Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type‐2

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type‐2 diabetic patients. The study was performed in 16 insulin treated type‐2 diabetics (eight male/eight female, age 47 ± 3 years, HbA1c 7·2 ± 0·2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8·7 ± 1·1 to 15·3 ± 1·0 mmol l^?1 (P<0·001) postprandially. This resulted in (i) a significant increase of resting blood flow (3·4 ± 0·3 to 4·8 ± 0·4 ml min^?1 100 ml^?1, P<0·01) and (ii) in a reduced peak reactive hyperaemia (52·3 ± 7·4 to 36·8 ± 4·3 ml min^?1 100 ml^?1, P<0·005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non‐diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type‐2 diabetic patients.     

Osteocalcin metabolism in the pulmonary circulation

The aim of this study was to evaluate the role of the pulmonary vessel endothelium in the removal of circulating osteocalcin, by measuring the osteocalcin levels in serum from pulmonary and radial artery blood from 39 patients undergoing aorto‐coronary bypass. Because of the discrepancies between methods of measurement, two methods were used. Significant differences were observed in group A (n = 18), tested with heterologous radioimmunoassay (2·85 ± 0·67 μg l^?1 in the pulmonary versus 2·69 ± 0·67 μg l^?1 in the radial artery serum, P<0·001) and in group B (n = 21), tested with a two‐site immunoradiometric assay (5·22 ± 1·46 versus 4·93 ± 1·36 μg l^?1, P<0·01). The percentage differences were –5·54 ± 4·76% (P<0·001) in group A and –4·99 ± 8·13% (P<0·01) in group B; the comparison between the percentage differences was not significant. These different osteocalcin concentrations between the two vascular compartments were considered a marker of osteocalcin degradation. Therefore, the study seems to demonstrate that, as well as kidney, liver and bone, the lung is a relevant site of osteocalcin catabolism. The proteolytic activity of pulmonary vessel endothelium seems to involve about 5% of the circulating peptide.     

Perfusion heterogeneity does not explain excess muscle oxygen uptake during variable intensity exercise

The association between muscle oxygen uptake (VO₂) and perfusion or perfusion heterogeneity (relative dispersion, RD) was studied in eight healthy male subjects during intermittent isometric (1 s on, 2 s off) one‐legged knee‐extension exercise at variable intensities using positron emission tomography and a‐v blood sampling. Resistance during the first 6 min of exercise was 50% of maximal isometric voluntary contraction force (MVC) (HI‐1), followed by 6 min at 10% MVC (LOW) and finishing with 6 min at 50% MVC (HI‐2). Muscle perfusion and O₂ delivery during HI‐1 (26 ± 5 and 5·4 ± 1·0 ml 100 g^?1 min^?1) and HI‐2 (28 ± 4 and 5·8 ± 0·7 ml 100 g^?1 min^?1) were similar, but both were higher (P<0·01) than during LOW (15 ± 3 and 3·0 ± 0·6 ml 100 g^?1 min^?1). Muscle VO₂ was also higher during both HI workloads (HI‐1 3·3 ± 0·4 and HI‐2 4·1 ± 0·6 ml 100 g^?1 min^?1) than LOW (1·4 ± 0·4 ml 100 g^?1 min^?1; P<0·01) and 25% higher during HI‐2 than HI‐1 (P<0·05). O₂ extraction was higher during HI workloads (HI‐1 62 ± 7 and HI‐2 70 ± 7%) than LOW (45 ± 8%; P<0·01). O₂ extraction tended to be higher (P = 0·08) during HI‐2 when compared to HI‐1. Perfusion was less heterogeneous (P<0·05) during HI workloads when compared to LOW with no difference between HI workloads. Thus, during one‐legged knee‐extension exercise at variable intensities, skeletal muscle perfusion and O₂ delivery are unchanged between high‐intensity workloads, whereas muscle VO₂ is increased during the second high‐intensity workload. Perfusion heterogeneity cannot explain this discrepancy between O₂ delivery and uptake. We propose that the excess muscle VO₂ during the second high‐intensity workload is derived from working muscle cells.     

Measurement of cardiac output with non-invasive Aesculon impedance versus thermodilution

Background: This study compared the non‐invasive thoracic electrical bioimpedance Aesculon^® technique (TEB_Aesculon) with thermodilution (TD) to evaluate whether TEB_Aesculon may offer a reliable means for estimating cardiac output (CO) in humans. Material and method: Cardiac output was measured with TD and TEB_Aesculon in 33 patients, with a mean age ± SEM of 59 ± 2·7 years, that underwent right heart catheterization for clinical investigation of pulmonary hypertension or severe heart failure. Four to five CO measurements were performed with each technique simultaneously in 33 patients at rest, 11 during exercise and seven during NO inhalation. Result: Cardiac output correlated poorly between TEB_Aesculon and TD at rest (r = 0·46, P<0·001), during exercise (r = 0·35, P<0·013) and NO inhalation (r = 0·41, P<0·017). CO was higher for TEB_Aesculon than TD with 0·86 ± 0·14 l min^?1 at rest (P<0·001) and 2·95 ± 0·69 l min^?1 during exercise (P<0·003), but similar during NO inhalation, with a tendency (P<0·079) to be 0·44 ± 0·19 l min^?1 higher for TEB_Aesculon than TD. CO increased from rest to exercise for TEB_Aesculon and TD with 6·11 ± 0·6 l min^?1 (P<0·001) and 3·91 ± 0·36 l min^?1 (P<0·001), respectively; an increase that was higher (P<0·002) for TEB_Aesculon than TD. During NO inhalation, compared to rest, CO decreased for TEB_Aesculon with 0·62 ± 0·11 l min^?1 (P<0·002), but not significantly for TD with 0·21 ± 0·12 l min^?1 (P<0·11). Bland–Altman analysis showed a poor agreement between TEB_Aesculon and TD. Conclusion: TEB_Aesculon overestimated CO compared to TD with ～17% at rest and ～34% during exercise, but the techniques showed similar results during NO inhalation. CO, furthermore, correlated poorly between TEB_Aesculon and TD. TEB_Aesculon may at present not replace TD for reliable CO measurements in humans.     

The erythropoietin and regenerative medicine: a lesson from fish

Background Erythropoietin (EPO), the main haematopoietic growth factor for the proliferation and differentiation of erythroid progenitor cells, is also known for its angiogenic and regenerative properties. Materials and methods In this study, we aimed to test the regenerative effects of EPO administration in an experimental model of Sea bass (Dicentrarchus labrax) subjected to amputation of the caudal fin. Results Erythropoietin‐treated fishes (3000 UI of human recombinant EPO‐alpha immediately after cutting and after 15 days) showed an increased growth rate of their fins compared with those untreated (anova variance: P: 0·01 vs. P: 0·04). By analysing fin length at established times (15 and 30 days after cut), EPO‐treated fishes always showed an increased length compared with untreated ones (T‐15: 1·1 ± 0·2 vs. 0·7 ± 0·2 cm, P: 0·03; T‐30: 1·9 ± 0·3 vs. 1·2 ± 0·2 cm, P: 0·01). Moreover, exogenous EPO administration induced an enormous increase in EPO‐blood levels at each observation time (T‐15: 2240 ± 210 vs. 16·7 ± 1·8 mU mL^?1, P < 0·001; T‐30: 2340 ± 190 vs. 17·1 ± 1·9 mU mL^?1, P < 0·001), whereas these levels remained quite unmodified in untreated fishes. Immunochemical analyses performed by confocal laser scanning microscopic observations showed an increased expression of EPO‐receptors and PECAM‐1 (an endothelial surface marker of vessels sprout) in the regenerating tissue, whereas no signs of inflammation or fibrosis were recognisable. Conclusions All these findings confirm EPO as a new factor involved in regenerative processes, also suggesting a potential, future utility for new therapeutical applications in the field of human regenerative medicine.     

Simultaneous quantification of myocardial perfusion,oxidative metabolism,cardiac efficiency and pump function at rest and during supine bicycle exercise using 1‐11C‐acetate PET – a pilot study

Background: PET using 1‐¹¹C‐acetate (ACE‐PET) applied at rest is used for measuring absolute myocardial blood flow (MBF) and oxidative metabolic rate (k_mono). We evaluated the feasibility of quantitative ACE‐PET during exercise. Methods: Five endurance athletes underwent dynamic PET scanning at rest and during supine bicycle stress. Exercise was maintained at a workload of 120 Watt for 17 min. The rate‐pressure product (RPP) was recorded repeatedly. MBF, k_mono in left (LV) and right (RV) ventricular wall, cardiac output (CO), cardiac efficiency and a lung uptake value reflecting left heart diastolic pressures were calculated from the PET data using previously validated models. Results: MBF increased from 0·71 ± 0·17 to 2·48 ± 0·25 ml min^?1 per ml, LV‐k_mono from 0·050 ± 0·005 to 0·146 ± 0·021 min^?1, RV‐k_mono from 0·023 + 0·006 to 0·087 + 0·014 min^‐1, RPP from 4·7 ± 0·8 to 13·2 ± 1·4 mmHg × min^?1 × 10³ and Cardiac Output from 5·2 ± 1·1 to 12·3 ± 1·2 l min ^?1 (all P < 0·001). Cardiac efficiency was unchanged (P = 0·99). Lung uptake decreased from 1·1 ± 0·2 to 0·6 ± 0·1 ml g^?1 (P < 0·001). Discussion: A number of important parameters related to cardiac function can be quantified non‐invasively and simultaneously with a short scanning protocol during steady state supine bicycling. This might open up new opportunities for studies of the integrated cardiac physiology in health and early asymptomatic disease.     

Myocardial velocities measured during adenosine, dobutamine and supine bicycle exercise: a tissue Doppler study in healthy volunteers

Background: Dobutamine stress echocardiography (DSE) quantified by tissue Doppler (TVI) have improved the diagnostic capacity of the procedure. Quantification of other stress modalities, e.g. adenosine stress echo (ASE) and exercise stress echocardiography (ESE) are necessary for assessing any pathophysiological differences in different forms of stress. Methods: Ten healthy individuals underwent ASE, DSE, and ESE during a span of 2–5 days. Left ventricular (LV) apical images at rest and peak stress (max) were postprocessed using TVI on a GE System FiVe equipment. ECG‐derived QRS duration (QRSD, ms), heart rate (HR, bpm), TVI‐estimated basal systolic velocities (S2V, cm s^?1), ejection time (S2T, ms) and strain (S, %) were computed off‐line and compared. Longitudinal displacement imaging, tissue tracking, was also made. Results: Data for ASE, DSE and ESE during peak stress were (HR: 84 ± 12***, 142 ± 19, 137 ± 27; P<0·001) (QRSD: 92 ± 18**, 74 ± 13, 79 ± 9; P<0·05), (S2T: 307 ± 34***, 175 ± 53, 192 ± 25; P<0·001) and (S%: 26·0 ± 3·0, 21·2 ± 7·3, 22·1 ± 5·1; P = n.s.) respectively. Velocity response, registered in the LV septum at max, was lowest during ASE (7·4 ± 1·4) highest during DSE (13·0 ± 2·7; P<0·001 versus ASE) and somewhat intermediate during ESE (11·3 ± 3·5; P<0·001 versus ASE). In contrast, strain and displacement did not differ. Conclusion: ASE evokes significantly less LV systolic response compared with both DSE and ESE. Increased velocity (P<0·05 versus rest) and strain (P>0·05) response at a much lower HR indicates that adenosine has minor effects on contraction presumably secondary to vasodilatation. Powerful chronotropic response to DSE and ESE is probably prerequisite for strong velocity response at the expense of strain and displacement. TVI‐assisted stress echocardiography thereby shows different LV systolic response in healthy individuals, depending on stress modality.     

Ursodeoxycholic acid reduces lipid peroxidation and mucin secretagogue activity in gallbladder bile of patients with cholesterol gallstones

Background Recently it has been postulated that gallbladder mucin hypersecretion observed in the pathogenesis of cholesterol gallstone disease may be induced by biliary lipid peroxidation. Ursodeoxycholic acid treatment reduces mucin concentration and the formation of cholesterol crystals in the gallbladder bile of patients with cholesterol gallstones and this effect might be mediated by a decrease of biliary lipid peroxidation. Material and methods In a double‐blind, placebo‐controlled trial patients with symptomatic cholesterol gallstones received either ursodeoxycholic acid (750 mg daily) (n = 10) or placebo (n = 12) 10–12 days prior to cholecystectomy. As a marker for lipid peroxidation malondialdehyde was measured in bile together with mucin concentration. In addition, the mucin secretagogue activity of the individual bile samples was assessed in cultured dog gallbladder epithelial cells. Results Ursodeoxycholic acid therapy resulted in a significant reduction of lipid peroxidation in bile as determined by the biliary malondialdehyde concentration (1·36 ± 0·28 vs. 2·05 ± 0·38 µmol L^?1; P < 0·005) and the malondialdehyde (µmol L^?1)/total bile acid (mmol L^?1) ratio (0·02 ± 0·005 vs. 0·06 ± 0·01; P < 0·001). Furthermore, a decrease in mucin concentrations (0·7 ± 0·3 vs. 1·3 ± 0·5 mg mL^?1; P < 0·005) and of the mucin secretagogue activity of gallbladder bile (0·9 ± 0·2 vs. 2·2 ± 0·3 times control; P < 0·001) was observed. Conclusions The reduction of lipid peroxidation and mucin secretagogue activity of gallbladder bile induced by ursodeoxycholic acid treatment may contribute to the beneficial effects of this drug on gallbladder bile composition and symptoms in cholesterol gallstone patients.     

Evidence of diminished coronary flow in pulmonary hypertension ‐ explaining angina pectoris in this patient group?

Background: Many patients with pulmonary hypertension (PH) have symptoms of angina without evidence of occlusive coronary artery disease. For the first time, this study addresses the influence of progressively increasing pulmonary artery pressure (PAP) on left anterior descending artery flow in a rat model of PH. The role of pulmonary artery dilatation, septal wall motion abnormality, cardiac output or diastolic blood pressure in determining coronary blood flow (CBF) during PH was determined. Methods: Pulmonary hypertension was induced in 6‐week‐old female nude rats (n = 44) using monocrotaline. Animals underwent right heart catheterization and echocardiography, and blood pressure measurement was taken at baseline, 21 and 35 days. Results: A total of 103 echocardiographic studies were carried out at three fixed time points in rats with variable PAP. CBF decreased from 46·6 ± 14·3 to 24·7 ± 12·3 cm s^?1 (P<0·001) over time. Pulmonary artery diameter increased from 2·30 ± 0·19 to 2·83 ± 0·30 mm (P<0·001), and left ventricular (LV) cardiac output decreased from 143 ± 23 to 78 ± 30 ml min^?1 (P<0·001). Using observed solution estimates of 0·00170 (P = 0·0005) and ?1·75 (P = 0·006) for these variables, we calculated that CBF increased by 5·90 cm s^?1 (15·6%, CI: 14·5–17·1%) or decreased by ?4·86 cm s^?1 (?12·9%, CI: ?14·1–11·9%) for every standard deviation increase in LV cardiac output or pulmonary artery diameter, respectively. CBF decreased significantly with increasing PAP. Pulmonary artery diameter and LV cardiac output appear to be independent determinants of coronary flow in PH. Conclusions: Coronary flow reduction in murine PH has potential to be clinically meaningful and should therefore further studied in a clinical trial.     

Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects

Background To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat‐derived factor retinol‐binding protein‐4 (RBP‐4) in HIV‐infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART). Materials and methods Fourteen HIV‐positive, HAART‐naïve subjects were compared with 10 HIV‐negative healthy controls and reassessed after a 1‐year treatment with HAART. Plasma visfatin and RBP‐4 were determined by ELISA, whereas leptin and adiponectin by RIA. Body composition was measured with dual X‐ray absorptiometry (DXA). Homeostasis model assessment (HOMA‐IR) was assessed using insulin and glucose levels. Results Visfatin and RBP‐4 levels in HIV‐positive subjects were comparable with those of HIV‐negative controls before treatment with HAART. Treatment with HAART for 12 months resulted in a 6·9‐fold and 7·1‐fold increase of visfatin and RBP‐4 levels (+54·0 ± 9·7 ng mL^?1, P < 0·0001 and +95·3 ± 31·7 ng mL^?1, P < 0·01), respectively. Leptin (?2·7 ± 1·6 ng mL^?1, P = 0·054) was unchanged and adiponectin (?2·8 ± 0·7 µg mL^?1, P < 0·01) decreased. Changes of visfatin concentrations correlated significantly with the increases of RBP‐4 (r = 0·78, P = 0·001), fat‐free mass (FFM, r = 0·75, P < 0·05) and change of HOMA‐IR (r = 0·64, P < 0·05). Parameters of glucose metabolism and body fat mass were unchanged during the observation period. Conclusions Treatment with HAART induced a pronounced increase of plasma visfatin and RBP‐4 as well as a decrease of adiponectin in HIV‐infected patients on HAART. Although body weight, fat mass and parameters of glucose metabolism remained stable, the changes in the adipocytokines might herald subsequent alterations of these parameters.     

Intravenous adrenaline infusion causes vasoconstriction close to an intramuscular microdialysis catheter in humans

Aim: To test if a small muscle injury influences the vascular reactivity to adrenaline in human skeletal muscle. Methods: Blood flow was measured by ¹³³Xenon clearance in the gastrocnemius muscle of eight male subjects at basal and during i.v. infusion of adrenaline (0·1 nmol kg^?1 min^?1) or placebo. Measurements were done with (expts 2 and 3) or without (expt 1) the influence of a small muscle injury induced by inserting a microdialysis catheter. ¹³³Xenon was administered either (expt 1) conventionally into the muscle via a fine needle, or (expts 2 and 3) through a fine tube close to the inserted microdialysis catheter. Expt 3 (control expt) was identical to expt 2 except that placebo was infused instead of adrenaline. Mean ± SEM, n = 8. Results: The blood flow tended to increase during the adrenaline infusion in expt 1 (1·17 ± 0·10 to 1·39 ± 0·15, N.S.), whereas it decreased during the adrenaline infusion in expt 2, from 1·39 ± 0·14 to 1·03 ± 0·14 ml min^?1 100 g tissue^?1 (P<0·001). The blood flow change in response to adrenaline infusion was significantly different in expt 1 and expt 2 (P<0·05). Blood flow also decreased during the placebo infusion in expt 3 (1·15 ± 0·10 to 1·00 ± 0·09, P<0·01), but this decrease was significantly smaller than in response to the adrenaline infusion in expt 2, P<0·01. Conclusion: The present results are consistent with the hypothesis that the small muscle injury caused by the inserted microdialysis catheter influences the vascular reactivity to adrenaline in a vasoconstrictive direction.     

Cardiac adrenergic innervation within the first 3 months after acute myocardial infarction

It is widely accepted that myocardial infarction results in adrenergic denervation of the infarcted and peri‐infarcted myocardium. On the contrary, the concept of re‐innervation of adrenergic nerve fibres is less well established. Although there is evidence of partial re‐innervation occuring several months after myocardial infarction, the extent and time scale of re‐innervation are only poorly known. In this study we investigated changes in cardiac adrenergic innervation and myocardial perfusion during the early convalescence period (the first 3 months) after an acute myocardial infarction. Single‐photon emission computed tomographic imaging was conducted in 15 men 1 week and 3 months after an acute myocardial infarction with I¹²³‐metaiodobentzylguanidine (MIBG) and Tc^99m‐sestamibi (MIBI) to determine the extent of adrenergic denervation and impaired perfusion, respectively. A MIBG and MIBI defect was determined as regional uptake ≤30% of maximal myocardial activity. The size of the MIBG defect calculated as a percentage of left ventricular mass remained unchanged between 1 week and 3 months after myocardial infarction (31·1 ± 17·3% vs. 30·5 ± 16·8%, respectively). Accordingly, MIBG activity of the infarct and peri‐infarct zones (expressed as a percentage of MIBG activity of the myocardium with normal perfusion) showed no significant change (23·7 ± 10·0% vs. 25·3 ± 11·0% and 39·0 ± 11·3% vs. 40·8 ± 12·8%, respectively) during the follow‐up. On the other hand, the size of MIBI defect decreased significantly during the follow‐up (14·2 ± 11·5% vs. 11·4 ± 9·7%, P<0·05, respectively) indicating improved myocardial perfusion. The results demonstrate that cardiac adrenergic re‐innervation is a slow process; despite a significant increase in myocardial perfusion we found no evidence of adrenergic re‐innervation during the first 3 months after acute myocardial infarction.     

The exercise heart rate profile in master athletes compared to healthy controls

Endurance exercise protects the heart via effects on autonomic control of heart rate (HR); however, its effects on HR indices in healthy middle‐aged men are unclear. This study compared HR profiles, including resting HR, increase in HR during exercise and HR recovery after exercise, in middle‐aged athletes and controls. Fifty endurance‐trained athletes and 50 controls (all male; mean age, 48·7 ± 5·8 years) performed an incremental symptom‐limited exercise treadmill test. The electrocardiographic findings and HR profiles were evaluated. Maximal O₂ uptake (52·6 ± 7·0 versus 34·8 ± 4·5 ml kg^?1 min^?1; P<0·001) and the metabolic equivalent of task (15·4 ± 1·6 versus 12·2 ± 1·5; P<0·001) were significantly higher in athletes than in controls. Resting HR was significantly lower in athletes than in controls (62·8 ± 6·7 versus 74·0 ± 10·4 beats per minute (bpm), respectively; P<0·001). Athletes showed a greater increase in HR during exercise than controls (110·1 ± 11·0 versus 88·1 ± 15·4 bpm; P<0·001); however, there was no significant between‐group difference in HR recovery at 1 min after cessation of exercise (22·9 ± 5·6 versus 21·3 ± 6·7 bpm; P = 0·20). Additionally, athletes showed a lower incidence of premature ventricular contractions (PVCs) during exercise (0·0% versus 24·0%; P<0·001). Healthy middle‐aged men participating in regular endurance exercise showed more favourable exercise HR profiles and a lower incidence of PVCs during exercise than sedentary men. These results reflect the beneficial effect of endurance training on autonomic control of the heart.     

N-terminal pro-brain natriuretic peptide used for the prediction of coronary artery stenosis

Background The level of the inactive N‐terminal fragment of pro‐brain (B‐type) natriuretic peptide (NT‐proBNP) is a prognostic marker in patients with acute and chronic coronary artery disease (CAD). It might also be valuable for non‐invasive diagnosis of coronary artery disease. Materials and methods The NT‐proBNP was measured in 781 consecutive patients with normal left ventricular function referred for coronary angiography owing to symptoms or signs of CAD. The diagnostic value of NT‐proBNP was assessed for predicting CAD at angiography. Results Elevated NT‐proBNP levels were associated with the extent of CAD and with the female sex (P < 0·001). The ability of NT‐proBNP to predict significant coronary disease at angiography was assessed separately for men using a cut‐off point of 85 pg mL⁻¹, positive likelihood ratio 2·2 (95% CI, 1·7–3·0), negative likelihood ratio 0·53 (95% CI 0·45–0·63) and area under the receiver‐operating‐characteristic (ROC) curve 0·72: for women, it was assessed using a cut‐off point of 165 pg mL⁻¹, positive likelihood ratio 2·4 (95% CI, 1·7–3·4), negative likelihood ratio 0·55 (95% CI, 0·44–0·70) and area under ROC curve 0·71. In multiple logistic‐regression analysis, NT‐proBNP added significant independent predictive power to other clinical variables in models predicting CAD (odds ratio 2·76, 95% CI, 1·76–4·32, P < 0·001). Conclusions The NT‐proBNP is a marker of non‐obstructive CAD and of significant coronary stenosis. In conjunction with other clinical information, measurement of NT‐proBNP with the use of sex‐specific reference ranges may improve the non‐invasive prediction of CAD.     

Effects of walking with blood flow restriction on limb venous compliance in elderly subjects

Venous compliance declines with age and improves with chronic endurance exercise. KAATSU, an exercise combined with blood flow restriction (BFR), is a unique training method for promoting muscle hypertrophy and strength gains by using low‐intensity resistance exercises or walking. This method also induces pooling of venous blood in the legs. Therefore, we hypothesized that slow walking with BFR may affect limb venous compliance and examined the influence of 6 weeks of walking with BFR on venous compliance in older women. Sixteen women aged 59–78 years were partially randomized into either a slow walking with BFR group (n = 9, BFR walk group) or a non‐exercising control group (n = 7, control group). The BFR walk group performed 20‐min treadmill slow walking (67 m min^?1), 5 days per week for 6 weeks. Before (pre) and after (post) those 6 weeks, venous properties were assessed using strain gauge venous occlusion plethysmography. After 6 weeks, leg venous compliance increased significantly in the BFR walk group (pre: 0·0518 ± 0·0084, post: 0·0619 ± 0·0150 ml 100 ml^?1 mmHg^?1, P<0·05), and maximal venous outflow (MVO) at 80 mmHg also increased significantly after the BFR walk group trained for 6 weeks (pre: 55·3 ± 15·6, post: 67·1 ± 18·9 ml 100 ml^?1 min^?1, P<0·01), but no significant differences were observed in venous compliance and MVO in the control group. In addition, there was no significant change in arm compliance in the BFR walk group. In conclusion, this study provides the first evidence that 6 weeks of walking exercise with BFR may improve limb venous compliance in untrained elder female subjects.     

Reduced cardiac sympathetic autonomic tone after long-term nasal continuous positive airway pressure in obstructive sleep apnoea syndrome

The increased sympathetic activation that occurs in obstructive sleep apnoea (OSA) may play an important role in associated morbidity. We investigated the effect of long-term (3 month) nasal continuous positive airway pressure (CPAP) on the autonomic nervous system assessed by heart rate variability (HRV). Fourteen patients (12 men), mean age 61·4 ± 8·1 years, with OSA underwent continuous synchronized electrocardiographic and polysomnographic monitoring. The apnoea/hypopnoea index (AHI) decreased from 50·6 ± 13·7 to 2·2 ± 2·5 events h^?1 after CPAP. HRV analysis showed significant decreases in low frequency (LF; from 7·12 ± 1·06 to 6·22 ± 1·18 ln ms² Hz^?1; P<0·001), high frequency (HF; from 5·91 ± 0·87 to 5·62 ± 0·92 ln ms² Hz^?1; P<0·05) and LF/HF (from 1·21 ± 0·12 to 1·11 ± 0·15 ln ms² Hz^?1; P<0·001) when the patients were asleep. The decrease in LF/HF was prolonged into the daytime (from 1·33 ± 0·22 to 1·24 ± 0·21 ln ms² Hz^?1; P<0·001). Treatment of OSA by CPAP significantly reduced the parameters of cardiac sympathetic tone, a favourable effect.     

Early activation of the coagulation system during lower body negative pressure

We considered that a moderate reduction of the central blood volume (CBV) may activate the coagulation system. Lower body negative pressure (LBNP) is a non‐invasive means of reducing CBV and, thereby, simulates haemorrhage. We tested the hypothesis that coagulation markers would increase following moderate hypovolemia by exposing 10 healthy male volunteers to 10 min of 30 mmHg LBNP. Thoracic electrical impedance increased during LBNP (by 2·6 ± 0·7 Ω, mean ± SD; P < 0·001), signifying a reduced CBV. Heart rate was unchanged during LBNP, while mean arterial pressure decreased (84 ± 5 to 80 ± 6 mmHg; P < 0·001) along with stroke volume (114 ± 22 to 96 ± 19 ml min^?1; P < 0·001) and cardiac output (6·4 ± 2·0 to 5·5 ± 1·7 l min^?1; P < 0·01). Plasma thrombin–antithrombin III complexes increased (TAT, 5 ± 6 to 19 ± 20 μg l^?1; P < 0·05), indicating that LBNP activated the thrombin generating part of the coagulation system, while plasma D‐dimer was unchanged, signifying that the increased thrombin generation did not cause further intravascular clot formation. The plasma pancreatic polypeptide level decreased (13 ± 11 to 6 ± 8 pmol l^?1; P < 0·05), reflecting reduced vagal activity. In conclusion, thrombin generation was activated by a modest decrease in CBV by LBNP in healthy humans independent of the vagal activity.     

Haemodynamic effects of patent foramen ovale and atrial septal defect closure: a comparison during percutaneous shunt closure

Objectives: We investigated the haemodynamic effect of percutaneous closure of an intra‐atrial shunt, using non‐invasive finger pressure measurements. Background: Percutaneous closure of both patent foramen ovale (PFO) and atrial septal defect (ASD) is widely practised. Currently no data are available on short‐term haemodynamic changes induced by closure. Methods: Twenty‐five consecutive patients (mean age 49 ± 17 years, 10 men) who underwent a percutaneous closure of a PFO (n = 15) or ASD (n = 10) were included in this study. During the procedure blood pressure and heart rate (HR) were monitored continuously with a Finometer^®. Changes in systolic, mean, and diastolic pressure, stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were computed from the pressure registrations using Modelflow^® methodology. Results: Baseline characteristics were similar for the PFO and ASD patients. After PFO closure none of the haemodynamic parameters changed significantly. After ASD closure the systolic, mean, and diastolic pressures increased 7·1 ± 5·4 (P = 0·003), 3·8 ± 3·5 (P = 0·007) and 2·0 ± 3·0 mmHg (P = ns) respectively. HR decreased 5·1 ± 5·3 beats per minute (P = 0·01). SV, CO and TPR increased 8·5 ± 6·4 ml (13·5%; P = 0·002), 0·21 ± 0·45 l min^?1 (5·6%; P = ns) and 0·02 ± 0·14 dynes (4·1%; P = ns) respectively. The changes in SV differ between the PFO and ASD patients (P = 0·009). Conclusions: Using non‐invasive finger pressure measurements, we found that SV, mean and systolic blood pressure increased immediately after percutaneous closure of an ASD in adults, whereas the percutaneous PFO closure had no effect on haemodynamic characteristics.     

Diameter and compliance of the greater saphenous vein - effect of age and nitroglycerine

Objectives: The greater saphenous vein (GSV) is commonly used in autologous vein graft surgery. GSV diameter has proven to influence graft patency, and furthermore venous compliance might be of importance. The purpose of the study was to evaluate the effect of age on GSV diameter and compliance, and to evaluate the effect of nitroglycerine (NTG). Methods: The diameter and compliance of the GSV, with and without NTG, were examined with B‐mode ultrasound in 12 elderly (70·3 ± 1·2 year) and 15 young (25·1 ± 0·6 year) men. The GSV diameter at the thigh and calf level was measured at rest, after 6 min of venous stasis (60 mmHg) and after NTG administration. Pressure–area curves during a linear venous pressure decrease were produced. Venous compliance was calculated using the quadratic regression equation (area) = β₀ + β₁ (cuff pressure) + β₂ (cuff pressure)². Results: GVS diameter between the groups showed significant lower diameter in elderly compared to young men (P<0·05). Venous occlusion increased GSV diameter in elderly men (P<0·01) as well as young men (P<0·001). NTG increased GSV diameter in elderly men (P<0·01) with an equal trend in young men. During venous occlusion, after administration of NTG, GSV diameter increased further in both elderly (P<0·01) and young men (P<0·001). GSV compliance was decreased in elderly (β₁, 0·037 ± 0019, β_2,?0·000064 ± 00017) versus young men (β₁, 0·128 ± 0·013, β₂, ?0·00010 ± 000018) [P<0·001 (β₁), P<0·02 (β₂)]. Conclusions: Baseline GSV diameter as well as GSV compliance is decreased in elderly men compared to the young subjects. As reduced GSV diameter as well as reduced compliance is related to decreased graft patency, these findings might be of importance for the uses of GSV as graft material in cardiovascular bypass surgery. The clinical value has to be clarified in future studies.     

Hypoglycaemia leads to an increased QT interval in normal men

Hypoglycaemia is presumed to be the cause of death in about 3% of insulin-treated diabetic patients. Some of these patients suffer from hypoglycaemic brain damage, but the majority have no evident brain damage and are supposed to have died from other causes such as a cardiac arrhythmia. The putative mechanism is a hypoglycaemia-induced prolongation of the QT interval which increases the risk of malignant ventricular tachycardia. The aim of the present study was to examine the electrocardiogram during and after hypoglycaemia in healthy men. To that end, hypoglycaemia was induced by an intravenous infusion of insulin (2·5 mU kg^?1 min^?1) in 10 healthy men to reach a venous blood glucose level of 2·1 ± 0·3 mmol l^?1 for 65 ± 9 min. Before hypoglycaemia, after 20 and 50 min of hypoglycaemia and 20 and 45 min after normalization of the blood glucose, the QT interval was measured by a ruler and corrected for the heart rate. Results are given as mean ± SD and comparisons were made with an ANOVA , except for symptom scores and plasma adrenaline where non-parametric tests were used. When this indicated significance, further analysis was performed with a two-tailed t-test. During hypoglycaemia the corrected QT interval increased from 380 ± 20 ms^½ to 440 ± 30 ms^½ (P<0·001), and the amplitude of the T wave decreased (P = 0·002). The serum potassium level decreased from 4·3 ± 0·3 mmol l^?1 to 3·5 ± 0·2 mmol l^?1 (P<0·001) and the plasma adrenaline concentration increased from 0·20 ± 0·04 nmol l^?1 to 2·46 ± 2·58 nmol l^?1 (P<0·01). The results of this study confirm that a prolongation of the QT interval occurs during hypoglycaemia, but the significance of this finding still has to be proven.