Liver mitochondrial function in familial amyloidotic polyneuropathy.

The objective of the present study was to analyze hepatic mitochondrial function in patients with familial amyloidotic polyneuropathy (FAP) undergoing cadaveric donor orthotopic liver transplantation. From February 2005 to May 2007, eight patients with FAP, ranging in age from 34 to 41 years and with Model for End-Stage Liver Disease scores ranging from 24 to 29. Underwent orthotopic transplantation using a liver from a deceased donor by the piggyback method. Immediately before beginning the recipient hepatectomy in a patient with FAP, a biopsy was obtained for analysis of mitochondrial function (FAP group). The control group consisted of 15 patients undergoing hepatic surgery to treat small tumors of the liver. Mitochondrial respiration was determined on the basis of oxygen consumption by energized mitochondria using a polarographic method. The membrane potential of the mitochondria was determined spectrofluorometrically. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at 5%. State 3 and 4 values, respiratory control ratio, and membrane potential were 47 +/- 8 versus 28 +/- 10 natoms O/min/mg protein (P < .05); 14 +/- 3 vs 17 +/- 7 nat.O/min/mg.prot.mit. (P > .05); 3.6 +/- .5 vs 1.7 +/- 0.7 (P < .05); and 135 +/- 5.2 vs 135 +/- 6 mV (P > .05) for control versus FAP patients, respectively, demonstrating a decreased energy status of the liver in FAP.

Evaluation of the respiratory muscle strength of cirrhotic patients: relationship with Child-Turcotte-Pugh scoring system.

Pulmonary abnormalities are observed in chronic hepatopathy. The measurement of the maximum inspiratory and expiratory pressure may evaluate lung function and the risks associated with hepatic transplantation. Thus, the present work sought to evaluate the respiratory muscle strength of 29 patients between 17 and 63 years old who were enrolled for liver transplantation. The patients were classified according to Child-Turcotte-Pugh score as A, B, or C, and also according to a physiotherapeutic evaluation, which included measurement of respiratory muscle strength by means of a digital manovacuometer, which determines the maximum inspiratory pressure (MaxIP) and the maximum expiratory pressure (MaxEP). The tests were performed with seated individuals having their nostrils obstructed by a nasal clip. The MaxIP was measured during the effort initiated in the residual volume, whereas the MaxEP was measured during the effort initiated in the total pulmonary capacity, keeping pressures stable for at least 1 second. The statistical analysis was performed through using the Mann-Whitney test with a 5% level of significance. The MaxIP values of Child A 95.5 +/- 40.507 cm H(2)O (average +/- DP) and Child B 87.2 +/- 35.02 patients were higher than those for Child C patients (34.83 +/- 3.68; P < .05). Similar results were observed for the MaxEP of Child A and B groups (116.25 +/- 31.98 and 97.28 +/- 31.08, respectively; P < .05), versus the Child C group (48.16 +/- 22.60). Between groups A and B, the MaxEP were similar (P > .05). We concluded that Child C patients display muscle weakness significantly greater than that of subjects classified as Child A or B.

Effects of ischemic liver preconditioning on hepatic ischemia/reperfusion injury in the rat.

To minimize bleeding during major liver resections or liver transplantation, surgical measures have been adopted that induce ischemia-reperfusion injury (I/R) which may significantly contribute to morbidity and mortality of partial liver resections. Several methods have sought to minimize I/R hepatic lesions. The present project assessed the protective role of ischemic preconditioning (IPC) in rat livers. The IPC was accomplished by clamping the hepatic pedicle for 5 minutes, followed by a 5-minute reperfusion (R) period before a 2-hour ischemia. Thereafter, reperfusions of 1, 3, and 24 hours were compared among IPC and control groups without IPC. Liver biopsy and blood samples were measured for mitochondrial respiratory control ratio (RCR), serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT). IPC protected liver mitochondrial function. Serum aminotransferase levels were significantly lower among animals undergoing IPC compared with groups without IPC. Thus, we verified the effects of IPC for hepatocellular protection against I/R lesions.

Effect of hyperbaric oxygen on liver regeneration in a rat model.

Hyperbaric oxygen therapy is a treatment that has been gradually implemented for the treatment of several pathologic conditions. The present study evaluated the effect of hyperbaric oxygen therapy for hepatic regeneration and its relationship to mitochondrial function. Male Wistar rats underwent partial hepatectomy (70%) and subsequently underwent two sessions of hyperbaric oxygen (90 minutes each, at a pressure of 2 ATA). The animals were sacrificed at 24 and 48 hours after surgery. Hepatic regeneration was evaluated by the dry weight of the remaining liver, the hepatic regeneration rate, the hepatic DNA content, and the hepatocyte proliferation rate using the "proliferating cell nuclear antigen" (PCNA) content. Function of the mitochondria was evaluated by its oxygen consumption during respiratory states 3 and 4, its respiratory control ratio (RCR), its membrane potential, as well as its osmotic swelling. We also measured serum levels of aminotransferases. The results revealed an increased dry weight of the remaining liver, regeneration rate, and DNA content at 24 and 48 hours after hepatectomy. The hepatocyte proliferation rate was significantly higher among animals treated with hyperbaric oxygen therapy at 48 hours after surgery. There was no significant difference in aminotransferase levels. Mitochondrial respiration revealed reduced oxygen consumption in state 3 after 48 hours. These results demonstrated that hyperbaric oxygen stimulates hepatic regeneration at 24 and 48 hours after 70% hepatectomy. The effect of hyperbaric oxygen on hepatic tissue occurs without tissue damage and protects mitochondria after 48 hours.

Serum transaminase levels in the acute phase of chronic extrahepatic cholestasis

Serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) levels are normal or discretely increased in rats with chronic extrahepatic cholestasis (CEHC). During the acute phase (first 72 h after biliary obstruction), however, serum transminase values are quite elevated due to a mechanism not yet fully elucidated. Thus, this is a good experimental model, not involving hepatocellular necrosis, for the study of serum ALT and AST levels during the acute phase of CEHC. Male Wistar rats (250-350 g) were divided into two groups: group A(N = 60) was submitted to sham operation for bile duct ligation (BDL), and group B (N = 60) was submitted to BDL. Thirty and 120 min after BDL there was a 1.5-fold increase in both serum ALT and AST levels compared to sham-operated rats (P<0.05). Serum ALT levels were higher than AST levels as early as 30 min after BDL and the highest serum values for both transaminases were observed at 360 min which was also the last value measured. Serum AST levels increased 120 min after BDL, with no further significant increase thereafter

Serum gama-glutamyl transpeptidase in chronic extrahepatic cholestasis

Studies in the literature have shown the inhibitory action action of bilirubin on serum gama-glutamyl transpeptidase (CGT) activity. In spite of this, CGT is a sensitive diagnostic indicator, comparable to alkaline phosphatase for the diagnosis of chronic extrahepatic cholestais (CEHC). To evaluate the relationship of bilirubin, alkaline phosphatase (AP) activity and GGT activity in CEHC we studied 30 patients with CEHC divided into two groups: A, 14 male and female subjects with bilirubin levels of 10.1 to 44 mg/dl. Serum GGT activity was meaured by diluting serum samples 1:5 and 1:10. GGT values were equivalent in the two groups, there was no correlation between bilirubin and GGT (r = +0.179, P > 0.01) and there was a significant correlation between GGT and AP(r = +0.627, P < 0.01). The present results show that, if GGT inhibition by bilirubin did occur, this inhibitions was not sufficient to prevent the increase in serum GGT levels and that the sensitivity of GGT as a marker for CEHC is simular to that of alkaline phosphatase

Inhibitory effect of different anticoagulants on gamma-glutamyl transpeptidase activity

Increased gama-glutamyl transpeptidase (GGT) levels have been observed in pacients with several types of liver diseases. However, since GGT activity can be inhibited or incrased by several substances, the interpretation of these increased levels should be made with caution. The present study was designed to determine plasma GGT activity in blood samples obtained from 24 adult volunters (13 males and 11 females aged 20 to 40 years) with the use of three different anticoagulants, i.e., ethylenediaminetetraacetic acid (EDTA), calcium fluoride and calcium citrate, and to compare it with GGT activity in serum obtanied from the same blood samples. Serum GGT activity wa significantly higher than plasma GGT activity (P < 0.001) and singnificantly higher in men than in women (P < 0.05), though plasma GGT activity was similar for both sexes

Effect of hepatic artery ligation on liver metabolism in rats

The rats an experimental model of orthotopic liver transplant that does not need arterial revascularization of the transplanted liver. the objective of the present study was to investigate the effect of hepatic artery ligation on hepatic metabolism in rats. After 2, 3, or 24 h hepatic artery ligation, no significant differences in serum levels of alanine aminotransferase were observed. Bile flow decreased significantly 3 h after arterial ligation (P < 0.05) and returned to normal after 24 h (P < 0.05)

Heparin-induced increase in plasma and serum gama-glutamyl transpeptidase activity

Gama-Glutamyl transpeptidase (GGT) activity may be a sensitive index of hepatobiliary dysfunction. GGT activity, however, has been shown to be affected by several factors in different clinical situations. The present study was designed to determine the effect of heparin on serum and plasma GGT activity. Blood samples were collected from 15 normal male Wistar rats weighing 200-250 g for the determination of GGT activity in plasma prepared with heparin (group P(H),N = 10), in serum (group S,N = 15) and in serum with heparin added (group S + H,N = 10). GGT activity was 45.1 + or - 9.5 U/l (mean + or - SD) for serum compared with 161.2 + or - 46.1 U/l for serum plus heparin and 93.3 + or - 30.9 U/l for plasma prepared with heparin. The mean for each group was significantly different from the means for the other groups. These data demonstrate that GGT activity measurements should be made on serum in the absence of heparin, which produces elevated results