Effect of bariatric surgery on peripheral flow-mediated dilation and coronary microvascular function.

BACKGROUND AND AIMS: To assess the effects of bariatric surgery (BS) on peripheral endothelial function and on coronary microvascular dilator function. METHODS AND RESULTS: We studied 50 morbidly obese patients (age 38 ± 9, 13 M) who underwent BS and 20 comparable obese controls (age 41 ± 11, 6 M) without any evidence of cardiovascular disease. Peripheral vascular dilator function was assessed by brachial artery diameter changes in response to post-ischemic forearm hyperaemia (flow-mediated dilation, FMD). Coronary microvascular function was assessed by measuring coronary blood flow (CBF) velocity response to i.v. adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery by transthoracic Doppler echocardiography. The tests were performed at baseline and at 3-month follow-up. At baseline, FMD and CBF response to adenosine and CPT were similar in the 2 groups. Compared to baseline, FMD at follow-up improved significantly in BS patients (5.9 ± 2.7% to 8.8 ± 2.4%, p < 0.01), but not in controls (6.3 ± 3.2% vs. 6.4 ± 3.1%, p = 0.41). Similarly, a significant improvement of CBF response to adenosine (1.63 ± 0.47 to 2.45 ± 0.57, p < 0.01) and to CPT (1.43 ± 0.26 to 2.13 ± 0.55, p < 0.01) was observed in BS patients but not in controls (1.55 ± 0.38 vs. 1.53 ± 0.37, p = 0.85; and 1.37 ± 0.26 vs. 1.34 ± 0.21, p = 0.48, respectively). The favourable vascular effects of BS were similar independently of the presence and changes of other known cardiovascular risk factors and of basal values and changes of serum C-reactive protein levels. CONCLUSIONS: Our data show that, in morbidly obese patients, together with peripheral endothelial function, BS also improves coronary microvascular function. These effects suggest global improvement of vascular function which can contribute significantly to the reduction of cardiovascular risk by BS reported in previous studies.

Laparoscopic resection with intraoperative radiotherapy: a new step in the multimodal treatment of advanced colorectal cancer.

BACKGROUND: Local recurrence is one of the most important problems related to resection of rectal cancer in locally advanced cases (T3-T4). Total mesorectal excision (TME) is the mainstay of surgical therapy, although many articles have been published about the availability of intraoperative radiotherapy (IORT) for the control of locally advanced rectal cancers. METHODS: The authors describe six patients affected by advanced rectal cancer (T3N1) whom they treated with neoadjuvant radiochemotherapy and laparoscopic rectal resection combined with TME and IORT. RESULTS: The operative time did not exceed 6 h in any case with IORT treatment. The procedure itself and the transfer of patients to the radiotherapy room accounted for about 2 h. The postoperative course was uneventful in every case, and all the patients were discharged within the first 8 postoperative days. CONCLUSIONS: This report describes the technical aspect and the feasibility of IORT associated with laparoscopic surgical resection for rectal cancer.

Clinical evaluation of fibrin glue in the prevention of anastomotic leak and internal hernia after laparoscopic gastric bypass: preliminary results of a prospective, randomized multicenter trial.

BACKGROUND: Gastro-jejunal anastomotic leak and internal hernia can be life-threatening complications of laparoscopic Roux-en-Y gastric bypass (LRYGBP), ranging from 0.1-4.3% and from 0.8-4.5% respectively. The safety and efficacy of a fibrin glue (Tissucol) was assessed when placed around the anastomoses and over the mesenteric openings for prevention of anastomotic leaks and internal hernias after LRYGBP. METHODS: A prospective, randomized, multicenter, clinical trial commenced in January 2004. Patients with BMI 40-59 kg/m2, aged 21-60 years, undergoing LRYGBP, were randomized into: 1) study group (fibrin glue applied on the gastro-jejunal and jejuno-jejunal anastomoses and the mesenteric openings); 2) control group (no fibrin glue, but suture of the mesenteric openings). 322 patients, 161 for each arm, will be enrolled for an estimated period of 24 months. Sex, age, operative time, time to postoperative oral diet and hospital stay, early and late complications rates are evaluated. An interim evaluation was conducted after 15 months. RESULTS: To April 2005, 204 patients were randomized: 111 in the control group (mean age 39.0+/-11.6 years, BMI 46.4 +/- 8.2) and 93 in the fibrin glue group (mean age 42.9+/-11.7 years, BMI 46.9+/-6.4). There was no mortality or conversion in both groups; no differences in operative time and postoperative hospital stay were recorded. Time to postoperative oral diet was shorter for the fibrin glue group (P = 0.0044). Neither leaks nor internal hernias have occurred in the fibrin glue group. The incidence of leaks (2 cases, 1.8%) and the overall reoperation rate were higher in the control group (P=0.0165). CONCLUSION: The preliminary results suggest that Tissucol application has no adverse effects, is not time-consuming, and may be effective in preventing leaks and internal hernias in morbidly obese patients undergoing LRYGBP.

Growth hormone secretion and leptin in morbid obesity before and after biliopancreatic diversion: relationships with insulin and body composition.

Obesity is characterized by increased leptin levels and insulin resistance, whereas blunted GH secretion is paired with normal, low, or high plasma IGF-I levels. To investigate body composition in human obesity and the interactions among the GH-IGF-I axis, leptin, and insulin resistance [measured with the homeostasis model assessment (HOMA) score], we studied 15 obese females, aged 23-54 yr (mean age, 42.7 +/- 2.6), with a body mass index (BMI) of 44.02 +/- 1.45 kg/m(2), who underwent treatment by biliopancreatic diversion (BPD), before and after surgery (16-24 months; BMI, 28.29 +/- 0.89 kg/m(2)). Our controls were 15 normal females, aged 28-54 yr (mean age, 40.8 +/- 2.3 yr), with a BMI of 27.52 +/- 0.53 kg/m(2). Insulin and leptin levels and HOMA scores were higher pre-BPD than in the controls. The GH response to GHRH was blunted, with a GH peak and GH area under the curve (AUC) significantly lower than those in controls. IGF-I and IGF-binding protein-3 (IGFBP-3) were also lower than control values. After surgery, BMI, fat mass, lean body mass, HOMA, insulin, and leptin significantly decreased. Furthermore, the GH response to GHRH severely increased; IGF-I and IGFBP-3 levels did not significantly vary. Considering all subjects, correlation analysis showed a strong positive correlation between insulin and leptin, and a negative correlation between insulin and GH peak and between insulin and GH AUC. Regression analysis performed grouping pre- and post-BPD indicated that leptin and GH peak or AUC could best be predicted from insulin levels. The surgical treatment of severe obesity after stabilization of body weight decreases BMI and fat mass while preserving normal lean body mass as well as positively influencing insulin sensitivity and thus aiding the normalization of leptin levels. The insulin reduction may be mainly involved in the increase in the GH response to GHRH through various possible central and peripheral mechanisms while decreasing the peripheral sensitivity to GH itself, as shown by the stable nature of the IGF-I and IGFBP-3 values. Our findings suggest that the changes in insulin levels are the starting point for changes in both leptin levels and the somatotrope axis after BPD.

Comparison of positive end-expiratory pressure with reverse Trendelenburg position in morbidly obese patients undergoing bariatric surgery: effects on hemodynamics and pulmonary gas exchange.

BACKGROUND: Anesthetized morbidly obese patients often exhibit impaired pulmonary gas exchanges, mostly because of a reduction in functional residual capacity. At present, several approaches are suggested to ventilate these patients. METHODS: The efficiency of positive end-expiratory pressure (PEEP) and reverse Trendelenburg position (RTP) were compared in order to improve oxygenation in 20 morbidly obese patients undergoing bariatric surgery. RESULTS: Both PEEP and RTP determined a significant decrease in alveolar-arterial oxygen difference and an increase in total respiratory compliance (Ctot). RTP resulted in lower airway pressures than PEEP with similar improvements in Ctot and oxygenation. Concerning hemodynamic parameters, cardiac output (CO) significantly decreased with both PEEP and RTP. CONCLUSIONS: RTP and PEEP can be considered adequate ventilatory settings for morbidly obese patients, without any significant difference with regard to gas exchange improvement. However, the decrease in CO may partially counteract the beneficial effects on oxygenation of these ventilatory settings.

Volatile anesthesia in bariatric surgery.

BACKGROUND: Obesity causes anesthesiologists a broad variety of perioperative theoretical and practical problems. The aim of this study was to compare two protocols of anesthesia employing Isoflurane and Sevoflurane and evaluate the cardiorespiratory parameters, postoperative recovery and analgesia. METHODS: 90 patients underwent biliopancreatic diversion. 60 patients (group A) received Isoflurane and 30 patients (group B) were anesthetized with Sevoflurane. Intraoperative monitoring consisted of EKG, invasive arterial pressure, SpO2, EtCO2, Etanest, Spirometry, urinary output and TOF. Cardiorespiratory parameters and end tidal expiratory concentrations of volatile agents were collected during specific phases of surgery: 1) before induction of anesthesia, 2) after intubation, 3) after skin incision, 4) after positioning of costal retractors, 5) in the reverse Trendelenburg position, 6) end of surgery. During the postoperative period the Aldrete test was carried out to evaluate the recovery from anesthesia. VAS was administered for 6 hours after the end of surgery to set the quality of analgesia. RESULTS: No statistically significant differences in cardiorespiratory parameters were found between the two groups. Extubation time was significantly less in the Sevoflurane Group than in the Isoflurane (15 +/- 7 min vs 24 +/- 5 min, p < 0.05). The Sevoflurane Group showed an Aldrete score significantly higher than the Isoflurane (8.8 +/- 0.3 vs 8.1 +/- 0.4, p < 0.05). VAS values did not show statistical differences. CONCLUSION: The introduction of Sevoflurane, a volatile agent with rapid pharmacokinetic properties, seems to offer an interesting application in these patients.

Opioid dysregulation after biliopancreatic diversion: effect of naloxone on preprandial and postprandial growth hormone (GH)-releasing hormone-induced GH release in surgically induced weight loss.

Previously, we have shown that in the opposite extremes of nutritional status (obesity and anorexia nervosa [AN]), the growth hormone (GH) response to GH-releasing hormone (GHRH) is not inhibited by the ingestion of a normal 800-kcal meal at noon. In obese subjects, GHRH-induced GH release is significantly increased (known as the "paradoxical response"). An opiate antagonist infusion (naloxone [NAL]) inhibited this postprandial meal-induced augmenting effect in obese subjects, suggesting opioid involvement in the paradoxical response. The paradoxical postprandial GH release persisted in obese subjects, who after biliopancreatic diversion (BPD) experienced a reduction in body weight, despite the elevation of fasting GH levels. We therefore tested a group of patients, before and after BPD, composed of 10 females, aged 23 to 54 years, who after surgery had experienced a significant reduction in body weight (mean body mass index [BMI], 25.78 +/- 1.01 kg/mg v 44.68 +/- 1.73 kg/mg). The subjects were studied 16 to 24 months after operation, in a phase of stabilized body weight. They underwent, in randomized order, the following tests: GHRH (1 microg/kg as an intravenous [IV] bolus) at 1:00 PM, in the fasting state; GHRH (1 microg/kg) at 1:00 PM, 45 minutes after a standard 800-kcal meal consumed between noon and 12:15 PM; and fasting state and postprandial GHRH (1 microg/kg) during NAL infusion (1.6 mg/h x 2.5 h, starting at noon). We found that NAL inhibited the paradoxical postprandial GH increase only in pre-BPD subjects (GH area under the concentration time curve [AUC] in microg/L/90 min)-before meal: after GHRH 237.54 +/- 62.28, after NAL + GHRH 699.2 +/- 271.57; after meal: after GHRH 575.46 +/- 109.68, after NAL + GHRH 156.17 +/- 24.96. On the other hand, NAL failed to have significant effects in post-BPD subjects (GH AUC in microg/L/90 min)-before meal: after GHRH 871.11 +/- 256.38, after NAL + GHRH 449.19 +/- 119.13; after meal: after GHRH 1,981.54 +/- 319.92, after NAL + GHRH 1,665.91 +/- 315.4. It could be hypothesized that the opioid system is radically modified by the surgical procedure, and that opioids are not the only mediators in the paradoxical response, which persists after BPD, despite the reversion of the hyposecretory GH state, which is a characteristic of obese subjects.

The effects of the reverse trendelenburg position on respiratory mechanics and blood gases in morbidly obese patients during bariatric surgery.

Anesthesia adversely affects respiratory function, particularly in morbidly obese patients. Although many studies have been performed to determine the optimal ventilatory settings in these patients, this question has not been answered. The aim of this study was to evaluate the effect of reverse Trendelenburg position (RTP) on gas exchange and respiratory mechanics in 15 obese patients undergoing biliopancreatic diversion. A standardized anesthetic regimen was used and patients were examined at standard times: 1) after tracheal intubation, 2) after laparotomy, 3) after positioning of subcostal retractors, 4) with retractors in RTP. The measurements of respiratory mechanics were repeated for a wide range of tidal volumes by using the technique of rapid occlusion during constant flow inflation. We noted a wide alveolar-arterial oxygen difference [P(A-a)O(2)] in all patients, particularly during Phase 3. When the patients were placed in RTP, P(A-a)O(2) showed a significant improvement and a return toward baseline values. As for mechanics, total respiratory system compliance was significantly higher in RTP than in the other phases. In conclusion, our data suggest that RTP is an appropriate intraoperative posture for obese subjects because it causes minimal arterial blood pressure changes and improves oxygenation.

Evaluation of pre- and postprandial growth hormone (GH)-releasing hormone-induced GH response in subjects with persistent body weight normalisation after biliopancreatic diversion.

BACKGROUND: Obesity is characterised by growth hormone (GH) abnormalities, including a blunted response to stimulation and a 'paradoxical' increase after meals. The blunted GH release is reversed by a surgical intestinal bypass procedure. However, this does not mean that normal GH dynamics have been restored. The present study assessed whether post-surgical weight reduction in obese patients normalised the modulation of GH release produced by metabolic fuels. SUBJECTS: Ten obese female subjects, aged 23-54 y, were studied before and after biliopancreatic diversion (BPD). All patients, after surgery, had experienced a significant reduction in body weight (mean body mass index (BMI) 25.78 +/- 1.01 kg/m2 vs 44.68 +/- 1.73 kg/m2). Two groups were also studied as controls: Ten normal body weight female subjects and ten patients suffering from anorexia nervosa (AN, mean BMI 17.46 +/- 1.12 kg/m2). MEASUREMENTS: We have studied the GH response to a GH releasing hormone (GHRH) bolus (1 microg/kg i.v., at 13.00 h) before and after a standard meal. RESULTS: In post-BPD subjects, the GH response to GHRH in the fasting state, was clearly augmented in comparison with the pre-BPD values (peak values 18.06 +/- 4.56 vs 3.24 +/- 0.68 microg/L). In post-BPD subjects the postprandial GH response was further augmented in comparison with the fasting test (peak 30.12 +/- 4.99 microg/L, P < 0.05). This pattern was similar to that observed in anorexic patients. CONCLUSION: The surgical procedure restores a normal GH response to GHRH in the fasting state, but the 'paradoxical' GH response after meals remains present, suggesting a persistent GH derangement in such patients, which is not related to body weight per se. The surgical procedure makes obese patients similar to anorexics, in the relationships between metabolic fuels and GH secretion. The persistence of the GH postprandial response to GHRH in post-BPD subjects suggests a role for metabolic fuels in the regulation of somatostatin (SRIF) secretion.

A surgical option for familial chylomicronemia associated with insulin-resistant diabetes mellitus.

BACKGROUND: The goal of the present work is to present an effective surgical approach for the treatment of a medically-resistant form of hyperlipidemia. METHODS: Two siblings with familial lipoprotein-lipase deficiency and subsequent hyperchylomicronemia, widespread skin xanthomas and severe insulin-resistant diabetes mellitus came to our observation after several unsuccessful attempts at medical treatment. In order to lower plasma lipids through lipid malabsorption, a modified bilio-pancreatic diversion operation was employed. The rationale in deciding to use this surgical approach was based also on the likely hypothesis that diabetes, in these subjects, was secondary to high circulating and tissue levels of lipids. Insulin sensitivity in the two treated subjects, as well as in 24 healthy volunteers constituting the control group, was assessed by euglycemic hyperinsulinemic clamp and indirect calorimetry, obtaining total end-clamp glucose uptake (M) and end-clamp glucose oxidation (ECGO) rates. RESULTS: Within 3 weeks of surgery, plasma triglycerides and cholesterol levels had decreased from 4500 and 500 mg/dl (with dietary restrictions) to lower than 450 and 150 mg/dl (on a free, lipid-rich diet) respectively. Fasting plasma glucose levels had decreased from above 300 (under daily repeated subcutaneous injections of insulin) to 80-100 mg/dl (without administration of insulin or oral hypoglycemic agents). Body weight and fat free mass were maintained in both subjects after surgery. In both patients, before surgery M and ECGO were significantly lower than in normal subjects, while after surgery they were not significantly different from normal subjects, confirming the positive metabolic effect of the operation. CONCLUSION: The surgical option used in these patients may represent an interesting and effective new possibility for treatment of those severe cases of hyperlipemia leading otherwise to metabolic complications and a low quality of life.

Twenty-four-hour energy and nutrient balance in weight stable postobese patients after biliopancreatic diversion.

To better understand the long-term weight stability of postobese patients who underwent biliopancreatic diversion (BPD), we studied 24-h energy and nutrient balance in eight women at least 3 yr after surgery (PO) and compared the results to those obtained in eight normal never-obese control women (C), matched by age and weight. Body composition was measured by dual-energy x-ray absorptiometry (DXA). All the patients were on an ad libitum diet; 24-h energy and nutrient intake were measured on the experimental day. Twenty-four-hour energy expenditure (EE) and 24-h nutrient oxidation rates were measured in a respiratory chamber, and energy and nutrient balances were calculated after correcting for 24-h fecal nutrient loss. No differences in body composition were found between PO and C. PO had a higher gross energy intake than C (10.6 +/- 3.4 vs. 8.0 +/- 2.2 MJ/d; p < 0.05); however, due to the higher energy fecal loss in PO as compared to C (2.4 +/- 1.3 vs. 0.09 +/- 0.01 MJ/day; p < 0.01), 24-h metabolizable energy intake (MEJ) was not different in the two groups. The energy fecal loss in the PO patients was mostly in the form of lipid. EE at 24 h was not different in PO as compared to C. Therefore energy balance, computed as the difference between 24-h MEI and 24-h EE, was similar in the two groups. Respiratory quotient was significantly higher in PO than in C (1.00 +/- 0.08 vs. 0.83 +/- 0.03; p < 0.01). Carbohydrate (-135 +/- 37 g/d in PO vs. 63 +/- 23 g/d in C; p < 0.001), and lipid (48 +/- 14 g/d in PO vs. -23 +/- 6 g/d in C; p < 0.001) balances were different in the two groups. We conclude that chronic lipid malabsorption was the main metabolic abnormality explaining the achievement of energy balance in postobese subjects after biliopancreatic diversion. A chronic reduction of lipid absorption seems to play a key role in the long-term weight stability of this group of postobese subjects.

Glucose-induced thermogenesis in postobese women who have undergone biliopancreatic diversion.

We evaluated the metabolic response to a standard (75-g) oral-glucose-tolerance test (OGTT) in eight post-obese women (PO) who underwent biliopancreatic diversion and in eight healthy control women (C). All subjects had been weight-stable for > or = 2 y. Blood samples for glucose, insulin, C-peptide, and nonesterified free fatty acids were taken at baseline and during 180 min after the glucose load. Plasma glucose and insulin concentrations at baseline and during the OGTT were similar in the two groups, suggesting the absence of an insulin-resistant state in the PO. Continuous indirect calorimetry was performed throughout the test. Glucose-induced thermogenesis (GIT) was higher in PO than in C (8.6 +/- 2.6 vs 4.3 +/- 1.9%; P < 0.01). These data indicate that GIT and insulin-glucose metabolism are not impaired in postobese patients when a near ideal body weight is reached and maintained after weight loss; this suggests that thermogenic deficiencies and hyperinsulinemia-insulin resistance are alterations secondary to obesity.

Turnover and oxidation rates of plasma-free fatty acids in obese patients treated with dexfenfluramine.

In order to assess a possible direct metabolic effect of dexfenfluramine (dF) apart from its action on food intake reduction, 10 obese postmenopausal women and 10 obese men (BMI = 32.19 +/- 1.99 kg/m2) were studied in a single-blind fashion: 4 weeks on placebo (D-28 to D0) and 4 weeks on dF (D0 to D28). A balanced diet, computed on the basis of basal metabolic rate x 1.4, was followed throughout the study. The patients' alimentary diary was checked for compliance. FFA turnover and oxidation rate, using 1-14C palmitate intravenous infusion, was determined basally (D0), after single high-dose (30 mg, D1) and after long-term (15 mg b.i.d., D28) administration. Indirect calorimetric measurements were performed using a mass spectrometer, and the usual metabolic parameters were computed. The isotope method was used in order to assess plasma FFA oxidation rate. Plasma FFA were analyzed by high-performance liquid chromatography (HPLC) and specific activity was determined at 55, 60, 65 and 70 min by counting dpm in HPLC eluates corresponding to the retention time of palmitate. The turnover rate was not significantly modified after single high-dose dF administration when compared to basal values (6.24 +/- 1.62 at D1 vs. 5.63 +/- 2.07 mmol/kg/min at D0), but was significantly increased at D28 compared with D0 (6.35 +/- 1.96 mmol/kg/min; p < 0.05). A significant increase in FFA oxidation rate was observed with respect to basal values after dF administration both at D1 (0.81 +/- 0.33 at D1 vs. 0.61 +/- 0.21 mmol/kg/min at D0; p < 0.01) and at D28 (0.77 +/- 0.34 mmol/kg/min; p < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)

Dependency of the O2 consumption/O 2 transport relationship on amino acid supply in sepsis.

In sepsis tissue O2 uptake may be abnormally limited because of a depressed O2 consumption/O2 transport relationship. This study has been performed to assess patterns of O2 consumption, CO2 production and O2 transport in septic patients undergoing total parenteral nutrition; more in particular, this study has investigated the interdependence between the patterns of blood O2 uptake and simultaneous CO2 release, and the availability of substrates (amino acids, glucose and fat). It has been shown that the O2 consumption/O2 transport relationship is significantly influenced by the exogenous amino acid load, which tends to increase O2 uptake and O2 consumption at any given O2 transport, thus suggesting a favourable effect of amino acid administration on energy metabolism. The data on CO2 production and CO2 release, in addition to reconfirming the results of previous studies, have shown that the changes in O2 uptake and in CO2 production mediated by substrate doses have a quantifiable impact on blood O2-CO2 exchange interactions.

Metabolic effects and disposition of sebacate, an alternate dicarboxylic fuel substrate.

Disodium sebacate is a 10-carbon-atom dicarboxylic acid, proposed as substrate for parenteral nutrition. We investigated its pharmacokinetic profile and thermogenic effect during a short-time infusion (5 h at 10 g/h) in 7 male volunteers. Sebacate in serum and urine was measured by high-performance liquid chromatography. A single-compartment model with two linear elimination routes was fitted. Metabolic measurements (VO2, VCO2, respiratory quotient, metabolic rate) were continuously performed for 8 h (5 h during and 3 h after the infusion) by a canopy indirect calorimeter. The apparent volume of distribution of sebacate was 8.39 +/- 0.69 liters, and the plasma fractional removal rate constant was 0.0086 +/- 0.00077 min-1. The average half-life and plasma clearance were 80.6 min and 72 ml/min, respectively. The increase in metabolic rate, the decrease in respiratory quotient and the changes in ketone body, glucagon and insulin levels during the infusion were not significant. 24-hour catecholamine excretion was within normal limits. Calories administered by sebacate seem to be available for utilization without relevant metabolic side effects.

Use of even-numbered carbon atom dicarboxylic salts in parenteral nutrition as fuel substrate.

Sebacic acid (C10), a saturated, straight-chain dicarboxylic acid with 10 carbon atoms in disodic salt form, was given intravenously to two groups of healthy male volunteers in order to evaluate its possible use in total parenteral nutrition. The first group, composed of six subjects, received 1000 mg of sebacate as a bolus; six other subjects (second group) received 10 g of sebacate dissolved in 500 mL of double-distilled water at an infusion rate of 3.33 g/h over 3 hours. The serum sebacate data for each subject were analyzed by computer, using biexponential fit corresponding to a 2-compartment open model. The distribution half-life (t1/2) was 0.34 +/- 0.06 hour and the elimination phase was rather rapid (Ke = 2.10 +/- 0.38/h); the volume of the central compartment was 2.79 +/- 0.54 L and the volume of tissue compartment 3.72 +/- 0.14 L. These data showed a good tissue fixation of sebacate. The plasma clearance was evaluated to be 5.96 +/- 2.19 L/h and the renal clearance was 19.22 +/- 10.69 L/h, indicating that a tubular secretion of C10 takes place. The serum concentration of sebacate raised to the maximal value at the end of the infusion (180 minutes), corresponded to 480.50 +/- 43.02 micrograms/mL. Respiratory and metabolic parameters were evaluated by indirect calorimetry from the beginning of the infusion for 210 minutes. The O2 consumption (VO2 mL/min per square meter) remained essentially unchanged throughout the experiment (from 154.3 +/- 28.3 at 0 to 155.3 +/- 39.5 at time 180 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue uptake and oxidation of disodium sebacate in man.

In order to better ascertain its possible use as an alternative fuel substrate in total parenteral nutrition, sebacate (Sb) metabolism was studied in seven overnight-fasting healthy male volunteers, who received a constant iv infusion (99 mmoles over 8 hours) of disodium sebacate. Sb oxidation rate was determined using an isotopic sebacate (disodic salt of (1-10)14C-sebacic acid) infusion (100 mu Ci from the fourth to the eighth hour of the cold sebacate infusion). Blood samples were collected during and after sebacate infusion at intervals of 30 minutes and Sb serum concentrations were determined by high performance liquid chromatography. Excreted radioactivity (mu Ci/min) was measured by bubbling the expired air into an apparatus containing 3 mEq hyamine to trap CO2 from a 20-L Douglas-bag. CO2 production and O2 consumption were measured before and at 4 and 8 hours after starting the infusion. Twenty-four hour nitrogen excretion with urine was obtained. The RQ and the percent of calories derived from lipid oxidation were calculated by indirect calorimetry. The Sb serum level at the plateau phase was (mean +/- SD) 4.54 +/- 0.71 mumole/mL, the overall rate of tissue uptake was 180.89 +/- 4.50 mumole/min, and the percent oxidation was 6.14 +/- 0.44%. At the end of Sb infusion the RQ dropped to 0.839 +/- 0.043, the percent of calories due to sebacate oxidation was 1.59 +/- 0.52%, and the calories derived from lipids increased to 37.77 +/- 12.90%. These data show that a definite amount of the sebacate infused is oxidized in human tissues.

Short-term infusion of azelaic acid vs intralipid in healthy subjects evaluated by indirect calorimetry.

Medium-chain dicarboxylic acids (MCDA) are usually considered byproducts of beta-oxidation when omega-oxidizable medium-chain monocarboxylic acids are accumulated, as in beta-oxidation impairment. However, evidence exists of a mitochondrial and cytoplasmatic peroxisomal carnitine independent beta-oxidation of these diacids. Our purpose was to evaluate whether MCDA could be used as source of calories. The metabolic response to intravenous administration of azelaic acid (AA) vs Intralipid (IL) was evaluated in six healthy overnight fasting male volunteers who received an infusion of 10 g of AA over 80 min and as a control 10 g of IL. AA reached a peak concentration at 80 min, (589 +/- 61 micrograms/ml) and was rapidly cleared from plasma (82 +/- 5 micrograms/ml at 240 min). Respiratory and metabolic parameters were evaluated by indirect calorimetry from the beginning of the infusion for 240 min. In both groups the CO2 production (VCO2) remained unchanged with no significant change from basal values. The O2 consumption (VO2 ml/min/m2) increased over basal values reaching a peak at the end of the infusion in both groups (AA from 119.4 +/- 16.9 to 143.0 +/- 27.6; IL from 124.7 +/- 16.8 to 152.3 +/- 29.5). Respiratory quotient (RQ) consequently decreased significantly (AA from 0.85 +/- 0.06 to 0.76 +/- 0.06; IL from 0.89 +/- 0.06 to 0.78 +/- 0.03) and calories derived from lipids increased. Metabolic rate (MR kcal/hr/m2) showed a slight increase (AA from 34.0 +/- 4.4 to 40.3 +/- 6.8; IL from 35.9 +/- 5.1 to 41.3 +/- 10.5). There was no significant difference between AA and IL treatment in all measurements.(ABSTRACT TRUNCATED AT 250 WORDS)