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Biomedical subjects

A Nygren

Publications and source records attributed to A Nygren.

At least 73 records · Page 4Linked to original sources

Effects of ischaemic training on local aerobic muscle performance in man.

The aim of the study was to compare the effects of ischaemic and non-ischaemic training on aerobic performance. In 10 subjects, peak oxygen uptake (peak VO2) and time to fatigue (TTF) for one-legged exercise were measured before and after 4 weeks (4 times week-1) of one-legged training. Each training session started with one leg training for 45 min with 20% blood-flow reduction induced by local application of a supra-atmospheric external pressure of 50 mmHg (ischaemic leg; I-leg). We have previously shown that this decreases leg blood flow by about 20%. The contralateral leg (non-restricted-flow leg; N-leg), serving as a control, then trained with an identical power-output profile for 45 min but without flow restriction. In the I-leg the average training-induced increments in TTF and peak VO2 were 27 and 24%, respectively. In the N-trained leg TTF and peak-VO2 increased 10 and 14%, respectively. Both increments were significantly greater (P < 0.05) in the I-trained leg. Moreover, the performance increase in the I-trained leg was exaggerated (P < 0.05) in the ischaemic test condition, i.e. there was a specificity in the training response. In conclusion, ischaemia acts as an additive stimulus to training leading to an exaggerated increase in endurance and peak-VO2 compared to identical training without blood-flow restriction. The main explanation is probably an enhanced local adaptation in the I-trained leg.

Adult↗

Muscle fibre types and enzyme activities after training with local leg ischaemia in man.

Eight healthy men performed supine one-legged training on a bicycle ergometer 45 min per leg four times per week for 4 week. The ergometer and lower body were inside a pressure chamber, the opening of which was sealed at the level of the crotch. One leg trained with impeded leg blood flow (I-leg), induced by an increased (50 mmHg) chamber pressure, at the highest tolerable intensity. The contralateral leg trained at the same power under normal pressure (N-leg). Before and after training biopsies were taken from the vastus lateralis of both legs and maximal one-legged exercise tests were executed with both legs. Biopsies were repeated when the subjects had been back to their habitual physical activity for 3 months. Training increased exercise time to exhaustion, but more in the I-leg than in the N-leg. After training, the I-leg had higher activity of citrate synthase (CS), a marker of oxidative capacity, and lower activity of the M-subunit of lactate dehydrogenase isoenzymes. It also had a higher percentage of type-I fibres and a lower percentage of IIB fibres, larger areas of all fibre types and a greater number of capillaries per fibre. It is concluded that ischaemic training changes the muscle metabolic profile in a direction facilitating aerobic metabolism. An altered fibre-type composition may contribute, but is not enough prerequisite for the change.

Adult↗

Therapy-resistant hypertension associated with central obesity, insulin resistance, and large muscle fibre area.

Obesity and an enhanced insulin response to oral glucose tolerance test are associated with therapy resistance in hypertension. In order to explore this association further we studied the insulin sensitivity of subjects with essential hypertension resistant to triple drug therapy (RH), with the euglycemic insulin clamp technique. Well controlled hypertensives, matched for age, gender and body mass index (BMI) served as controls. Male subjects (7 RH and 7 controls) were further investigated by biopsies of Musculus Vastus lateralis since structural conditions in skeletal muscles might have a role in the above association. Irrespective of pre-study drug therapy, therapy-resistant hypertensives had a lower insulin sensitivity index than controls (p < 0.05). In spite of the BMI-match waist/hip ratio (WHR) in the RH males tended to be higher (p < 0.07). Insulin clearance tended to be lower in RH subjects (p = 0.09). BMI correlated with a reduced muscular capillary density (r = -0.77, p < 0.01). The average cross-sectional muscle fibre area was larger in RH subjects (p < 0.05). The mean muscle fibre area correlated with basal serum insulin (r = 0.63; p < 0.05). Rarefaction of the muscular capillary bed appears to be related to obesity. Larger muscle fibres might be an effect of the growth factor properties of insulin and could possibly correspond to hypertrophy of smooth muscle in the resistance vessels. This factor might contribute to the association of hyperinsulinemia and hypertension and attenuate the response to antihypertensive therapy.

Adult↗

Arterial pressure, plasma renin activity, atrial natriuretic factor, and sodium excretion during induced hyper- and hypoinsulinemia in therapy-resistant hypertensives.

We investigated whether short-term changes in serum insulin would effect a reduction of arterial pressure in subjects with therapy-resistant essential hypertension. Six patients were examined twice with a 3 week's interval in a single-blind cross-over design with euglycemic insulin clamps (A and B). A reduction of endogenous serum insulin was achieved by continuous infusion of 50 microgram octreoid (a somatostatin analogue) per hour. During clamp A low dose insulin infusion (5 mU/m2/min) was given, whereas during clamp B insulin was infused at a rate of 60 mU/m2/min. Preceding each clamp a standard drug therapy was given for one week (50 mg atenolol+ 30 mg furosemide per day). During clamp A plasma insulin was reduced from 21.4 +/- 7.5 to 10.8 +/- 1.2 mU/l (p < 0.01) whereas plasma insulin rose during clamp B from 20.0 +/- 7.5 to 99.0 +/- 17.2 mU/l (p < 0.001). The mean arterial blood pressure did not decrease during clamp A (low dose insulin infusion). There was an increased natriuresis during the high-insulin clamp (70 vs. 38 mmol, p = 0.13), but no difference in arterial pressure between the clamps. The results do not support the notion that high insulin levels contribute to hypertension in therapy resistant hypertensive patients by any direct and immediate mechanism.

Adult↗

Effect of intravenous contrast media on proximal and distal tubular hydrostatic pressure in the rat kidney.

The effect of i.v. injection of contrast media (CM, 1,600 mg I/kg b.w.) on proximal and distal tubular hydrostatic pressure (PTHP, DTHP) in the rat was investigated using a micropuncture technique. The PTHP and DTHP after injection of diatrizoate, iohexol, ioxaglate, or mannitol returned to control values within approximately 20 min. However, following iotrolan injection PTHP was still elevated above control levels after 35 min while DTHP remained elevated throughout the experiment (50 min). Iotrolan has a lower osmotic potential than the other CM when given in equivalent iodine doses. The concentration of iotrolan may thus increase more along the tubules than the other CM and consequently lead to a higher viscosity of urine, resulting in increases in PTHP and DTHP. The high intratubular pressure induced by iotrolan may explain our previous findings of reduced single nephron glomerular filtration rate caused by this CM.

Animals↗

The influence of indomethacin, theophylline, and propranolol on ethanol augmentation of glucose-induced insulin secretion.

The effect of indomethacin, theophylline, and propranolol on ethanol augmentation of insulin secretion after intravenous glucose stimulation was studied. Intravenous glucose tolerance tests were performed with and without pretreatment with oral ethanol. The role of indomethacin was evaluated in six healthy subjects; the effect of theophylline and propranolol on ethanol augmentation in insulin secretion was studied in five and six subjects, respectively. Ethanol pretreatment was followed by increased insulin (P < .01) and C-peptide areas (P < .01) after intravenous glucose (Area, 0 to 20 minutes). Indomethacin suppressed the ability of ethanol to augment insulin (P < .01) and C-peptide (P < .01) responses. Neither theophylline nor propranolol affected ethanol augmentation of insulin secretion. In conclusion, indomethacin probably interferes with the mechanism for ethanol augmentation of glucose-induced insulin secretion. It is suggested that inositol phospholipids take part in the effect of ethanol to augment insulin secretion, and that indomethacin interferes with the metabolism of inositol phospholipids.

Adult↗

Influence of contrast media on single nephron glomerular filtration rate in rat kidney. A comparison between diatrizoate, iohexol, ioxaglate, and iotrolan.

The effects of slow (10 min) i.v. infusions of contrast media (CM, 1,600 mg I/kg b.w.) on single nephron glomerular filtration rate (SNGFR) in the rat kidney were investigated using a micropuncture technique. Diatrizoate, iohexol, or ioxaglate did not change SNGFR, although a tendency towards a transient suppression was seen during the infusion phase. Iotrolan infusion, however, decreased SNGFR (p < 0.05) and the value still remained below the control value 25 min after the start of infusion. Iotrolan is a nonionic dimeric CM and has a lower osmotic effect in the tubules than the ionic dimeric CM and the monomeric CM when given in iodine equivalent doses. These characteristics of iotrolan have probably some influence on the depression of SNGFR after iotrolan injection.

Animals↗

Effects of ischaemic training on force development and fibre-type composition in human skeletal muscle.

Force (peak torque) of m. quadriceps femoris was measured during 60 repeated, voluntary dynamic knee extensions in 10 men before and after a 4-week training regimen of one-legged cycle exercise. Biopsies for histochemical analysis were obtained from the lateral vastus muscle after the training period. One leg was trained with the blood flow to the leg muscles reduced by local supra-atmospheric external pressure of 50 mmHg ('Ischaemic leg, I-leg'). Employing the same work-load profile the other leg was trained at normal atmospheric pressure ('Non-restricted-flow leg, N-leg'). In response to I-training, Maximum Peak Torqued (MPT; the highest torque produced in any contraction) and Initial Peak Torque (IPT; the average peak torque of the initial 12 contractions) decreased by 8% (P less than 0.01) and 9% (P less than 0.001), respectively. Final Peak Torque (FPT; the average peak torque of the final 12 contractions) increased by 13% (P less than 0.05) after I-training. No changes in MPT, IPT or FPT occurred following N-training. After training the proportion of slow-twitch fibres was higher (P less than 0.05) and the mean slow-twitch fibre area was larger (P less than 0.05) in the I-than in the N-trained leg. The results indicate that blood flow-restricted training, in contrast to non-restricted-flow training, decreases maximum voluntary dynamic force, possibly by inducing an increase in the share of the muscle cross-sectional area consisting of slow-twitch fibres. That flow-restricted training improves maintenance of force during short-term local exercise may reflect ischaemically induced changes in the metabolic characteristics of skeletal muscle.

Adult↗

Insulin sensitivity in alcoholics in a withdrawal state.

Insulin sensitivity in non-diabetic alcoholics in a withdrawal state was investigated using a euglycaemic clamp technique on two occasions with an interval of 1 week. Insulin was infused at a rate of 40 mU m-2 min-1 (n = 9) and 20 mU m-2 min-1 (n = 9). Hepatic glucose production was estimated with tritiated glucose in six subjects. The fasting glucose level at the first examination, 5.1 +/- 0.2 mmol l-1, exceeded that found at the second examination, 4.7 +/- 0.1 mmol l-1 (P less than 0.05), although the C-peptide concentration was higher at the first examination (2.7 +/- 0.3 vs. 1.6 +/- 0.2 ng ml-1; P less than 0.001). Both glucose uptake (5.0 +/- 0.6 vs 6.2 +/- 0.7 mg kg-1 min-1; P less than 0.05) and tissue sensitivity (M/I; 0.08 +/- 0.02 vs. 0.1 +/- 0.02 mg kg-1 min-1/mU l-1; P less than 0.05) increased between the first and second euglycaemic clamp (40 mU m-2 min-1). At the low insulin infusion rate (20 mU m-2 min-1), the tissue sensitivity to insulin increased (0.09 +/- 0.01 vs. 0.13 +/- 0.02 mg kg-1 min-1/mU l-1; P less than 0.05). Hepatic glucose production did not change during the examination period (2.2 +/- 0.2 vs. 2.3 +/- 0.1 mg kg-1 min-1), neither was there a change in the suppression of hepatic glucose output during hyperinsulinaemia (40 mU m-2 min-1). Our findings indicate that, in non-diabetic alcoholics, insulin sensitivity in peripheral tissues is decreased during the early part of a withdrawal period.

Adult↗

Influence of verapamil on regional renal blood flow: a study using multichannel laser-Doppler flowmetry.

In anaesthetized male Sprague-Dawley rats the influence of the calcium entry blocker verapamil (2.4 mg h-1 kg-1, i.v.) on renal superficial cortical (CO) and outer medullary (OM) blood flow was investigated with the aim of elucidating further the intrarenal heterogeneity in vasoreactivity. The blood flow of the two regions was monitored simultaneously with a laser-Doppler flowmeter, using fibre probes with an outer diameter of 0.75 mm. One probe was directed towards the cortex and a second probe was inserted through the cortex and positioned in the outer medulla, measuring the flow within a hemisphere with a depth of 0.5-1.0 mm. The OM probe position was verified by dissecting the kidneys after each experiment. Insertion of the OM probe did not affect whole-kidney glomerular filtration rate, renal plasma flow or electrolyte excretion. Thirty minutes of verapamil infusion increased OM blood flow by 26%, but did not change CO blood flow (-1%). In spite of the increase in OM blood flow, the urine osmolality remained unaltered. Sodium excretion increased by 39%, while potassium excretion was unchanged. Mean arterial blood pressure decreased by 13%. In conclusion, this study has further supported the suggestion that the vasoreactivity is higher in the juxtamedullary than in the superficial cortical vasculature. The heterogeneity of the response is most probably due to the previously documented pressure drop along the interlobular arteries, which will create different haemodynamic conditions for the juxtamedullary and superficial afferent arterioles.

Animals↗

Muscle oxidative capacity and work performance after training under local leg ischemia.

Healthy young men executed supine one-legged cycle training four times per week for 4 wk with legs and the cycle ergometer inside a pressure chamber, the opening of which was sealed by a rubber membrane at the level of the crotch. Each training session started by training one leg under ischemic conditions induced by increased chamber pressure (50 mmHg) at the highest intensity tolerable for 45 min. Then the other leg was trained with the same power profile but normal atmospheric chamber pressure. Before and after the training period, both legs executed one-legged exercise tests under both normal and increased chamber pressure and muscle biopsies were taken from the vastus lateralis. Ischemic training increased performance more than normal training, the difference being greater for exercise executed under ischemic conditions. The difference in performance increase between the legs was paralleled by a greater muscle citrate synthase activity in the ischemically than in the normally trained leg.

Adult↗

Clinical symptoms of sleep apnea syndrome and automobile accidents.

Patients with clinical features of sleep apnea syndrome (SAS) and self-reported sleep spells at the wheel do poorly in simulated monotonous driving. To evaluate whether drivers with defined symptoms of SAS (heavy snoring, sleep disturbances and daytime sleepiness) compensate in real traffic by careful driving or not, the rate of car accidents over a 5-year period was investigated. A questionnaire was addressed to 140 patients with and 142 controls without symptoms associated to SAS. Seventy-three of the patients had a complete triad of SAS-associated symptoms. Fifty-two percent of these patients reported habitual sleep spells at the wheel, as opposed to less than one percent by the controls. The ratio of drivers being involved in one or more combined-car accident was similar for patients and control drivers, but for single-car accidents the ratio was about 7 times higher for patients with a complete triad of symptoms of SAS compared to controls (p less than 0.001). When corrected for mileage driven, the total number of single-car accidents was almost 12 times higher among patients with sleep spells whilst driving, compared to controls (p less than 0.001). It is concluded that drivers with the clinical features of SAS are at increased risk especially for single-car accidents and that the risk seems to vary with the severity of symptoms.

Accidents, Traffic↗

Enhancement of human immunodeficiency virus (HIV) replication in human monocytes by low titres of anti-HIV antibodies in vitro.

Low concentrations of serum obtained from a patient with acquired immunodeficiency syndrome (AIDS) enhanced the replication of human immunodeficiency virus type 1 (HIV-1) in a particular subclone of the CD-4-positive monocytoid cell line U937 clone 2. Cells of this subclone have a high expression of Fc receptors and a considerable degree of Fc-mediated phagocytic activity. IgG purified from the serum was also able to enhance the replication. These results indicate that low concentrations of human anti-HIV antibody may enhance HIV replication on human monocyte-macrophages. Furthermore, two mouse IgG1 monoclonal antibodies against gp120, the envelope glycoprotein of HIV-1, also induced enhancement at low concentrations. The binding of radiolabelled gp120 to the cells was increased at the same low concentrations. Antibodies against envelope glycoproteins may cause enhancement of HIV infection. Both normal and enhanced replication of HIV were completely inhibited by the masking of the binding site of CD4 molecules with F(ab')2 fragments of anti-CD4 antibody. Moreover, CD4-positive, Fc gamma RI-negative K562 cells and mouse macrophages failed to show any infection in the presence of antibody. These results suggest that CD4 molecules on the cell surface are necessary to cause enhancement of infection of HIV on monocyte-macrophages.

Acquired Immunodeficiency Syndrome↗

The effect of glipizide on extraction of insulin by the human cirrhotic and noncirrhotic liver.

The effect of glipizide on hepatic uptake of insulin was studied in five patients with liver cirrhosis and five patients with varying diseases in the biliary system and pancreas. All patients had portal catheters for diagnostic purposes. The hepatic uptake of insulin was estimated from the clearance rate for insulin obtained after a constant rate infusion into a peripheral vein and the portal vein. Each patient was examined on two consecutive mornings, the second investigation carried out one hour after oral glipizide administration. The fractional hepatic uptake was significantly lower in cirrhotic patients (17% +/- 6%) than in the other patients (52% +/- 7%; P less than .01). After glipizide, an increase in the estimated uptake of insulin occurred in cirrhotic patients (from 17% +/- 6% to 39% +/- 6%; P less than .01), whereas an insignificant decrease was observed in the other patients (from 52% +/- 7% to 43% +/- 11%).

Adult↗