Page 15 - Coronary hemodynamics in acute myocardial infarction - Matthijs Bax

General introduction and outline of the thesis
in days tot weeks. Secondly, reperfusion arrhythmias including ventricular 1 tachycardia and ventricular fibrillation occurring within seconds to minutes
after reflow are self-limiting or treatable and hence, reversible phenomena.22, 23
Lethal reperfusion injury as a controversial concept of myocyte cell death due
to reperfusion itself rather than ongoing ischemia.24, 25 Observations suggest that this irreversible and lethal reperfusion injury may explain up to 50% of the ultimate infarct size. Among important contributory factors are oxidative stress, calcium overload, mitochondrial permeability transition pore opening and hypercontraction of myocytes, rapid wash-out of lactic acid.26
The last form is vascular reperfusion injury or microvascular obstruction and refers to progressive damage to the vasculature during reperfusion phase.27, 28 It is recognized as expanding zone of no-reflow despite the open epicardial artery and as deterioration of coronary flow reserve.29 Post ischemic irreversibly injured myocardial cells may demonstrate an acceleration of the necrotic process when exposed to reperfusion including massive swelling probably aggravating obstruction of the smaller vessels.27 This microcirculatory disorder has also been demonstrated in post ischemic brain, kidney, small intestine and skeletal muscle. Various factors seem to contribute to no-reflow. Endothelial cells play a pivotal role in this process through regulation of vascular permeability, hemostasis, recruitment and homing of neutrophils and control of the vascular tone. Furthermore, capillary damage contributes significantly to this process. Besides gaps in the endothelium and neutrophil infiltration, the capillaries in the no-reflow areas show large protrusions of endothelial cytoplasm into the vascular lumen probably acting to occlusion of capillary lumens.27 The observed marked myocardial cell swelling is a manifestation of the loss of the capacity of the damaged cells to regulate cell volume.18 Tissue edema influencing reflow was due primarily to the accumulation of intracellular fluid consequently compressing capillaries.30 Oxidative stress elicited by reperfusion influence leucocyte to endothelial cell adhesion and alters Na+-H+ exchange affecting endothelial cell swelling. Reactive oxygen metabolites promote the formation of inflammatory agents that recruit and activate polymorphonuclear leukocytes.31 Besides physical leucocytes impaction in the capillary lumen partly due to their amount, the interaction with endothelial cells, the increased stiffness of the neutrophils in an ischemic, acid environment, the lower perfusion pressures based on macrovascular and
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