Chapter 4 Myocardial cell injury during ischemia and reflow
The transition from reversible to irreversible injury in the ischemic heart and the possibility of recovery following reflow is influenced by the following external and internal factors (Piper, 1990):o(a)The conditions of the ischemic region define the recovery. Such regional factors are: the time and the completeness of the vascular stenosis or occlusion; the role of the vascular resistance to flow; the existence of sufficient collateral flow; the presence or absence of a vascular no-reflow phenomenon; the tissue pressure, cellular and interstitial edema. The status of the surrounding myocardium also contributes to the outcome.(b)The injured cell type is also critical. Of importance is the myocyte syncytium connected by intercalated disks, the endothelium, and the vasculature.(c)The outcome and recovery are influenced by the relative deficiency of ATP and CrP and by the ability of the energy-producing machinery to resume ATP and CrP synthesis. The outcome is also determined by the ability of the plasma membrane to control the intracellular environment and of the lysosomal system to contain the catabolic enzymes.(d)There are promoting and retarding factors, such as the availability of glycolysis, the acidity of the ischemic tissue, which inhibits catalytic functions, and the inactivation of the cardiac contractile function that spares energy substrate.(e)Cell interactions may contribute to further enhance cell injury. Such interactions include the adhesion of leukocytes and the mechanical stress by surrounding myocardium.(f)The time course of injury and the existence of a transition phase from reversible to irreversible injury are influential concepts, but whether they are applicable to all forms of injury is unknown. The recovery phase is characterized by a myocardium which turns on synthetic functions. However, the available data do not shed sufficient light on the resumption of synthetic activity. The nuclear morphology is changed very early following ischemic injury. This and metabolic alterations may be the most interesting aspects of the phase of stunning and hibernation and of the reversible phase of injury. It is important not to focus exclusively on the myocytes alone, because leukocytes, macrophages, platelets, fibroblasts, and the interstitium shape the fate of the ischemic tissue significantly. Although reflow is a "conditio sine qua non" to recovery, there is ample evidence that reflow can be injurious. Methods are being developed which reduce the deleterious effects of reperfusion. © 1998 Elsevier B.V. All rights reserved.
Gurbel, PA; Serebruany, V; Mergner, WJ; Kolodgie, F
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