Introduction

Abstract

Acute ischemia most often is the result of intrinsic obstruction of major arteries by clot. Emboli from the heart and thrombosis of a diseased artery are the most frequent causes of obstruction. It is widely held that early restoration of blood flow will prevent damage; however, recent reports suggest that even short periods of ischemia may cause cellular injury.1Bulkley GB. The role of oxygen free radicals in human disease processes.Surgery. 1983; 94: 407-411PubMed Google Scholar Tolerance to ischemia may be difficult to assess because some cells are more susceptible to anoxia than others. Presumably these differences reflect the oxygen requirements of a particular cell, and it is interesting to compare the oxygen needs of tissues. There is, for example, a fourfold difference between respiratory rates of the skin and the retina, and apparently the brain is particularly vulnerable to hypoxia. Traditionally it has been said that the brain can withstand only a few minutes of hypoxia, but muscle may survive 4 to 6 hours of ischemia without apparent harm.2Malan E Tattoni G. Physio-and anatopathology of acute ischemia of the extremities.J Cardiovasc Surg. 1963; 4: 2-8Google Scholar Recent clinical and experimental evidence suggests that these views may be inaccurate. Even short periods of ischemia are capable of causing cell damage that may not be apparent when one is viewing the overall function of the organ system. There is much evidence to suggest that the outcome after a period of ischemia depends not only on the specific tissue tolerance to hypoxia and the duration of the ischemia but also on local changes that can interfere with restoration of perfusion. This has been called, among other things, the “no-reflow” phenomenon.3Ames A Wright RL Kowada M et al.Cerebral ischemia—the no-reflow phenomenon.Am J Pathol. 1968; 52: 437-445PubMed Google Scholar Assuming that all of the clot is removed from the arterial system, one usually anticipates recovery. Is there persistent cell damage from transient episodes of severe ischemia? It appears that there may be. Studies of ischemic brain have revealed depletion of high-energy phosphate compounds and a persistent increase in tissue lactate, which is thought to produce cellular dysfunction.4Siesjo BK Rehncrona S. Cellular metabolic changes in complete and severe incomplete ischemia.in: Induced skeletal muscle ischemia in man. Karger, Basin1982: 3-24Google Scholar Studies of other cells have shown that the maintenance of normal cell volume depends on tissue perfusion.5Stern JR Eggleston LV Herns R Krebs H. Accumulation of glutamic acid in isolated brain tissue.Biochem J. 1949; 44: 410-416Crossref Scopus (65) Google Scholar In the absence of oxygen, tissues gain weight because of an increase in cell water content, perhaps reflecting cell membrane damage. The exact cause of cellular damage associated with hypoxia is not clear, but toxic oxygen radicals have been implicated. Studies of ischemic intestine, kidney, and heart have suggested that these toxic species are capable of inflicting serious damage.6McCord JM. Oxygen-derived free radicals in postischemic tissue injury.N Engl J Med. 1985; 312: 159-163Crossref PubMed Scopus (4976) Google Scholar A sudden burst in production of these radicals with restoration of flow has been seen. Partial ischemia may on occasion be more injurious than total ischemia, at least in skeletal muscle.7Perry MO Shires III, GT Albert S. Cellular changes with graded limb ischemia and reperfusion.J Vasc Surg. 1984; 1: 536-540PubMed Scopus (45) Google Scholar, 8Roberts JP Perry MO Hariri RJ Shires GT. Incomplete recovery of muscle cell function following partial but not complete ischemia.Circ Shock. 1985; 17: 253-258PubMed Google Scholar This damage is not related to persistent depletion of energy systems, and it is postulated that it may be caused by toxic oxygen radicals. Whatever the reason, it is clear that restoration of blood flow may not entirely solve the problem, even if accomplished early. The implications of these observations are important. The early correction of ischemia is essential, but a better understanding of the metabolic derangements that attend ischemia is critical. The strategy of managing acute ischemic events is complex; it requires a skillful blend of early detection, effective restoration of blood flow, and monitoring that permits the application of those supportive measures that assist the injured cell to return to normal function.