Biomedical subjects

K Madsen

Publications and source records attributed to K Madsen.

At least 37 records · Page 2Linked to original sources

PubMed1999

Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys.

The orexigenic role of central neuropeptide Y (NPY) in nonhuman primates has been questioned. Therefore, we have studied the effect of central NPY on feeding in ad libitum-fed male rhesus macaques. NPY dose-dependently increased food intake, with the maximal effect obtained by 50 microg (960 min food intake +/- SEM, 104 +/- 5 to 188 +/- 11 g; vehicle vs. NPY; n = 6). Blood glucose levels were unaffected by intracerebroventricular administration of NPY, but animals receiving either 20 or 50 microg displayed increased plasma levels of insulin and cortisol at few time points. To assess the pharmacological specificity of this response, a novel Y1 antagonist, [(Ile,Glu,Pro,Daba,Tyr,Arg,Leu,Arg,Tyr-NH2)2 cyclic (2,4'),(2',4)-diamide] (Y1ANT), was synthesized. Receptor binding experiments demonstrated that Y1ANT preferentially binds to Y1 and Y4 receptors (pKi 10.12 +/- 0.06 and 9.11 +/- 0.05 nmol/L, respectively). Functional analysis revealed that Y1ANT is a Y1 antagonist and a partial Y4 agonist. Central administration of Y1ANT blocked NPY-induced feeding. In food-deprived monkeys, Y1ANT attenuated the feeding response. However, Y1ANT had no effect on food intake in satiated monkeys. Thus, endogenous NPY is likely to be involved in the regulation of food intake in the nonhuman primate, and this effect is at least partially mediated via Y1-like receptors.

Animals↗

PubMed1998

A new series of highly potent growth hormone-releasing peptides derived from ipamorelin.

A new series of GH secretagogues derived from ipamorelin is described. In an attempt to obtain oral bioavailability, by reducing the size and the number of potential hydrogen-bonding sites of the compounds, a strategy using the peptidomimetic fragment 3-(aminomethyl)benzoic acid and sequential backbone N-methylations was applied. Several compounds from this series release GH with high in vitro potency and efficacy in a rat pituitary cell assay and high in vivo potency and efficacy in anesthetized rats. The tetrapeptide NNC 26-0235 (3-(aminomethyl)benzoyl-D-2Nal-N-Me-D-Phe-Lys-NH2) shows, following iv administration, comparable in vivo potency to ipamorelin, GHRP-2, and GHRP-6 with an ED50 in swine at 2 nmol/kg. NNC 26-0235 demonstrated a 10% oral bioavailability in dogs, and NNC 26-0235 and ipamorelin were able to increase basal GH level by more than 10-fold after oral administration of a dose of 1.8 and 2.7 mg/kg, respectively. The tripeptide NNC 26-0323 (3-(aminomethyl)benzoic acid-N-Me-D-2Nal-N-Me-D-Phe-ol) which showed moderate in vitro potency but lacked in vivo potency demonstrated a 20% oral bioavailability in rats.

Administration, Oral↗

PubMed1998

Novel orally active growth hormone secretagogues.

A novel class of growth hormone-releasing compounds with a molecular weight in the range from 500 to 650 has been discovered. The aim of this study was to obtain growth hormone secretagogues with oral bioavailability. By a rational approach we were able to reduce the size of the lead compound ipamorelin (4) and simultaneously to reduce hydrogen-bonding potential by incorporation of backbone isosters while retaining in vivo potency in swine. A rat pituitary assay was used for screening of all compounds and to evaluate which compounds should be tested further for in vivo potency in swine and oral bioavailability, fpo, in dogs. Most of the tested compounds had fpo in the range of 10-55%. In vivo potency in swine after iv dosing is reported, and ED50 was found to be 30 nmol/kg of body weight for the most potent compound.

Administration, Oral↗

PubMed1998

Methodological aspects of measuring human skeletal muscle electrolyte content and ouabain binding capacity.

The aim of the study was to evaluate the use of freeze-dried and dissected small muscle biopsy specimens ("dry") for the determination of human muscle electrolyte content and ouabain binding capacity, compared with an easier method, without this freeze-drying step ("wet"). Freeze-drying and dissection of muscle biopsy specimens reduced the variation in the determination of muscle potassium and magnesium content. The total coefficient of variation was 8.6% in the dry determination of muscle potassium content and 13.5% in the wet determination (P < 0.05). In the determination of muscle magnesium content, the total coefficient of variation was 7.4% in the dry determination and 13.7% when determined wet (P < 0.005). Muscle sodium content had a very large coefficient of variation, independent of the method used. The content of dry solids was too high in biopsies which were incubated in Tris-vanadate buffer (31.9%), compared to biopsies which were not incubated in Tris-vanadate buffer (24.9%, P < 0.001). Hereby, the measured ouabain binding capacity became too high when measured wet. In conclusion, muscle electrolyte content and ouabain binding capacity should be determined after drying and microdissection of the biopsies, because this method confers the least variation and the highest accuracy.

Aged↗

PubMed1998

Shape- and weight-based self-esteem and the eating disorders.

OBJECTIVES: To determine the psychometric properties of the Shape- and Weight-Based Self-Esteem (SAWBS) Inventory in women with eating disorders, and to compare SAWBS scores in women who have eating disorders with women from psychiatric and normal control groups. METHOD: Women with eating disorders (n = 48), women with other psychiatric disorders (n = 44), and undergraduate control women (n = 82) completed the SAWBS Inventory and measures of depression, self-esteem, and eating disorder symptomatology. Twenty women from the eating disorder group completed the SAWBS Inventory a second time 1 week later. RESULTS: Similar to previous work in undergraduate samples, SAWBS scores were stable over 1 week, and demonstrated concurrent and discriminant validity in women with eating disorders. In between-group comparisons, SAWBS scores were higher among women with eating disorders than in either control group, even after controlling for age, socioeconomic status, body mass index, and self-esteem. A differing relationship between depression and SAWBS emerged as a function of group; SAWBS scores differed significantly among depressed, but not nondepressed women from the three groups. CONCLUSION: The psychometric properties of the SAWBS Inventory were established in women with eating disorders. As expected, SAWBS scores were higher in women with eating disorders than in the control groups. Clinical implications of these findings are discussed.

Adult↗

PubMed1998

Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity.

Glucagon-like peptide 1 (GLP-1) has great potential in diabetes therapy due to its glucose-dependent stimulation of insulin secretion, but this is limited by its rapid degradation, primarily by dipeptidyl peptidase IV. Four analogues, N-terminally substituted with threonine, glycine, serine or alpha-aminoisobutyric acid, were synthesised and tested for metabolic stability. All were more resistant to dipeptidyl peptidase IV in porcine plasma in vitro, ranging from a t1/2 of 159 min (Gly8 analogue) to undetectable degradation after 6 h (Aib8 analogue; t1/2 for GLP-1 (7-36) amide, 28 min). During i. v. infusion in anaesthetised pigs, over 50% of each analogue remained undegraded compared to 22.7 % for GLP-1 (7-36) amide. In vivo, analogues had longer N-terminal t1/2 (intact peptides: means, 3.3-3.9 min) than GLP-1 (7-36) amide (0.9 min; p < 0.01), but these did not exceed the C-terminal t1/2 (intact plus metabolite: analogues, 3.5-4.4 min; GLP-1 (7-36) amide, 4.1 min). Analogues were assessed for receptor binding using a cell line expressing the cloned receptor, and for ability to stimulate insulin or inhibit glucagon secretion from the isolated perfused porcine pancreas. All bound to the receptor, but only the Aib8 and Gly8 analogues had similar affinities to GLP-1 (7-36) amide (IC50; Aib8=0.45 nmol/l; Gly8=2.8 nmol/l; GLP-1 (7-36) amide=0.78 nmol/l). All analogues were active in the isolated pancreas, with the potency order reflecting receptor affinities (Aib8 > Gly8 > Ser8 > Thr8). N-terminal modification of GLP-1 confers resistance to dipeptidyl peptidase IV degradation. Such analogues are biologically active and have prolonged metabolic stability in vivo, which, if associated with greater potency and duration of action, may help to realise the potential of GLP-1 in diabetes therapy.

Animals↗

PubMed1998

Endogenous hyaluronan in the normal and traumatized rabbit iris.

PURPOSE: Hyaluronan concentration in the iris tissue after iridectomy was studied in order to establish the influence of trauma on the production of hyaluronan in the anterior chamber of the eye and whether the iris participates in this process or not. METHOD: Hyaluronan was measured with a radiometric assay at different time points after surgery and identified with specific histochemical staining. RESULTS AND CONCLUSIONS: The concentration of hyaluronan in iris tissue peaked two days after surgery, reaching an average of 115.3 (S.E.M.:+/-12.2) microg/g. It then decreased slowly to almost normal values after 3 to 5 weeks. Histochemistry demonstrated the most intense hyaluronan staining in the iris stroma and in iridial processes around the iridectomy two days after the operation. Our findings indicate in situ synthesis of hyaluronan in the iris tissue.

Animals↗

PubMed1998

The prenatal diagnosis of cloacal exstrophy.

PURPOSE: We assess and clarify diagnostic features for making the prenatal diagnosis of cloacal exstrophy. MATERIALS AND METHODS: We evaluated 9 patients born with cloacal exstrophy at our institutions (2 prospectively and 7 retrospectively) for diagnostic features on prenatal ultrasound studies. We also thoroughly reviewed the literature on 13 previous prenatally diagnosed cloacal exstrophy cases. Diagnostic criteria were assessed by combining the findings in our patients and those in previous reports. RESULTS: Of the 22 patients with prenatal ultrasound studies and cloacal exstrophy whom we analyzed 1 of our 9 and 2 in the literature had a cloacal membrane that persisted at 22 weeks of gestation. Major ultrasound criteria for diagnosing cloacal exstrophy prenatally are nonvisualization of the bladder, a large midline infraumbilical anterior wall defect or cystic anterior wall structure (persistent cloacal membrane), omphalocele and lumbosacral anomalies. Seven less frequent or minor criteria include lower extremity defects, renal anomalies, ascites, widened pubic arches, a narrow thorax, hydrocephalus and 1 umbilical artery. CONCLUSIONS: We propose major and minor criteria to assist in the prenatal diagnosis of cloacal exstrophy. Despite these major and minor criteria the certainty of establishing a prenatal diagnosis remains challenging. Persistence of the cloacal membrane beyond the first trimester in 1 patient was an exception to the classic concept of cloacal exstrophy embryogenesis. An accurate prenatal diagnosis requires validation of these criteria by further correlation of prenatal and postnatal observations.

Cloaca↗

PubMed1998

Improved running economy following intensified training correlates with reduced ventilatory demands.

PURPOSE: To compare the effects of three types of intensive run training on running economy (RE) during exhaustive running and to establish possible relationships with changes in ventilatory function and/or muscle fiber type distribution. METHODS: Thirty-six male recreational runners were divided into three groups and assigned to either exhaustive distance training (DT), long-interval training (LIT), or short-interval training (SIT) three times 20-30 minxwk(-1) for 6 wk. VO(2 max) and RE were measured during treadmill running before and after training. Muscle fiber type distribution of the vastus lateralis muscle was established from biopsy material. RESULTS: VO(2max) (Lxmin(-1) increased by 5.9% (P < 0.0001), 6.0% (P < 0.0001), and 3.6% (P < 0.01) in DT, LIT, and SIT, respectively, and running speed at VO(2max) by 9% (P < 0.0001), 10% (P < 0.0001), and 4% (P < 0.05), respectively. Time-to-exhaustion at 87% of pretraining VO(2max) (mean 3.83) mxs(-1) increased by 94% in DT (P < 0.0001), 67% in LIT (P < 0.0001). Running economy improved by 3.1% in DT (P < 0.05), 3.0% in LIT (P < 0.01), and 0.9% SIT (NS): pulmonary ventilation (VE) was on average 11 Lxmin(-1) lower following training (P < 0.0001). The individual decrements in VE correlated with improvements in RE (r = 0.77; P < 0.0001) and may account for 25-70% of the decrease in aerobic demand. Muscle fiber composition, and respiratory exchange ratio, stride length, and stride frequency during running were unaltered with training. CONCLUSIONS: Recreational runners can improve RE and aerobic run performance by exchanging parts of their conventional aerobic distance training with intensive distance or long-interval running, whereas short-interval running is less efficient. The improvement in RE may relate to reduced ventilatory demands. Muscle fiber type distribution was unaltered with training and showed no associations with RE.

Adult↗

PubMed1998

Renal growth and development in mice lacking AT1A receptors for angiotensin II.

To examine the role of the type 1A (AT1A) angiotensin receptor in renal growth and development, we analyzed F2 progeny from a series of crosses between F1 mice that were heterozygous for a targeted disruption of the AT1A receptor gene [Agtr1A-(+/-)]. Among 21-day-old weanling F2 mice, we found that 194 (32%) were homozygous for the wild-type allele Agtr1A-(+/+), 299 (49%) were Agtr1A-(+/-), and 119 (19%) were Agtr1A-(-/-). This differed significantly from the proportions predicted by Mendelian genetics (P = 0.01), suggesting that the complete absence of AT1A receptors is associated with a mild survival disadvantage. Agtr1A-(-/-) mice grew normally, and we found no significant differences in body weight or heart and kidney weights in Agtr1A-(+/+) and Agtr1A-(-/-) mice examined at 21, 60, and 100 days. Protein and DNA content of kidneys and hearts were also similar in weanling or adult Agtr1A-(+/+) and Agtr1A-(-/-) mice. By light microscopy with immunohistochemistry, kidneys from Agtr1A-(-/-) were essentially normal, with two exceptions: 1) there was marked hypertrophy of the juxtaglomerular apparatus (JGA) and proximal expansion of renin-producing cells along the afferent arterioles, and 2) some glomeruli showed evidence of mesangial expansion. We did not find the severe renal vascular lesions or papillary atrophy that have been observed in angiotensinogen- or angiotensin converting enzyme-deficient animals. We conclude that the AT1A receptor is not essential for the normal organogenesis of the kidney; however, its absence is associated with mild mesangial expansion and JGA hypertrophy.

Angiotensin II↗

PubMed1998

Ipamorelin, the first selective growth hormone secretagogue.

The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1. In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%). A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anaesthetised rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml). In conscious swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma. Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine. None of the GH secretagogues tested affected FSH, LH, PRL or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol. Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation. This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release. In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of ipamorelin makes this compound a very interesting candidate for future clinical development.

Adrenocorticotropic Hormone↗

PubMed1997

Fine-needle aspiration of 697 palpable breast lesions with histopathologic correlation.

BACKGROUND: Fine-needle aspiration breast biopsy has been used increasingly as an alternative to excisional biopsy. The purpose of this study is to evaluate the accuracy of fine-needle aspiration with histopathologic confirmation. METHODS: A retrospective study was performed using a computer database over a 5-year period. All women who had had fine-needle aspiration breast biopsy with histopathologic confirmation of the diagnosis were included. Fine-needle aspirations were interpreted as malignant, suspicious, or benign. Histopathologic diagnosis included core-needle biopsy, open excisional biopsy, or mastectomy specimen. RESULTS: A total of 697 patients fulfilled the criteria. Only 5 (0.7%) of the specimens were inadequate for study. There were 401 total malignant fine-needle aspiration diagnoses, with only 3 false-positive specimens. All three were ductal hyperplasia, one from a previously radiated breast. There were 125 suspicious readings; 84 of these were malignant and 41 were false-suspicious specimens. Most of the false-suspicious lesions were fibrocystic disease. Of the 166 lesions interpreted as benign, there were 13 false-negative specimens. The test had a 97% sensitivity, 78% specificity, 92% positive predictive value, and 92% negative predictive value. CONCLUSIONS: Fine-needle aspiration is a sensitive test that can be useful as an adjunct in the diagnosis of breast cancer. "Malignant" and "benign" interpretations are highly predictive but must be used only in the context of other diagnostic modalities. "Suspicious" lesions require further investigation.

Biopsy, Needle↗

PubMed1997

Muscle glycogen synthesis in recovery from intense exercise in humans.

The present study examined the role of lactate and glucose as substrates for glyconeogenesis in muscle in recovery from high-intensity exercise in humans. Seven subjects performed approximately 100 min of intense intermittent one-legged knee extensor exercise on two occasions: with [high lactate (HL)] and without [control (C)] intense arm exercise between the leg exercise bouts, leading to end exercise arterial plasma lactate concentrations of 16.0 +/- 1.6 and 9.2 +/- 1.6 mmol/l, respectively (P < 0.05). At the end of exercise, muscle lactate and glycogen were similar in HL and C (20.5 +/- 1.3 vs. 17.3 +/- 2.0 mmol/kg wet wt and 48.1 +/- 11.3 vs. 56.3 +/- 8.6 mmol/kg wet wt, respectively). Muscle glycogen increased (P < 0.05) during the first 5 min of recovery only in HL, but after 90 min of recovery the muscle glycogen concentration was the same in C and HL (61.2 +/- 12.0 vs. 71.5 +/- 10.9 mmol/kg wet wt). Muscle lactate not released to the blood could maximally account for 28 (C) and 54% (HL) of the increase in muscle glycogen during 90 min of recovery or < 10% of glycogen synthesis after full recovery. The total net glucose uptake corresponded to 84 (C) and 57% (HL) of the glycogen synthesized. Apparently, muscle glyconeogenesis may occur in humans, but the role of lactate as a substrate is minor. Instead, blood glucose appears to be the most important precursor for muscle glycogen synthesis after intense exercise.

Adult↗

PubMed1997

Antioxidant status and lipid peroxidation after short-term maximal exercise in trained and untrained humans.

The purpose of this study was to measure resting muscle and blood antioxidant status in untrained (n = 8) and jump-trained (n = 8) humans and to evaluate free radical-mediated muscle damage after a strenuous jump test consisting of six bouts of 30-s continuous jumping separated by 2 min of rest. Resting muscle antioxidant activities [superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), and manganese SOD] were significantly higher in jump-trained compared with untrained subjects. Blood antioxidant enzyme activities and muscle catalase, however, were not different between the two groups. Creatine kinase activities increased significantly (P < 0.0001) after the jump test in untrained individuals, but remained unchanged in the jump trained. Plasma and muscle malonaldehyde (MDA) after the jump test were not significantly different from rest. These data suggest that jump training is associated with elevated activities of SOD and the coupled enzymes GPX and GR in muscle tissue, but other antioxidants remain unchanged. High-intensity jump exercise induces muscle enzyme leakage in untrained humans, but muscle lipid peroxidation, measured as changes in MDA, was not different in the two groups despite the varied muscle antioxidant enzyme levels.

Adult↗

PubMed1996

Effect of muscle acidity on muscle metabolism and fatigue during intense exercise in man.

1. The aim of this study was to examine the effect of muscle pH on muscle metabolism and development of fatigue during intense exercise. 2. Seven subjects performed intense exhaustive leg exercise on two occasions: with and without preceding intense intermittent arm exercise leading to high or moderate (control) blood lactate concentrations (HL and C, respectively). Prior to and immediately after each exercise bout, a muscle biopsy was taken from m. vastus lateralis of the active leg. Leg blood flow was measured and femoral arterial and venous blood samples were collected before and frequently during the exhaustive exercises. 3. The duration of the exercise was shorter in HL than in C (3.46 +/- 0.28 vs. 4.67 +/- 0.55 min; means +/- S.E.M.; P < 0.05). Before exercise muscle pH was the same in C and HL (7.17 vs. 7.10), but at the end of exercise muscle pH was lower in HL than in C (6.82 vs. 6.65; P < 0.05). The release of potassium during exercise was higher (P < 0.05) in HL compared with C, but the arterial and femoral venous plasma potassium concentrations were the same at exhaustion in HL and C. 4. Muscle lactate concentration was higher in HL compared with C (3.7 +/- 0.4 vs. 1.6 +/- 0.2 mmol (kg wet weight)-1; P < 0.05), but the same at exhaustion (26.5 +/- 2.7 vs. 25.4 +/- 2.4 mmol (kg wet weight)-1). Total release of lactate in HL was lower than in C (18.7 +/- 4.5 vs. 50.4 +/- 11.0 mmol; P < 0.05), but rate of lactate production was not different (9.0 +/- 1.0 vs. 10.2 +/- 1.3 mmol (kg wet weight)-1 min-1). The rate of muscle glycogen breakdown was the same in C and HL (8.1 +/- 1.2 vs. 8.2 +/- 1.0 mmol (kg wet weight)-1 min-1). 5. The present data suggest that elevated muscle acidity does not reduce muscle glycogenolysis/glycolysis and is not the only cause of fatigue during intense exercise in man. Instead, accumulation of potassium in muscle interstitium may be an important factor in the development of fatigue.

Adult↗

PubMed1996

Calcium content and respiratory control index of isolated skeletal muscle mitochondria: effects of different isolation media.

Calcium (Ca) content measured with graphite furnace atomic absorption spectrometry and polarographical measurement of respiratory control index (RCI) were performed on isolated skeletal muscle mitochondria. Four different isolation media were used in order to develop a method for isolating physiologically intact mitochondria in small samples with an endogenous Ca content as close as possible to in vivo conditions. With ruthenium red in the isolation medium, the mean Ca content decreased fourfold to 19.3 +/- 6.8 nmol/mg protein and RCI increased about 25% to 6.9 +/- 1.1 compared with a standard medium. With EGTA or EGTA plus ruthenium red, the mean Ca content decreased further to 5.8 +/- 1.0 and 5.1 +/- 0.9 nmol/mg protein and the mean RCI values increased to 8. 4 +/- 1.2 and 8.8 +/- 1.3, respectively. Isolated mitochondria from human muscle samples using EGTA and ruthenium red in the isolation medium had mean Ca values of 11.0 +/- 0.9 nmol/mg protein and mean RCI values of 12.2 +/- 1.6. The data indicate that the Ca concentration in the skeletal muscle mitochondria is inversely proportional to RCI, and the mitochondrial functional property is significantly improved upon lowering the intramitochondrial Ca accumulation by the incorporation of a chelating agent (EGTA) and a potent Ca antagonist, ruthenium red, in the isolation media.

Adult↗

PubMed1996

Reduced arterial O2 saturation during supine exercise in highly trained cyclists.

Performance of intense dynamic exercise in highly trained athletes is associated with a reduced arterial haemoglobin saturation for O2 (SaO2) and lower arterial PO2 (PaO2). We hypothesized that compared with upright exercise, supine exercise would be accompanied by a smaller reduction in SaO2 because of a lower maximal O2 uptake (VO2max) and/or a more even ventilation-perfusion distribution. Eight elite bicyclists completed progressive cycle ergometry to exhaustion in both positions with concomitant determinations of ventilatory data, arterial blood gases and pH. During upright cycling VO2max averaged 75 +/- 1.6 mL O2 min-1 kg-1 (+/-SEM) and it was 10.6 +/- 1.7% lower during supine cycling (P < 0.001). Also the maximal pulmonary and alveolar ventilation were lower during supine cycling (by 15 +/- 2% and 21 +/- 3%, respectively; P < 0.001) which related to a 0.8 +/- 0.1 L lower tidal volume (P < 0.001). In all subjects and independent of work posture PaO2 and SaO2 decreased from rest to exhaustion (from 99 +/- 3 to 82 +/- 2 Torr and 98.1 +/- 0.2 to 95.2 +/- 0.4%, respectively; P < 0.001); alveolar-arterial PO2 difference increased from 6 +/- 2 to 37 +/- 3 Torr in both body positions. At exhaustion arterial PCO2 was lower in upright than in supine (33.4 +/- 0.6 vs. 35.9 +/- 0.9 Torr; P < 0.01), suggesting a greater relative hyperventilation in upright. Arterial pH was similar in upright and supine at rest (both 7.41 +/- 0.01) and at exhaustion (7.31 +/- 0.01 vs. 7.32 +/- 0.01, respectively). We conclude that despite a lower Vo2max and supposedly an improved ventilation-perfusion distribution, altering body position from upright to supine does not influence arterial O2 desaturation during intense exercise.

Adult↗

PubMed1996

Calcium content and respiratory control index of skeletal muscle mitochondria during exercise and recovery.

The purpose of this study was to evaluate the relationship between mitochondrial Ca2+ concentration and the respiratory control index (RCI; state III/state IV) in isolated mitochondria before and after exhaustive exercise at 75% of maximal O2 consumption. Muscle biopsies of 100-150 mg from 12 moderately trained men were sampled at rest, immediately after exercise, and 30 or 60 min after exercise. The mitochondrial Ca2+ content after exhaustive exercise was significantly higher than the preexercise level [15.1 (range 39.4) vs. 11.6 (range 6.5) nmol/mg protein, respectively; P < 0.05], and RCI increased from 11.6 (range 14.4) at rest to 13.7 (range 15.0) at exhaustion (P < 0.05). After 60 min of recovery, the mitochondrial Ca2+ content was still high [18.8 (range 29.9) nmol/mg protein], but the RCI value was significantly depressed because of the increased state IV value and, in fact, was lower than the preexercise value [8.6 (range 5.1); P < 0.05]. Our results show that the mitochondrial Ca2+ content is increased in human skeletal muscle after prolonged exhaustive exercise and that this is followed by an elevated RCI value, with slightly increased state III and decreased state IV respiration. The restoration of the elevated mitochondrial Ca2+ level is slow and could be related to an increased state IV respiration, which together indicate uncoupled Ca2+ respiration during recovery.

Adult↗