Comparison of postoperative liver dysfunction following halothane and sevoflurane anesthesia in women undergoing mastectomy for cancer

The incidence of an abnormal increase in the serum levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) following anesthesia with halothane and 65% nitrous oxide in oxygen (halothane group) or with sevoflurane and 65% nitrous oxide in oxygen (sevoflurane group) was compared in women undergoing surgery for breast cancer. An abnormal increase in GOT and GPT, both defined as higher than 50 IU, occurred postoperatively in 2 of the 150 patients (1.7%) in the sevoflurane group, and in 37 of the 200 (18.5%) in the halothane group (P<0.001). The elevated levels of serum transaminases after sevoflurane ranged from 50 to 65 IU whereas those after halothane ranged from 50 to 1000 IU, except for a value greater than 5000 IU in 1 patient. In the halothane group, there was a significant association between postoperative increases in serum transaminases and previous exposure to inhalation anesthetics, postoperative mitomycin therapy, and radiation therapy (all P<0.001). The results of multivariate analysis, when data from all patients were taken together, showed that the type of anesthetic (halothane) was the highest factor related to postoperative increases in GOT and GPT (odds ratio 35.85; 95% confidence interval 5.92–217.37), followed next by prior exposure to inhalation anesthetics (8.65; 2.96–25.27), postoperative radiation therapy (4.37; 1.70–11.19), and postoperative mitomycin therapy (3.56; 1.23–10.35). These data suggest that sevoflurane is less likely to cause anesthesia-related liver dysfunction than halothane.     

Celiac plexus block does not alter hepatic injury in rats

We previously demonstrated that upper abdominal surgery on rats pretreated with phenobarbital and anesthetized with halothane caused centrilobular necrosis of the liver, which may be secondary to hepatic hypoxia induced by vasoconstriction. This study examined the possibility that celiac plexus blockade might decrease the degree of injury seen in the surgical model. Rats, pretreated with phenobarbital, were anesthetized with halothane, enflurane, isoflurane, or fentanyl with 100% oxygen. At the start of the hepatic artery dissection, the celiac plexus was blocked by injection of bupivacaine. Subsequently, the rat livers were evaluated for presence and degree of centrilobular necrosis. Animals anesthetized with halothane or fentanyl had a significantly greater incidence of centrilobular necrosis than controls (rats pretreated with phenobarbital who received no anesthesia or surgery). Hepatic injury in rats anesthetized with isoflurane or enflurane did not differ from that in controls. We conclude that celiac plexus blockade with bupivacaine provides no protection against hepatic necrosis in this model.     

Effects of halothane, isoflurane, enflurane, thiopental, and fentanyl on blood gas values in rats exposed to hypoxia

In rats pretreated with phenobarbital breathing 10% oxygen, subanesthetic doses of halothane, isoflurane, enflurane, thiopental, and fentanyl caused hepatic injury. Because hypoxia per se can produce such injury, we hypothesized that the anesthetic-induced injury resulted from increased hypoxemia secondary to respiratory depression. Male Sprague-Dawley rats were pretreated with phenobarbital; half of the rats were fed and the other half were deprived of food for the 24 h before study. Isoflurane anesthesia was given for the placement of a catheter into the femoral artery. After 1 h of recovery, the rats were exposed to 10% oxygen. Control samples were obtained and halothane, isoflurane, enflurane, thiopental, or fentanyl was administered. Rats given food had higher PaCO2 and lower pH values than starved rats. Also, arterial oxygen saturation (SaO2) tended to be lower in rats given food. At concentrations of 0.15-0.2 MAC or higher, halothane, isoflurane, and enflurane slightly increased PaCO2 values relative to values for a control group exposed only to hypoxia. However, SaO2 and PaO2 did not show significant drug-induced changes. Fentanyl transiently decreased PaO2 and SaO2. Thiopental caused no changes. Thus, we conclude that subanesthetic doses of anesthetics may depress the ventilatory response to hypoxia but that this depression is inconsistent and appears to be too small to cause hepatic damage.     

Effect of oxygen concentration, hyperthermia, and choice of vendor on anesthetic-induced hepatic injury in rats

Although hypoxic rats exposed to anesthetics may develop hepatic injury, divergent results have been obtained. These discrepancies might be due to different levels of hypoxia, hypothermia, or choice of vendor. Male Sprague-Dawley rats purchased from Zivic-Miller were pretreated with phenobarbital for 4 days. After 24 h without phenobarbital, they were exposed to 2 h of hypoxia and halothane, enflurane, isoflurane, thiopental, or fentanyl. Rectal temperature was kept between 36.5 degrees C and 38.5 degrees C. All agents given in 10% oxygen produced more hepatic injury than did control conditions (exposure to 10% oxygen alone) (P less than 0.01). Only halothane given in 12% and 14% oxygen produced hepatic injury. No agent given in 20% or 100% oxygen demonstrated hepatotoxicity. In a separate study, rectal temperatures were kept between 32 degrees C and 34 degrees C during 2 h of exposure to 0.3 MAC halothane, enflurane, or isoflurane in 10% oxygen. Hypothermia prevented hepatotoxicity by enflurane and isoflurane, but not by halothane. Finally, although livers of rats obtained from Zivic-Miller were injured, specific pathogen-free rats from Charles River were not injured or were less injured by enflurane, thiopental, or fentanyl. Apparently, minor changes in experimental conditions can substantially affect results; hepatic hypoxia per se, anesthetic metabolism (especially that of halothane), and perhaps anesthesia itself may produce hepatic injury.     

Liver reperfusion-induced decrease in dynamic compliance and increase in airway resistance are ameliorated by preischemic treatment with melatonin through scavenging hydroxyl radicals in rat lungs

Objectives

Acute lung injury is frequently observed in patients subsequent to liver ischemia and reperfusion (I/R) injury. However, the changes in pulmonary function, eg, lung dynamic compliance (C_dyn) and airway resistance (RI), are not well understood. We sought to study the alternations in pulmonary function during liver I/R and the protective effects of preischemic treatment with melatonin.

Methods

Animals were divided into 3 groups: sham-operated, liver I/R, and intraperitoneal (i.p.) pretreatment with melatonin (15 mg/kg). Liver I/R was performed by clamping the hepatic artery and portal vein for 30 minutes followed by releasing for 2 hours. The C_dyn and RI were studied at baseline and at 2 hours of reperfusion. We assessed the level of pulmonary hydroxyl radicals by methylguanidine (MG) content in the bronchoalveolar lavage fluid (BALF) as well as the liver damage using plasma levels of lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT).

Results

After 2 hours of liver reperfusion, C_dyn was reduced by ∼25%, while RI increased by ∼16% (P < .05). The decreased C_dyn and increased RI were markedly attenuated by melatonin pretreatment (P < .05). Melatonin pretreatment also protected the liver against I/R injury (P < .05), as seen by reduced LDH, GOT and GPT along with markedly reduced hydroxyl radicals (P < .05).

Conclusions

Preischemic treatment with melatonin protected lung function against damage by liver I/R. The improvement in lung function was strongly associated with decreased hydroxyl radicals in the lungs.     

Risk factors for liver abscess formation in patients with blunt hepatic injury after non-operative management

Purpose

To identify risk factors for liver abscess formation in patients with blunt hepatic injury who underwent non-operative management (NOM).

Methods

From January 2004 to October 2008, retrospective data were collected from a single level I trauma center. Clinical data, hospital course, and outcome were all extracted from patient medical records for further analysis.

Results

A total of 358 patients were enrolled for analysis. There were 13 patients with liver abscess after blunt hepatic injury. Patients with abscess had a significant increase in glutamic oxaloacetic transaminase (GOT, p = 0.006) and glutamic pyruvic transaminase (GPT, p < 0.0001), and a decrease in arterial blood pH (p = 0.023) compared to patients without abscess in the univariate analyses. In addition, high-grade hepatic injury and transarterial embolization (TAE, p < 0.001) were also risk factors for liver abscess formation. Five factors (GOT, GPT, pH level in the arterial blood sample, TAE, and high-grade hepatic injury) were included in the multivariate analysis. TAE, high-grade hepatic injury, and GPT level were statistically significant. The odds ratios of TAE and high-grade hepatic injury were 15.41 and 16.08, respectively. A receiver operating characteristic (ROC) analysis was used for GPT, and it suggested cutoff values of 372.5 U/L. A prediction model based on the ROC analysis had 100 % sensitivity and 86.7 % specificity to predict liver abscess formation in patients with two of the three independent risk factors.

Conclusions

TAE, high-grade hepatic injury, and a high GPT level are independent risk factors for liver abscess formation.     

Recombinant human erythropoietin reduces rhabdomyolysis-induced acute renal failure in rats

BackgroundRhabdomyolysis is one of the causes of acute renal failure. Erythropoietin (EPO) has been found to interact with its receptor (EPO-R) expressed in a large variety of non-haematopoietic tissues to induce a range of pleiotropic cytoprotective actions. In this study, we used recombinant human erythropoietin (rhEPO) to study the effects on the glycerol-induced rhabdomyolysis with acute renal failure in rats.MethodsTwenty-four rats were divided into three groups as glycerol group, glycerol + EPO group and normal saline + EPO group. Rhabdomyolysis was induced by intramuscular injection of 10 ml kg^?1 50% glycerol in rats. Ten minutes later, the rats received an intravenous injection of rhEPO (300 U kg^?1). Biochemical substances, including haemoglobin, blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and creatine phosphokinase (CPK), were measured at 0, 1, 3, 6, 9, 12, 18, 24 and 48 h. Rats were sacrificed 48 h later after glycerol administration and the kidneys were removed immediately for pathology and immunohistochemistry (IHC).ResultsIntramuscular injection of glycerol significantly increased blood BUN, Cre, GOT, GPT and CPK levels and induced severe histopathologic damage in the kidneys. Nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) were increased and E-cadherin was decreased after glycerol administration, as detected by IHC in the kidneys. Post-treatment with rhEPO decreased blood BUN, Cre, GOT, GPT and CPK levels, decreased markers of kidney injury and suppressed the release of NF-κB and iNOS after rhabdomyolysis.ConclusionTreatment with rhEPO suppressed the activities of NF-κB and iNOS, decreased BUN, Cre, GOT, GPT and CPK levels, and decreased the markers of kidney injury after rhabdomyolysis. These actions ameliorated rhabdomyolysis-induced acute renal failure in rats.     

Clinical studies on changes in serum transaminase, lactate dehydrogenase, total bilirubin and alkaline phosphatase levels after hepatectomy with and without the hemihepatic vascular occlusion technique

Changes of serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), total-bilirubin (T-Bil) and alkaline-phosphatase (AL-P) before operation and for one week of the postoperative period were studied in 45 patients (32 cirrhotic, 13 non-cirrhotic patients) who underwent hepatectomy with the hemihepatic vascular occlusion technique, and compared with 108 patients (42 cirrhotic, 66 non-cirrhotic patients) without it. The blood loss during hepatectomy with hemihepatic vascular occlusion markedly decreased 1500 ml on the average, compared with non-occluded patients. Serum GPT, GOT and LDH level elevated in several postoperative days, however, there was no difference between both groups. Serum total bilirubin level of patients without hemihepatic vascular occlusion elevated more than those with it. This difference was statistically significant. This tendency was more evident in the patients with cirrhosis. Serum AL-P level of patients without hemihepatic vascular occlusion decreased statistically less than those with it. This tendency was more prominent in patients with cirrhosis. With these results, there was no evidence of augmenting the postoperative liver damage by hemihepatic vascular occlusion, even in the patient with cirrhosis. Moreover, the elevation of postoperative serum total bilirubin level was suppressed by hemihepatic vascular occlusion because of the minimum blood loss and minimum blood transfusion.     

The effect of halothane, isoflurane, and blood loss on hepatotoxicity and hepatic oxygen availability in phenobarbital-pretreated hypoxic rats

This study evaluated the role of ventilatory and circulatory depression in anesthesia-induced hepatotoxicity in rats. Male Sprague-Dawley rats (181 animals) were pretreated with phenobarbital and exposed to hypoxia (FIO2 = 0.14) for 2 hr. The animals were divided into four groups: group 1 received 1% inspired halothane in the hypoxic gas mixture; group 2 received 1.4% inspired isoflurane and hypoxia; group 3 had 25-30% of their blood volume removed 2 hr before exposure to hypoxia; and group 4 served as a control with no treatment other than hypoxia. Hepatic blood flow was studied using microspheres; oxygen availability to the liver was calculated using values of hepatic blood flow and oxygen content of arterial and portal venous blood; and liver injury was quantitatively evaluated. Ventilation was depressed in rats that received halothane and, to a lesser extent, isoflurane. The lowest portal blood flow was observed in groups 1 and 3. Hepatic arterial blood flow was lowest in group 1 and highest in group 3. There was an inverse relationship between hepatic oxygen availability and severity of histologic lesions. The most severe lesions and lowest oxygen availability was associated with halothane. Hemorrhage and isoflurane were associated with less diminution of oxygen availability and less severe hepatic lesions. The least decrease in oxygen availability and the least severe histologic changes occurred in control rats subjected to hypoxia only.     

Comparison of the requirements for hepatic injury with halothane and enflurane in rats

A rat model of enflurane-associated hepatotoxicity was compared with the halothane-hypoxia (HH) model (adult male rats, phenobarbital induction, 1% halothane, 14% O2, for 2 hr). The enflurane-hypoxia heating (EHH) model involved exposing phenobarbital-pretreated male adult rats to 1.5-1.8% enflurane at 10% O2 for 2 hr with external heating to help maintain body temperature. Exposure to either anesthetic without temperature support led to a decrease in body temperature of 7-9 degrees C, while heating the animals during anesthesia resulted in only a 0.5-2 degree decrease. Reducing the oxygen tension to 10% O2 combined with heating the animals during exposure produced significant decreases in the oxidative metabolism of both halothane and enflurane as compared to exposures of 14% O2. The same conditions also caused a significant increase in the reductive metabolism of halothane, indicating that a severe hepatic hypoxia or anoxia occurs during anesthesia at 10% O2 with external heating. The time course of lesion development in the HH model paralleled results obtained with an oral dose of CCl4: gradual progression of necrosis up to 24 hr. EHH resulted in a classic hypoxic/anoxic injury with elevated serum glutamate pyruvate transaminase values and a watery vacuolization of centrilobular hepatocytes immediately after exposure. The HH model required phenobarbital pretreatment of the rats for expression of hepatic injury; EHH did not. Heating of the animals during anesthesia exposure was necessary for enflurane-induced hepatoxicity but had little effect on the HH model. Exposure to 5% O2 without anesthetic mimicked EHH in both requirements for and type of hepatic injury.     

Flutamide-induced hepatic disorder and serum concentrations of flutamide and its metabolites in patients with prostate cancer

Severe hepatotoxicity occurred in a prostate cancer patient treated with 375 mg of flutamide per day, 125 mg three times a day, for 11 weeks. Serial measurements of serum concentrations of flutamide and its metabolites in the patient showed an unusually high serum level and delayed elimination of flutamide and suggested decreased metabolic activity of oxidation of flutamide to OH-flutamide. In 37 patients with prostate cancer we periodically monitored the serum concentrations of flutamide as well as liver function parameters. In 2 patients, glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) elevated over 100 IU/L, and treatment with flutamide was discontinued. Slight elevation of GOT and GPT over 40 to 100 IU/L was also detected in 5 patients, and flutamide was withdrawn. The elevated GOT and GPT in these 7 patients recovered to the pretreatment levels after discontinuation of the treatment. In these patients with flutamide-induced hepatic disorders, the average serum concentration of flutamide was higher (2.76 times, and that of OH-flutamide was lower (0.76 times), as compared with patients who maintained normal liver function.     

I-653 resists degradation in rats

The ability of rats pretreated with phenobarbital to metabolize a new volatile anesthetic, I-653, was compared with the metabolism of halothane, isoflurane, and methoxyflurane. Each anesthetic was administered for 2 hours at 1.6 MAC (inspired). Control rats were given phenobarbital but not exposed to an anesthetic. In rats pretreated with phenobarbital and exposed to I-653, fluoride ion concentrations in serum and excretion of fluoride ion and organic fluoride in the urine were almost indistinguishable from values measured in control rats. In contrast, rats pretreated with phenobarbital metabolized small but significant amounts of isoflurane. In rats pretreated with ethanol and exposed to I-653, the 24-hour excretion of urinary organic fluoride was nearly ten times greater than that observed in control rats. Marked increases in organic fluoride (as high as 1000 times control values) and/or fluoride ion were found in serum and/or urine after anesthesia of phenobarbital-pretreated rats with halothane or methoxyflurane. The relative stability of I-653 indicates that it may possess minimal toxic properties.     

氟烷、安氟醚、七氟醚肝毒性与TXB_2、6－keto－PGF（1α）含量变化（氟烷性肝炎的研究Ⅲ）

雄性ＳＤ大鼠饮用含苯巴比妥钠（１ｍｇ／ｍｌ）的饮水１周后，随机分为四组，每组８例，分别吸入：Ｃ，１４％Ｏ＿２／８６％Ｎ＿２；Ｅ，１４％Ｏ＿２／８６％Ｎ＿２／１．２ＭＡＣ安氟醚；Ｓ，１４％Ｏ＿２／８６％Ｎ＿２／１．２ＭＡＣ七氟醚；Ｈ，１４％Ｏ＿２／８６％Ｎ＿２／１．２ＭＡＣ氟烷１ｈ。２４ｈ后发现Ｈ组血浆ＡＬＴ活性显著高于其它各组，并有明显的小叶中心性肝细胞坏死及汇管区炎细胞浸润，血窦重度充血。Ｅ组可见部分肝小叶内有小叶中心性坏死及空泡变性。Ｈ组肝匀浆及血浆中ＴＸＢ＿２含量显著高于其它各组。６－ｋｅｔｏ－ＰＧＦ１ａ各组间均无显著差异。提示氟烷性肝炎与ＴＸＡ＿２／ＰＧＩ＿２平衡失调有一定的关系。     

An animal model of halothane hepatotoxicity: roles of enzyme induction and hypoxia.

Exposure of phenobarbital-pretreated male Sprague-Dawley rats to halothane, 1 per cent, for two hours under conditions of hypoxia (FIO2 0.14) resulted in extensive centrilobular necrosis within 24 hours. Accompanying the morphologic damage were an increase in serum glutamic pyruvic transminase (SGPT) and a decrease in hepatic microsomal cytochrmoe P-450. Glutathione levels in the liver were unchanged. Phenobarbital-pretreated rats anesthetized with halothane, 1 per cent, at FIO2 0.21 had only minor morphologic changes at 24 hours. Hepatic injury was not apparent in any non-phenobarbital-induced rat or in any induced animal exposed to ether at FIO2 0.10 or to halothane at FIO2 0.99. There was a 2.6-fold increase in the 24-hour urinary excretion of fluoride in those rats in which extensive centrilobular necrosis developed. The in-vivo covalent binding to lipids of 14C from 14C-halothane also was increased markedly when 14C-halothane was administered intraperitoneally to phenobarbital-induced rats maintained hypoxic (FIO2 0.14) for two hours. These results support the authors' hypothesis that halothane is metabolized to hepatotoxic intermediates by a reductive or non-oxygen-dependent cytochrome P-450-dependent pathway. This animal model of halothane-induced hepatotoxicity may be clinically relevant. A decrease in hepatic blood flow during halothane anesthesia may decrease the PO2 available to hepatocytes and thus direct the metabolism of halothane along its reductive, hepatotoxic pathway.     

Heme oxygenase 1 expression in postischemic reperfusion liver damage: effect of L-arginine

Ischemia/reperfusion (I/R) injury is a multifactorial process that affects liver function after transplantation and resectional surgery. Alterations in hepatic microcirculation and decreased hepatic flow can cause local hypoxia and consequently liver damage, which is worsened by reperfusion. The aim of this study was to evaluate if treatment with L-arginine improved hepatic function in rats with I/R injury. Animals were treated with L-arginine, ischemized for 30 min, and reperfused for 3 h. Plasmatic levels of GOT, GPT, lipid hydroperoxides (LOOH), and total thiol groups (RSH) were evaluated. In addition, we analyzed hepatic LOOH and RSH levels, DNA fragmentation, heme oxygenase 1 (HO-1) expression, and histological modifications. Our results demonstrate a significant improvement in hepatic function of I/R rats compared to the control group. Treatment with L-arginine increased the expression of HO-1. These data suggest that L-arginine could be useful in preventing oxidative damage during hepatic surgery.     

Hypoxia per se can produce hepatic damage without death in rats

To evaluate the importance of hypoxia itself on halothane-induced hepatic injury in the rat, the question of whether hypoxia could injure the liver without causing death was investigated. Male Sprague-Dawley rats pretreated with phenobarbital (1 mg/ml of drinking water, 4 days) and deprived of food for 24 hours were exposed to 6%, 7%, 8%, or 10% inspired oxygen with 0%, 5%, or 7.5% carbon dioxide for 2 hours. Several rats died when given 6% oxygen with 0% or 7.5% carbon dioxide, but all other rats survived. Without carbon dioxide, oxygen at a concentration of 7% or 8% produced more injury than did room air, and 6% oxygen produced the most severe damage. These results demonstrate that in rats hypoxia per se may be an important factor in causing hepatic damage.     

Effects of the herbal medicine Inchinko-to on liver function in postoperative patients with biliary atresia--a pilot study

Background/Purpose:

A continuation of liver fibrosis after undergoing successful Kasai operation has become the important clinical issue in the long-term follow-up of patients with biliary atresia (BA). The aim of this study is to evaluate the efficacy of the herbal medicine Inchinko-to (TJ-135) on the treatment of liver fibrosis in patients with BA without jaundice, especially from the viewpoint of the long-term effects of TJ-135.

Methods:

Six postoperative patients with BA ranging between 3 and 13 years of age with normal serum total bilirubin levels (total bilirubin < 1.0 mg/dL [17 μmol/L]) received TJ-135 from 2 to 4 years. The liver enzyme (glutamic oxaloacetic transaminase [GOT], glutamic pyruvic transaminase [GPT], gamma glutamyl transpeptidase[γ-GTP]transpeptidase[γ-GTP] levels and hyaluronic acid (HA) levels were compared before and after the administration of TJ-135. The monthly collected data were averaged on a 1-year basis. The record of one postoperative patient with BA and a normal serum total bilirubin level was incorporated as a control. This patient showed portal hypertension and did not receive TJ-135.

Results:

Five of the six patients who showed abnormal values for liver enzymes, exhibited a significant decrease in serum GOT, γ-GTP, or GPT levels after a 1 to 3-year administration of TJ-135, and the improvement in these parameters persisted thereafter. Furthermore, one patient who had an abnormally high value of HA also showed a significant decrease in the serum level of HA. In the remaining patient with normal liver enzyme values, no significant change was observed during the administration of TJ-135. The control patient exhibited a chronological decrease in the serum GOT and GPT levels by 5 years of age, but the serum γ-GTP and HA levels remained stable throughout the postoperative period.

Conclusions:

The long-term effectiveness of TJ-135 was only found in those patients with abnormal liver enzyme levels and HA, thereby suggesting that TJ-135 has a protective and antifibrotic effect on the liver.     

Ischemic damage prevention by coenzyme Q10 treatment of the donor before orthotopic liver transplantation: biochemical and histologic findings

This study was undertaken to determine whether pretreatment of the donor rat with coenzyme Q10 (CoQ10) would protect against hepatic ischemia induced for 30 minutes at normothermic body temperature. Fresh liver transplants were used as controls (minus warm ischemia of 30 minutes) and gave a 1-week survival rate of 84.6%. CoQ10 was administered intravenously (10 mg/kg body weight) to the donor rat 1 hour before induction of warm ischemia (group A). In another group (B), the same dose was given intravenously not only to the donor rat but also to the recipient rat 1 hour before grafting. None of the placebo group survived more than 2 days. The 1-week survival rates of the groups pretreated with CoQ10 were 45.5% for group A and 50% for group B. There was no significant difference between groups A and B. A statistically significant difference was demonstrated between the placebo group and both CoQ10-treated groups (p less than 0.05). It was therefore assumed that CoQ10, accumulated in the donor liver, was a primary factor in improving survival. Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphatase (SALP), total bilirubin, and total protein were measured by means of light and electron microscopic examination of the liver 6 months after transplantation. Long-term-surviving rats with transplanted, ischemically damaged liver that was pretreated with CoQ10 showed a decrease in the activity of SGOT and SGPT and an increase in levels of total protein to the normal range (as well as to those levels exhibited by fresh-liver-transplanted rats) with practically no change in levels of SALP, total bilirubin, or in histologic findings. These results indicate that donor pretreatment with CoQ10 is useful for increasing survival after warm ischemic damage of rat liver grafts.     

Preventative effect of PGE1 for postoperative liver damage

The efficacy of a low dose of PGE₁-use on the postoperative liver damage was evaluated. PGE₁ was infused in with the mean rate of 0.026µg·kg^–1·min^–1 during surgical procedure to 93 patients under GO-enflurane anesthesia (the PG). Serum GOT, GPT and total bilirubin (TBIL) values measured before, at the end of (End) and 3 days (3d) after the operation were compared to those obtained from 43 patients without PGE₁ administration (the control).This dose of PGE₁ did not change blood pressure and heart rate, but slightly decreased Pa_{O 2}. In patients with preoperative normal values of GOT, GPT and TBIL, increases in GOT, GPT and TBIL observed at End in the PG were significantly lower than those in the control (31.9 vs 72.2IU, 25.9 vs 61.9IU, 0.68 vs 0.83mg·dl^–1, respectively). GOT, GPT and TBIL at 3d significantly increased in both groups, and these levels were identical between the two groups. In patients with preoperative abnormal values, only GOT at End increased in both groups, while no significant difference between the PG and the control group was noted. GOT at 3d and GPT at End and 3d did not significantly changed in either group. These results suggest that the low dose of PGE₁ administered during an operation prevents the development of postoperative liver damage, but does not treat the damaged hepatic cells.(Iwatsuki N, Yasuda A, Tokutomi S, et al.: Preventative effects of PGE₁ for postoperative liver damage. J Anesth 6: 131–137, 1992)     

Hypoxia and halothane metabolism in vivo: release of inorganic fluoride and halothane metabolite binding to cellular constituents.

Fluoride release and covalent binding of halothane metabolites were studied in rats pretreated with phenobarbital and anesthestized with halothane in the presence of high (40 per cent) and low (7 per cent) oxygen tensions. The purpose of producing hypoxia was to promote the reductive pathways involved in the metabolism of halothane. Halothane anesthesia under hypoxic conditions caused a significant elevation in the plasma fluoride concentration. There was also a greater than three-fold increase in covalent binding of 14C-halothane metabolites to microsomal lipids in hypoxic rats. The lipid/protein binding ratio in control animals averaged 0.76, while hypoxic animals had a binding ratio of 3.24. The findings demonstrate that defluorination of halothane does occur during hypoxic conditions. It is hypothesized that the products produced by this reductive metabolic pathway are also potentially more hepatotoxic than the oxidative metabolites, based upon the increased covalent binding of halothane metabolites under hypoxic conditions.