ism itself. A number of hypotheses have been articulated to Advances in liver surgery and transplantation have provide mechanistic explanations for reperfusion injury: free lead to a steady increase in the number of these interradical generation and attack of unsaturated lipids, proteins, ventions. Prompt quantitative assessment of hepatic and nucleic acids; increased turnover of membrane phosphofunction and a patient's subsequent morbidity and morlipids; and disturbances of calcium homeostasis at the cellutality following surgery remain difficult despite the curlar level. 1,2 Regardless of the mechanism of reperfusion inrently utilized historic markers of hepatic parenchymal jury, it is widely acknowledged that such injury is associated injury (e.g., aspartate transaminase [AST], lactate dehywith the concomitant release of intracellular enzymes, 3-5 indrogenase [LDH], g-glutamyl transpeptidase [GGT]). Including glycohydrolases, most of which are of lysosomal oricreases in serum glycohydrolase activities appear to gin (the exception being the broad-specificity b-glucosidase, provide sensitive and quantitative markers of hepatic ischemia/reperfusion injury. In 10 male swine (25 to 35 which is primarily of cytosolic origin). kg body weight) following 30, 45, and 90 minutes of acute
The liver is one of the organs that is most sensitive to hepatic ischemia, the systemic release of eight different ischemia. [5][6][7] Advances in liver surgery and liver transplantaglycohydrolases and lipid peroxides into serum were detion in particular have stimulated the search for quantitative termined and compared with pre-and postischemic sebiochemical markers that would provide surgeons and clinirum levels of LDH, GGT, and AST. The rapid release of cians with a means of assessing objectively and expeditiously glycohydrolases into serum was directly proportional to the functional integrity of the liver after various surgeries the length of the ischemic period from 30 to 90 minutes have been performed, in particular those which require iso-(e.g., b-glucosidase, mean 1.9-fold increase at 30 minutes; lating the organ from its normal blood supply for significant 8.3-fold at 45 minutes; and 22.8-fold at 90 minutes; P õ periods of time. The enzymes that have been used historically .002) and the activities peaked within the first 3 hours' and which are still relied upon today to monitor liver function postischemia. In contrast, AST, LDH, and GGT were repostsurgically, include lactate dehydrogenase (LDH), g-gluleased slowly and peaked 20 to 30 hours after hepatic tamyl transpeptidase (GGT), and aspartate transaminase blood flow was restored. In swine with fatal outcomes (AST). Increased plasma activities of a number of glycohydro-(90 minutes of ischemia), all enzyme levels increased lases have been found to result from a variety of liver injuries, continuously during the final hours of life. However, in including: carbon tetrachloride-induced liver cirrhosis, 8 parswine that survived hepatic ischemia/reperfusion injury tial hepatectomy, 9,10 hepatic dearterialization, 11 hepatic cryo-(45 minutes of ischemia) the glycohydrolases, but not surgery, 12 and cold and warm hepatic ischemia. [13][14][15] Free radi-AST, LDH, and GGT, declined after 2 to 3 hours' postischcals produced by liver injury are thought to be the mediators emia and the serum lipid peroxide levels followed the responsible for hepatic damage and have been described in same pattern. Serum b-galactosidase and b-glucosidase many animal models. 6,7,[16][17][18] In 1991, Chang et al. 19 reported levels are sensitive markers that rise as quickly as tradithat following liver transplantation in the pig the activity tional enzyme markers (AST, LDH, GGT) following helevels of several glycohydrolases of lysosomal and cytosolic patic ischemic injury; moreover, the glycohydrolases origin (e.g., b-galactosidase, b-glucuronidase, and b-glucosihave the added value of serving as predictors of survival. dase) increased markedly in serum. They found that after an (HEPATOLOGY 1996;24:157-162.) ischemic period lasting approximately 2 hours, and within 15 to 180 minutes after reestablishing the hepatic circulation, the plasma levels of these enzymes increased 50 to 150 times Periods of ischemia as brief as 30 to 40 minutes followed above their respective presurgical levels. However, not all by reperfusion with oxygenated blood usually result in some glycohydrolases they analyzed followed this pattern; for exdegree of injury to the organ in question. The extent of the ample, serum a-mannosidase and a-glucosidase levels did injury may be moderate and reversible and compatible with not increase after liver transplantation. Furthermore, the life, or it may be so severe and extensive as to cause cell temporal patterns observed in the serum levels of LDH and death, organ failure, and ultimately the demise of the organ-AST were markedly different from those of the three glycohydrolases they measured. The former two markers of hepatic injury increased more slowly, peaked 20 to 30 hours later and remained elevated longer than the serum glycohydrolases.
Abbreviations: LDH, lactate dehydrogenase; GGT, g-glutamyl transpeptidase; AST, aspartate transaminase.