Estimation of jugular venous O2 saturation from cerebral oximetry or arterial O2 saturation during isocapnic hypoxia.

OBJECTIVE: Near-infrared spectroscopy (NIRS) has the potential for providing valuable information about oxygen delivery to the brain. However, questions have been raised about the accuracy of these measurements. This study was undertaken to compare noninvasive cerebral saturation measurements to jugular venous saturation under conditions of hypoxia and hypercapnia. METHODS: Data was obtain on forty-two subjects. Cerebral oxygenation was measured with a Somanetics INVOS 4100-SSA placed on the forehead of the subjects. PETCO2 was controlled to approximately 2 and 7 mmHg above resting values and PETO2 was controlled to 80, 45, 60 and 41 mmHg consecutively for four of five minutes each. Internal jugular blood gas measurements were made via a retrograde catheter. RESULTS: Both the cerebral oximetry measured saturation (rSO2) and the jugular venous saturation (SjvO2) were significantly increased by increasing the PETCO2 at all levels of hypoxia. The increase in the rSO2 was less than the increase in SjvO2. The rSO2 had a bias of 5.2% and a precision of 10.7% compared to the measured SjvO2. DISCUSSION: Cerebral oxygen saturation measured by cerebral oximetry compares well to the measured SjvO2 in normal subjects, despite multiple physiological reasons for differences. The closer relationship of SjvO2 to rSO2 than SaO2 under the conditions of these experiments indicates that the measurement reflects primarily intracranial saturation. However, outcome studies under clinical conditions are needed to determine the clinical utility of cerebral oximetry.

Effects of alfentanil on the ventilatory response to sustained hypoxia.

BACKGROUND: The ventilatory response to acute hypoxia is biphasic, with an initial rapid increase followed by a slower decline. In humans, there is evidence that the magnitude of the decline in ventilation is proportional to the size of the initial increase. This study was done to define the role of exogenous opioids in the ventilatory decline seen with prolonged hypoxia. METHODS: Ten healthy persons were exposed to isocapnic hypoxia for 25 min, followed by 5 min of isocapnic normoxia and 5 min of isocapnic hypoxia. These conditions were repeated during a computer-controlled alfentanil infusion. RESULTS: Serum alfentanil levels were constant among the volunteers (38+/-12 ng/ml). Alfentanil decreased both the initial and second acute hypoxic responses (from 1.27+/-0.73 to 0.99+/-0.39 l x min(-1) x %(-1), P < 0.05; and from 0.99+/-0.70 to 0.41+/-0.29 l x min(-1) x %(-1), P < 0.05, respectively). The magnitude of the decrease in ventilation during the 25 min of hypoxia was not changed (10+/-3.3 l/min for control; 12.3+/-7.5 l/min for alfentanil). CONCLUSIONS: Alfentanil reduced the acute ventilatory response to hypoxia. The absolute value of hypoxic ventilatory decline was not increased, but a measure of residual hypoxic ventilatory decline (the ratio of ventilation between the second and first steps into hypoxia) was decreased, which supports the hypothesis that opioids potentiate centrally mediated ventilatory decline.

Accuracy of a cerebral oximeter in healthy volunteers under conditions of isocapnic hypoxia.

BACKGROUND: A cerebral oximeter measures oxygen saturation of brain tissue noninvasively by near infrared spectroscopy. The accuracy of a commercially available oximeter was tested in healthy volunteers by precisely controlling end-tidal oxygen (P[ET]O2) and carbon dioxide (P[ET]CO2) tensions to alter global cerebral oxygen saturation. METHODS: In 30 healthy volunteers, dynamic end-tidal forcing was used to produce step changes in P[ET]O2 resulting in arterial saturation ranging from approximately 70% to 100% under conditions of controlled normocapnia (each person's resting P[ET]CO2) or hypercapnia (resting plus 7-10 mmHg). Blood arterial (SaO2) and jugular bulb venous (S[jv]O2) saturations during each P(ET)O2 interval were determined by co-oximetry. The cerebral oximeter reading (rSO2) and an estimated jugular venous saturation (S[jv]O2), derived from a combination of SaO2 and rSO2, were compared with the measured S(jv)O2. RESULTS: The S(jv)O2 was significantly higher with hypercapnia than with normocapnia for the same SaO2. The rSO2 and S(jv)O2 were both highly correlated with S(jv)O2 for individual volunteers (mean r2 = 0.91 for each relation); however, the slopes and intercepts varied widely among volunteers. In three of them, the cerebral oximeter substantially underestimated the measured S(jv)O2. CONCLUSIONS: During isocapnic hypoxia in healthy persons, cerebral oxygenation as estimated by near infrared spectroscopy precisely tracks changes in measured S(jv)O2 within individuals, but the relation exhibits a wide range of slopes and intercepts. Therefore the clinical utility of the device is limited to situations in which tracking trends in cerebral oxygenation would be acceptable.

Unindicated preoperative testing: ASA physical status and financial implications.

STUDY OBJECTIVE: To determine if the ordering of unindicated preoperative laboratory tests is different for healthy (ASA physical status I and II) versus sicker (ASA physical status III) patients, and to examine the financial implications at our institution of unindicated preoperative testing. DESIGN: Prospective, cross-sectional study. SETTING: University hospital. PATIENTS: 383 consecutive patients scheduled for elective surgery and seen by an anesthesiologist in the Preoperative Clinic. Complete data was available for 312 patients. MEASUREMENTS AND MAIN RESULTS: Preoperative laboratory tests ordered by the surgeon were compared to those tests considered indicated by one of several anesthesiologists for ASA physical status I and II versus ASA physical status III patients. An average of 72.5% of tests ordered by surgeons were considered not indicated by the anesthesiologists. ASA physical status III patients had significantly fewer unindicated complete blood count, platelet count, prothrombin time, partial thromboplastin time, chemistry 12 profile, and chest radiography orders than did ASA physical status I and II patients. Our hospital could generate approximately $80,000 in variable and semifixed cost savings by eliminating these unindicated preoperative tests for the 5,100 patients seen in Preoperative Clinic annually (29% of the total surgical patients). CONCLUSIONS: A large percentage of preoperative tests ordered by surgeons at our institution are not indicated. Eliminating unindicated tests would cut hospital revenues in a climate where testing is fee-for-service and would save the hospital money in a managed-care or capitated system.

The hyperventilation of cirrhosis: progesterone and estradiol effects.

Progesterone and estradiol are metabolized in the liver and are elevated in patients with cirrhosis. Progesterone stimulates ventilation by activating progesterone receptors in the central nervous system; estradiol may facilitate progesterone's actions by increasing progesterone receptors. This study evaluated whether progesterone and estradiol contribute to the respiratory alkalosis common in cirrhotic patients. Arterial blood gases and progesterone and estradiol levels were obtained in 50 patients with cirrhosis. Multiple linear regression revealed a statistically significant correlation between PaCO2 and progesterone and estradiol (r = .54, P < .05). Patients with severe hyperventilation (PaCO2 < or = 30 mm Hg) had statistically higher levels of progesterone and estradiol than did patients with mild hyperventilation (30 < PaCO2 < or = 35) or normal ventilation (PaCO2 > 35) (P < .05). Although the progesterone levels were two orders of magnitude lower than those associated with hyperventilation in pregnant patients, the increased ventilatory effect may be because of the altered blood-brain barrier (BBB) present in cirrhotic patients. Progesterone and estradiol appear to contribute to the hyperventilation in cirrhotic patients.

Anesthesia for scoliosis: dwarfism and congenitally absent odontoid process.

Scoliosis surgery presents the anesthetist with specific clinical challenges. Since scoliosis is the most common problem for which patients of congenitally short stature present to the operating room, the preoperative evaluation of dwarfs is discussed here in the context of a patient with spondyloepiphyseal dysplasia congenita. In the case described, many of the deformities associated with dwarfism were present. The significance of these to the preoperative, intraoperative, and postoperative care is discussed. Consideration is given to cervical spine abnormalities, congenital absence of the odontoid process, pulmonary function abnormalities, and mucopolysaccharidosis (a syndrome which may compromise airway management). The intraoperative monitoring of somatosensory evoked potentials and their significance are also discussed.

Effects of anaesthetics and sedatives on the control of breathing.

Most anaesthetics and sedatives affect breathing via several mechanisms, including effects on respiratory drive, wakefulness, and airway patency. Existing information about the effects of anaesthetic drugs on control of breathing has been obtained using techniques which focus on chemical control of breathing (i.e., the response to hypoxia and/or hypercapnia) and only occasionally take these other factors into account. In addition, a single drug is usually studied in isolation, despite the fact that anaesthetists often employ multiple drugs which may cause synergistic ventilatory depression. Finally, the pattern of change in O2/CO2 and the time of measurement of ventilation can influence the results of laboratory tests. For example, the effect of morphine on the CO2 response differs with steady-state versus rebreathing tests and, for the same dose of morphine, as a function of wakefulness. The measured hypoxic ventilatory response depends on the degree of hypercapnia, level of consciousness, and the time elapsed after the induction of hypoxia, since the response is characterized by an acute increase in ventilation followed by a subsequent decline. Unconsciousness induced by anaesthetics and sedatives may cause hypoventilation due to obstruction of the upper airway by either the epiglottis or the soft palate. For these reasons, clinicians should be aware that drugs which cause ventilatory depression in the laboratory may have different (possibly much greater) effects in their patients.

Effect of a subanesthetic minimum alveolar concentration of isoflurane on two tests of the hypoxic ventilatory response.

BACKGROUND: These experiments were designed to study the effect of 0.1 minimum alveolar concentration isoflurane on the hypoxic ventilatory response as measured by two common methods of hypoxic testing: when normocapnic hypoxia was induced abruptly and when it was induced gradually. We hypothesized that any disparity in results would be due to an isoflurane effect that was manifested differently in the two tests. METHODS: After 20 min for uptake and equilibration of 0.1 minimum alveolar concentration end-tidal isoflurane or carrier gas in hyperoxia, isocapnic hypoxia was induced either abruptly over 60-80 s ("step" test) or gradually over 10 min ("ramp" test), followed by 20 min of isocapnic hypoxia at 45 mmHg end-tidal oxygen. Control of the hypoxic and isocapnic stimuli was accomplished accurately by a computer-controlled dynamic end-tidal forcing system. Eight subjects performed each test in the presence and absence of isoflurane. RESULTS: For both step tests and ramp tests, 0.1 minimum alveolar concentration isoflurane had no effect on minute ventilation during the defined periods of hypoxia. With isoflurane, delta VE45, the acute change in ventilation from hyperoxia to hypoxia, was 97 +/- 20% (mean +/- SEM) of the control response for step tests and 100 +/- 25% of the control response for ramp tests. The step tests produced significantly larger acute hypoxic responses than did the ramp tests, but by the end of 20 min of hypoxia, ventilation was similar for both tests. CONCLUSIONS: Neither method of hypoxic testing demonstrated the level of isoflurane effect reported by others. A comparison of the two methods of hypoxic testing suggests that ramp tests, as commonly performed, do not allow adequate time for full expression of the acute hypoxic ventilatory response. Step tests also better separated the opposing hypoxic effects of carotid body stimulation and central ventilatory depression.

The effect of anti-exotoxin A on the adherence of Pseudomonas aeruginosa to hamster tracheal epithelial cells in vitro.

One of the most important initial events of colonization and infection of epithelial tissues is the adherence of bacteria to mucosal surfaces. Bacterial adhesion to the epithelial cell may be mediated by a variety of adhesins, including exoproducts. One of these exoproducts, exotoxin A (EA) is a three-domain bacterial toxin that kills mammalian cells by gaining entry to the cytosol and inactivating protein synthesis. In the present study, HTE cultures, 2-4 weeks in vitro (containing both ciliated and non-ciliated cells), were treated for 1 hr with two different non-mucoid strains of Pseudomonas aeruginosa (1 x 10(8) organisms/ml) in the presence of anti-EA. 50 randomly selected fields were evaluated via SEM at x2500 magnification and the number of bacterial clusters/field quantitated. The results of this study indicate, first, that both piliated (ATCC15692) and non-piliated (PAKp) P. aeruginosa will bind to the HTE cells and, second, that treatment of HTE cells with either strain of P. aeruginosa in the presence of anti-EA will reduce bacterial binding by 25% to 50%. Thus, EA may participate in the adhesion of P. aeruginosa to respiratory tract epithelia.

Type IV collagen localization in hamster tracheal epithelial cell cultures.

Hamster tracheal epithelial (HTE) cell cultures when grown on collagen coated Millicell-HA filters for 28 d in vitro have an incomplete basal lamina-like structure at the basal plasmalemma/collagen interface. EM evaluation of 42 d HTE cell cultures also revealed the presence of hemidesmosome-like structures on the basal plasmalemma. In order to better characterize this discontinuous basal lamina-like material, HTE cultures at 7, 14, 21, and 28 d were evaluated for the presence of type IV collagen, a basal lamina component. Immunocytochemical treatment of HTE cultures at these time points resulted in the presence of reaction product at the base of the cell layer. When immunocytochemical procedures for the localization of type IV collagen were carried out with normal mouse trachea, the results were also positive. Immunoblotting evaluation of HTE cell supernatants and conditioned media also indicated the presence of type IV collagen. Taken altogether, the presence of what appears to be basal lamina, hemidesmosome-like structures and immunocytochemical and immunoblot data showing the presence of type IV collagen in HTE cultures suggest that HTE cells may be producing basal lamina components but cannot organize them into a complete basal lamina.

Does a subanesthetic concentration of isoflurane blunt the ventilatory response to hypoxia?

The normal ventilatory response to the sudden imposition of sustained hypoxia is characterized by an acute increase followed by a modest decline in ventilation. Since subanesthetic concentrations of potent inhalational anesthetics greatly attenuate the acute response, we hypothesized that ventilation might decrease to less than normoxic levels when hypoxia is sustained. We therefore measured the ventilatory response to 20 min of sustained hypoxia (PETO2 45 mmHg) at two levels of strict isocapnia--normocapnia (PETCO2 1-2 mmHg above resting) and hypercapnia (PETCO2 49 mmHg)--in eight healthy male subjects during inhalation of 0.1 MAC isoflurane or carrier gas (control). An abrupt end-tidal step from normoxia to isocapnic hypoxia was induced using a dynamic end-tidal forcing system. Isoflurane and control experiments were performed on separate days; the order of isoflurane and control days and the order of normocapnia and hypercapnia within days were randomized. Subjects were studied while fasted, always at the same time of day, and were required to watch a documentary videotape to minimize differences in level of consciousness. With normocapnia, there was no difference in ventilation at any time between isoflurane and control (prehypoxic 9.6 +/- 1.5 vs. 9.5 +/- 2.6 1/min, peak hypoxic 24.7 +/- 10.4 vs. 26.2 +/- 10.4 1/min, final hypoxic 15.0 +/- 4.4 vs. 15.9 +/- 3.5 1/min; mean +/- SD). With hypercapnia, prehypoxic ventilation increased to the same level for isoflurane and control (24.8 +/- 6.7 vs. 24.8 +/- 9.6 1/min). Although peak hypoxic ventilation was slightly less in isoflurane than in control hypercapnic experiments, this was not significant (49.6 +/- 16.3 vs. 56.5 +/- 24.3 1/min; P = .22).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dopamine on ventilatory response to incremental exercise in man.

We investigated whether dopamine, an inhibitory neuromodulator in the carotid body, would alter the ventilatory response typically associated with metabolic (lactic) acidosis during exercise. Six subjects performed incremental cycle ergometer exercise to exhaustion during infusions of dopamine (3 micrograms.kg-1.min-1) or saline. Ventilation and pulmonary gas exchange were computed breath-by-breath; arterialized venous blood was collected every 90 sec for measurement of lactate, potassium and blood gases. The resting ventilatory response to an isocapnic step decrease in end-tidal PO2 to 50 Torr was used as an index of carotid body drive. Dopamine diminished the hypoxic ventilatory response but had no effect on the ventilatory response during exercise. Peak lactate, potassium, and ventilation were unaffected by dopamine, and the degree of respiratory compensation for the metabolic acidosis was the same as in control experiments. Therefore, either the carotid bodies respond differently to hypoxia than to acute metabolic acidosis and/or hyperkalemia during heavy exercise, or the carotid bodies are not the sole mediators of hyperventilation above the lactate threshold.

3,5,3'-triiodothyroacetic acid therapy for thyroid hormone resistance.

3,5,3'-Triiodothyroacetic Acid (Triac) is reputed to suppress pituitary secretion of TSH with minimal metabolic effects. Triac has been used successfully to treat eight patients with thyroid hormone resistance. We gave Triac to a woman with selective pituitary resistance for treatment of hyperthyroidism (patient 1) and to a man with generalized resistance and chronic schizophrenia to determine whether it would improve his schizophrenia (patient 2). Patient 1 was given 0.35-3.5 mg Triac/day; patient 2 was given 0.7-4.2 mg/day. Dosages were increased by 0.7 mg/day every 2 weeks. Serum T3, T4, free T4, TSH, TSH response to TRH, systolic time intervals (STI), angiotensin-converting enzyme (ACE), and lipids were monitored bimonthly. In both patients, there was no change in symptoms, weight, lipids, or STI. In patient 1, basal TSH suppressed from 16.3 to 1.5 mU/L; in patient 2, from 2.0 to 0.5 mU/L. The peak TSH response to TRH stimulation decreased from 144 to 12.5 mU/L in patient 1 and from 14.2 to 2.8 mU/L in patient 2. Serum T4 decreased from 160 to 109 nmol/L in patient 1 and from 270 to 192 nmol/L in patient 2. ACE levels were persistently elevated in both patients. Resting energy expenditure, measured by oxygen consumption, was increased by Triac in both patients (12% in patient 1 and 9% in patient 2). Although Triac suppressed TSH and T4 secretion in both patients, it did not reduce peripheral action of thyroid hormone as expressed in STI, resting energy expenditure, and ACE. We conclude that in these two patients with resistance to thyroid hormone, at the doses used to suppress TSH and T4 secretion, the intrinsic peripheral action of Triac offset whatever decrease in thyroid hormone secretion it produced.

Fitness as a determinant of oxygen uptake response to constant-load exercise.

Exercise performed above the lactate threshold (OLa) produces a slowly-developing phase of oxygen uptake (VO2) kinetics which elevates VO2 above that predicted from the sub-OLa VO2-work rate relationship. This phenomenon has only been demonstrated, to date, in subjects who were relatively homogeneous with respect to fitness. This investigation therefore examined whether this behaviour occurred at a given absolute VO2 or whether it was a characteristic of supra-OLa exercise in a group of subjects with over a threefold range of OLa (990-3000 ml O2.min-1) and peak VO2 (1600-5260 ml O2.min-1). Twelve healthy subjects performed: 1) exhausting incremental cycle ergometer exercise for estimation of OLa (OLa) and peak VO2, and 11) a series of constant-load tests above and below OLa for determination of the VO2 profile and efficiency of work. During all tests expired ventilation, VO2 and carbon dioxide production were monitored breath-by-breath. The efficiency of work determined during incremental exercise (28.1 +/- 0.7%, means +/- SE, n = 12) did not differ from that determined during sub-OLa constant-load exercise (27.4 +/- 0.5%, p greater than 0.05). For constant-load exercise, VO2 rose above that predicted, from the sub-OLa VO2-work rate relationship, for all supra-OLa work rates. This was evident above 990 ml O2.min-1 in the least fit subject but only above 3000 ml O2.min-1 in the fittest subject. As a consequence the efficiency of work was reduced from 27.4 +/- 0.5% for sub-OLa exercise to 22.6 +/- 0.4% (p less than 0.05) at the lowest supra-OLa work rate (i.e. OLa + 20 W, on average).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of acute caloric restriction on work efficiency.

Whether caloric restriction can alter the efficiency of muscular work raises important questions regarding the control of energetic coupling processes and the efficacy of exercise as a treatment for obesity. To address these issues, oxygen uptake (VO2) was determined at rest and during incremental cycle ergometry in 13 moderately obese (133 +/- 3% ideal body weight, means +/- SEM) women during weight maintenance and after 3 wk of caloric restriction (800 kcal/d). Work efficiency was calculated from the linear portion of the VO2-work rate relationship. Caloric restriction decreased body weight 4.0 +/- 0.4 kg (p less than 0.05), VO2 at rest 32 +/- 3 mL/min (p less than 0.05), and VO2 during unloaded (0 W) cycling 47 +/- 14 mL/min (p less than 0.05). However, work efficiency was unchanged (ie, -0.3 +/- 1.2%, NS). We conclude that, despite metabolic adaptations resulting in decreased energy expenditure at rest and during zero Watt cycling, acute caloric restriction does not alter work efficiency.

Effects of exercise training on resting energy expenditure during caloric restriction.

Resting energy expenditure (REE), maximum oxygen uptake (VO2max), and body composition were measured in seven moderately obese women during 9 wk of dietary restriction (800 kcal/d). During weeks 4-6, subjects underwent exercise training (30 min cycling/d, 5 d/wk, at 70% VO2max). The first 3 wk of caloric restriction decreased REE by 13% (from 1437 +/- 76 to 1254 +/- 66 kcal/24 h, means +/- SEM, p less than 0.05). Exercise training increased VO2max (from 1717 +/- 108 to 1960 +/- 120 mL/min, means +/- SEM, p less than 0.05) but did not elevate the dietary-depressed REE (from 1254 +/- 66 to 1262 +/- 62 kcal/24 h). The greatest decrease in body fat (3.7 +/- 0.4 kg) occurred during exercise training, resulting in a small apparent increase in REE when expressed per kilogram total body weight. However, expressed per unit lean body mass, REE remained suppressed throughout the period of caloric restriction. We conclude that exercise training of sufficient intensity to substantially increase VO2max does not reverse the dietary-induced depression of REE.

Low density lipoprotein receptor regulation and the cellular basis of atherosclerosis: implications for nutritional and pharmacologic treatment of hypercholesterolemia.

Blood levels of lipids and lipoproteins are prominent among the factors identified as contributing to the development of coronary artery disease. Studies have demonstrated that reduction of low density lipoprotein (LDL) levels lowers the risk of coronary events and retards the progression of atherosclerotic lesions. LDL receptors play a central role in the metabolism of LDL: they maintain cellular cholesterol homeostasis by effects on cholesterol synthesis, modulate the plasma level of lipoproteins by clearing LDL from the circulation and deliver cholesterol to the adrenal glands and gonads for steroid hormone synthesis and to the liver for bile acid synthesis. The 2 major strategies that have been developed so far to lower LDL levels involve the use of bile acid-binding resins, which bind cholesterol in the intestinal lumen, thereby leading to a decrease in intracellular cholesterol, which increases the rate of synthesis of LDL receptors and increases the rate of LDL clearance; and, more recently, the use of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the biosynthesis of cholesterol. Further studies are required to assess whether HMG-CoA reductase inhibitors, used alone or concomitantly with bile acid-binding resins, are safe and effective for long-term use in patients with elevated LDL levels.

Influence of inspired oxygen concentration on the dynamics of the exercise hyperpnoea in man.

In order to determine the role of the carotid bodies on the ventilatory control characteristics during the non-steady-state phase of exercise in man, six normal males performed cycle ergometry with four repetitions of a 6 min, constant-load work bout at inspired O2 fractions (FI,O2) of 0.12, 0.15, 0.21, 0.30 and 1.00. Each test began with unloaded pedalling; this was followed by a constant load which was 90% of the subject's anaerobic threshold at FI,O2 = 0.12. Ventilation (VE), CO2 output (VCO2) and O2 uptake (VO2) were determined breath-by-breath during the test and the time constants of response (tau VE, tau VCO2 and tau VO2) were established by least-squares techniques, following interpolation (1 s), temporal alignment and averaging of the four responses. In each subject, tau VE and tau VCO2 increased as functions of increasing FI,O2, and were inverse functions of the proportional contribution to VE of peripheral chemoreceptor drive (as estimated from hyperoxic-transition or 'Dejours' tests). tau VE averaged 40 s at FI,O2 = 0.12 and 112 s at FI,O2 = 1.00, each response being well fitted by a single exponential. However, tau VO2 was not significantly affected by the alterations in FI,O2. Although there was no discernible peripheral chemosensitivity at FI,O2 = 0.30 or 1.00, the tau VE increased appreciably between these inspirates. We therefore conclude that the peripheral chemoreceptors are important, but not exclusive determinants of the exponential response characteristics during the non-steady-state phase of the exercise hyperpnoea in man. This supports the contention of a component of the control being humorally mediated even during moderate exercise.

Whole body protein breakdown rates and hormonal adaptation in fasted obese subjects.

Fasting is known to result in marked decreases in urinary urea nitrogen excretion over a 7-day period. In the present studies, changes in whole body protein breakdown rates and in the circulating levels of a number of hormones involved in protein anabolism and catabolism were systematically studied in nine obese subjects after 12 h and after 7 days of fasting. Whole body protein breakdown rates, measured with a primed continuous infusion of L-[U-14C]lysine, were decreased after 7 days of fasting (1.54 +/- 0.12 g/kg . day) compared to those after 12 h of fasting (1.96 +/- 0.10 g/kg . day). Plasma insulin decreased and glucagon increased after 7 days of fasting, resulting in an increased glucagon to insulin molar ratio. Plasma cortisol, urinary free cortisol excretion plasma rT3 levels, and branched chain amino acid levels increased after 7 days of fasting. Serum lysine levels, used for the calculations of whole body protein breakdown rates, were not changed. We conclude: 1) decreased whole body protein breakdown contributes significantly to the decreased nitrogen excretion observed with fasting in obese subjects; and 2) a decrease in circulating levels of free T3 may lead to this adaptive decrease in protein breakdown in fasted obese subjects, since the other hormones measured either did not change or changed in a catabolic direction.