Inflammation in ischemic heart disease: Response to tissue injury or a pathogenetic villain?

Time for primary review 32 days. The presence of inflammatory cells in the ischemic myocardial tissues has traditionally been believed to represent pathophysiologic response to injury [1]. It is only recently that inflammation has been related to the pathogenesis of acute coronary syndromes [2,3], reperfusion injury to ischemic myocardium [4], restenosis after angioplasty [5–7], failure of cardiac transplant [8], and chronic heart failure [9]. Accordingly, the relationship between inflammation with atherosclerosis and myocardial ischemia is now an area of active investigation. Accumulation of polymorphonuclear leukocytes (PMN) and their activation are key features of inflammatory reaction associated with acute myocardial ischemia-reperfusion [3]. Experimental studies have shown that influx of PMNs into tissues results in tissue injury beyond that caused by ischemia alone [10,11]. It has also become apparent that the recruitment of PMNs during ischemia-reperfusion involves numerous mediators [3,4]. The causative role of PMNs in reperfusion injury in animals is supported by the observations of reduction in microvascular dysfunction and tissue injury by strategies that prevent PMN influx in tissues by either a decrease in the number of circulating PMNs [12], or prevent PMN activation [13]. Other studies [14] have shown that inhibition of release of PMN-derived mediators of tissue injury [14] or blockade of adhesion molecules on PMNs [15,16] and/or endothelial cells [17] also reduce tissues injury. Many aspects of inflammation as a participant in myocardial ischemia in animal models have been reviewed in the recent past [16–19]. In this report, we review our current understanding of inflammation in myocardial ischemia in patients with myocardial ischemia. If the concept of a causative role of inflammation, especially PMN accumulation and activation, in ischemic heart disease (IHD) is proven, anti-inflammatory therapy may be designed to prevent and treat this common … * Corresponding author. Tel.: +1-352-379-4160; fax: +1-352-379-4161 mehta{at}medmac.ufl.edu