bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Hypercholesterolaemia on Physiological Recruitment of Coronary Vascular Reserve in Swine
Authors: Bergelson Bruce A. , Yu Tse-Kuan , Ruocco Nicholas A.
Published: August 2015

1. The endothelium participates in the regulation of coronary vascular tone. As evidence exists from studies performed on epicardial vessels that hypercholesterolaemia impairs endothelial function, we tested the hypothesis that hypercholesterolaemia impairs coronary vascular reserve in an intact animal.

2. Domestic swine, maintained on a regular (n = 9) or a 2% high-cholesterol (n = 9) diet for 3 months were instrumented with a catheter in the left atrium for microsphere injection, a catheter in the anterior interventricular vein for venous sampling and an 82% stenosis in the left anterior descending artery. Papaverine was used to determine coronary vascular reserve. Regional coronary flow as reflected by perfusion (microsphere measurement), lactate consumption, oxygen consumption and haemodynamics were obtained at baseline, after 10 mg of papaverine and after atrial pacing at a rate of 120 beats/min and 150 beats/min.

3. Cholesterol was elevated in animals on the high cholesterol diet (350 ± 50 mg/dl versus 99 ± 10 mg/dl, P<0.001). Baseline haemodynamics were similar between groups. Baseline transmural flow and its augmentation with papaverine were comparable in the two groups in the control (circumflex) and stenosed (left anterior descending artery) zones. In both groups, perfusion increased in the control zone in response to increased oxygen demand, whereas in the stenosis zone no increase was observed in either group (P not significant for normal versus high cholesterol diet). Endocardial flow reserve in the stenosis zone was exhausted in both groups. Epicardial flow in the stenosis zone increased significantly in the normal (P<0.02) but not in the hypercholesterolaemic animals (P not significant).

4. The endocardial/epicardial ratio in the control zone at baseline revealed greater endocardial dominance in the normal compared with the hypercholesterolaemic animals (1.35 versus 1.10, P<0.01). With papaverine, similar ratios indicated a similar reserve potential in both groups. During increased oxygen demand, normal animals continued to demonstrate endocardial dominance whereas it diminished in the hypercholesterolaemic group. In the stenosis zone, endocardial blood flow dominated at baseline in the normal animals and to a lesser extent in the hypercholesterolaemic animals (1.30 versus 1.10, P = 0.10). During increased oxygen demand, endocardial dominance decreased significantly in both groups of animals; however, it remained greater than 1.0 only in the normal animals.

5. Exposure to elevated cholesterol levels did not impair an animal's ability to augment coronary blood flow in response to an increase in oxygen demand. In contrast to this lack of effect on recruitment of coronary reserve, regional coronary blood flow was altered in the hypercholesterolaemic animals.
Enhanced Phospholipase A2 Activity in Cultured Cardiomyocytes from Newborn Spontaneously Hypertensive Rat
Authors: Brussel Elisabeth Millanvoye-Van , Devynck Marie-Aude
Published: August 2015

1. Changes in membrane lipid composition and metabolism could participate in myocardial membrane dysfunction in essential or experimental hypertension. Phospholipid-bound fatty acid profile and metabolism are altered in cultured heart myocytes of newborn genetically hypertensive rats. The present study was designed to investigate the participation of phospholipase A2 in these modifications. 2. Phospholipase A2 activity of cultured cardiomyocytes of neonate spontaneously hypertensive rats and normotensive control Wistar—Kyoto rats was compared. The enzyme activity was measured using 2-[1-14C]arachidonyl-phosphatidylethanolamine as substrate. In both strains, Ca2+-dependent and independent phospholipase A2 activities were present. Only the Ca2+-dependent enzyme activity was altered in spontaneously hypertensive rat cardiomyocytes. With 0.2 mmol/l substrate and 5 mmol/l Ca2+, the phospholipase A2 activities were 79.0 ± 13.4 and 26.0 ± 3.6 nmol h−1 mg−1 of protein in spontaneously hypertensive and Wistar—Kyoto rat cardiomyocytes respectively (n = 10 in both cases, P = 0.001). The maximum velocity of the enzyme was three times higher in spontaneously hypertensive rat than in Wistar—Kyoto rat, without changes in the apparent affinity of the enzyme for its substrate.

3. The present results demonstrate an enhanced phospholipase A2 activity in cultured heart muscle cells of spontaneously hypertensive rats, which could be genetically determined.
Impact of Changes in Respiratory Frequency and Posture on Power Spectral Analysis of Heart Rate and Systolic Blood Pressure Variability in Normal Subjects and Patients with Heart Failure
Authors: Sanderson John E. , Yeung Leata Y. C. , Yeung Dickens T. K. , Kay Richard L. C. , Tomlinson Brian , Critchley J. A. J. H. , Woo Kam S. , Bernardi Luciano
Published: August 2015

1. Autonomic dysfunction is a major feature of congestive cardiac failure and may have an important role in determining progression and prognosis. The low-frequency/high-frequency ratio derived from power spectral analysis of heart rate variability has been proposed as a non-invasive method to assess sympatho-vagal balance. However, the effects of different respiratory rates or posture are rarely accounted for, but may be relevant in patients with heart failure in whom clinical improvement is accompanied by a fall in respiratory rate and an increased proportion of the day in the upright position.

2. We have assessed the effect of controlled respiration at different rates (10, 15, 20 breaths/min or 0.17, 0.25 and 0.33 Hz), while supine and standing, on power spectral analysis of heart rate and blood pressure variability in 11 patients with heart failure and 10 normal subjects.

3. Heart rate variance and low-frequency power (normalized units) were reduced in patients with heart failure (absent in six). During controlled breathing while supine, the power of the high-frequency component was significantly greater at 10 breaths/min than at 20 breaths/min in patients with heart failure, whether expressed in absolute units (P = 0.005) or percentage of total power (P = 0.03).

4. On standing, controlled breathing in patients with heart failure produced less change in high-frequency power (P = 0.054), but the low-frequency/high-frequency ratio at lower respiratory rates was reduced (P = 0.05). In normal subjects, as expected, respiratory rate had a highly significant effect on high-frequency power. Also, in normal subjects there was the expected increase in heart rate low-frequency power (P = 0.04) moving from supine to standing with an increase in the low-frequency/high-frequency ratio (P = 0.003), while in the patients with heart failure this was absent, reflecting blunted cardiovascular reflexes.

5. Systolic blood pressure low- and high-frequency components and their ratio were significantly affected by respiration (P > 0.03) and change in posture (P > 0.03) in both patients with heart failure and normal subjects, with a significant increase in the low-frequency/high-frequency ratio (P = 0.03) on standing in patients with heart failure, indicating that autonomic modulation of blood pressure is still operating in heart failure.

6. Thus, respiratory rate and changes in posture have a significant effect on measurements derived from spectral analysis of heart rate and blood pressure variability. Studies that use power spectral analysis as a measure of sympatho-vagal balance should control for these variables.
Serological Response to Helicobacter Pylori in Gastric and Non—Gastric Cancer
Authors: Menegatti Marcello , Vaira Dino , Holton John , Miranda Fernanda , Ricci Chiara , Gusmaroli Riccardo , Ainley Colin , Miglioli Mario , Barbara Luigi
Published: August 2015

1. We aimed to evaluate the seroprevalence of Helicobacter pylori (H. pylori) in gastric cancer, non-gastric cancer and outpatients by ELISA and isoelectric focusing, and to compare histology and serology for H. pylori in gastric cancer and outpatients.

2. In 124 patients with gastric cancer, 78 patients with non-gastric cancer and 110 outpatients, H. pylori seroprevalence was assessed by ELISA and isoelectric focusing. Gastric cancer and outpatients underwent endoscopy with biopsies.

3. Seroprevalence by ELISA was significantly higher in gastric cancer compared with non-gastric cancer (84% versus 56%, P < 0.001) but not with outpatients (84% versus 74%). Iso-electric focusing detection of H. pylori was comparable to ELISA: 85, 51 and 75% in gastric cancer, non-gastric cancer and outpatients respectively. Oligoclonal iso-electric focusing was significantly more frequent in gastric cancer compared with non-gastric cancer and outpatients: 69% versus 45 and 46% respectively, P < 0.01. The reliability of H. pylori detection by antral biopsy was significantly lower in gastric cancer compared with outpatients: 36% versus 74% (P < 0.001). In gastric cancer, ELISA and iso-electric focusing were significantly more reliable than histology in H. pylori detection (84 and 85% versus 36% respectively) (P < 0.001).

4. Serological immune response to H. pylori in gastric cancer, non-gastric cancer and outpatients seems different both quantitatively and qualitatively; serology was more reliable than histology in detection of H. pylori in gastric cancer.
Mitochondrial Protein Content and in Vivo Synthesis Rates in Skeletal Muscle from Critically Ill Rats
Authors: Rooyackers Olav E. , Kersten Alexande R H. , Wagenmakers Anton J. M.
Published: August 2015

1. Recently we reported decreased activities of two mitochondrial marker enzymes (citrate synthase and cytochrome c oxidase) in skeletal muscle from a rat model of critical illness (zymosan injection). In the present study we investigated (i) whether these decreases in enzyme activity reflect a reduction in mitochondrial content and (ii) whether this potential reduction in mitochondrial content was the result of decreased mitochondrial protein synthesis rates.

2. Mitochondrial protein content was calculated from the activities of cytochrome c oxidase in whole-muscle homogenates and purified mitochondria. Synthesis rates of mitochondrial protein in vivo were studied by measuring the incorporation of [3H]phenylalanine into mitochondrial protein using the flooding dose technique.

3. Mitochondrial protein content was reduced to 54% of that measured in the pair-fed rats and to 71% of that measured in control rats fed ad libitum 2 days after the zymosan treatment The decreased mitochondrial protein content observed 2 days after zymosan challenge was preceded by a reduced rate of synthesis of mitochondrial protein 16 h after treatment. Both changes were of greater magnitude than the general muscle wasting and the decreased rate of synthesis of mixed protein observed in the zymosan-treated rats.

4. We conclude that the acute phase of critical illness in zymosan-treated rats is characterized by a substantial reduction in muscle mitochondria that is at least in part caused by a decreased rate of synthesis of mitochondrial protein. This derangement in mitochondrial protein metabolism may be related to the impaired muscle function observed during and after critical illness.
Chronic Sodium-Potassium-ATPase Inhibition with Ouabain Impairs Renal Haemodynamics and Pressure Natriuresis in the Rat
Authors: Kurashina Toshiaki , Kirchner Kent A. , Granger Joey P. , Patel Ami R.
Published: August 2015

1. Chronic Na+,K+-ATPase inhibition with ouabain induces hypertension in the rat. To examine the role of the kidney in this process, the effect of changes in renal perfusion pressure on glomerular filtration rate, renal blood flow and urinary sodium excretion were determined in rats treated intraperitoneally with ouabain (27.8 μg day−1 kg−1 body weight) or vehicle for 6 weeks.

2. After ouabain administration, baseline mean arterial pressure was significantly higher (P < 0.05) in ouabain-treated rats (151 ± 2 mmHg; n = 9) than in control rats (116 ± 4 mmHg; n = 8).

3. At equivalent renal perfusion pressures, glomerular filtration rate was significantly lower (P < 0.05) in ouabain-treated rats compared with control rats. Glomerular filtration rate was 721 ± 73μl/min at 150 mmHg, and fell significantly to 322 ± 64 μl/min at 100 mmHg. In the control group, glomerular filtration rate was well autoregulated. The glomerular filtration rate autoregulatory index was calculated to determine the ability to maintain glomerular filtration rate during changes in renal perfusion pressure (0 reflects perfect autoregulation; >1 reflects the absence of autoregulation). This index was greater in the ouabain group than in the control group (1.54 ± 0.2 compared with 0.29 ± 0.2; P < 0.05). Renal blood flow showed a similar pattern.

4. Absolute urinary sodium excretion rate was less in ouabain-treated rats than in control rats at equivalent renal perfusion pressures. The slope of the relationship between absolute urinary sodium excretion rate and renal perfusion pressure was greater (P < 0.05) in the control group than in the ouabain group (309.1 ± 57.1 compared with 82.1 ± 14.8 μmol min−1 mmHg−1).

5. Thus, chronic inhibition of Na+,K+-ATPase induces less efficient autoregulation of glomerular filtration rate and renal blood flow as well as a rightward shift in the pressure natriuresis relationship, such that a 25–30 mmHg higher renal perfusion pressure is necessary to excrete any given sodium load. These abnormalities may contribute to the development and maintenance of hypertension in this model.
Plasma Arachidonic Acid-Rich Phospholipids in Crohn's Disease: Response to Treatment
Authors: Pereira Stephen P. , Cassell Theresa B. , Engelman Jeffrey L , Sladen Gordon E. , Murphy Gerard M. , Dowling R. Hermon
Published: August 2015

1. Increased concentrations of plasma polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease. However, it is not known whether there are corresponding changes in circulating phospholipids - the major source of fatty acids in the plasma.

2. Fasting plasma samples were obtained from 17 control subjects and 13 patients with active Crohn's disease [Simple Index of Crohn's Disease Activity (SICDA) >6] before, and 2 and 8 weeks after, treatment with either a peptide diet or oral prednisolone.

3. Before treatment, the Crohn's disease patients had mildly active disease (SICDA 9.9 ± 0.8, erythrocyte sedimentation rate 26.4 ± 6.5 mm/h, serum C-reactive protein 2.8 ± 0.4 mg/l). The proportions of the polyunsaturated phosphatidylcholine species, 16:0–20:4 (10.0 ± 0.7%) and 16:0–22:6 (7.1 ± 0.8%), were both significantly higher than those in healthy controls (7.6 ± 0.5%, P < 0.01 and 5.3 ± 0.5%, P < 0.05 respectively).

4. After 2 weeks treatment, the SICDA in the Crohn's disease patients decreased to 3.2 ± 0.6 (P < 0.0001 compared with the pretreatment value), and there were corresponding falls in the erythrocyte sedimentation rate (to 12.6 ± 2.7 mm/h, P < 0.05) and C-reactive protein concentration (to 1.7 ± 0.3 mg/l, P < 0.05)—these improvements being maintained at 8 weeks. There was also a fall to normal values in 16:0–20:4 (to 7.7 ± 0.6%, P < 0.01 compared with the pretreatment value) and in 16:0–22:6 (to 5.7 ± 0.5%, P not significant), by week 8.

5. The proportions of polyunsaturated phosphatidylcholine molecular species were increased in the plasma of patients with active Crohn's disease, but fell to normal levels during disease remission. These observations are consistent with the theory that, in active Crohn's disease, the mucosal phospholipids containing polyunsaturated fatty acids are increased, contribute to eicosanoid synthesis and ‘spill’ into the plasma.
Recovery of 13CO2 and 14CO2 in Human Bicarbonate Studies: A Critical Review with Original Data
Authors: Leijssen D. P. C. , Elia M.
Published: August 2015

1. In order to establish biological and/or methodological explanations for the wide variability in recovery (50–100%) of labelled CO2 after administration of [13C]bicarbonate or [14C]bicarbonate, 34 human bicarbonate studies involving 480 subjects were analysed, and potential methodological issues were investigated in the laboratory.

2. Overall, continuous infusion studies reported a higher recovery than bolus studies (84 ± 11% versus 69 ± 12%; P < 0.001). No significant differences in recovery were found between 14C and 13C studies, children and adults, obese and lean subjects, or rest and exercise (steady state). Higher recoveries were found during feeding than during fasting (84 ± 8% versus 74 ± 7%; P < 0.001). Different methods used to analyse the results (0–10%) and different study protocols, which include differences in the duration of infusions and background drift in 13C enrichment (0–10%), contribute to the variability.

3. The laboratory studies suggest multiple sources of potential error, including loss of CO2 from the scintillation fluid (up to >30%, but only in 14C studies in which the scintillation fluid is not alkalized), diffusion of CO2 through syringes and tubing (0 to > 10%), non-linearity of CO2 analysers (up to 8%), inaccuracies in the measurement of bicarbonate concentrations (13C studies) or the strength of CO2-trapping agents (14C studies; 0–8%).

4. It is concluded that much of the variability in the recovery of labelled bicarbonate is likely to be attributable to methodological differences, and that attention to these will ensure better interpretation of metabolic studies that involve oxidation of carbon-labelled substrates.
Subcutaneous Abdominal Adipose Tissue Blood Flow: Variation within and between Subjects and Relationship to Obesity
Authors: Summers Lucinda K. M. , Samra Jaswinder S. , Humphreys Sandy M. , Morris Richard J. , Frayn Keith N.
Published: August 2015

1. We assessed the variation in subcutaneous abdominal adipose tissue blood flow within and between subjects and investigated whether it is correlated with body mass index.

2. We measured body mass index and subcutaneous abdominal adipose tissue blood flow in 38 fasting subjects on the same day and on different days and, in a subgroup of 16 subjects, after a mixed meal.

3. In 190 measurements in the fasted state, subcutaneous abdominal adipose tissue blood flow was significantly more variable between subjects than could be accounted for by the within-subject variation alone. Subcutaneous abdominal adipose tissue blood flow was also significantly more variable between days within subjects than could be accounted for by within-day variation alone. Fasting and post-prandial subcutaneous abdominal adipose tissue blood flow were negatively correlated with body mass index, as was the post-prandial rise in subcutaneous abdominal adipose tissue blood flow. Multiple regression analysis showed that fasting blood flow was not dependent on insulin concentration after allowing for body mass index. There was no correlation between post-prandial subcutaneous abdominal adipose tissue blood flow and insulin concentration.

4. Insulin does not appear to have a direct vasodilatory effect in subcutaneous adipose tissue. Obese subjects have lower fasting and post-prandial subcutaneous abdominal adipose tissue blood flow. This may be because of a blunted response to sympathetic stimulation, or it may be another aspect of the insulin-resistant state.
Small Artery Structural Alterations of Patients with Microvascular Angina (Syndrome X)
Authors: Bund S. J. , Tweddel A. , Hutton I. , Heagerty A. M.
Published: August 2015

1. There is increasing evidence that a substantial number of patients who suffer from angina have normal epicardial arteries (Syndrome X), and it has been suggested that these individuals have a generalized disorder of small vessels not confined to the intramyocardial vasculature.

2. Small arteries were therefore obtained from biopsies of skin and subcutaneous fat from nine normotensive patients with Syndrome X and nine matched control subjects. Vessels were dissected and mounted as ring preparations in a myograph for morphological and functional assessment.

3. Morphological measurements revealed a significant increase in media thickness/lumen diameter ratio in arteries from patients with Syndrome X. Contractile responses to U46619 were similar in arteries from patients and control subjects. Endothelium-dependent relaxation induced with acetylcholine and bradykinin was greater in arteries from patients although differences were not statistically significant. Endothelium-independent relaxation induced by forskolin and sodium nitroprusside was not different.

4. In conclusion, these data demonstrate that subcutaneous small arteries from patients with Syndrome X are characterized by increased media thickness/lumen diameter ratios, although contractile responses were normal. Additionally, endothelium-dependent relaxation was not impaired in arteries from these patients. Thus, no significant functional abnormalities were associated with the observed structural differences.
Assessment of Postural Differences in Regional Pulmonary Perfusion in Man by Single-Photon Emission Computerized Tomography
Authors: Ross David J. , Wu Pearl , Mohsenifar Zab
Published: August 2015

1. With the advent of single-photon emission computerized tomography, controversy has arisen with regard to the significance of gravitational influences on regional pulmonary perfusion (Q̊r) in the supine versus prone postures. We investigated the dorsal—ventral distributions of Q̊r in prone (n = 5) and supine (n = 5) normal subjects, as assessed by single-photon emission computerized tomography after intravenous injection of technetium-99m-labelled macroaggregated albumin at end-tidal expiration. Reconstructed serial (one pixel thickness) coronal sections were traced on a computer screen, to yield the encompassed radioactive counts and number of pixels per each image. Coronal section data (expressed as mean radioactive counts/pixel) were expressed in a ‘profile’ and normalized to the maximum coronal section of each lung (%maximum).

2. Coefficients of variation and linear regression slopes for the prone versus supine profiles for left and right lungs were not statistically different (unpaired Student's t-test). The coronal section with maximum Q̊r was identified in the more dependent lung regions and, hence, affected by gravity.

3. We conclude that, in contrast to previous canine models, which have suggested postural differences in dorsal-ventral perfusion gradients, in normal man gravity primarily determines the non-dependent to dependent distribution of Q̊r. We speculate that interspecies differences in physiology may be teleological and related to the different perfusion demands of the quadruped compared with upright man.
Plasma RRR-α-tocopherol Concentrations Are Lower in Smokers Than in Non-Smokers after Ingestion of a Similar Oral Load of this Antioxidant Vitamin
Authors: Munro Lisa H. , Burton Graham , Kelly Frank J.
Published: August 2015

1. Using deuterium-labelled α-tocopherol (vitamin E), the plasma kinetics of α-tocopherol derived from supplemental RRR-α-tocopherol and RRR-α-tocopheryl acetate were determined in asymptomatic individuals who smoke and, for comparison, in a group of healthy non-smokers.

2. Venous blood samples were withdrawn 6, 12 and 27 h after the oral administration of a gelatin capsule containing an equimolar mixture of RRR-α-tocopherol and RRR-α-tocopheryl acetate. Plasma concentrations of endogenous and administered forms of α-tocopherol were determined by a combination of HPLC and GC-MS.

3. Both the free phenol and the acetate ester concentrations of α-tocopherol were lower in smokers than in non-smokers: 0.99 versus 1.60 (P < 0.05) and 0.66 versus 1.49 (P < 0.05) μmol/mmol cholesterol for RRR-α-tocopherol and RRR-α-tocopheryl acetate respectively. The highest concentation of α-tocopherol derived from administered RRR-α-tocopherol and its acetate ester were observed in plasma at 12 h (compared with 6-h and 27-h measurements) in most subjects.

4. Although the two forms of α-tocopherol were administered in equal doses, plasma from smokers contained significantly higher concentrations of RRR-α-tocopherol derived from the free phenol form than from the acetate form (0.99 versus 0.66 μmol/mmol cholesterol, P < 0.05, 12 h). Non-smokers did not exhibit preferential uptake of either form of vitamin E.

5. These results suggest that individuals who smoke have either a reduced ability to absorb α-tocopherol, particularly when it is presented as the acetate ester, or increased clearance of newly absorbed α-tocopherol compared with non-smokers.
Dietary Fish Oil Reduces Survival and Impairs Bacterial Clearance in C3H/Hen Mice Challenged with Listeria Monocytogenes
Authors: Fritsche K. L. , Shahbazian L. M. , Feng C. , Berg J. N.
Published: August 2015

1. To investigate the effect of dietary fat source on host resistance to intracellular pathogens, weanling female C3H/Hen mice were fed one of three experimental diets containing, 20% by weight, lard, soybean oil or 17% menhaden fish oil plus 3% corn oil. After 4 weeks, survival of mice (n = 12/treatment group) injected intraperitoneally with 2 × 106 colony forming units of live Listeria monocytogenes was determined. In a second study, bacterial clearance from the liver and spleen at 2, 4 and 7 days post-challenge was determined (n = 8/treatment group).

2. We found that the survival of mice fed the diets with soybean oil or menhaden fish oil was significantly lower than those fed lard (P < 0.05). Survival rates were 58% (7/12), 33% (4/12) and 100% (12/12), respectively, for mice fed soybean oil, menhaden fish oil and lard. In the second study, mice fed menhaden fish oil had approximately 1 login greater bacteria in their spleens at day 4 than mice fed lard or soybean oil (P < 0.001). There were no significant treatment differences in the number of bacteria recovered from liver samples.

3. In summary, dietary fat source significantly affects murine resistance to Listeria, with diets rich in n-3 polyunsaturated fatty acids, such as from fish oil, having the most detrimental effect.
Isometric Contraction of Arm Flexor Muscles as a Method of Evaluating Cardiac Vagal Tone in Man
Authors: Al-Ani M. , Robins K. , Al-Khalidi A. H. , Vaile J. , Townend J. , Coote J. H.
Published: August 2015

1. We have previously shown that brief voluntary isometric contractions of upper arm flexor muscles performed for one respiratory cycle elicit a significant decrease in the R—R interval. The present study was designed to determine if similar changes are produced by non-voluntary electrically evoked contractions and, if so, to establish the consistency and repeatability of the associated changes in the R—R interval.

2. The heart rate (R—R interval) response to voluntary or non-voluntary brief isometric contraction equivalent to 40% of the maximum voluntary contraction was studied in 10 healthy young male subjects during controlled ventilation at supine rest.

3. The absolute values of R—R intervals occurring in any one of 10 arbitrary phases of a respiratory cycle were measured and plotted by a computer.

4. Both voluntary and non-voluntary contractions elicited similar changes in heart rate and R—R interval, which were greater during expiration than during inspiration.

5. This confirms our previous finding that the magnitude of the R—R interval changes, with brief isometric contraction, is positively related to the degree of cardiac vagal tone.

6. Analysis of the variability between repeated tests initiated in either inspiration or expiration revealed that there was significantly less variability with the electrically induced contraction.

7. It was concluded that electrically induced contractions of 40% maximal voluntary contraction are a viable alternative to voluntary contractions and provide a more controllable means of measuring cardiac vagal withdrawal.
An Analysis of Arterial Disease Mortality and BUPA Health Screening Data in Men, in Relation to Outdoor Temperature
Authors: Donaldson G. C. , Robinson D. , Allaway S. L.
Published: August 2015

1. Laboratory studies have shown that cold exposure causes an increase in blood pressure, cholesterol and erythrocyte count. However, whether the mild cold exposures received during everyday life are sufficient to cause such changes is unclear.

2. To test this, outdoor temperatures in central London between 1986 and 1992 were related to both haematological and blood pressure data on 50–69-year-old men attending BUPA health screening examinations in London, and to mortality in South-East England. Since any association with temperature may be an artifact due to common, temperature-independent, annual rhythms in the parameters, these data were also analysed after removal of these circannual components by digital filtering.

3. It was found that short-term falls in temperature produced significant increases in Hb, erythrocyte count, packed cell volume, mean corpuscular Hb concentration, serum albumin, systolic and diastolic blood pressure, and significant decreases in mean corpuscular volume and erythrocyte sedimentation rate. Mean corpuscular Hb, leucocyte count, platelet count and serum cholesterol concentrations were unchanged. Time-series analysis showed that these changes occurred almost immediately in response to a fall in temperature, but persisted for longer intervals of up to 1–2 days.

4. Mortalities from ischaemic heart disease and cerebrovascular disease were also significantly increased by short-term falls in temperature.

5. These findings indicate that in the general population the cold exposures of normal life are sufficient to induce significant and prolonged haemoconcentration and hypertension, which may explain why deaths from arterial disease are more prevalent in the winter.
Comparison between Reproducibility and Sensitivity of Muscle Sympathetic Nerve Traffic and Plasma Noradrenaline in Man
Authors: Grassi Guido , Bolla Giambattista , Seravalle Gino , Turri Carlo , Lanfranchi Antonio , Mancia Giuseppe
Published: August 2015

1. Although plasma noradrenaline and muscle sympathetic nerve traffic have been shown to be suitable markers of sympathetic activity in man, no study has systematically compared the reproducibility and sensitivity of these two indices of adrenergic tone.

2. Reproducibility data were collected in 10 subjects, in whom plasma noradrenaline was assessed by HPLC on blood samples withdrawn from an antecubital vein and efferent postganglionic muscle sympathetic nerve activity was measured by microneurography from a peroneal nerve, together with arterial blood pressure (Finapres technique). Measurements were obtained in a first session (session 1), 60 min later (session 2) and after 14 days (session 3). While muscle sympathetic nerve activity values recorded in the three different experimental sessions were closely and significantly correlated with each other (r always >0.90, P < 0.001), noradrenaline showed a less significant correlation between sessions 1 and 2 (r = 0.71, P < 0.05) or no correlation between sessions 1 and 3 (r = 0.45, P not significant).

3. Sensitivity data were collected by evaluating muscle sympathetic nerve activity and noradrenaline values in three different age groups (young, middle-age and old subjects, n = 18), in three groups with different blood pressures (normotensive, mild and severe hypertensive subjects, n = 30) and in a group of eight subjects before and after a physical training programme, i.e. conditions known to increase or reduce sympathetic cardiovascular drive. Muscle sympathetic nerve activity was significantly increased by aging and hypertension, and reduced by physical training. The noradrenaline changes were much less marked and consistent.

4. These data suggest that muscle sympathetic nerve activity has a greater short- and medium-term reproducibility than noradrenaline. In several conditions known to modify sympathetic cardiovascular drive muscle sympathetic nerve activity also appears to change more clearly than noradrenaline.
Effect of High-Dose Chemotherapy on Intestinal Permeability in Humans
Authors: Keefe D. M. K. , Cummins A. G. , Dale B. M. , Kotasek D. , Robb T. A. , Sage R. E.
Published: August 2015

1. Mucositis is a common side-effect of chemotherapy which is difficult to assess except by invasive means such as upper gastrointestinal endoscopy. Differential absorption of mono- and di-saccharides, such as rhamnose and lactulose, is a non-invasive measure of intestinal damage.

2. The purpose of the study was to assess the duration and severity of intestinal damage in patients undergoing high-dose chemotherapy and autologous blood stem-cell transplantation for malignant disease.

3. Thirty-five patients were studied before treatment and at 7, 28, 60 and 90 days after treatment.

4. The median lactulose/rhamnose ratios before treatment and at 7 and 90 days post-treatment were 0.09, 0.62 and 0.06 respectively. Altered permeability was due to both increased lactulose permeation and decreased rhamnose absorption. These abnormalities suggest a defect in tight-junction integrity as well as a decrease in surface area of small bowel.

5. We conclude that chemotherapy given for malignant disease is associated with a transient abnormality in intestinal sugar permeability, which peaks at 7 days after treatment and is composed of both mono- and di-saccharide absorption abnormalities.
Effects of Ordinary Meals on Plasma Concentrations of 3,4-Dihydroxyphenylalanine, Dopamine Sulphate and 3,4-Dihydroxyphenylacetic Acid
Authors: Eldrup Ebbe , Møller Svend Erik , Andreasen JAN , Christensen Niels Juel
Published: August 2015

1. Plasma concentrations of 3,4-dihydroxyphenylalanine (DOPA), dopamine sulphate (DA-S), and 3,4-dihydroxyphenylacetic acid (DOPAC) in humans have been claimed to be indexes of sympathetic nervous activity, but the source and significance of plasma DOPA, DOPAC and DA-S have not been completely elucidated.

2. The effects of ordinary meals on plasma concentrations of total dopamine, mainly DA-S, DOPAC and DOPA were studied in seven healthy subjects. Venous blood was collected every hour for 25 h, while subjects were either fasting or received three meals at 9.00 hours, 13.00 hours and 18.00 hours. Catecholamines and metabolites were determined by reverse-phase HPLC with electrochemical detection. Neutral amino acids were measured by ionexchange chromatography with photometric detection.

3. The food contained relatively little DOPA as compared with phenylalanine, tyrosine, isoleucine and tryptophan. The content of DA and DA-S varied considerably, with the greatest amount in the evening meal of open sandwiches.

4. Plasma DOPA decreased significantly after the meals at 13.00 hours and 18.00 hours, whereas concentrations of the other amino acids increased as expected.

5. Plasma DA-S increased significantly after meals and especially after the evening meal. Increments in DA-S above basal values after a meal were closely related to the content of DOPA+DA+DA-S in the meal. Plasma DOPAC increased significantly after the evening meal.

6. The decrease in plasma DOPA observed after a meal was probably due to uptake of DOPA by muscle tissue. Changes in plasma DA-S and DOPAC during this 25-h study reflected to a large extent the content of DOPA, DA and DA-S in the meals.
Maternal Serum Vascular Endothelial Growth Factor during Early Pregnancy
Authors: Evans Phylip , Wheeler Timothy , Anthony Frederick , Osmond Clive
Published: August 2015

1. The objectives of the study were: (i) to investigate the serum concentrations of vascular endothelial growth factor (VEGF) in pregnant and non-pregnant women; and (ii) to study the relationship between the levels of maternal serum VEGF and the serum concentrations of human chorionic gonadotrophin (hCG) and progesterone during the first trimester.

2. Total immunoreactive VEGF was measured by competitive RIA using recombinant human VEGF165 and a polyclonal antiserum. Serum VEGF was measured in 60 non-pregnant women of child-bearing age. These data were compared with serum VEGF measured in 363 women between 41 and 91 days of gestation.

3. The median serum VEGF concentration was 1.10 μg/l (interquartile range 0.91–1.30) in the nonpregnant women and 2.13 μg/l (interquartile range 1.62–2.77) in the pregnant women. Serum levels of VEGF were significantly higher among the pregnant cohort (P < 0.0001). Serum VEGF concentration was positively correlated with gestational age, increasing until ten completed weeks of pregnancy. Serum VEGF was negatively correlated with maternal height and weight, and positively correlated with serum hCG and serum progesterone (P ≤ 0.0001 in all cases). Serum VEGF was lower in the pregnant women who smoked (P = 0.06).

4. Our data show a positive and highly significant correlation between maternal serum levels of VEGF and hormones reflecting placental function (hCG, progesterone). We speculate that VEGF production is increased by progesterone and hCG, and that VEGF has a positive influence on trophoblast development. VEGF may also be involved in the initiation of the maternal cardiovascular adaptation to pregnancy.
Changes in Pulmonary Venous Return during Head-up Tilting in Man
Authors: Guazzi Marco , Tamborini Gloria , Maltagliati Anna
Published: August 2015

1. In a supine position, the heart fills to close to the limits of pericardial constraint and the pericardium may act to redistribute central blood volume from the left side of the heart back to the more compliant lung.

2. We probed whether, and through which mechanisms, a redistribution of blood from the lungs to the left heart occurs during vertical displacement and compensates for reduced venous return.

3. We investigated 16 normal volunteers with Doppler-echocardiography during 20°, 40° and 60° head-up tilting. Tilting was stopped at 10 min in 10 subjects (group 1) and at 45 min in 6 subjects (group 2).

4. At 10 min we observed a reduction in right ventricular diastolic dimension and left ventricular end-diastolic pressure, as estimated by the difference between the duration of the pulmonary venous flow during atrial contraction (Z wave) and that of the mitral A wave. We also recorded a decrease during systole (X wave) and an increase during diastole (Y wave) of the pulmonary venous forward flow velocity. These variations were evident at 20° and became progressively greater with increasing degrees of tilting. In group 2, changes at 10 min and at 45 min for any degree of displacement were similar.

5. A decrease in right ventricular dimensions (ventricular interdependence) and underfilling of the lung compartment due to volume redistribution to the periphery (diminished lung contribution to pericardial constraint) augment compliance within the pericardial space, reduce downstream pressure for pulmonary venous return and move the pulmonary venous flow predominantly to ventricular diastole, allowing diastolic filling.

6. During head-up tilting a favourable interaction between heart and lungs increases compliance within the pericardial space and facilitates redistribution of blood from the lungs, resulting in a sustained compensation for the reduced venous return.
Seasonal Variations in Cyclic GMP Response on Whole-Body Cooling in Women with Primary Raynaud's Phenomenon
Authors: Leppert Jerzy , Ringqvist Åsa , Ahlner Johan , Myrdal Urban , Walker-Engström Marie-Louise , Wennmalm Åke , Ringqvist Ivar
Published: August 2015

1. Primary Raynaud's phenomenon (PRP) is characterized by increased vasoconstrictor tone that develops during exposure to cold. The symptoms are most pronounced during the winter months with low outdoor temperature. The l-arginine—nitric oxide (NO)—cyclic GMP (cGMP) pathway plays an important role in counteracting vasospasm. The aim of the present study was to investigate if the venous cGMP response to whole-body cooling in women with PRP varied with the season of the year.

2. The study was performed as an open parallel-group comparison between women with PRP and healthy female controls during the winter months of February 1994 and 1995 and in the summer month of August 1994. Blood samples were drawn just before and 40 min after whole-body cooling.

3. There were no significant changes in venous cGMP after whole-body cooling in women with PRP during the winter months of February 1994 and 1995. Cold exposure in the summer month of August resulted, however, in a significant increase in venous cGMP (P < 0.01). In contrast, the healthy women responded with a significant increase in venous cGMP on all three test occasions: February 1994 (P < 0.05), August 1994 (P < 0.05) and February 1995 (P < 0.01)

4. A seasonal variation in venous cGMP response to whole-body cooling was observed only in women with PRP. Healthy women responded to cold exposure with an increase in venous cGMP during summer and winter, whereas females with PRP showed an increase only during summer. Results from the present study might indicate seasonal variation in the regulation of constitutive nitric oxide synthetase in women with PRP, which may contribute to new therapeutic approaches.
The 67gallium-transferrin Pulmonary Leak Index in Pneumonia and Associated Adult Respiratory Distress Syndrome
Authors: Groeneveld A. B. Johan , Raijmakers Pieter G. H. M.
Published: August 2015

1. The aim of the study was to determine the role of increased microvascular protein permeability, as measured by the 67gallium (Ga)-transferrin pulmonary leak index, in pneumonia and associated adult respiratory distress syndrome (ARDS).

2. Eighteen consecutive patients with microbiologically confirmed pneumonia (radiographic infiltrates, purulent sputum) and needing respiratory monitoring (n = 2) or mechanical ventilation (n = 16) in the intensive care unit were studied prospectively. The pulmonary leak index using 67Ga-transferrin and 99mTc red blood cells was measured with a mobile probe system over both lung apices (normal value below 14.1 × 10−3 min−1) within 72 h of intensive care unit admission, and the lung injury score was calculated from radiographic, ventilatory and lung mechanical data.

3. Patients with pneumonia (lung injury score <2.5, n = 10) had a lower (P < 0.01) pulmonary leak index, averaged for both lungs, with a median of 23.9 [range (7.0–47.0) × 10−3 min−1] than patients with pneumonia-associated ARDS (lung injury score ≥2.5, n = 8), and an average pulmonary leak index of 37.5 [(23.4–144.2) × 10−3 min−1], so that, for all patients, the pulmonary leak index, averaged for both lungs, directly related to the lung injury score (rs = 0.61, P < 0.01). A normal average pulmonary leak index excluded pneumonia-associated ARDS. Patients with unilateral pneumonia had a greater inter-lung difference (P < 0.01) in the pulmonary leak index between affected and unaffected lung than patients with bilateral pneumonia. The index did not have prognostic significance.

4. The 67Ga-transferrin pulmonary leak index parallels the degree of radiographic, ventilatory and lung mechanical abnormalities of pneumonia and evolving ARDS. The data support the idea that the clinical manifestations of pneumonia culminating in ARDS directly relate to the degree of microvascular injury. Conversely, the pulmonary leak index may be used to monitor the effect of anti-inflammatory drugs in the adjunctive treatment for severe pneumonia aimed at circumventing mechanical ventilation in future studies.
Interactions between Endothelin-1-induced Contractions and Bronchodilators in Human Isolated Bronchi
Authors: Clayton Robert A. , Nally Jane E. , Thomson Neil C. , McGrath John C.
Published: August 2015

1. The aim of this study was to compare the ability of four different bronchodilators (atrial natriuretic peptide, salbutamol, sodium nitroprusside and isosorbide dinitrate) to reverse and also to protect against contractions evoked by the spasmogens endothelin-1 and methacholine in human isolated bronchial rings.

2. Contractions evoked by either endothelin-1 or methacholine were reversed by atrial natriuretic peptide (10−9−10−6 mol/l), salbutamol (10−9−10−5 mol/l), sodium nitroprusside (10−9−10−5 mol/l) and isosorbide dinitrate (10−7−10−4 mol/l).

3. Sodium nitroprusside produced a significantly (P < 0.05 for data points) greater mean maximal inhibition of endothelin-1-induced tone than methacholine-induced tone; however, the other dilators were equally effective at reversing either endothelin-1- or methacholine-induced contractions. Comparing sodium nitroprusside and salbutamol, sodium nitroprusside was significantly (P < 0.05 for data set) less effective than salbutamol at reversing either endothelin-1- or methacholine-induced contractions.

4. To compare the ability of these bronchodilator substances to protect against spasmogen challenge, cumulative concentration—response curves to either endothelin-1 (10−10−3 × 10−7 mol/l) or methacholine (10−9−3 × 10−4 mol/l) were constructed in the presence and absence of each bronchodilator. Atrial natriuretic peptide, at a concentration of 10−6 mol/l, significantly attenuated contractions evoked by methacholine. In contrast, contractions evoked by endothelin-1 were enhanced by atrial natriuretic peptide at concentrations of 3 × 10−7 and 10−6 mol/l. Preincubation of salbutamol at a concentration of 10−6 mol/l significantly attenuated methacholine-induced contractions, but responses to endothelin-1 were not altered by preincubation of salbutamol at concentrations of 3 × 10−7, 10−6 and 3 × 10−6 mol/l. Sodium nitroprusside (10−6 mol/l) and isosorbide dinitrate (3 × 10−5 mol/l) did not alter responses evoked by subsequent addition of either endothelin-1 or methacholine. At a concentration of 10−4 mol/l, however, isosorbide dinitrate significantly attenuated endothelin-1-evoked contractions.

5. These results show that drugs which reverse agonist-induced tone in isolated bronchial rings may not necessarily protect against subsequent challenge with this agonist. This suggests that the pharmacology of relaxation may be dissimilar to that of protection.
‘Physiological’ Hyperinsulinaemia Increases Distal Artery Systolic Blood Pressure without Changing Proximal Blood Pressure
Authors: O'Callaghan Christopher James , Komersova Karla , Krum Henry , Louis William John
Published: August 2015

1. Although epidemiological data links essential hypertension with insulin resistance, ‘physiological’ insulin concentrations have not had pressor effects in humans. Our previous studies suggested that hyperinsulinaemia might have effects on distal blood pressure which are not detected more proximally. Therefore, we used non-invasive techniques to determine the acute effects of insulin on proximal and distal blood pressure.

2. Blood pressure was measured in the finger (Finapres) and arm (Dinamap monitor) during a two-stage euglycaemic clamp. Values obtained during the insulin infusion were compared with a control infusion.

3. Plasma insulin concentrations were 7.0 ± 1.0 μ-units/ml at baseline and remained within the accepted post-prandial ‘physiological’ range during low- and high-dose insulin infusions (28.9 ± 2.1 and 101.7 ± 6.8 μ-units/ml respectively). From a baseline value of 130 ± 3 mmHg, finger systolic blood pressure rose by 9.9 ± 1.9 mmHg during the low-dose infusion (compared with 7.5 ± 2.7 mmHg in control, P < 0.05) and by 21.9 ± 2.3 mmHg during the high-dose infusion (compared with 14.6 ± 3.1 mmHg in control, P < 0.01). Compared with control, insulin did not have an additional effect on arm pressures.

4. Although finger systolic pressure was increased by hyperinsulinaemia, this occurred in the absence of a change in mean blood pressure or in arm pressures. These data therefore suggest that insulin augmented pulse wave reflection. This novel haemodynamic effect of insulin could contribute to the association of insulin resistance with essential hypertension.