Arterial ketone body ratio does not correlate with ischemic changes during major hepatectomy

BACKGROUND/AIMS: The arterial ketone body ratio (AKBR) has been proposed as an accurate indicator of hepatic mitochondrial redox potential. However, recent studies of the utility of the AKBR as a biochemical marker have been called into question. It is not clear whether the AKBR is closely related to ischemic changes during major hepatectomy. METHODOLOGY: Arterial acetoacetate and beta-hydroxybutyrate concentrations were measured in eleven patients who underwent major hepatectomy. The ratio between them (AKBR) was calculated before and after vascular occlusion during the hepatectomy procedure. RESULTS: The AKBR increased following normothermic arterial or portal venous ischemia as compared to the levels prior to vascular occlusion in 36.4% of the patients who underwent major hepatectomy. An AKBR of less than 0.5 prior to vascular occlusion did not correlate with preoperative hepatocellular function. An AKBR of less than 0.7 throughout surgery was not a consistent risk factor for postoperative complications or liver dysfunction. CONCLUSIONS: The AKBR does not correlate with ischemic changes or postoperative complications after major hepatectomy.     

Arterial ketone body ratio and adenosine triphosphate concentration in hepatic ischemia and reperfusion

BACKGROUND/AIMS: The arterial ketone body ratio (AKBR) and the cellular adenosine triphosphate (ATP) concentration have been proposed as indicators of liver function. However, recent studies of the utility of the AKBR as a biochemical marker have been called into question. Furthermore, there is no practical data defining the relationship between ATP concentration and ischemia-reperfusion (IR) changes during liver surgery. METHODOLOGY: The relationship of the AKBR and arterial ATP concentration to IR during hepatectomy was investigated. In 20 patients who underwent hepatectomy, arterial acetoacetate, beta-hydroxybutyrate, and ATP concentrations were measured. The ratio of acetoacetate to beta-hydroxybutyrate (AKBR) was calculated before and after vascular occlusion. RESULTS: The AKBR 15 minutes after clamping was lower than the preclamping values in all of the patients. It increased after unclamping, returning toward the preclamping levels. An AKBR of less than 0.5 prior to clamping did not correlate with preoperative hepatocellular function. An AKBR of less than 0.7 throughout IR was not a consistent risk factor for postoperative complications and liver dysfunction. The arterial ATP concentration did not correlate with the changes during IR or with preoperative hepatocellular function. CONCLUSIONS: Although the AKBR changed during IR as a general indicator of cellular activity, the absolute value of the AKBR was not an accurate predictor of liver function. The arterial ATP concentration also was not a suitable clinical biochemical marker of hepatic function.     

Plasma amino acid profile in relation to arterial ketone body ratio in surgical patients

A total of 357 plasma amino acid profiles from 93 surgical patients were statistically analyzed in relation to the changes in arterial ketone body ratio, which reflects the hepatic mitochondrial redox state. When the arterial ketone body ratio was above 0.7, all plasma amino acid levels were within the normal range. When it was between 0.7 and 0.4, plasma levels of aspartate, glutamate, valine, isoleucine, leucine, ornithine, and arginine decreased, and plasma levels of tyrosine, phenylalanine, proline, and methionine increased. Furthermore, when it was below 0.4, almost all plasma amino acids markedly increased. These results indicate that arterial ketone body ratio accurately reflects the alterations in plasma amino acid profile, and can serve as an indicator for providing nutritional support by amino acid supplement in surgical patients.     

Significance of arterial ketone body ratio as a parameter of oxygen metabolism in cardiac surgery]

Postoperative course after cardiac surgery is characterized by a progressive increased cellular oxygen demand and limited oxygen supply. It is mandatory to assess the adequacy of tissue oxygenation and to correct inadequate oxygenation rapidly in cardiac surgery. The present study was designed to evaluate the relationship between the arterial ketone body ratio (AKBR) and the status of oxygen demand and supply relationship in cardiac surgery. We measured oxygen consumption, oxygen delivery, oxygen extraction, mixed venous oxygen saturation, lactate, lactate/pyruvate (L/P) and AKBR in 43 patients undergoing open heart surgery at selected 10 periods before, during and after cardiopulmonary bypass (CPB). AKBR significantly decreased immediately after the beginning of CPB and returned to pre-CPB level more quickly than lactate and L/P did. AKBR at several periods a significant correlation with lactate and L/P at delayed periods. There was a significant correlation between AKBR and L/P during and after CPB. Furthermore, oxygen consumption, oxygen extraction, mixed venous oxygen saturation, and lactate were correlated with AKBR significantly. But there was no correlation between the parameter of oxygen metabolism and both lactate and L/P. In conclusion, it appears from these data that AKBR in cardiac surgery may be helpful as a rapid guide for estimating the degree of anaerobiosis.     

Prognostic implications of the response of arterial ketone body ratio and insulin secretion to glucose load in major hepatectomy

Impaired glucose tolerance is a serious obstacle to major hepatic resection. To assess the predictability of surgical risk in major hepatectomy for patients with chronic liver diseases from the viewpoint of glucose metabolism, we evaluated the insulinogenic index (II) and redox tolerance index (RTI) in 48 patients who underwent major hepatectomy at our university hospital due to hepatocellular carcinoma. Patients with low II and low RTI fell into the high risk group. Based on this finding, the Z score was developed as an index of patient risk for major hepatectomy: Z = 3.11 x [II] + 1.43 x [RTI] - 2.27. When the Z score was negative, mortality reached 33.3%, but when it was positive the mortality was only 3.2%. Intraportal insulin supplementation after hepatectomy to patients with a negative Z score could reduce mortality. Preoperative evaluation of surgical risk by Z score seems to be useful for predicting patient prognosis after hepatectomy.     

Changes in hepatic fatty acid degradation and blood lipid and ketone body content during development of the rat

The following have been measured during the development of the laboratory rat: the rate of oxidation of palmitoylcarnitine, decanoylcarnitine, and 14C-palmitate by liver mitochondria; the concentrations of ketone bodies in the blood; the plasma concentrations of non-esterified fatty acids, glycerol, and triglyceride. In each case, a rise after birth and a fall at weaning were observed. These changes can be correlated with the dietary changes which occur at these times. However, during the suckling period, when a constant high fat content diet is consumed, further marked changes in the parameters measured were observed which cannot be related to nutritional factors.     

Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus

Giant gastric ulcers are defined as ulcers with a diameter greater than 3 cm. Previously they have not been described in lung transplant recipients. We report a high incidence of symptomatic giant gastric ulcers and identify the risk factors for ulcer development in these patients. We examined the records of all 95 patients who had undergone lung transplantation at our institution from November 1991 to July 1995. Fourteen of the patients who underwent lung transplantation developed symptoms that required esophagogastroduodenoscopy. Three of these patients (21%) were found to have giant gastric ulcers. The relative risk of giant gastric ulcer in symptomatic patients undergoing endoscopy after lung transplantation is over 40 times that of population controls. The patients who developed giant gastric ulcers, despite H2 antagonist use, had all received bilateral lung transplantation and had received nonsteroidal antiinflammatory drugs, cyclosporine, and high-dose intravenous corticosteroids. The risk of developing giant gastric ulcers is significantly increased in patients who have undergone bilateral orthotopic lung transplantation. Clinicians should be made aware of this complication in order to avoid use of ulcerogenic medications in this population. Avoidance of these medications could potentially minimize the risk of this complication.     

Arterial and pulmonary arterial concentrations of the enantiomers of bupivacaine after epidural injection in elderly patients

Bupivacaine HCl is a 50:50 racemic mixture of the levo [S(-)] and dex [R(+)] enantiomers. The R(+) enantiomer exhibits greater cardiac tissue binding and toxicity. To determine whether the lung exhibits selective uptake of one of the enantiomers of bupivacaine, we measured pulmonary artery and radial artery blood concentrations of the two enantiomers after a lumbar epidural injection of 20 mL of 0.75% bupivacaine in 10 elderly patients undergoing one-stage bilateral total knee arthroplasty. Significantly lower concentrations of R(+) than S(-) were noted in both pulmonary artery and arterial blood. Both enantiomers were absorbed by the lung to a similar extent within the first 5 min after epidural injection (extraction ratio approximately equal to 0.1 or 10%). Mean time of maximal concentration (Tmax) was 6 min. In 3 of the 10 patients, Tmax occurred in 1-3 min. We conclude that the lung absorbs both the R(+) and S(-) enantiomers of bupivacaine to a similar extent after epidural injection and that this is of doubtful clinical significance. This study also suggests that peak concentrations of bupivacaine may occur earlier after epidural injection in certain elderly patients than previously believed. Implications: In the first 5 min after epidural injection, approximately 10% of the local anesthetic bupivacaine was absorbed by the lung. Absorption of the two enantiomers (mirror images) of bupivacaine were similar. Lung absorption of bupivacaine is unlikely to influence local anesthetic toxicity.     

Metabolism of digitoxin in man and its modification by spironolactone

The effect of spironolactone on the metabolism of intravenously administered 3H-digitoxin (80 muCi) was investigated in eight patients. In three of them the labelled glycoside was given on a second occasion after spironolactone treatment had been discontinued for at least 65 days. Of total urinary radioactivity 79% was unaltered drug and 12% consisted of water soluble compounds. No digitoxigenin or digoxigenin and only trace amounts (less than 2 %) of digoxin and the bis- and monoglycosides of digoxigenin were found. After spironolactone total urinary radioactivity was unchanged but the fraction eliminated as unchanged digitoxin fell from 79 to 66 % and the water soluble compounds increased from 12 to 26 % (p less than 0.05). In addition spironolactone caused a 20 ( reduction in the half-life of serum radioactivity (p less than 0.01) and a 16 % reduction in the volume of distribution (p less than 0.05). Induction of hepatic enzymes by spironolactone is proposed to explain the alteration in the metabolism of digitoxin in man. Both the altered metabolic pattern and the reduction in the volume of distribution appear to contribute to the reduction in half-life.     

Oxygen desaturation during sedation for colonoscopy in elderly patients

BACKGROUND/AIMS: Conscious sedation increases the tolerance of patients to endoscopic examination, but arterial oxygen desaturation during endoscopy has often been reported. Elderly patients are considered to be at special risk. However, sedation-induced changes in cardiovascular function in the elderly have not been well investigated. Therefore, this study examined the effects of sedation on pulse rate, systolic blood pressure, and arterial oxygen saturation in elderly patients. METHODOLOGY: Twenty patients aged less than 60 years and 20 patients aged 60 years or more, scheduled to undergo colonoscopic removal of colorectal polyps, received 0.05 or 0.025 mg/kg body weight, respectively, of midazolam intravenously. Before, during, and after endoscopy, pulse rate, systolic blood pressure, and arterial oxygen saturation were recorded every 5 min with a pulse oximeter. RESULTS: Administration of midazolam had no significant effect on pulse and arterial systolic blood pressure in either group. In contrast, midazolam significantly reduced the levels of arterial oxygen saturation during and after endoscopy in both age groups. However, although patients aged 60 years or more received midazolam at half dosage, arterial oxygen saturation during endoscopy was significantly lower and the incidence of 5% or more oxygen desaturation was significantly higher than in the patients aged less than 60 years. CONCLUSIONS: Midazolam increases the tolerance of elderly patients to endoscopy, but it significantly lowers the level of arterial oxygen saturation and increases the incidence of desaturation. Continuous monitoring is especially valuable during endoscopy in the elderly.     

Concurrent occurrence of elevated ketone body and depressed carnitine level in underfed guinea-pigs

Food ingestion of male guinea-pigs was restricted to 10 g/day. Total carnitine content of liver of the underfed animals fell to 3.75 mumoles per liver (46.1% of control). Serum level of total carnitine was 35.0 nmoles/ml (64.4%) in the underfed animals while they developed high ketonemia, 384.2 nmoles/ml (555.2%). In "restricted' animals the carnitine levels also decreased in the muscles.     

Body composition during weight loss in obese patients estimated by dual energy X-ray absorptiometry and by total body potassium

OBJECTIVE: To validate the ability of DXA to measure total body composition before and after weight loss and the composition of the lost body mass. DESIGN: Cross sectional and follow-up study of body composition before and after a weight loss of 10.6 +/- 6.8 kg. SUBJECTS: 31 obese subjects with a mean body weight of 105.2 +/- 15.2 kg at baseline, and a mean body weight of 94.6 +/- 16.5 kg at follow-up. MEASUREMENTS: Body composition was measured by dual X-ray absorptiometry, total body potassium counting, and high precision scales before and after a weight loss. RESULTS: DXA and the scales showed a strong linear relation (r = 1). At baseline, however, DXA underestimated the body weight by a maximum of 3.2 kg because the subjects were too large for the scan table. After weight loss body weight measurements were accurate. Before and after weight loss the linear relations between DXA and TBK for FFM were strong (r = 0.92 and 0.93). Bland and Altman plots showed limits of agreement of +/-9 kg before and after weight loss; DXA underestimated FFM in women and overestimated FFM in men. DXA accounted for 80% of the lost body weight. The composition of the lost body mass did not differ from that estimated by TBK (7.6% FFM and 92.4% FM by TBK; 11% FFM and 89% FM by DXA). CONCLUSION: DXA estimates accurately the body composition and the composition of weight loss in groups of obese subjects. However, the scan table may be too small for patients weighing more than 95 kg.     

Shivering threshold during spinal anesthesia is reduced in elderly patients

BACKGROUND: Both accidental and perioperative hypothermia are common in the elderly. The elderly are at risk because their responses to hypothermia may be delayed or less efficient than in those of younger subjects. For example, the vasoconstriction threshold during isoflurane anesthesia is approximately 1 degree C less in elderly than younger patients. However, the extent to which other cold defenses are impaired in the elderly remains unclear, especially in those older than 80 yr. Operations suitable for spinal anesthesia provided an opportunity to quantify shivering thresholds in patients of varying ages. Accordingly, the hypothesis that the shivering threshold is reduced as a function of age during spinal anesthesia was tested. METHODS: Twenty-eight ASA Physical Status 1-3 patients undergoing lower extremity orthopedic procedures were studied. Spinal anesthesia was induced without preanesthetic medication, using bupivacaine sufficient to produce a dermatomal level near T9. Electrocardiogram signals were recorded at 10-min intervals. Subsequently, an observer masked to patient age and core temperature identified the onset of sustained electromyographic artifact consistent with shivering. The tympanic membrane temperature triggering shivering identified the threshold. RESULTS: Three patients did not shiver at minimum core temperatures exceeding 36.2 degrees C. Fifteen patients aged < 80 yr (58 +/- 10 yr) shivered at 36.1 +/- 0.6 degrees C; in contrast, ten patients aged > or = 80 yr (89 +/- 7 yr) shivered at a significantly lower mean temperature, 35.2 +/- 0.7 degrees C (P = 0.002). The shivering thresholds in seven of the ten patients older than 80 yr was less than 35.5 degrees C, whereas the threshold equaled or exceeded this value in all younger patients (P = 0.0002). CONCLUSIONS: Age-dependent inhibition of autonomic thermoregulatory control in the elderly might be expected to result in hypothermia. That it usually does not suggests that behavioral regulation (e.g., increasing ambient temperature, dressing warmly) compensates for impaired autonomic control. Elderly patients undergoing spinal anesthesia, however, may be especially at risk of hypothermia because low core temperatures may not trigger protective autonomic responses. Furthermore, hypothermia in the elderly given regional anesthesia may not be perceived by the patient (who typically feels less cold after induction of the block), or by the anesthesiologist (who does not observe shivering). Consequently, temperature monitoring and management usually is indicated in these patients.     

Fas antigen expression of hepatocytes and its modification by immunosuppressants

Active cell death induced by ligation of the Fas antigen (Fas-Ag) with its antibody, Fas ligand (Fas-L), has been known to play a major role in cell killing via apoptosis by cytotoxic T lymphocytes (CTL). Thus, in liver transplantation, Fas-Ag expression of hepatocytes and its modification by immunosuppressive agents such as FK 506 or CsA can theoretically influence allograft survival. Mouse hepatocytes (BALB/c) were isolated and cultured with or without FK 506 or CsA, and Fas-Ag expression was determined by flow cytometry. Fas-Ag expression in the control was 17.2 +/- 2.5% after 24 hr of culture. When FK 506 or CsA was added, Fas-Ag expression with FK 506 at a concentration of 0.01-0.1 microg/ml was significantly lower than that with CsA (P < 0.05). When the cells were incubated with apoptosis-inducing anti-Fas-Ag monoclonal antibody, agarose gel electrophoresis of the control cells yielded a typical pattern of DNA fragmentations. The cells with FK 506 at 0.01 microg/ml yielded the least DNA fragmentation. These findings suggested that in the in vivo setting, the hepatocytes of the allograft would have a lower chance of being attacked by CTL in the host treated with FK 506.     

Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association

The mammalian guanosine triphosphate (GTP)ase-activating protein RanGAP1 is the first example of a protein covalently linked to the ubiquitin-related protein SUMO-1. Here we used peptide mapping, mass spectroscopy analysis, and mutagenesis to identify the nature of the link between RanGAP1 and SUMO-1. SUMO-1 is linked to RanGAP1 via glycine 97, indicating that the last 4 amino acids of this 101- amino acid protein are proteolytically removed before its attachment to RanGAP1. Recombinant SUMO-1 lacking the last four amino acids is efficiently used for modification of RanGAP1 in vitro and of multiple unknown proteins in vivo. In contrast to most ubiquitinated proteins, only a single lysine residue (K526) in RanGAP1 can serve as the acceptor site for modification by SUMO-1. Modification of RanGAP1 with SUMO-1 leads to association of RanGAP1 with the nuclear envelope (NE), where it was previously shown to be required for nuclear protein import. Sufficient information for modification and targeting resides in a 25-kD domain of RanGAP1. RanGAP1-SUMO-1 remains stably associated with the NE during many cycles of in vitro import. This indicates that removal of RanGAP1 from the NE is not a required element of nuclear protein import and suggests that the reversible modification of RanGAP1 may have a regulatory role.     

Simultaneous MIDCAB and subtotal gastrectomy in an elderly patient with severe ischemic heart disease

An 81 year old man with severe ischemic heart disease and left ventricular dysfunction was scheduled for a subtotal gastrectomy for his advanced gastric cancer. His cardiac function was so poor that we performed minimally invasive coronary artery bypass grafting (MIDCAB; coronary artery bypass grafting without cardiopulmonary bypass for LAD through a small left thoracotomy), just before the abdominal operation. Anesthesia was induced and maintained with fentanyl, vecuronium and sevoflurane. To control heart rate below 60 bpm during local coronary occlusion for bypass grafting, edrophonium 5 mg was administered just before the occlusion. During the bypass grafting procedure, the patient's heart rate was maintained at 50-60 bpm and his hemodynamic profile slightly declined but was permissible. After bypass grafting, his cardiac performance was improved with low dose dobutamine. Subsequently subtotal gastrectomy was carried out. His postoperative course was uneventful. Combined MIDCAB and abdominal operation may be beneficial for selected patients with severe ischemic heart disease.