cells and cardiac myocytes, and activation of neutrophil secretory processes releasing, for example, proteolytic enzymes and reactive oxygen. Understanding the dynamic interplay between the mediators, adhesion pathways, and secretory processes that results in myocardial damage will allow a rational approach to controlling the detrimental inflammatory consequences of ischemia and reperfusion.

Sphingolipid therapy in myocardial ischemia–reperfusion injury

“…Ischemia-Reperfusion (I/R) injury is characterized by the formation of oxygen radicals upon re-introduction of molecular oxygen to ischemic tissue, resulting in widespread lipid and protein oxidative modifications, mitochondrial injury, and cell death [4][5][6]. It is also characterized by an inappropriate inflammatory response in the microcirculation, resulting in an increase in leukocyte-endothelial cell interactions mediated by the up-regulation of both leukocyte and endothelial cell adhesion molecules [7,8]. The resulting increase in leukocyte accumulation and activation leads to massive release of tissue proteases and NADPH mediated free radical production further exacerbating endothelial cell, smooth muscle and microvascular injury [9].…”

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

“…Decreased levels of serum DNase I activity have also been observed in SLE patients (10). Furthermore, deficiencies in components of the classical pathway of complement are wellknown predisposing factors for this disease (11,12), and complement activation by tissue ischemia and reperfusion (a process known to generate necrotic cells) has been well established (13). Complement therefore contributes to tissue damage, but it also has important protective functions.…”

Lipoxin A4stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin

“…P-selectin promotes rolling of leukocytes, a key step in leukocyte-endothelium interaction, thus facilitating PMN adherence (13,16). Leukocytes adhere to the endothelium, and some of them transmigrate, thus potentiating endothelial dysfunction and tissue injury (17,18). Endothelial dysfunction, characterized by a reduced release of nitric oxide (NO), also has been shown to be critically related to increased leukocyteendothelium interaction via up-regulation of endothelial cell adhesion molecules (19).…”