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Biomedical subjects

Agostino Pierro

Publications and source records attributed to Agostino Pierro.

At least 37 records · Page 2Linked to original sources
PubMed2004

Gastric transposition in children--a 21-year experience.

PURPOSE: The purpose of this study was to analyze the outcome in 173 children (104 M, 69 F) undergoing transposition since 1981. METHODS: The most common indications for esophageal replacement included failed repair of different varieties of esophageal atresia (127), caustic injury (23), and peptic strictures (8). A total of 81% of the patients were referred from other hospitals (50% from other countries). Age at operation ranged from 7 days to 17 years. The gastric transposition was performed using blunt mediastinal dissection only in 90 patients with an additional 81 patients undergoing lateral thoracotomy. The retrosternal position was used in 2 patients. RESULTS: There were no graft failures including those who had previously failed gastric tube or Scharlilike operations. Anastomotic leakage occurred in 12% (all but 1 resolved spontaneously). Anastomotic stricture requiring dilatation occurred in 19.6%. Half of these patients had previous caustic esophageal injury. There were 9 deaths in the group (5.2%). One death occurred intraoperatively, 5 in the early postoperative period, and there were 3 late deaths. In more than 90% of our patients, the outcome was considered good to excellent in terms of absence of swallowing difficulties or other gastrointestinal symptoms. Many, however, preferred to eat small frequent meals. Poor outcome was particularly associated with multiple previous attempts at esophageal salvage. There was no deterioration in the function of the gastric transposition in those patients followed up for more than 10 years. CONCLUSIONS: Gastric transposition for esophageal substitution is an acceptable procedure. It is attended by 5% mortality and a 12% leak rate. A total of 19.6% of the patients needed anastomotic dilatation for stricture. In the long term, good function has been maintained. Gastric transposition compares favorably with alternative methods of esophageal replacement.

Adolescent↗
PubMed2004

Intestinal ischemia reperfusion injury and multisystem organ failure.

Intestinal ischemia-reperfusion is a common pathway for many diseases in infants, children, and adults, and this may lead to multiple organ dysfunction syndrome and death. While several studies have investigated reperfusion injury in cardiac, cerebral, and hepatic disease, limited work has been published on intestinal ischemia-reperfusion and its multiorgan effects. The authors have developed models of intestinal ischemia-reperfusion in rats and have demonstrated that intestinal reperfusion causes liver energy failure at normothermia. This is followed by 100% mortality within 4 hours of reperfusion. Moderate hypothermia (32 degrees C to 33 degrees C) induced throughout ischemia and reperfusion prevents liver energy failure, intestinal damage, and neutrophil infiltration in the lungs. Moderate hypothermia in this model of intestinal ischemia and reperfusion prevents mortality. Further studies are needed to establish whether therapeutic hypothermia is a useful intervention in the treatment of infants and children with intestinal injuries caused by ischemia and reperfusion.

Adenosine Triphosphate↗
PubMed2004

Meta-analysis of laparoscopic versus open pyloromyotomy.

OBJECTIVE: To perform a meta-analysis of studies comparing open pyloromyotomy (OP) and laparoscopic pyloromyotomy (LP) in the treatment of infantile hypertrophic pyloric stenosis. BACKGROUND: LP has become increasingly popular for the management of pyloric stenosis. Despite a decade of experience, the real benefit of LP over the open procedure remains unclear. METHODS: Using a defined search strategy, studies directly comparing OP with LP were identified (n = 8). Data for infants treated by both approaches were extracted and used in our meta-analysis. OP and LP were compared in terms of complications, efficacy, operating time, and recovery time. Weighted mean difference (WMD) between continuous variables and 95% confidence intervals (95% CI) were calculated. For dichotomous data, relative risk (RR) and 95% CI were determined. RESULTS: Only 3 studies were prospective, and just 1 study was a prospective randomized controlled trial. Mucosal perforations and incomplete pyloromyotomy were both more common with LP. Compared with OP, LP is associated with higher complication rate (RR 0.81 [0.5, 1.29], P = 0.4), similar operating time (WMD 1.52 minutes [-0.26, 3.29], P = 0.09), shorter time to full feeds (WMD 8.66 hours [7.25, 10.07], P < 0.00001), and shorter postoperative length of stay (WMD 7.03 hours [3.74, 10.32], P = 0.00003). CONCLUSIONS: OP is associated with fewer complications and higher efficacy. Recovery time appears significantly shorter following LP. A prospective randomized controlled trial is warranted to fully investigate these and other outcome measures.

Digestive System Surgical Procedures↗
PubMed2004

Necrotizing enterocolitis.

Necrotizing enterocolitis is the principal cause of surgical referral in preterm neonates and the most common gastrointestinal emergency among infants. Its pathophysiology is unclear and it carries high levels of mortality and morbidity. This article provides an overview of necrotizing enterocolitis including risk factors, preventative strategies and medical and surgical management.

Enterocolitis, Necrotizing↗
PubMed2003

Early full blood count and severity of disease in neonates with necrotizing enterocolitis.

Thrombocytopaenia occurs during necrotizing enterocolitis (NEC), and nadir platelet count is associated with extent of disease. In paediatric meningococcal disease, the product of neutrophil and platelet count at admission is prognostically useful. We therefore aimed to determine whether the first full blood count (FBC) after diagnosis of NEC is useful as a score for poor outcome and severity of disease. Between 1987 to 2001, neutrophils (N), platelets (P) and their product (PN) was available in 187 neonates treated for NEC at our institution. Neonates with NEC were grouped according to the extent of disease (no gangrene, focal, multifocal and pan-intestinal). Data were not normally distributed so Mann-Whitney U test or analysis of variance (ANOVA) on logged data were used ( p<0.05 was considered significant). Receiver operating characteristics (ROC) curves were used to examine the relationship between specificity and sensitivity. A perfect test would have an ROC curve area of 1. Initial P count and PN product of non-survivors were both significantly lower than in survivors ( p<0.0001), whereas N was not different ( p<0.08). Low Log(10)PN was significantly associated with greater extent of disease (ANOVA; no gangrene vs multifocal, p<0.01, vs panintestinal, p<0.0005), suggesting that the initial FBC could be prognostically useful. Area under the ROC survival curve for neutrophils was 0.58, for platelets 0.75 and for PN product 0.71; thus, although no test performed extremely well, initial platelet count and NP product could be useful in evaluating disease severity in neonates with NEC and for further monitoring.

Blood Cell Count↗
PubMed2003

Neonatal endotoxemia affects heart but not kidney bioenergetics.

PURPOSE: The aim was to determine the effects of early and late endotoxemia on neonatal cardiac and renal mitochondrial energetics. METHODS: Suckling rats received intraperitoneal 300 microgram/kg lipopolysaccharide; controls received saline. Heart and kidney mitochondria were isolated after 2 hours (early) or 6 hours (late sepsis). State 3 (maximum mitochondrial flux) and 4 O(2) consumption and complex I activity were measured. Results, expressed as mean +/- SEM normalized to citrate synthase (CS), were compared using paired t tests. RESULTS: Mortality rate was zero within 2 hours, 2.7% between 2 and 6 hours of endotoxemia, and 100% 6 to 8 hours; therefore, we consider that 2 hours and 6 hours represent early and late endotoxemia, respectively. Endotoxic heart mitochondria had unaltered O(2) consumption at 2 hours but significantly decreased state 3 after 6 hours, resulting in significantly decreased respiratory control ratio. Complex I activity, which could affect O(2) consumption, was decreased significantly at 6 hours (9.8 +/- 0.6 mU/U CS; n = 15) versus controls (11.3 +/- 0.8, n = 15; P =.04), but not at 2 hours. There were no differences in these measurements at either 2 hours or 6 hours in kidney mitochondria. CONCLUSIONS: The respiratory chain is affected late in endotoxemia. Neither early nor late endotoxemia affects oxidative function of kidney mitochondria.

Animals↗
PubMed2003

When can I be proficient in laparoscopic surgery? A systematic review of the evidence.

PURPOSE: The aim of this study was to quantify the learning curve in laparoscopic surgery. METHODS: A systematic review of the evidence using a defined search strategy (PubMed, Medline, OVID, Embase, ERIC, Cochrane databases) was performed. Studies without statistical evaluation of the learning curve and opinion articles were excluded. The authors analysed 7 common laparoscopic procedures: cholecystectomy, fundoplication, colectomy, herniorrhaphy, splenectomy, appendicectomy, and pyloromyotomy. The "initial" and "late" stages of experience were compared with regards to the following outcome measures: operating time, conversion rate, complication rate, and length of stay in hospital. RESULTS: A total of 3,641 articles were reviewed, of which, 37 (25,777 patients) fulfilled the entry criteria (5 in children). In all articles, the definition of proficiency was subjective, and the number of operations required to reach it was highly variable. There were improvements in all 4 outcome measures for cholecystectomy, fundoplication, colectomy, herniorrhaphy, and splenectomy between the "initial" and "late" experience. No data were available for the learning curves in appendicectomy or pyloromyotomy. CONCLUSIONS: The number of procedures required to reach proficiency in laparoscopic surgery has not been defined clearly. These findings are important for training, ethical and medico-legal issues.

Appendectomy↗
PubMed2003

Cardiac and renal mitochondria respond differently to hydrogen peroxide in suckling rats.

BACKGROUND: Overwhelming septicemia with multiple organ failure is one of the main causes of mortality with neonatal surgery. Liver, kidney, and heart are organs for which oxidative metabolism is particularly important. Hydrogen peroxide (H(2)O(2)), a major mediator of sepsis, inhibits liver metabolism. Our aim was to determine the effects of H(2)O(2) on neonatal renal and cardiac oxidative metabolism. MATERIALS AND METHODS: Mitochondria were isolated from the heart and kidney of 11 to 15-day-old rats. Oxygen consumption was measured polarographically in mitochondria incubated with different concentrations of H(2)O(2). State 3 oxygen consumption, which represents maximum mitochondrial oxidative flux, was measured in the presence of adenosine diphosphate. State 4 oxygen consumption, which represents oxygen consumption that is wasted and not used for adenosine triphosphate (ATP) generation, was measured after all adenosine diphosphate was used. beta-Oxidation flux and carnitine palmitoyltransferase I activity were measured radiochemically with increased levels of H(2)O(2). RESULTS: H(2)O(2) impaired state 3 oxygen consumption at all concentrations tested in cardiac and renal mitochondria. H(2)O(2) had no significant effect on heart mitochondrial state 4 oxygen consumption but significantly increased that of kidney. Heart, but not kidney, beta-oxidation flux was inhibited by H(2)O(2). Neither cardiac nor renal carnitine palmitoyltransferase I activity was affected by H(2)O(2). CONCLUSIONS: H(2)O(2) inhibits maximal rates of ATP generation by heart and kidney mitochondria but has a more severe effect on kidney mitochondria because more oxygen is wasted and not used for ATP generation. This decrease in ATP generation may be a factor in the dysfunction of these organs during sepsis.

Adenosine Triphosphate↗
PubMed2003

The effect of aryepiglottoplasty for laryngomalacia on gastro-oesophageal reflux.

OBJECTIVE: to investigate whether relief of airway obstruction in laryngomalacia by aryepiglottoplasty affects gastro-oesophageal reflux. METHODS: a prospective study of consecutive infants and children with suspected laryngomalacia. Gastro-oesophageal reflux was measured before and after diagnostic microlaryngobronchoscopy and aryepiglottoplasty. RESULTS: of the six cases who underwent aryepiglottoplasty and completed the study, three had significant pre-operative reflux according to age. In this group the reflux improved significantly after aryepiglottoplasty. In the other three cases, reflux was not age-significant pre-operatively nor did it change significantly post-operatively. CONCLUSIONS: when partial airway obstruction due to laryngomalacia co-exists with gastro-oesophageal reflux, treatment of the airway problem improves respiratory symptoms in all cases and reduces gastro-oesophageal reflux in patients with age-significant reflux. This suggests that there are two clinical groups, those with severe, age-significant reflux, possibly caused by airway obstruction, whose gastro-oesophageal reflux benefits from aryepiglottoplasty; and those whose reflux is physiological and not influenced by aryepiglottoplasty. Therefore aryepiglottoplasty can be expected to reduce gastro-oesophageal reflux in those infants with laryngomalacia who have age-significant reflux.

Airway Obstruction↗
PubMed2003

Surgical treatments of infants with necrotizing enterocolitis.

With the improvements in neonatal intensive care, necrotizing enterocolitis (NEC) has become the most common gastrointestinal emergency amongst infants in neonatal intensive care units. The incidence of NEC varies between 1 and 8% of neonatal intensive care unit admissions and the disease has a mortality rate between 20 and 40%. There are a number of surgical options available to the paediatric surgeon depending on the clinical condition of the infant and the extent of the disease. However owing to a paucity of prospective data in this field and a lack of randomized controlled trials there is little consensus as to which is the most appropriate. Primary peritoneal drainage has become very popular in North America and Europe for the treatment of perforated NEC in very low-birthweight infants. It is a useful manoeuvre in the resuscitation of critically ill infants and in some of these infants, further operation may be avoided completely by inserting a peritoneal drain. Others however remain too unwell to undergo laparotomy and may die. Two randomized controlled trials are currently underway to determine the real benefit of peritoneal drainage. Laparotomy in very small neonates has become safer with improvements in anaesthesia and intensive care management. Resection and primary anastomosis has been proposed as a valid treatment modality in neonates with both focal and multifocal disease. The advantage of resection and primary anastomosis over stoma formation is still controversial. Different surgical techniques such as diverting jejunostomy or 'clip and drop' have been described to deal with extensive disease and avoid massive small bowel resection. Prospective studies and randomized controlled trials are needed to define the best operative treatment for neonates with severe NEC.

Emergency Treatment↗
PubMed2003

Body temperature and heat production in suckling rat endotoxaemia: beneficial effects of glutamine.

BACKGROUND/PURPOSE: Sepsis is an important cause of neonatal mortality. The aim of the study was to investigate the metabolism of endotoxic neonatal rats and the potential beneficial effect of glutamine. METHODS: Suckling rats received intraperitoneal saline (control; C), endotoxin (300 microg/g LPS; E), saline+glutamine (2 mmol/g; CG), endotoxin+glutamine (EG), saline+leucine (2 mmol/g; CL) or endotoxin+leucine (EL). Sepsis score (0-8) and rectal temperature were monitored. Hypothermia was defined as rectal temperature less than 32 degrees C. Oxygen consumption (VO2, mL/kg/h), a determinant of heat production, was measured by indirect calorimetry. Data (mean +/- SEM) were compared by analysis of variance (ANOVA), paired t test or Fisher's Exact test. RESULTS: Endotoxic (E) rats had significantly lower VO2 than C rats from 90 minutes postinjection to the end of the experiment, 210 minutes (VO2 from 150 to 210 minutes: C 671 +/- 45; E 429 +/- 36, P <.0004; n = 8; paired t test). VO2 of CL or CG rats was elevated between 90 and 210 minutes compared with control, but significantly (P <.01) only in the L group (C 706 +/- 31; CG 871 +/- 63; CL 984 +/- 31; n = 7-9, ANOVA). VO2 was significantly higher (P <.05) in EG rats than E rats (E 460 +/- 29; EG 654 +/- 68; n = 9-10). In the EL group, VO2 was raised but was not significantly different from E (E 460 +/- 29; EL 637 +/- 52; n = 8-10). EG rats were significantly less hypothermic between 90 and 210 minutes (58 of 132 measurements) compared with E (95 of 147; P =.0007, Fisher's Exact test), whereas the EL group were similarly hypothermic (74 of 120) to E (P =.7). Sepsis score was significantly lower in the EG group than both E and EL groups (E 4.9 +/- 0.3; EG 3.6 +/- 0.3; EL 5.0 +/- 0.3; n = 40; P <.01; ANOVA). CONCLUSIONS: Neonatal endotoxaemia lowers VO2, heat production, and body temperature. Glutamine and leucine both cause nutrient-induced thermogenesis in control animals and restore VO2 of endotoxic animals. Glutamine additionally increases rectal temperature, reduces incidence of hypothermia, and improves clinical signs of endotoxic rats. This suggests that glutamine may be beneficial for nutrition in neonatal sepsis.

Animals↗
PubMed2003

Hypothermia throughout intestinal ischaemia-reperfusion injury attenuates lung neutrophil infiltration.

BACKGROUND/PURPOSE: Secondary organ damage to the lungs is an important consequence of intestinal ischaemia reperfusion (IIR) injury. Moderate hypothermia ameliorates gut necrosis and liver energy failure after IIR but potential beneficial effects on lung neutrophil infiltration after reperfusion of ischaemic bowel have not been investigated. METHODS: Adult Sprague-Dawley rats underwent 60 minutes intestinal ischaemia followed by 120 minutes of reperfusion. The animals were maintained at either normothermia (36 degrees to 38 degrees C) or moderate hypothermia (30 degrees to 32 degrees C). Four groups were studied: (A) sham normothermia; (B) IIR normothermia; (C) sham hypothermia; and (D) IIR hypothermia. Lungs and terminal ileum were removed for measurement of myeloperoxidase activity (a marker of neutrophil infiltration). Results are expressed as milliunits per milligrams protein, mean +/- SEM, and one-way analysis of variance (ANOVA) with Tukey post-test was used for group comparisons. RESULTS: Lungs: IIR at normothermia significantly increased lung neutrophil infiltration assessed by myeloperoxidase activity compared with sham-operated controls (normothermia sham 4.6 +/- 1.0, n = 8; normothermia IIR 37.7 +/- 13.8, n = 8; P =.011). Moderate hypothermia during IIR significantly attenuated lung neutrophil infiltration (7.2 +/- 2.1, n = 9) compared with normothermia IIR (P =.016) such that myeloperoxidase activity was similar to that found in sham normothermia (4.6 +/- 1.0, n = 8) and sham hypothermia (3.1 +/- 1.3, n = 8). Intestine: Gut myeloperoxidase activity was 0.9 +/- 0.5 in sham normothermia (n = 9) and 2.3 +/- 0.6 after normothermic IIR (n = 8). After IIR at hypothermia gut myeloperoxidase activity (0.5 +/- 0.2; n = 8) was significantly less than normothermic IIR (P =.035) and higher than sham hypothermia (0.2 +/- 0.1, n = 9; P =.01). CONCLUSIONS: These results indicate that moderate hypothermia may prevent damage to another distant organ, ie the lungs, by preventing recruitment of neutrophils. This may be of benefit in decreasing distal organ damage in diseases in which intestinal ischaemia-reperfusion is implicated in the pathogenesis.

Animals↗
PubMed2003

Carbon dioxide elimination during laparoscopy in children is age dependent.

UNLABELLED: The absorption of carbon dioxide (CO2) used for positive pressure pneumoperitoneum may lead to an increased CO2 load. CO2 elimination during laparoscopy has not been investigated previously in paediatrics. The aim of this study was to characterise the pattern of CO2 elimination during laparoscopic surgery in infants and children. METHODS: Twenty children undergoing laparoscopy and 19 children undergoing laparotomy for elective abdominal operations were studied. Pneumoperitoneum was achieved using insufflation of unheated CO2. CO2 elimination (metabolically produced + absorbed; milliliters per kilogram per minute) was measured minute by minute during the operation by indirect calorimetry. End-tidal CO2 (kPa) was recorded every 10 minutes. The above variables were assessed before CO2 insufflation, during pneumoperitoneum, and after desufflation. RESULTS: Before insufflation, CO2 elimination was 4.6 +/- 0.3 ml/kg/min and increased after 15 minutes of pneumoperitoneum to 5.2 +/- 0.3 (P <.001). Post desufflation, CO2 elimination decreased toward preinsufflation values, but did not return to baseline by the end of operation (5.8 +/- 0.3; P <.001). End-tidal CO2 was 4.7 +/- 0.2 preinsufflation, peaked at 1 hour (5.3 +/- 0.2; P <.001) and subsequently decreased in response to ventilatory adjustments. The total amount of CO2 insufflated was positively correlated with patient age (r2 = 0.27; P <.01). CO2 elimination was age related, as indicated by multilevel model analysis and by negative correlations between maximum increase in CO2 elimination and both age (r2 = 0.27; P <.01) and weight (r2 = 0.29; P <.01). These data suggest that the younger or smaller the child, the larger the increase in CO2 elimination. Seven patients (35%) responded to desufflation with a sharp transient increase in CO2 elimination, which did not appear to be related to patient age, length of pneumoperitoneum, abdominal pressure, or type of operation. CONCLUSIONS: During pneumoperitoneum, younger children absorb proportionately more CO2 than older individuals. The short-lived increase in CO2 elimination postdesufflation may be related to an increase in venous return from the lower limbs after release of the abdominal pressure. These findings suggest that small children warrant close monitoring during laparoscopy and during the immediate postoperative period.

Adolescent↗
PubMed2003

Is intralesional injection of OK-432 effective in the treatment of lymphangioma in children?

BACKGROUND: Intralesional injection of OK-432 has been proposed as an effective treatment of lymphangioma. The aim of this study was to review our experience with OK-432 injection of lymphangioma and to identify factors associated with successful outcome. METHODS: We made a case note review of 19 children who received OK-432 injection. Median duration of follow-up was 17 months. RESULTS: Lesions were diagnosed antenatally in 4 children, at birth in 4 children, and between 1 month and 11 years in the remainder. Anatomic locations were head/neck in 14, axilla in 1, and multiple locations in 4. Median number of injections per child was 2 (range, 1 to 5). Disappearance of the lesion was achieved after OK-432 injection in 2 patients (11%) and a marked reduction in 5 (26%); all these lesions were in the head and neck. Lesions larger than 5 cm and those outside the head and neck region did not respond well to OK-432 injection. Fourteen children (74%) required surgical excision after injection. Complications of OK-432 injection included partial tracheal obstruction, fever, local inflammatory response, and abscess formation. CONCLUSIONS: OK-432 injection was effective in approximately one third of children with lymphangioma. Lesions outside the head and neck and those larger than 5 cm are unlikely to respond to this therapy. Injection of lymphangioma surrounding the airways may be hazardous.

Antineoplastic Agents↗
PubMed2002

Hepatic glutamine metabolism during endotoxemia in neonatal rats.

OBJECTIVES: The liver plays a central role during endotoxemia. We investigated the biochemical changes that occur in neonatal liver during early stages of endotoxemia. METHODS: Twenty neonatal rats (10 to 15 d; n = 10/group) were studied. Endotoxemic rats received intraperitoneal injections of 300 microg/kg of 12.5 mg/L of lipopolysaccharide and control rats received isovolemic normal saline. Two hours after injection, all lipopolysaccharide-injected animals exhibited signs of endotoxemia. Livers were removed and extracted into 12% perchloric acid. 1H and 31P magnetic resonance spectroscopy measured hepatic levels of glutamine, glutamate, alanine, lactate, glucose, beta-hydroxybutyrate, adenosine triphosphate, and adenosine diphosphate. Unpaired t test compared groups. RESULTS: No mortality occurred during the first 2 h after injection. Endotoxemia significantly decreased hepatic levels of glutamine (P < 0.001), glucose (P = 0.047), and beta-hydroxybutyrate (P < 0.001). There was no difference in hepatic levels of glutamate (P = 0.050), alanine (P = 0.165), lactate (P = 0.478), adenosine triphosphate (P = 0.165), and adenosine diphosphate (P = 0.136) between groups. CONCLUSIONS: Early endotoxemia caused significant changes in the hepatic metabolism of glutamine, glucose, and beta-hydroxybutyrate. These findings increase our understanding of the pathophysiology of neonatal endotoxemia.

Animals↗
PubMed2002

Fatty acid oxidation in neonatal hepatocytes: effects of sepsis and glutamine.

OBJECTIVE: Little is known about fat use during sepsis during the neonatal period. Intramitochondrial O(2) consumption is inhibited in isolated hepatocytes from suckling septic rats and this impairment is reversed by glutamine. We investigated the effect of neonatal sepsis on fat oxidation and whether glutamine can directly affect fatty acid oxidation. METHODS: Suckling Wistar rats (11 d) received an intraperitoneal injection of 300 microg/kg of lipopolysaccharide (Escherichia coli 055:B5); controls received normal saline. At 2 h, hepatocytes were isolated. Hepatocytes were incubated at 37 degrees C with 0.5 mM [1-(14)C]palmitate or 0.5 mM [1-(14)C]palmitate plus 10 mM glutamine. After 1 h, the perchloric acid-soluble (14)C-radioactivity (representing mainly ketone bodies) and (14)CO(2) were measured. Hepatocyte O(2) consumption from 0.5 mM palmitate was measured with and without 2.5 ng/mL myxothiazol to estimate intramitochondrial O(2) consumption. RESULTS: There were no significant differences in fatty acid oxidation between control and endotoxemic hepatocytes measured as acid-soluble radioactivity (which represents mainly ketogenesis, plus Krebs cycle intermediates), as (14)CO(2) production, or as the sum of acid-soluble radioactivity plus (14)CO(2) generation. Glutamine significantly increased fatty acid oxidation (acid-soluble radioactivity plus (14)CO(2)) in hepatocytes from control and endotoxic animals. CONCLUSIONS: The finding of no significant difference in fatty acid oxidation between hepatocytes from control and endotoxemic rats is surprising given that intramitochondrial O(2) consumption from palmitate is decreased. This may reflect altered use of acetyl-coenzyme A to ketone bodies and Krebs cycle intermediates. Glutamine enhanced fatty acid oxidation from control and endotoxemic hepatocytes, suggesting that it may promote substrate oxidation during endotoxemia.

Animals↗
PubMed2002

Differential effects of neonatal endotoxemia on heart and kidney carnitine palmitoyl transferase I.

BACKGROUND/PURPOSE: The heart and kidney are both affected in sepsis-related multiple organ failure. Both utilize fatty acid substrates during the neonatal period, and impairment of oxidative metabolism during sepsis could lead to bioenergetic failure. The enzyme carnitine palmitoyl transferase I (CPT I) is important in the control of fat oxidation in the neonatal period. The aim of this study was to determine the effects of sepsis on neonatal cardiac and renal CPT I. METHODS: Suckling rats received 300 microgram/kg lipopolysaccharide intraperitoneally. Mitochondria were isolated from the heart and kidney after 2 hours. CPT I and II activity were measured radiochemically. Protein levels of M- and L- isoforms of CPT I, both of which are present in heart, were determined by Western blotting. RESULTS: CPT I activity was decreased significantly in the heart but not in the kidney by endotoxemia, whereas CPT II activity was the same in each organ. To investigate the mechanism of this decrease, we carried out Western blotting of the CPT I isoforms in heart mitochondria. Neither M- nor L- isoform was decreased in amount. To determine whether free-radical attack could directly inhibit CPT I activity, control heart mitochondria were incubated with free-radical generating systems. Although hydrogen peroxide had no effect on CPT I activity, the reactive oxygen species nitric oxide, superoxide, and peroxynitrite, all of which are generated in the heart during sepsis, significantly inhibited CPT I activity. CONCLUSIONS: The activity of CPT I, a rate-controlling step of fat oxidation, is significantly impaired in heart but not in kidney during neonatal sepsis. This may be caused by direct attack by free radicals, suggesting that antioxidant strategies could be of use in preventing sepsis-related cardiac damage.

Animals↗