Biomedical subjects

L Tappy

Publications and source records attributed to L Tappy.

At least 37 records · Page 2Linked to original sources

PubMed2002

Effect of a program of moderate physical activity on mental stress-induced increase in energy expenditure in obese women.

BACKGROUND: Energy restriction and physical activity are major components of weight reduction programs. Energy restriction is known to affect the sympathetic nervous system activity and to reduce several components of energy expenditure, including the stimulation of energy expenditure elicited by mental stress. The effect of physical activity on this parameter remains unknown. METHODS: This study was designed to assess the effect of physical training on the stimulation of energy expenditure during mental stress. Seven obese women (age 33 +/- 3 years, BMI 34.9 +/- 1.4 kg/m(2)) were studied before and after a 6 week program of aquagym (2 sessions of 50 min/week). Energy expenditure was measured by means of indirect calorimetry under hyperinsulinemic conditions before and during a 30 min mental stress. O(2) max was measured before and after physical training by means of the test of Balke. RESULTS: O(2) max was 23.4 ml/kg/min before physical training, and increased to 26.1 ml/kg/min at the completion of the training program (p<0.05). Body weight, resting energy expenditure and insulin-mediated glucose disposal [oxidative and non oxidative] were not modified after training. Mental stress increased energy expenditure by 12.3% before physical training (p<0.002 vs resting conditions) and by 12.6% after physical training (p<0.003 vs resting conditions, NS vs before physical training). CONCLUSION: Physical training per se does not alter the stimulation of energy expenditure induced by mental stress.

Adult↗

PubMed2001

Effects of a glucose meal on energy metabolism in patients with cirrhosis before and after liver transplantation.

HYPOTHESIS: Liver transplantation results in hepatic denervation. This may produce alterations of liver energy and substrate metabolism, which may contribute to weight gain after liver transplantation. DESIGN: Prospective clinical study. SETTING: Liver transplantation clinics in a university hospital. PATIENTS: Seven nondiabetic patients with cirrhosis were recruited while on a waiting list for liver transplantation. Seven healthy subjects were recruited as controls. INTERVENTION: Orthotopic liver transplantation. MAIN OUTCOME MEASURES: Evaluation of energy and substrate metabolism after ingestion of a glucose load with indirect calorimetry was performed before, 2 to 6 weeks after, and 5 to 19 months after transplantation. Whole-body glucose oxidation and storage and glucose-induced thermogenesis were calculated. RESULTS: Patients with cirrhosis had modestly elevated resting energy expenditure and normal glucose-induced thermogenesis and postprandial glucose oxidation and storage. These measures remained unchanged after liver transplantation despite a significant increase in postprandial glycemia. Patients, however, gained an average of 3 kg of body weight after 5 to 19 months compared with their weight before transplantation. CONCLUSION: Liver denervation secondary to transplantation does not lead to alterations of energy metabolism after ingestion of a glucose load.

Blood Glucose↗

PubMed2001

Early metabolic and splanchnic responses to enteral nutrition in postoperative cardiac surgery patients with circulatory compromise.

OBJECTIVES: To assess the hemodynamic and metabolic adaptations to enteral nutrition (EN) in patients with hemodynamic compromise. DESIGN AND SETTING: Prospective study in a university hospital surgical ICU, comparing baseline (fasted) with continuous EN condition. PATIENTS: Nine patients requiring hemodynamic support by catecholamines (dobutamine and/or norepinephrine) 1 day after cardiac surgery under cardiopulmonary bypass. INTERVENTION: Isoenergetic EN via a postpyloric tube while catecholamine treatment remained constant. Baseline (fasted) condition was compared to continuous EN condition. MEASUREMENTS AND MAIN RESULTS: Cardiac index (CI), mean arterial pressure (MAP), pulmonary and wedge pressures, indocyanine green (ICG) clearance, gastric tonometry, plasma glucose and insulin, and glucose turnover (6,62H2-glucose infusion) were determined repetitively every 60 min during 2 h of baseline fasting condition and 3 h of EN. During EN CI increased (from 2.9 +/- 0.5 to 3.3 +/- 0.5 l min-1 m-2), MAP decreased transiently (from 78 +/- 7 to 70 +/- 11 mmHg), ICG clearance increased (from 527 +/- 396 to 690 +/- 548 ml/min), and gastric tonometry remained unchanged, while there were increases in glucose (158 +/- 23 to 216 +/- 62 mg/dl), insulin (29 +/- 23 to 181 +/- 200 mU/l), and glucose rate of appearance (2.4 +/- 0.2 to 3.3 +/- 0.2 mg min-1 kg-1). CONCLUSIONS: The introduction of EN in these postoperative patients increased CI and splanchnic blood flow, while the metabolic response indicated that nutrients were utilized. These preliminary results suggest that the hemodynamic response to early EN may be adequate after cardiac surgery even in patients requiring inotropes.

Adaptation, Physiological↗

PubMed2001

Mechanisms of action of beta-glucan in postprandial glucose metabolism in healthy men.

OBJECTIVE: To assess whether beta-glucan (which is fermented in the colon) lowers postprandial glucose concentrations through mechanisms distinct from a delayed carbohydrate absorption and inhibits de novo lipogenesis. DESIGN: Administration of frequent small meals each hour over 9 h allows a rate of intestinal absorption to be reached which is independent of a delayed absorption. A group of 10 healthy men received either an isoenergetic diet containing 8.9 g/day beta-glucan or without beta-glucan for 3 days. On the third day, the diet was administered as fractioned meals ingested every hour for 9 h. SETTING: Laboratory for human metabolic investigations. SUBJECTS: Ten healthy male volunteers. MAIN OUTCOME MEASURES: Plasma glucose and insulin concentrations, glucose kinetics, glucose oxidation, de novo lipogenesis. RESULTS: On the third day, plasma glucose and free fatty acid concentrations, carbohydrate and lipid oxidation, and energy expenditure were identical with beta-glucan and cellulose. Plasma insulin concentrations were, however, 26% lower with beta-glucan during the last 2 h of the 9 h meal ingestion. Glucose rate of appearance at steady state was 12% lower with beta-glucan. This corresponded to a 21% reduction in the systemic appearance rate of exogenous carbohydrate with beta-glucan, while endogenous glucose production was similar with both diets. De novo lipogenesis was similar with and without beta-glucan. CONCLUSION: Administration of frequent meals with or without beta-glucan results in similar carbohydrate and lipid metabolism. This suggests that the lowered postprandial glucose concentrations which are observed after ingestion of a single meal containing beta-glucan are essentially due to a delayed and somewhat reduced carbohydrate absorption from the gut and do not result from the effects of fermentation products in the colon.

Blood Glucose↗

PubMed2001

New data and new concepts on the role of the liver in glucose homeostasis.

The liver plays a central role in the control of glucose production. It is also involved in the regulation of insulin secretion and sensitivity through neural pathways. This review will address recent developments in the mechanisms by which hepatic metabolism affects glucose homeostasis in health and disease. Oral glucose feeding elicits several systemic and hepatic alterations of intermediary metabolism through the activation of neural pathways. How this may affect glucose metabolism will be briefly discussed, and alterations of glucose homeostasis in liver disease will be briefly described. There is evidence that a portion of intrahepatic glucose can be converted into lipids in the process of de-novo lipogenesis. How this may be involved in the control of glycaemia and lipid concentrations will be reviewed. Finally, molecular mechanisms by which the alteration of liver metabolism may affect systemic glucose homeostasis will be outlined.

Blood Glucose↗

PubMed2001

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.

Adult↗

PubMed2001

Effects of free fatty acids on insulin sensitivity and hemodynamics during mental stress.

Mental stress is known to decrease systemic vascular resistance and increase muscle blood flow and to acutely enhance insulin-mediated glucose disposal in healthy humans. These effects are abolished in obese patients. We therefore proposed the hypothesis that elevated free fatty acid levels may be responsible for the abnormal responses to mental stress in obesity by inhibiting endothelial cell function. To test this hypothesis, we studied a group of eight lean females during a hyperinsulinemic clamp study with and without lipid infusion. A 30-min mental stress was applied during 30 min after 150 min of hyperinsulinemia. In the study without lipid infusion, mental stress increased heart rate by 26.5%, blood pressure by 7.9%, and cardiac index (measured with thoracic bioimpedance) by 35.9%; it decreased systemic vascular resistance by 21.9% and increased insulin-mediated glucose disposal by 18.9%. During lipid infusion, the increase in heart rate was not affected, but the increase in cardiac index, the decrease in systemic vascular resistance, and the increase in insulin-mediated glucose disposal were all inhibited. In contrast, the rise in blood pressure was increased about 2-fold (control plus 6 mm Hg vs. lipid plus 13 mm Hg, P: < 0.01). These results indicate that lipid inhibits the stimulation of glucose uptake and enhances the pressor effect of mental stress, presumably by altering endothelial cell function.

Adult↗

PubMed2001

Counterregulatory responses to hypoglycemia in patients with maturity-onset diabetes of the young caused by HNF-1alpha gene mutations (MODY3).

Mutations of HNF-1alpha lead to severe beta cell dysfunction, resulting in decreased glucose-induced insulin secretion. HNF-1alpha is also expressed in liver, kidney and pancreatic alpha cells, but the functional consequences of HNF-1alpha mutations in these organs remain unknown. We therefore assessed the counterregulatory responses to hypoglycemia in six patients with HNF-1alpha mutations (MODY3), five patients with non-insulin-dependent diabetes mellitus (NIDDM) and in nine healthy controls. Plasma glucagon concentrations and endogenous glucose production were measured every 15 min during a hyperinsulinemic clamp with progressive hypoglycemia. Plasma glucagon concentrations were similar at basal glycemia (73+/-6, 69+/-5 and 69+/-7 ng/l) and reached peak values of 88+/-9, 88+/-11 and 89+/-7 ng/l at a glycemia of 3.6 mmol/l in MODY3 patients, patients with NIDDM and controls respectively (NS). Suppression of endogenous glucose production by insulin was blunted in MODY3 patients (3.3+/-1.2 micromol/kg per min) and in patients with NIDDM (4.4+/-0.6 micromol/kg per min) compared with controls (1.7+/-0.5 micromol/kg per min, P<0.05 compared with both MODY3 patients and patients with NIDDM). During hypoglycemia, endogenous glucose production increased to 8.6+/-2.1, 8.8+/-0.7 and 7.0+/-1.0 micromol/kg per min in MODY3 patients, patients with NIDDM and controls respectively (all NS). These data indicate that mutations of HNF-1alpha in MODY3 do not result in a decreased glucagon secretion or alterations of glucose production during hypoglycemia.

Blood Glucose↗

PubMed2001

In normal men, free fatty acids reduce peripheral but not splanchnic glucose uptake.

Raising plasma free fatty acid (FFA) levels reduces muscle glucose uptake, but the effect of FFAs on splanchnic glucose uptake, total glucose output, and glucose cycling may also be critical to producing lipid-induced glucose intolerance. In eight normal volunteers, we measured glucose turnover and cycling rates ([2H7]glucose infusion) during a moderately hyperglycemic (7.7 mmol/l) hyperinsulinemic clamp, before and after ingestion of a labeled (dideuterated) oral glucose load (700 mg/kg). Each test was performed twice, with either a lipid or a saline infusion; four subjects also had a third test with a glycerol infusion. As shown by similar rates of exogenous glucose appearance, the lipid infusion did not reduce first-pass splanchnic glucose uptake (saline 1.48+/-0.18, lipid 1.69+/-0.17, and glycerol 1.88+/-0.17 mmol/kg per 180 min; NS), but it reduced peripheral glucose uptake by 40% (P < 0.01 vs. both saline and glycerol infusions). Before oral ingestion of glucose, total glucose output was similarly increased by the lipid and glycerol infusions. Total glucose output was significantly increased by FFAs after oral ingestion of glucose (saline 3.68+/-1.15, glycerol 3.68+/-1.70, and lipid 7.92+/-0.88 micromol x kg(-1) x min(-1); P < 0.01 vs. saline and P < 0.05 vs. glycerol). The glucose cycling rate was approximately 2.7 micromol x kg(-1) x min(-1) with the three infusions and tended to decrease all along the lipid infusion, which argues against a stimulation of glucose-6-phosphatase by FFAs. It is concluded that in situations of moderate hyperinsulinemia-hyperglycemia, FFAs reduce peripheral but not splanchnic glucose uptake. Total glucose output is increased by FFAs, by a mechanism that does not seem to involve stimulation of glucose-6-phosphatase.

Adult↗

PubMed2001

[Physiopathology of obesity].

Obesity results from an imbalance between energy intake and energy expenditure. Human studies indicate that obese individuals have an increased basal metabolic rate secondary to an increased fat-free mass. A blunted dietary thermogenesis is observed but is not of sufficient magnitude to lead to a major weight gain. Indirect evidence suggests that physical activity may be low in obese individuals. In healthy lean subjects, overfeeding leads to a stimulation of spontaneous physical activity. The ensuing increase in energy expenditure may play a role in the prevention of weight gain. This response, however, shows a high interindividual variability. There is overall little evidence that major alterations of energy expenditure are present in obese individuals. It is likely that an alteration of mechanisms of food intake control plays a prominent role in the pathogenesis of this disease.

Energy Intake↗

PubMed2000

Effect of liver transplantation on hepatic glucose metabolism in a patient with type I glycogen storage disease.

BACKGROUND: In type I glycogenosis, mutation of the glucose-6-phosphatase gene results in absent glucose-6-phosphatase activity in liver cells leading to fasting hypoglycemia. Liver transplantation is expected to normalize glucose homeostasis. METHODS: Endogenous glucose production (6,6 2H2 glucose) was measured after an overnight fast and during exogenous 13C-labeled glycerol infusion in a patient with glycogenosis type I 24 months after liver transplantation and in a group of healthy subjects. RESULTS: Compared with healthy subjects, the glycogenosis patient had normal fasting glucose production and glucose and insulin concentrations after liver transplantation, but mildly elevated plasma glucagon concentrations. Gluconeogenesis from exogenous glycerol (13C glucose synthesis) was similar and did not lead to enhancement of glucose production in both healthy controls and the patient. CONCLUSIONS: Liver glucoregulatory function is restored by orthotopic liver transplantation in type I glycogenosis.

Adolescent↗

PubMed2000

Postprandial hepatic glycogen synthesis in liver transplant recipients.

BACKGROUND: The liver plays a central role in glucose homeostasis by releasing glucose in the fasting state and by taking up and converting into glycogen part of the glucose absorbed from the gastrointestinal tract after meal ingestion. METHODS: To determine whether the hepatic denervation that accompanies liver transplantation interferes with these functions, we assessed glucose tolerance to an oral glucose load in seven patients at 2-6 weeks after orthotopic liver transplantation, in six patients after kidney transplantation, and in six healthy controls. Hepatic glycogen synthesis was non-invasively assessed over the 4 hours after ingestion of a glucose load by monitoring hepatic uridine diphosphoglucose turnover with 13C galactose and acetaminophen. RESULTS: Liver and kidney transplant recipients had increased postprandial glucose concentrations but normal hepatic uridine diphosphoglucose turnover, indicating an unaltered hepatic glycogen synthesis. CONCLUSIONS: These results indicate that denervated liver transplants have an adequate glucoregulatory function. Postprandial hyperglycemia in liver transplant recipients is therefore not due to alterations of liver glucose metabolism.

Adult↗

PubMed2000

Assessment of postprandial hepatic glycogen synthesis from uridine diphosphoglucose kinetics in obese and lean non-diabetic subjects.

BACKGROUND: Obese patients are frequently characterized by insulin resistance and decreased insulin-mediated glycogen synthesis in skeletal muscle. Whether they also have impaired postprandial hepatic glycogen synthesis remains unknown. AIM: To determine whether postprandial hepatic glycogen synthesis is decreased in obese patients compared to lean subjects. METHODS: Lean and obese subjects with impaired glucose tolerance were studied over 4h after ingestion of a glucose load. Hepatic uridine diphosphoglucose kinetics were assessed using 13C-galactose infusion, with monitoring of urinary acetaminophen-glucuronide isotopic enrichment to estimate hepatic glycogen kinetics. RESULTS: Estimated net hepatic glycogen synthesis amounted to 18.6 and 22.6% of the ingested load in lean and obese subjects, respectively. CONCLUSION: Postprandial hepatic glycogen metabolism is not impaired in non-diabetic obese subjects.

Adult↗

PubMed2000

Effects of short-term carbohydrate or fat overfeeding on energy expenditure and plasma leptin concentrations in healthy female subjects.

OBJECTIVE: To determine the effects of excess carbohydrate or fat intake on plasma leptin concentrations and energy expenditure. DESIGN: Ten healthy lean females were studied: (a) during a 3 day isoenergetic diet (ISO); (b) during 3 day carbohydrate overfeeding (CHO OF); and (c) during 3 day fat overfeeding (FAT OF). During each test, basal metabolic rate, the energy expended during mild physical activity and recovery, and 24 h energy expenditure (24 h EE) were measured with indirect calorimetry. The concentrations of glucose and lactate were monitored in subcutaneous interstitial fluid over a 24 h period using microdialysis. Plasma hormone and substrate concentrations were measured in a blood sample collected in the morning of the fourth day. RESULTS: CHO OF increased plasma leptin concentrations by 28%, and 24 h EE by 7%. Basal metabolic rate and the energy expended during physical activity were not affected. FAT OF did not significantly change plasma leptin concentrations or energy expenditure. There was no relationship between changes in leptin concentrations and changes in energy expenditure, suggesting that leptin is not involved in the stimulation of energy metabolism during overfeeding. Interstitial subcutaneous glucose and lactate concentrations were not altered by CHO OF and FAT OF. CONCLUSIONS: CHO OF, but not FAT OF, increases energy expenditure and leptin concentration.

3-Hydroxybutyric Acid↗

PubMed2000

Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man.

AIMS: This study was undertaken to determine the effects of a short-term dexamethasone treatment on hepatic sensitivities to insulin and glucagon. METHODS: Eleven healthy subjects were studied during one or several of four protocols. In all protocols, somatostatin was infused continuously to inhibit pancreatic hormone secretion. In protocol 1, basal insulin was infused over 300 min while glucagon was infused at a rate of 0.5 mg/kg(-1)/min(-1)during 180 min, then at a rate of 1.5 ng/kg(-1)/min(-1)during 150 min. In protocol 2, the same experiment was performed after a 2 day treatment with 8 mg/day dexamethasone. In protocol 3, the two-step glucagon infusion was performed during insulin infusion at a rate aimed to reproduce the hyperinsulinemia observed during protocol 2. In protocol 4, continuous basal insulin and low glucagon (0.5 mg/kg(-1)/min(-1)) were infused over 330 min. RESULTS: In protocol 1, plasma glucose rose transiently by 2.0 +/- 0.3 mmol/l when the glucagon rate was increased and glucose production increased by 1.4 +/- 0.5 micromol/kg(-1)/min(-1). In protocol 2, the insulin infusion rate (1.85 +/- 0.36 nmol/kg(-1)/min(-1)) required to maintain glycemia was 3.3-fold higher than during protocol 1. Glucagon-induced stimulation of glycemia (by 1.47 +/- 0.5 mmol/l) and endogenous glucose production (by 0.8 +/- 0.3 micromol/kg(-1)/min(-1)) were blunted, but not abolished. In protocol 3, endogenous glucose production was suppressed by 75% by hyperinsulinemia and was not stimulated when the glucagon infusion rate was increased. In protocol 4, endogenous glucose production did not change significantly with time. CONCLUSION: These results indicate that high dose glucocorticoids induce a marked hepatic insulin resistance. Stimulation of glucose production by hyperglucagonemia was maintained in spite of hyperinsulinemia which can be attributed to either hepatic insulin resistance and/or increased hepatic glucagon sensitivity.

Adult↗

PubMed2000

Effects of enteral carbohydrates on de novo lipogenesis in critically ill patients.

BACKGROUND: Conversion of glucose into lipid (de novo lipogenesis; DNL) is a possible fate of carbohydrate administered during nutritional support. It cannot be detected by conventional methods such as indirect calorimetry if it does not exceed lipid oxidation. OBJECTIVE: The objective was to evaluate the effects of carbohydrate administered as part of continuous enteral nutrition in critically ill patients. DESIGN: This was a prospective, open study including 25 patients nonconsecutively admitted to a medicosurgical intensive care unit. Glucose metabolism and hepatic DNL were measured in the fasting state or after 3 d of continuous isoenergetic enteral feeding providing 28%, 53%, or 75% carbohydrate. RESULTS: DNL increased with increasing carbohydrate intake (f1.gif" BORDER="0"> +/- SEM: 7.5 +/- 1.2% with 28% carbohydrate, 9.2 +/- 1.5% with 53% carbohydrate, and 19.4 +/- 3.8% with 75% carbohydrate) and was nearly zero in a group of patients who had fasted for an average of 28 h (1.0 +/- 0.2%). In multiple regression analysis, DNL was correlated with carbohydrate intake, but not with body weight or plasma insulin concentrations. Endogenous glucose production, assessed with a dual-isotope technique, was not significantly different between the 3 groups of patients (13.7-15.3 micromol * kg(-1) * min(-1)), indicating impaired suppression by carbohydrate feeding. Gluconeogenesis was measured with [(13)C]bicarbonate, and increased as the carbohydrate intake increased (from 2.1 +/- 0.5 micromol * kg(-1) * min(-1) with 28% carbohydrate intake to 3.7 +/- 0.3 micromol * kg(-1) * min(-1) with 75% carbohydrate intake, P: < 0. 05). CONCLUSION: Carbohydrate feeding fails to suppress endogenous glucose production and gluconeogenesis, but stimulates DNL in critically ill patients.

Adult↗

PubMed2000

Effect of diets high or low in unavailable and slowly digestible carbohydrates on the pattern of 24-h substrate oxidation and feelings of hunger in humans.

BACKGROUND: The pattern of substrate utilization with diets containing a high or a low proportion of unavailable and slowly digestible carbohydrates may constitute an important factor in the control, time course, and onset of hunger in humans. OBJECTIVE: We tested the hypothesis that isoenergetic diets differing only in their content of unavailable carbohydrates would result in different time courses of total, endogenous, and exogenous carbohydrate oxidation rates. DESIGN: Two diets with either a high (H diet) or a low (L diet) content of unavailable carbohydrates were fed to 14 healthy subjects studied during two 24-h periods in a metabolic chamber. Substrate utilization was assessed by whole-body indirect calorimetry. In a subgroup of 8 subjects, endogenous and exogenous carbohydrate oxidation were assessed by prelabeling the body glycogen stores with [(13)C]carbohydrate. Subjective feelings of hunger were estimated with use of visual analogue scales. RESULTS: Total energy expenditure and substrate oxidation did not differ significantly between the 2 diets. However, there was a significant effect of diet (P: = 0.03) on the carbohydrate oxidation pattern: the H diet elicited a lower and delayed rise of postprandial carbohydrate oxidation and was associated with lower hunger feelings than was the L diet. The differences in hunger scores between the 2 diets were significantly associated with the differences in the pattern of carbohydrate oxidation among diets (r = -0.67, P: = 0. 006). Exogenous and endogenous carbohydrate oxidation were not significantly influenced by diet. CONCLUSIONS: The pattern of carbohydrate utilization is involved in the modulation of hunger feelings. The greater suppression of hunger after the H diet than after the L diet may be helpful, at least over the short term, in individuals attempting to better control their food intake.

Adult↗

PubMed2000

Intestinal absorption in patients after cardiac surgery.

OBJECTIVES: We designed this study to assess intestinal absorption in patients with adequate or altered hemodynamic status after cardiac surgery and to test clinical tolerance to early enteral nutrition. DESIGN: Prospective, descriptive study. SETTING: Surgical intensive unit in a university teaching hospital. PATIENTS: Cardiac surgery patients, age 64+/-10 yrs (mean +/-SD) were subdivided into two groups according to hemodynamic status: group I, 16 patients with adequate hemodynamic status; group II, 23 patients with hemodynamic failure. These groups were compared with healthy controls (group III, n = 6). INTERVENTIONS: Paracetamol pharmacokinetic study on days 1 and 3 with nasogastric or postpyloric paracetamol administration. Early postpyloric or conventional gastric nutrition in group II. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations were measured on days 1 and 3, and area under the curve (AUC) was calculated. Absorption was strongly reduced on day 1 in all patients after gastric administration (lower peak paracetamol and AUC), but normal after postpyloric delivery. Duration of anesthesia and of circulatory bypass did not affect paracetamol absorption. On day 3, AUC was close to normal in case of hemodynamic failure. Peak absorption on day 1 was negatively correlated with opiate dose (r2 = 0.176, p = .008). Hypocaloric enteral nutrition was well tolerated. CONCLUSIONS: The close-to-normal AUC, during low cardiac output, despite lower peak paracetamol, shows absorption was not suppressed, only delayed, because of decreased pyloric motility. The decrease on day 1 can be attributed to opiates, known to alter pyloric function and to slow down the intestinal transit.

APACHE↗