bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of a Physiological Insulin Infusion on the Cardiovascular Responses to a High Fat Meal: Evidence Supporting a Role for Insulin in Modulating Postprandial Cardiovascular Homoeostasis in Man
Authors: Kearney M. T. , Cowley A. J. , Stubbs T. A. , MacDonald I. A. 
Published: August 2015

1. While the haemodynamic adjustments occurring after meal ingestion and the different effects of meals of different composition on these changes are well established, the mechanisms underlying these changes are less clear. Insulin, which has been shown to be both a positive inotrope and to stimulate vasodilatation in the skeletal muscle vascular bed, may account for the different cardiac and regional haemodynamic responses to high fat and high carbohydrate meals.
2. This study assessed the effect of an insulin infusion reproducing the plasma insulin profile seen after a high carbohydrate meal on the cardiovascular and regional haemodynamic response to a high fat meal. All measurements were carried out non-invasively in nine healthy lean subjects (mean age 24.5 ± 1.3 years).
3. The high fat meal resulted in increases in cardiac output (0.7 ± 0.321/min, P &lt; 0.001), heart rate (7.8 ± 2.1 beats/min, P &lt; 0.001) and insulin (25.1 ± 4.2 m-units/l, P &lt; 0.001), and a decline in systemic vascular resistance (−1.9 ± 0.9 units, P &lt; 0.05) and superior mesenteric artery vascular resistance (− 45 ± 9 units, P &lt; 0.01). After the high fat meal alone, calf vascular resistance and blood pressure did not change. After the high fat meal accompanied by insulin (peak insulin 86.1 ± 10.1 m-units/l) there were greater cardiac responses [(P &lt; 0.001); cardiac output, 1.17 ± 0.361/min, and heart rate, 13.4 ± 2.1 beats-/min], and a larger fall in systemic vascular resistance and superior mesenteric artery vascular resistance. Unlike the high fat meal alone, the high fat meal with insulin was accompanied by a fall in calf vascular resistance (8.3 ± 3.3 units) and blood pressure (3.8 ± 1.6 mmHg).
4. The results of this study support a role for insulin in modulating postprandial cardiovascular homoeostasis; in particular, by its depressor action on skeletal muscle vasculature, insulin may in part contribute to the fall in blood pressure seen in the elderly, who have an inadequate cardiac response to the fall in systemic vascular resistance occurring after meal ingestion.
Effect of Sustained Inspiratory Loading on Respiratory Sensation and Co2 Responsiveness in Normal Humans
Authors: Clague J. E. , Carter J. , Pearson M. G. , Calverley P. M. A. 
Published: August 2015

1. To examine the effects of sustained resistive loading on the relationship between inspiratory effort sensation and respiratory drive (P0.1) and to determine if the change in CO2 responsiveness after sustained loading is accompanied by altered effort perception, hypercapnic responses were measured before, immediately after and 15 min after sustained resistive loading in seven subjects (six men, one woman). Sustained resistive loading was set to exceed a diaphragm tension—time index of 0.2.
2. Mean time to task failure during sustained loading was 17.7 min (range 12.5–22.5 min). The mean inspiratory effort sensation score rose from 3.4 (SEM 0.8) to 8.1 (0.8), whereas P0.1 fell from 29.5 (3.6) to 18.1 (3.6)cmH2O.
3. Immediately after loading the slopes of the ventilatory and sensory responses to CO2 fell (ventilatory response: before loading 16.7 (2.4)1 min−1 kPa−1, immediately after loading 7.88 (2.18) 1 min−1 kPa−1; sensory response: before loading 1.95 (0.38)units/kPa; immediately after loading 1.12 (0.38) units/kPa; P &lt; 0.05. Changes reverted to preloading levels by 15 min.
4. Sustained loading can lead to a dissociation between respiratory drive, as reflected by P0.1, and inspiratory effort sensation, and this disturbance can persist once the load is removed. Impaired sensory perception may be the primary determinant of the change in CO2 responsiveness seen after sustained resistive loading.
Normal Insulin Release during Sustained Hyperglycaemia in Hypokalaemic Periodic Paralysis: Role of the Potassium Channel Opener Pinacidil in Impaired Muscle Strength
Authors: Ligtenberg J. J. M. , Van Haeften T. W. , Van Der Kolk L. E. , Smit A. J. , Sluiter W. J. , Reitsma W. D. , Links T. P. 
Published: August 2015

1. Hypokalaemic periodic paralysis is characterized by attacks of muscle weakness. Glucose, insulin and an abnormal regulation of ATP-sensitive potassium channels may be involved in these attacks. We studied the effect of hyperglycaemia and of the potassium channel opener pinacidil on insulin release and muscle strength in patients with hypokalaemic periodic paralysis.
2. Insulin release was assessed on two occasions in four patients with hypokalaemic periodic paralysis and in eight matched control subjects, with and without treatment with 25 mg pinacidil orally, during a hyperglycaemic glucose clamp at a blood glucose level of 10 mmol/l, in a placebo-controlled, double-blind study. Muscle strength was measured in the hypokalaemic periodic paralysis patients before and during hyperglycaemia using a handheld dynamometer.
3. During the clamp, the mean glucose concentration (10–180 min) in control subjects was 9.9 ± 0.07 and 10.0 ± 0.03 mmol/l with and without pinacidil respectively, and in patients with hypokalaemic periodic paralysis was 10.0 ± 0.04 and 10.1 ± 0.06 mmol/l respectively (not significantly different). In both groups, the areas under the insulin curve from 0 to 10 min (first-phase insulin release) and from 30 to 180 min (second phase) were not different on the pinacidil study day compared with on the placebo day. The areas under the insulin curve of the first and second phases also did not differ between control subjects and patients with hypokalaemic periodic paralysis (with or without pinacidil). The M/I ratio, a measure of insulin sensitivity, was not different in the two groups. On the placebo day, baseline muscle strength in patients with hypokalaemic periodic paralysis was 165 ± 16 N for the hip abductors and 168 ± 19 N for the knee flexors. During the period of hyperglycaemia on the placebo day, muscle strength did not decrease in either muscle group. On the pinacidil study day, an increase in muscle strength was found only in the two hypokalaemic periodic paralysis patients with the lowest mean muscle strength (&lt;150 N) on the placebo day. The two hypokalaemic periodic paralysis patients with a mean muscle strength on the placebo day &gt;150N showed no increase in muscle strength with pinacidil.
4. Insulin secretion and sensitivity were normal in patients with hypokalaemic periodic paralysis. Hyperglycaemia during hyperglycaemic clamping did not provoke paralytic attacks and did not result in a decrease in muscle strength. The potassium channel opener pinacidil had no effect on insulin secretion in hypokalaemic periodic paralysis patients or in normal subjects. Pinacidil may enhance muscle strength in those hypokalaemic periodic paralysis patients who suffer partial paralytic attacks.
Plasma and Urinary 8-iso-Prostane as An Indicator of Lipid Peroxidation in Pre-Eclampsia and Normal Pregnancy
Authors: Barden Anne , Beilin Lawrence J. , Ritchie Jackie , Croft Kevin D. , Walters Barry N. , Michael Constantine A. 
Published: August 2015

1. This study was designed to seek evidence for excessive lipid peroxidation in pre-eclamptic women using 8-iso-prostane as a novel bioactive marker of lipid peroxidation in vivo. Plasma free, total and urinary 8-iso-prostane were measured in 20 women with proteinuric pre-eclampsia, and compared with 18 age- and gestation-matched pregnant control subjects, before delivery and at 6 weeks postpartum.
2. Plasma free 8-iso-prostane was significantly elevated in the pre-eclamptic women compared with control subjects before delivery, and fell to control levels post-partum. Conversely, levels in women with normal pregnancy rose post-partum
3. Total plasma 8-iso-prostane levels were not significantly elevated in pre-eclamptic women compared with control subjects during pregnancy, but fell significantly in the pre-eclamptic women postpartum, suggesting that they had relatively higher levels compared with their non-pregnant state.
4. Urinary 8-iso-prostane excretion was significantly lower in the pre-eclamptic women compared with control subjects during pregnancy, suggesting that renal clearance of 8-iso-prostane is impaired in pre-eclampsia.
5. Increased levels of plasma free 8-iso-prostane in pre-eclampsia could be due to an increase in lipid peroxidation, an increase in phospholipase A2 activity or a reduction in renal clearance of 8-iso-prostane, or a combination of all three. The potent direct and indirect vasoconstrictor actions of 8-iso-prostane may contribute to the pathogenesis of pre-eclampsia.
Vascular Hyporesponsiveness in Aortic Rings from Cirrhotic Rats: Role of Nitric Oxide and Endothelium
Authors: Oriíz M. Clara , Fortepiani Lourdes A. , Martínez Concha , Atucha Noemí M. , García-Estañ Joaquín 
Published: August 2015

1. The role of nitric oxide as mediator of the vascular alterations present in different models of experimental liver cirrhosis is controversial. In the present study, we evaluated the role of nitric oxide and that of the endothelium in the response to phenylephrine and acetylcholine of isolated aortic rings from chronic bile duct-ligated (29 days) rats and their corresponding controls. Experiments were performed in rings with or without endothelium, in rings pretreated with N-ω-nitro-l-arginine methyl ester (10−4 mol/l) to inhibit nitric oxide synthesis and in rings pretreated with aminoguanidine (10−4 mol/l) to inhibit inducible nitric oxide synthesis.
2. Under basal conditions, the maximum absolute tension developed in response to cumulative addition of phenylephrine was significantly decreased in rings from bile duct-ligated animals (1.62 ± 0.06 g) compared with the control rings (2.15 ± 0.099). This hyporesponsiveness to phenylephrine of rings from bile duct-ligated animals was corrected after treatment with N-ω-nitro-l-arginine methyl ester and reduced, but not completely eliminated, in rings without endothelium. In contrast, aminoguanidine did not modify the lower response to phenylephrine rings from bile duct-ligated animals. ED50 values were not different between groups under any experimental conditions.
3. The endothelium-dependent vasodilatation to acetylcholine in phenylephrine-constricted rings was similar in both groups of animals, control and bile duct ligated, under all experimental conditions. N-ω-nitro-l-arginine methyl ester pretreatment and removal of the endothelium completely abolished the response to acetylcholine in cirrhotic and control rings.
4. These results demonstrate that in aortic rings from cirrhotic, bile duct-ligated rats, increased production of nitric oxide, mainly of endothelial origin, is responsible for the lower contractile response to phenylephrine. Our data, however, do not support the involvement of the inducible nitric oxide synthase isoform in this alteration. In contrast, endothelial vasodilatory response to acetylcholine is not altered in this model of cirrhosis, which indicates that not all mechanisms of nitric oxide release are abnormal.
Elevated Plasma Levels of Human Adrenomedullin in Cardiovascular, Respiratory, Hepatic and Renal Disorders
Authors: Cheung Bernard , Leung Raymond 
Published: August 2015

1. Adrenomedullin is a potent vasodilating peptide first isolated from phaeochromocytoma and adrenal medulla but also found in the heart, lungs and kidneys. It may also be a paracrine factor because endothelial and smooth muscle cells synthesize adrenomedullin as well as express the receptors. Adrenomedullin induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of nitric oxide.
2. We have developed a specific radioimmunoassay and measured the immunoreactivity of human adrenomedullin in the plasma of 58 male subjects: eight with essential hypertension, 12 with heart failure, 10 with ascites due to cirrhosis, 12 with chronic renal failure, four with hypoxia due to chronic obstructive pulmonary disease and 12 control subjects.
3. Plasma levels (mean ± SEM) in patients with essential hypertension (16.3 ± 1.9 pmol/l), congestive heart failure (17.5 ± 2.8 pmol/l) and renal failure (17.7 ± 2.5 pmol/l) were raised compared with control subjects (7.8 ± 1.4 pmol/l, P &lt; 0.05), confirming previous reports.
4. In addition, we observed that plasma levels of adrenomedullin were significantly raised in patients with ascites due to liver cirrhosis (15.5 ± 1.9 pmol/l) and chronic obstructive pulmonary disease with hypoxia (20.0 ± 1.5 pmol/l).
5. We concluded that the plasma level of adrenomedullin is raised in a variety of diseases.
Comparative Bioactivity of Atrial and Brain Natriuretic Peptides in An Ovine Model of Heart Failure
Authors: Rademaker Miriam Tessa , Charles Christopher John , Espiner Eric Arnold , Frampton Christopher Miles , Nicholls Michael Gary , Richards Arthur Mark 
Published: August 2015

1. Whereas many studies have detailed the effects of exogenous atrial natriuretic peptide (ANP) infusions in heart failure, and a limited number have examined the effects of brain natriuretic peptide (BNP), none have directly compared the bioactivity of similar doses of ANP and BNP under standard conditions of impaired cardiac function. We compared the hormonal, haemodynamic and renal effects of 3 h infusions of ANP, BNP and a vehicle control in eight sheep with pacing-induced heart failure (225 beats/min for 8–12 days).
2. Infusion of ANP and BNP increased plasma ANP (P &lt; 0.001) (276 ± 27 versus control 142 ± 26 pmol/l) and BNP (P &lt; 0.001) (257 ± 34 versus control 45 ± 5 pmol/l) respectively, in association with increased cyclic 3′,5′-guanosine monophosphate [control, 40 ± 6; ANP, 53 ± 6 (P &lt; 0.05); BNP, 57 ± 7 nmol/l (P &lt; 0.001)]. Metabolic clearance rate and half-life were similar for both peptides. Infusion of ANP and BNP similarly reduced mean arterial pressure [control, 73.0 ± 1.6; ANP, 67.6 ± 1.2 (P &lt; 0.01); BNP, 65.7 ± 1.7 mmHg (P &lt; 0.001)], left atrial pressure (both P &lt; 0.05) (control, 22.0 ± 0.7; ANP, 19.9 ± 1.0; BNP, 19.8 ± 0.9 mmHg) and peripheral resistance [control, 50.3 ± 4.1 mmHg l−1 min−1; ANP, 46.0 ± 2.8 (P &lt; 0.05); BNP, 43.8 ± 4.5 (P &lt; 0.01)], and increased urine volume (2-3-fold, both P &lt; 0.05), sodium excretion (&gt; 10-fold, both P &lt; 0.01) and haematocrit levels relative to control (both P &lt; 0.05). Infused BNP tended to raise plasma ANP levels (by 28 pmol/l), while ANP increased plasma BNP (by 18 pmol/l). Plasma aldosterone was reduced by approximately 40% by both peptides (both P &lt; 0.05).
3. In conclusion, ANP and BNP are both powerfully natriuretic, similarly suppress aldosterone and appear equipotent in reducing preload and after-load in this model of pacing-induced heart failure.
Evidence that Nitric Oxide Inhibits Steroidogenesis in Cultured Rat Granulosa Cells
Authors: Dave Shilpa , Farrance David P. , Whitehead Saffron A. 
Published: August 2015

1. A few studies have shown that nitric oxide may exert cytotoxic and/or steroidogenic effects on cultured ovarian cells but the source of this factor within the ovary remains equivocal.
2. In this study we have investigated the effects of nitric oxide on progesterone secretion, cell viability and cell morphology of cultured rat granulosa/ lutein cells and examined whether granulosa cells are an important source of nitric oxide.
3. Only very low or undetectable levels of nitrites were measured in granulosa/lutein-cell-only cultures, although there was a small but significant increase in nitrite release observed in granulosa/lutein cells obtained from oestrous rats compared with those obtained from proestrous rats.
4. There was a concentration-dependent inhibition of progesterone synthesis in the presence of the nitric oxide donors sodium nitroprusside and S-nitroso-N-acetyl-penicillamine which corresponded with an increased concentration of nitrite accumulation in the culture medium.
5. High concentrations of nitrites were measured in the medium of granulosa/lutein cells co-cultured with peritoneal macrophages and progesterone synthesis was inhibited. This effect of the macrophages was partially reversed by inhibitors of nitric oxide synthesis, aminoguanidine, NG-methyl-l-arginine and NG-l-arginine-methyl-ester, and the reversal of inhibition was inversely proportional to the concentration of nitrites measured in the medium. Dose—response curves for the three drugs on the inhibition of nitrite accumulation in macrophage cultures were obtained.
6. The nitric oxide scavenger c-PTIO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide.potassium salt] partially reversed the effects of S-nitroso-N-acetyl-penicillamine and macrophages on progesterone synthesis in granulosa/ lutein cells.
7. With the exception of the high dose of sodium nitroprusside, there was no evidence that any of the drugs reduced cellular viability, as assessed by measurement of cellular dehydrogenases and Trypan Blue exclusion, although high concentrations of nitrite in the culture medium derived either from the nitric oxide donors or macrophages were associated with a loss of morphological luteinization. 8. Based on the available evidence, we suggest that nitric oxide can inhibit steroidogenesis and that in vivo the source of nitric oxide may be from macrophages, which invade the ovary during the periovulatory period, and/or from endothelial cells of ovarian blood vessels.
Could the A2A11 Human Leucocyte Antigen Locus Correlate with Maximal Aerobic Power?
Authors: Rodas GIL , Ercilla Guadalupe , Javierre Casimiro , Garrido Eduardo , Calvo MAR , Segura Ramon , Ventura Josep Li. 
Published: August 2015

1. The power of the aerobic metabolic pathway correlates well with successful physical performance in endurance sports events. The ability to alter the pathway through training presents well-known limitations, and consequently a good genetic endowment is essential to participate in elite sporting activities.
2. In 32 subjects (16 healthy pairs of male twin sportsmen, 8 monozygotic and 8 dizygotic) zygosity was determined by means of the genetic analysis of human leucocyte antigen (HLA) system specificities at class I and II loci and other genetic variants. The subjects performed a progressive exercise test on a treadmill to ascertain the maximal oxygen uptake (V̇O2max), measured by an automatic breath-by-breath analyser. We have considered the relationship between the A, B and C loci of the HLA system and V̇O2max.
3. We found a high correlation between the presence of both HLA A2 and All and V̇O2max. In the A2A11 group (n = 6) we found a V̇O2max (mean ± SD) equal to 71 ± 4 ml min−1 kg−1. The group without this pair of alleles (n = 26) showed a much lower aerobic power (58 ±5 ml min−1 kg−1). Differences between the two groups were found to be largely significant (P &lt; 0.001). It is noteworthy that in two pairs of dizygotic twins, the higher V̇O2max value corresponded to the twin with the A2A11 allele.
4. The very marked concordance between the presence of the A2A11 locus of the HLA system and the V̇O2max could be of great interest for the identification of outstanding performers.
Complementary and Non-Coincident Increases in Heart Rate Variability and Irregularity during Fetal Development
Authors: Fleisher Lee A. , Dipietro Janet A. , Johnson Timothy R. B. , Pincus Steven 
Published: August 2015

1. Two distinct notions of variability have been defined to assess heart rate: deviation from a constant output (SD) and irregularity. One statistical measure of irregularity is approximate entropy, with greater irregularity corresponding to larger approximate entropy values. The specific aims of this investigation were to determine the manner in which SD and irregularity evolve during fetal development and whether this evolution is coincident or distinct.
2. Fetal heart rate was computed in 14 males and 17 females for 15 min of undisturbed recording using a fetal actocardiograph at 4 week intervals from 20 to 36 weeks gestation.
3. Mean heart rate decreased significantly with gestational ages (P &lt; 0.05). SD increased significantly from 4.4+0.3 ms (SEM) at 20 weeks to 7.7±0.4 ms at 36 weeks (P &lt; 0.05) and was similar between male and female fetuses (P = 0.57). Fixed approximate entropy increased significantly from 0.47 ±0.04 to 0.78 ±0.03, paralleling the change in SD (P &lt; 0.01). Notably, normalized approximate entropy, which decorrelates SD from regularity, increased significantly with gestational age (P &lt; 0.01) for males, while it remained relatively constant for females (P = 0.68). Approximate entropy was significantly lower at 20 weeks in males than females (P &lt; 0.05); however, the values were similar by 28 weeks gestation.
4. Our results demonstrate that variability increases, and that irregularity increases, independently in male fetuses but not female fetuses, consistent with an increase in the coupling of emerging networks with gestational age. The present study demonstrates the complementary information obtained by analyses of both measures of variability and regularity. This reinforces a difference in gender-based development as noted in the separate context of fetal lung maturation.
Autonomic Nervous Function during Haemodialysis Assessed by Spectral Analysis of Heart-Rate Variability
Authors: Cavalcanti Silvio , Severi Stefano , Chiari Lorenzo , Avanzolini Guido , Enzmann Guido , Bianco Francesco , Panzetta Giovanni 
Published: August 2015

1. Short-term autonomic response to haemodialysis-induced hypovolaemia was studied in 30 patients undergoing chronic haemodialysis by analysing power spectra of heart-period variability. Patients were classified as haemodynamically stable (15 patients) and unstable (15 patients) according to their past history of cardiovascular collapse during the treatment. Blood volume, systolic arterial pressure and heart period were measured during sessions that ended without the occurrence of collapse.
2. No significant differences were observed when comparing blood volume, heart rate and arterial pressure of stable and unstable patients during the dialysis, and the two groups could not be distinguished merely on the basis of these haemodynamic parameters. Conversely, spectral analysis of beat-to-beat heart-period variability showed markedly different power patterns: in stable patients power was mainly in the low-frequency (LF) band (0.06–0.15 Hz), whereas in unstable patients it was mainly in the high-frequency (HF) band (0.15–0.4 Hz).
3. The efficiency of the autonomic response to hypovolaemia was evaluated by the ratio between the powers in the LF and HF bands. Stable patients exhibited an LF/HF power ratio systematically greater than unstable patients during the entire dialysis, and on the basis of this index the two groups were clearly separated.
4. Results obtained with spectral analysis lead us to conclude that reduced efficiency in the autonomic control of cardiovascular functions could be the main cause of the haemodynamic instability of patients prone to collapse.