Obtaining a representative blood sample in lactate tracer studies

Reasons why venous tracer infusion with arterial sampling [(v-a) mode] has advantages compared to arterial infusion and venous sampling [(a-v) mode] for studies of blood lactate kinetics are presented. Arterial tracer infusion can result in biased tracer input due to streaming and unequal blood flow distribution. The procedure is impractical for human studies. Venous sampling from the jugular, or any other peripheral or great vein, provides a sample which may, or may not represent mixed venous systemic blood, which exists only in the pulmonary artery. Venous sampling will not represent cardiac lactate metabolism because the coronary arteries drain into the coronary sinus. Venous sampling, as well as pulmonary artery sampling, will also ignore lactate metabolism in the lungs which drain into the left atrium from bronchial and pulmonary circulations. Turnover rates calculated from either venous or arterial specific activities underestimate true tissue turnover. Correction for either measurement depends on good estimates of blood flows to lactate exchanging and non-exchanging tissue. Equilibration between lactate and pyruvate pools does not invalidate the use of tracers to measure lactate turnover. The (v-a) mode with venous infusion and arterial sampling has advantages for lactate tracer studies.     

Prandial lactate infusion inhibits spontaneous feeding in rats

To investigate the acute effects of lactate on spontaneous feeding, we infused lactate in the hepatic portal vein (0.5, 1.0, and 1.5 mmol lactate/meal) or in the vena cava (1.0 and 1.5 mmol lactate/meal) of ad libitum-fed rats during their first spontaneous nocturnal meal. Infusions (5 min, 0.1 ml/min) were remotely controlled, and a computerized feeding system recorded meal patterns. In separate crossover tests, meal size decreased independent of the infusion route after 1.0 and 1.5 mmol but not after 0.5 mmol lactate. The subsequent intermeal interval (IMI) tended to decrease only after vena cava infusion of 1.0 mmol lactate. The size of the second nocturnal meal increased after the 1.0 mmol lactate infusion. Hepatic portal infusion of 1.5 mmol lactate increased the satiety ratio [subsequent IMI (min)/meal size (g)] by 175%, which was higher than the insignificant 43% increase after vena cava infusion. Hepatic portal infusion of 1.5 mmol lactate also increased systemic plasma lactate but not glucose concentration at 1 min after the end of infusion. The results are consistent with the idea that meal-induced increases in circulating lactate play a role in the control of meal size (satiation). Moreover, the results suggest that lactate also contributes to postprandial satiety and that the liver is involved in this effect. The exact mechanisms of lactate's inhibitory effects on feeding and the site(s) where lactate acts to terminate meals remain to be identified.     

Simple validation for the hepatic venous cannula implanted chronically in conscious rats

A method for the detection of vena caval contamination in blood taken from hepatic venous cannulas in conscious rats was described. The procedures included 1) bolus injection of tritiated water (50 microCi) through a cannula into the abdominal inferior vena cava and 2) continuous blood sampling (less than 0.2 ml) from the hepatic venous cannula for 2 min into a 180-cm piece of Tygon tubing, starting concurrently with tracer injection. The washout of tritium was determined from samples in 15-cm sections of Tygon tubing. Because circulation from the inferior vena cava to the hepatic vein is interceded by the systemic circulation, the washout of tritium from a valid hepatic venous cannula should resemble the pattern determined elsewhere in the systemic circulation. In the current study, the reference systemic washout was determined in the superior vena cava of a group of rats similarly injected with tritiated water in the inferior vena cava. The maximum of tritium washout derived from a valid hepatic venous cannula should fall in the range encompassed by one standard deviation of the mean of the maximum of the reference (1,400 to 1,930 cpm/sample). The maximum of the washout pattern derived from the invalid cannula, which lay adjacent to the site of injection, was expected to exceed this range. On the basis of these criteria, hepatic blood flow (HBF) was determined by sulfbromophthalein (BSP) extraction in groups of rats with valid and invalid cannulas. HBF in rats with valid hepatic venous cannulas was 2.58 +/- 0.15 in the conscious state and 2.76 +/- 0.26 ml.min-1.g wet wt-1 in the ketamine-anesthetized state.(ABSTRACT TRUNCATED AT 250 WORDS)     

HEMIAZYGOS CONTINUATION TO CORONARY SINUS WITH NORMAL LEFT INNOMINATE VEIN

A case is described of absent hepatic segment of the inferior vena cava with hemiazygos continuation and drainage into the coronary sinus with associated atrial septal defect and patent ductus arteriosus. In all previously reported cases of inferior vena caval anomalies with persistent hemiazygos, the hemiazygos joined the homolateral superior vena cava. To our knowledge this is the first case to be reported of a patient who had hemiazygos continuation to the coronary sinus with a normal left innominate vein and a single right superior vena cava.     

Glucose infused through the portal vein enhances liver gluconeogenesis and glycogenesis from [3-14C]pyruvate in the starved rat

After a pulse of [3-14C]pyruvate, 24 hr starved rats were infused through the portal vein with two different doses of glucose (7.8 or 20.8 mg/min) or the medium, and blood was collected from the inferior cava vein at the level of the suprahepatic veins. The highest dose of glucose enhanced the appearance of [14C]glucose in blood from the 2nd to the 20th min after tracer delivery. It also enhanced production of [14C]glycogen and concentration of glycogen in the liver after 5 and 20 min. At 20 min of glucose infusion the appearance of [14C]glyceride glycerol in liver as well as liver lactate concentration and lactate/pyruvate ratio were increased. The low dose of glucose used enhanced liver values of [14C]glycogen, [14C]glycogen specific activity and glycogen concentration. Our results support the hypothesis that in the starved rat glucose is converted into C3 units prior to being deposited as liver glycogen and based on the liver zonation model (Jungermann et al., 1983) it is proposed that glucose stimulated gluconeogenesis by shifting the liver to the cytosolic redox state as a secondary consequence of increased glycolytic activity.     

Metabolism of 3H- and 14C-labelled lactate in starved rats

1. [2-³H,U-¹⁴C]- or [3-³H,U-¹⁴C]-Lactate was administered by infusion or bolus injection to overnight-starved rats. Tracer lactate was injected or infused through indwelling cannulas into the aorta and blood was sampled from the vena cava (A–VC mode), or it was administered into the vena cava and sampled from the aorta (V–A mode). Sampling was continued after infusion was terminated to obtain the wash-out curves for the tracer. The activities of lactate, glucose, amino acids and water were followed. 2. The kinetics of labelled lactate in the two modes differed markedly, but the kinetics of labelled glucose were much the same irrespective of mode. 3. The kinetics of ³H-labelled lactate differed markedly from those for [U-¹⁴C]lactate. Isotopic steady state was attained in less than 1h of infusion of [³H]lactate but required over 6h for [U-¹⁴C]lactate. 4. ³H from [2-³H]lactate labels glucose more extensive than does that from [3-³H]lactate. [3-³H]Lactate also labels plasma amino acids. The distribution of ³H in glucose was determined. 5. Maximal radioactivity in ³HOH in plasma is attained in less than 1min after injection. Near-maximal radioactivity in [¹⁴C]glucose and [³H]glucose is attained within 2–3min after injection. 6. The apparent replacement rates for lactate were calculated from the areas under the specific-radioactivity curves or plateau specific radioactivities after primed infusion. Results calculated from bolus injection and infusion agreed closely. The apparent replacement rate for [³H]lactate from the A–VC mode averaged about 16mg/min per kg body wt. and that in the V–A mode about 8.5mg/min per kg body wt. The apparent rates for [¹⁴C]lactate (`rate of irreversible disposal') were 8mg/min per kg body wt. for the A–VC mode and 5.5mg/min per kg body wt. for the V–A mode. Apparent recycling of lactate carbon was 55–60% according to the A–VC mode and 35% according to the V–A mode. 7. The specific radioactivities of [U-¹⁴C]glucose at isotopic steady state were 55% and 45% that of [U-¹⁴C]lactate in the A–VC and V–A modes respectively. We calculated, correcting for the dilution of ¹⁴C in gluconeogenesis via oxaloacetate, that over 70% of newly synthesized glucose was derived from circulating lactate. 8. Recycling of ³H between lactate and glucose was evaluated. It has no significant effect on the calculation of the replacement rate, but affects considerably the areas under the wash-out curves for both [2-³H]- and [3-³H]-lactate, and calculation of mean transit time and total lactate mass in the body. Corrected for recycling, in the A–VC mode the mean transit time is about 3min, the lactate mass about 50mg/kg body wt. and the lactate space about 65% of body space. The V–A mode yields a mass and lactate space about half those with the A–VC mode. 9. The area under the wash-out curve for [¹⁴C]lactate is some 20–30 times that for [³H]lactate, and apparent carbon mass is 400–500mg/kg body wt. and presumably includes the carbon of glucose, pyruvate and amino acids, which are exchanging rapidly with that of lactate.     

Comparative utilization of glycerol and alanine as liver gluconeogenic substrates in the fed late pregnant rat

The appearance of plasma [14C]glucose in the inferior cava vein after a pulse of 0.2 mmol of [U-14C]L-alanine or [U-14C]glycerol/200 g body wt given through the portal vein was studied in fed 21 day pregnant rats and virgin controls under pentobarbital anesthesia. In both groups values were much higher when [U-14C]glycerol was the administered tracer than when [U-14C]L-alanine, and they were augmented in pregnant versus virgin animals at 1 min when receiving [U-14C]glycerol and at 2 min when receiving [U-14C]L-alanine. 20 min after the tracers rats receiving [U-14C]glycerol showed much higher liver [14C]glycogen and [14C]glyceride glycerol than those receiving [U-14C]L-alanine. Radioactivity present in liver as [14C]glyceride glycerol was greater in pregnant than in virgin rats receiving [U-14C]glycerol whereas radioactivity corresponding to [14C]fatty acids was lower in the former group receiving either tracer. At 20 min after maternal treatments fetuses showed lower plasma [14C]glycerol than [14C]alanine values but plasma [14C]glucose and liver [14C]glycogen values were much greater in fetuses from mothers receiving [U-14C]glycerol than [U-14C]L-amine. Besides showing the higher gluconeogenic efficiency in pregnant than in virgin rats, results indicate that at late gestation glycerol is used as a preferential substrate for both glucose and glyceride glycerol synthesis in liver.     

Increased lactate appearance and reduced clearance during hypoxia in dogs

In order to assess the effects of severe hypoxia on whole body glucose and lactate kinetics, nine experiments were performed on anesthetized, ventilated mongrel dogs. [U-13C]glucose and [1-14C]lactate (n = 5), or [6-14C]glucose and [U-13C]lactate (n = 4) were infused using the primed-continuous infusion method. Cardiac output was measured by thermodilution. After a control period with 21% O2, inspired O2 was reduced for 90 minutes. Three of the experiments resulted in unstable hemodynamics and lactate levels, and are excluded from the mean data. Arterial PO2 fell from a control level of 106.8 +/- 11.9 to 24.2 +/- 3.5 mmHg during the last 45 minutes of hypoxia, and O2 transport fell to 52% of normoxic values. Arterial lactate concentration and the rate of appearance increased by 428% and 182%, respectively, from control to hypoxia. The metabolic clearance rate for lactate fell by 34%. Arterial glucose levels did not change significantly with hypoxia, but the rate of glucose disappearance rose by 70%, and the rate of glucose conversion to lactate increased 3-fold. It is concluded that acute severe hypoxia in anesthetized dogs causes 1) a large increase in arterial lactate levels, but no significant change in glycemia, 2) a large increase in the rate of lactate disappearance and only a small increase in the rate of glucose disappearance and 3) a fall in the metabolic clearance rate of lactate.     

Malignant Pheochromocytoma of the Organ of Zuckerkandl Requiring Aortic and Vena Caval Reconstruction

ObjectiveTo describe a case of a malignant pheochromocytoma located in the organ of Zuckerkandl that required aortic and vena caval resection and reconstruction.MethodsWe present a case report that includes clinical, laboratory, and radiographic data as well as photographs, results from pathology, and a brief review of the literature.ResultsA 46-year-old man was referred for evaluation of a 1.4-cm left adrenal mass incidentally discovered on an abdominopelvic computed tomography (CT) scan. Subsequent laboratory evaluation revealed the following values: urine norepinephrine, 252 [μg/24 h; urine normetanephrine, 1122 [μg/24 h; urine metanephrine, 162 μg/24 h; urine epinephrine, 7 [μg/24 h; urine vanillylman-delic acid, 8 mg/24 h; and plasma metanephrine, 98 pg/ mL. Imaging characteristics of the left adrenal mass were consistent with a benign adenoma, but CT also demonstrated a hypervascular paraaortic mass. ¹²³I-metaiodo-benzylguanidine scanning with fusion CT imaging demonstrated increased radiopharmaceutical uptake within the para-aortic mass consistent with a paraganglioma in the organ of Zuckerkandl. Findings from CT angiography of the abdomen and pelvis suggested aortic involvement and vena caval thrombus. The mass was excised en bloc, including portions of the aorta, inferior vena cava, and right ureter. The aorta and vena cava were reconstructed using Dacron grafts. The remaining right ureter and kidney were removed to avoid the possibility of a urine leak from an ureteroureterostomy. Final pathologic and operative findings confirmed a malignant pheochromocytoma of the organ of Zuckerkandl with invasion into the wall of the inferior vena cava and tumor thrombus extending into the lumen.ConclusionMalignant pheochromocytoma of the organ of Zuckerkandl involving the aorta and inferior vena cava is exceedingly rare, and although surgical resection and reconstruction can be radical and aggressive, this treatment offers the only chance for cure. (Endocr Pract. 2007;13:493-497)     

Systemic and renal hemodynamic responses to vascular blockade of vasopressin in conscious dogs with ascites

A role for arginine vasopressin has been implicated in the compensatory control of arterial blood pressure in several animal models with reported increases in plasma levels of arginine vasopressin. A threefold elevation in plasma vasopressin has been reported in conscious dogs following constriction of the inferior vena cava. In the present study, infusion of the arginine vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine] Arg8-vasopressin into conscious dogs with chronic caval constriction did not decrease mean arterial blood pressure. However, the dose of infused antagonist completely blocked the pressor response to 2 micrograms of exogenous vasopressin. Also the antagonist produced no effect on heart rate, plasma renin activity, or urinary volume and electrolyte excretions. A slight, transient increase (P less than or equal to 0.05) was observed in creatinine clearance and in PAH clearance following antagonist infusion, suggesting a possible decrease in renal vascular resistance. These data suggest that the direct vasoconstrictor actions of vasopressin contribute minimally, if at all, to blood pressure maintenance following chronic caval constriction. Alternatively, blockade of endogenous vasopressin receptors at the level of peripheral arterioles may have resulted in no depressor response due to a masking of this response by other compensatory hormonal and neural pressor systems.     

Effect of cortisol on hepatic gluconeogenesis in the fetal sheep

To determine whether the prenatal surge in cortisol induces the onset of gluconeogenesis in the fetal sheep, we performed studies in eight fetal sheep of 124 +/- 3 days gestational age. Catheters were inserted chronically in the descending aorta, inferior vena cava, and hepatic and umbilical veins, allowing the measurement of substrate flux across the liver and placenta. Cortisol was infused over a 48-h period, raising plasma cortisol concentrations from 3.5 +/- 2.5 ng/ml to 78 +/- 22 ng/ml at 24 h and 111 41 ng/ml at 48 h. At 24 and 48 h, [14C]lactate was infused into the inferior vena cava, and blood samples were obtained to measure plasma concentrations and specific activities of glucose and lactate. Comparison of the cortisol-treated group with an untreated control group of animals revealed no differences in blood gases, haemoglobin concentrations, or glucose and lactate levels. Similarly, there were no differences between groups in liver oxygen consumption, glucose and lactate flux, or gluconeogenesis from lactate. In two animals we demonstrated hepatic glucose production from lactate. One of these was in active labor at the time of study, and one aborted within hours of the study. We conclude that the prenatal cortisol surge alone is not responsible for the onset of hepatic gluconeogenesis in the perinatal period. However, cortisol may have a permissive action, promoting hepatic gluconeogenesis in response to other hormonal stimuli.     

Peroxisome proliferator-activated receptor alpha (PPARalpha) influences substrate utilization for hepatic glucose production

The hypoglycemia seen in the fasting PPARalpha null mouse is thought to be due to impaired liver fatty acid beta-oxidation. The etiology of hypoglycemia in the PPARalpha null mouse was determined via stable isotope studies. Glucose, lactate, and glycerol flux was assessed in the fasted and fed states in 4-month-old PPARalpha null mice and in C57BL/6 WT maintained on standard chow using a new protocol for flux assessment in the fasted and fed states. Hepatic glucose production (HGP) and glucose carbon recycling were estimated using [U-(13)C(6)]glucose, and HGP, lactate, and glycerol turnover was estimated utilizing either [U-(13)C(3)]lactate or [2-(13)C]glycerol infused subcutaneously via Alza miniosmotic pumps. At the end of a 17-h fast, HGP was higher in the PPARalpha null mice than in WT by 37% (p < 0.01). However, recycling of glucose carbon from lactate back to glucose was lower in the PPARalpha null than in WT (39% versus 51%, p < 0.02). The lack of conversion of lactate to glucose was confirmed using an [U-(13)C(3)]lactate infusion. In the fasted state, HGP from lactate and lactate production were decreased by 65 and 55%, respectively (p < 0.05) in PPARalpha null mice. In contrast, when [2-(13)C]glycerol was infused, glycerol production and HGP from glycerol increased by 80 and 250%, respectively (p < 0.01), in the fasted state of PPARalpha null mice. The increased HGP from glycerol was not suppressed in the fed state. While little change was evident for phosphoenolpyruvate carboxykinase (PEPCK) expression, pyruvate kinase expression was decreased 16-fold in fasted PPARalpha null mice as compared with the wild-type control. The fasted and fed insulin levels were comparable, but blood glucose levels were lower in the PPARalpha null mice than in controls. In conclusion, PPARalpha receptor function creates a setpoint for a metabolic network that regulates the rate and route of HGP in the fasted and fed states, in part, by controlling the flux of glycerol and lactate between the triose-phosphate and pyruvate/lactate pools.     

Effect of systemic venous pressure elevation on lymph flow and lung edema formation

Pulmonary lymph drains into the thoracic duct and then into the systemic venous circulation. Since systemic venous pressure (SVP) must be overcome before pulmonary lymph can flow, variations in SVP may affect lymph flow rate and therefore the rate of fluid accumulation within the lung. The importance of this issue is evident when one considers the variety of clinical interventions that increase SVP and promote pulmonary edema formation, such as volume infusion, positive-pressure ventilation, and various vasoactive drug therapies. We recorded pulmonary arterial pressure (PAP), left atrial pressure (LAP), and SVP in chronic unanesthetized sheep. Occlusion balloons were placed in the left atrium and superior vena cava to control their respective pressures. The superior vena caval occluder was placed above the azygos vein so that bronchial venous pressure would not be elevated when the balloon was inflated. Three-hour experiments were carried out at various LAP levels with and without SVP being elevated to 20 mmHg. The amount of fluid present in the lung was determined by the wet-to-dry weight ratio method. At control LAP levels, no significant difference in lung fluid accumulation could be shown between animals with control and elevated SVP levels. When LAP was elevated above control a significantly greater amount of pulmonary fluid accumulated in animals with elevated SVP levels compared with those with control SVP levels. We conclude that significant excess pulmonary edema formation will occur when SVP is elevated at pulmonary microvascular pressures not normally associated with rapid fluid accumulation.     

Glucagon response to exercise is critical for accelerated hepatic glutamine metabolism and nitrogen disposal

The aim of this study was to determine the role of glucagon in hepatic glutamine (Gln) metabolism during exercise. Sampling (artery, portal vein, and hepatic vein) and infusion (vena cava) catheters and flow probes (portal vein, hepatic artery) were implanted in anesthetized dogs. At least 16 days after surgery, an experiment, consisting of a 120-min equilibration period, a 30-min basal sampling period, and a 150-min exercise period, was performed in these animals. [5-(15)N]Gln was infused throughout experiments to measure gut and liver Gln kinetics and the incorporation of Gln amide nitrogen into urea. Somatostatin was infused throughout the study. Glucagon was infused at a basal rate until the beginning of exercise, when the rate was either 1) gradually increased to simulate the glucagon response to exercise (n = 5) or 2) unchanged to maintain basal glucagon (n = 5). Insulin was infused during the equilibration and basal periods at rates designed to achieve stable euglycemia. The insulin infusion was reduced in both protocols to simulate the exercise-induced insulin decrement. These studies show that the exercise-induced increase in glucagon is 1) essential for the increase in hepatic Gln uptake and fractional extraction, 2) required for the full increment in ureagenesis, 3) required for the specific transfer of the Gln amide nitrogen to urea, and 4) unrelated to the increase in gut fractional Gln extraction. These data show, by use of the physiological perturbation of exercise, that glucagon is a physiological regulator of hepatic Gln metabolism in vivo.     

A stable isotope technique for investigating lactate metabolism in humans

A stable isotope tracer method has been developed for studying lactate metabolism in humans. The method uses lactic acid triple labeled with 13C as the tracer. The stable isotope is infused to attain a level of approximately 1.5% of that of the circulating unlabeled lactate. Following the isolation of lactic acid from the blood, the percentage of triple labeled (13C)lactate is measured using gas chromatography mas spectrometry. We compared this method with tracer methodology using [14C]lactate and found comparable results.     

Role of Na+-K+-ATPase in insulin-induced lactate release by skeletal muscle

Hyperinsulinemia increases lactate release by various organs and tissues. Whereas it has been shown that aerobic glycolysis is linked to Na+-K+-ATPase activity, we hypothesized that stimulation by insulin of skeletal muscle Na+-K+-ATPase is responsible for increased muscle lactate production. To test this hypothesis, we assessed muscle lactate release in healthy volunteers from the [13C]lactate concentration in the effluent dialysates of microdialysis probes inserted into the tibialis anterior muscles on both sides and infused with solutions containing 5 mmol/l [U-13C]glucose. On one side, the microdialysis probe was intermittently infused with the same solution additioned with 2.10(-5) M ouabain. In the basal state, [13C]lactate concentration in the dialysate was not affected by ouabain. During a euglycemic-hyperinsulinemic clamp, [13C]lactate concentration increased by 135% in the dialysate without ouabain, and this stimulation was nearly entirely reversed by ouabain (56% inhibition compared with values in the dialysate collected from the contralateral probe). These data indicate that insulin stimulates muscle lactate release by activating Na+-K+-ATPase in healthy humans.     

The importance of glucose in the oxidative metabolism of the testis of the conscious ram and the role of the pentose cycle

1. [U-(14)C]Glucose was infused into one or both testicular arteries of ten conscious rams and the specific activity of the glucose taken up by the testis was compared with the specific activity of the carbon dioxide produced by the testis. 2. Equilibration had occurred after infusion for 3hr. when a mean of 68% of the carbon dioxide was being derived by the testis from blood glucose and 86% of the glucose taken up by the testis was being oxidized to carbon dioxide. After 5hr. infusion, these values were 71% and 83% respectively. 3. In four other conscious rams, [1-(14)C]glucose was infused into one testicular artery and [6-(14)C] glucose into the other and the ;specific yields' of carbon dioxide calculated for the two forms of glucose. 4. From these values, it was calculated that a mean of 9.3% of the glucose taken up by the testis was metabolized via the pentose cycle.     

Tracer priming the bicarbonate pool

We have described a technique whereby the time necessary to reach an equilibrium enrichment of expired CO2 during a primed-constant infusion of [U-13C]glucose was shortened from 7 to 8 h to 1 hour or less. We applied the theory of the primed-constant infusion technique to the bicarbonate pool, with the "constant infusion" of labeled carbon dioxide originating from oxidation of the infused [13C]glucose rather than from a labeled infusion of bicarbonate.     

Studies of glycogen synthesis and the Krebs cycle by mass isotopomer analysis with [U-13C]glucose in rats

Starved rats were infused intragastrically via indwelling duodenal cannulae with glucose at a rate of 30 mg/min/kg. The infusate contained [U-13C]glucose at an enrichment of 32 or 17%. At the end of the infusion, after 160 min, glucose and lactate were isolated from arterial and portal blood and from liver, and liver glycogen was isolated and hydrolyzed to glucose. The enrichment in glucose and lactate and the isotopomer distribution in glucose of masses from 180 to 186 were determined by gas chromatography-mass spectrometry (GC-MS). From analysis of these data we determined (a) gluconeogenesis proceeds at half the basal rate in the presence of a large infused glucose load, (b) one-quarter of the hepatic pyruvate pool is derived from nonglucose carbon, (c) half of the labeled molecules in liver glycogen are of mass 186 from the infused glucose and half are of masses 181-183, (d) the contribution of the indirect path from pyruvate when corrected for synthesis from unlabeled pyruvate ranges from 55 to 65%, (e) the rate of pyruvate carboxylase averages 90% that of citrate synthase, and (f) the rate of exchange of oxaloacetate with fumarate is about three times the rate of flux in the Krebs cycle (four times in the "forward" direction), and the enrichment in carbon 1 of oxaloacetate was 2.3 times that in carbon 4. In the Appendix a method to obtain the isotopomer distribution of newly formed glucose and glycogen glucose is described. An algorithm to correct for the contribution of natural abundance of 13C and the presence of 12C in commercial [U-13C]glucose is presented. A novel mathematical analysis to obtain the parameters of the Krebs cycle from the isotopomer distribution is developed in the Appendix. Equations to calculate the relative rates of pyruvate carboxylase (y), and the equilibration of oxaloacetate with fumarate from the isotopomer distribution are derived. Mass isotopomer analysis provides a novel and powerful tool for the study of carbohydrate metabolism and the operation of the Krebs cycle.     

Transhepatic approach for catheter ablation of accessory pathway in a child with complex congenital heart disease

We report on a 22-month-old boy with drug-resistant atrioventricular reentrant tachycardia and complex structural heart disease consisting of right atrial isomerism, mirror image orientation of the intrathoracic veins, hemi-azygos continuation to the left superior vena cava, separate drainage of the hepatic veins into the left-sided atrium, congenitally corrected transposition, pulmonary atresia, and atrial and ventricular septal defects.Access to the heart for radiofrequency (RF) ablation was obtained by percutaneous puncture of a hepatic vein, the left internal jugular vein, and femoral artery. The accessory pathway was localised to the free wall of the left-sided AV groove and successfully ablated. There were no procedure-related complications.RF ablation of an accessory pathway is feasible in young children with complex structural heart disease and abnormal systemic venous return. In such patients access to the heart must be planned with knowledge of the anatomy and judicious use of the hepatic venous approach.