Effect of beta blockade with and without sympathomimetic activity (ISA) on sympathovagal balance and baroreflex sensitivity

Beta blockers increase heart rate variability (HRV) and improve survival in coronary artery disease (CAD). The benefit of beta blockers with intrinsic sympathomimetic activity (ISA) in CAD still remains a matter of debate, and their effect on HRV has not yet been investigated. Therefore, we measured HRV, systolic blood pressure variability (BPV) and baroreflex sensitivity (BRS) under propranolol (PROP, without ISA, 160 mg q.d.), pindolol (PIN, with potent ISA, 15 mg q.d.) and placebo (PLA, q.d.) in 30 healthy subjects, aged 21–39 years, during controlled frequency breathing (0·30 Hz) in supine and tilt positions. PROP increased HRV in the high-frequency (0·15–0·40 Hz) band (PROP 7·4 ± 1·0; PLA 6·9 ± 1·4; PIN 6·8 ± 1·0 ln MI²; P = 0·003), decreased BPV in the low-frequency band (at 0·1 Hz, Mayer waves) (PROP 0·6 ± 0·7; PLA 1·3 ± 1·1; PIN 1·2 ± 1·2 ln mmHg²; P = 0·001) and enhanced BRS (PROP 14·6 ± 9·5; PLA 8·0 ± 6·8; PIN 8·7 ± 6·8 ms mmHg^?1; P = 0·001) in the supine position. After passive tilt, PROP decreased HRV in the low-frequency band (PROP 6·1 ± 0·9; PLA 6·5 ± 1·1; PIN 6·9 ± 0·7 ln MI²; P<0·001) and decreased Mayer waves (PROP 1·8 ± 0·8; PLA 2·4 ± 1·0; PIN 2·7 ± 0·8 ln mm Hg²; P<0·001). PIN increased the low-frequency HRV response, which is induced by passive tilt (PIN + 0·9 ± 1·0; PLA + 0·3 ± 1·3, PROP + 0·3 ± 1·0 ln MI²; P = 0·026). Our results prove that beta-adrenergic blockade with potent ISA does not increase HRV, has no beneficial effect on autonomic balance and even exaggerates sympathetic responses to passive tilt.     

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.     

Influence of exercise training on heart rate variability in post-menopausal women with elevated arterial blood pressure

Low heart rate variability (HRV) has been reported to be an independent risk factor for the development of coronary heart disease in women and has recently been identified as a risk factor for cardiac sudden death and all-cause mortality. We have recently demonstrated that endurance-trained post-menopausal women demonstrate higher levels of HRV than sedentary control subjects. The purpose of the present study was to test the hypothesis that 12 weeks of regular aerobic exercise would increase HRV in sedentary post-menopausal women with elevated arterial blood pressure (BP) (i.e. either high normal BP or stage I hypertension). A secondary aim was to test the hypothesis that the increase in HRV with exercise training, if observed, would be associated with an increase in spontaneous cardiac baroreflex sensitivity (SBRS), an important physiological determinant of HRV. To accomplish these aims, we studied eight sedentary post-menopausal women (age=54·5±1·3 years) before and after 12 weeks of aerobic exercise training (3·3±0·3 days per week at 70%±2% of maximal heart rate for 43±3 min per day). Maximal oxygen uptake and body weight did not change (P>0·05) with training, but percentage fat (35·5±2·6% vs. 34·5±2·3%, P<0·05) decreased and treadmill time to exhaustion increased (9·8±0·5 vs. 11·3±0·5 min, P<0·05). Supine resting levels of heart rate, RR interval and the standard deviation of the RR interval (time domain measure of HRV) were unchanged (all P>0·05) from baseline levels after 12 weeks of aerobic training. Similarly, the high-frequency, low-frequency and total power of HRV (frequency domain measures) were also unchanged from baseline (all P>0·05). SBRS was also not different before and after aerobic exercise training (1062 vs. 1363 ms mmHg^?1 respectively, P>0·05). In contrast, systolic and diastolic BP were reduced approximately 8 and approximately 5 mmHg with training (both P<0·05) respectively. These results indicate that 12 weeks of moderate-intensity aerobic exercise training does not increase HRV or SBRS, despite producing a clinically significant reduction in BP at rest in post-menopausal women with elevated BP. Considered together with our previous findings in female master endurance athletes, these findings suggest that more intense and prolonged exercise training may be required to produce increases in HRV and SBRS in sedentary post-menopausal women.     

Endurance training,overtraining and baroreflex sensitivity in female athletes

We examined heavy training-induced changes in baroreflex sensitivity, plasma volume and resting heart rate and blood pressure variability in female endurance athletes. Nine athletes (experimental training group, ETG) increased intense training (70–90% VO _2max) volume by 130% and low-intensity training (<70% VO _2max) volume by 100% during 6–9 weeks, whereas the corresponding increases in six control athletes (CG) were 5% and 10% respectively. Maximal oxygen uptake (VO _2max) in the ETG and CG did not change, but in five ETG athletes VO _2max decreased from 53·0 ± 2·2 (mean ± SEM) (CI 46·8–59·2) ml kg^–1 min^–1 to 50·2 ± 2·3 (43·8–56·6) ml kg^–1 min^–1 (P<0·01), indicating overtraining. Baroreflex sensitivity (BRS) measured using the phenylephrine technique and blood pressure variability (BPV) did not change, but the low-frequency power of the R–R interval variability increased in the ETG (P<0·05). The relative change in plasma volume was 7% in the ETG and 3% in the CG. The changes in BRS did not correlate with the changes in plasma volume, heart rate variability and BPV. We conclude that heavy endurance training and overtraining did not change baroreflex sensitivity or BPV but significantly increased the low-frequency power of the R–R interval variability during supine rest in female athletes as a marker of increased cardiac sympathetic modulation.     

Determination of baroreflex gain using auto-regressive moving-average analysis during spontaneous breathing

The heart rate component of the arterial baroreflex gain (BRG) was determined with auto-regressive moving-average (ARMA) analysis during each of spontaneous (SB) and random breathing (RB) protocols. Ten healthy subjects completed each breathing pattern on two different days in each of two different body positions, supine (SUP) and head-up tilt (HUT). The R–R interval, systolic arterial pressure (SAP) and instantaneous lung volume were recorded continuously. BRG was estimated from the ARMA impulse response relationship of R–R interval to SAP and from the spontaneous sequence method. The results indicated that both the ARMA and spontaneous sequence methods were reproducible (r=0·76 and r=0·85, respectively). As expected, BRG was significantly less in the HUT compared to SUP position for both ARMA (mean ± SEM; 3·5 ± 0·3 versus 11·2 ± 1·4 ms mmHg^–1; P<0·01) and spontaneous sequence analysis (10·3 ± 0·8 versus 31·5 ± 2·3 ms mmHg^–1; P<0·001). However, no significant difference was found between BRG during RB and SB protocols for either ARMA (7·9 ± 1·4 versus 6·7 ± 0·8 ms mmHg^–1; P=0·27) or spontaneous sequence methods (21·8 ± 2·7 versus 20·0 ± 2·1 ms mmHg^–1; P=0·24). BRG was correlated during RB and SB protocols (r=0·80; P<0·0001). ARMA and spontaneous BRG estimates were correlated (r=0·79; P<0·0001), with spontaneous sequence values being consistently larger (P<0·0001). In conclusion, we have shown that ARMA-derived BRG values are reproducible and that they can be determined during SB conditions, making the ARMA method appropriate for use in a wider range of patients.     

Restoration of peak vascular conductance after simulated microgravity by maximal exercise

We sought to determine if (i) peak vascular conductance of the calf was reduced following prolonged exposure to simulated microgravity, and (ii) if maximal cycle ergometry performed at the end of microgravity exposure stimulated a restoration of peak calf vascular conductance. To do this, peak vascular conductance of the calf was recorded following ischaemic plantar flexion exercise to fatigue in seven men after 16 days of head-down tilt (HDT) under two conditions: (i) after one bout of maximal supine cycle ergometry completed 24 h prior to performance of ischaemic plantar flexion exercise, and (ii) in a control (no cycle ergometry) condition. Following HDT, peak vascular conductance was reduced in the control condition (0·38 ± 0·02 to 0·24 ± 0·02 ml 100 ml^?1 min^?1 mmHg^?1; P = 0·04), but was restored when subjects performed cycle ergometry (0·33 ± 0·05 to 0·28 ± 0·04 ml 100 ml^?1 min^?1 mmHg^?1; P = 0·46). After HDT, time to fatigue during ischaemic plantar flexion exercise was not different from pre-HDT 24 h after performance of exhaustive cycle ergometry (120 ± 24 vs. 122 ± 19 s), but was decreased in the control condition (116 ± 11 vs. 95 ± 8 s; P = 0·07). These data suggest that a single bout of maximal exercise can provide a stimulus to restore peak vascular conductance and maintain time to fatigue during performance of ischaemic plantar flexion exercise.     

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.     

Autonomic nervous function at rest in aerobically trained and untrained oldermen

Therelationship between aerobictraining, vagal influence on the heart and ageing was examined by assessing aerobic fitness andresting heart rate variability in trained and untrained older men. Subjects were 11 trained cyclistsand runners (mean age=6±61·6 years) and 11 untrained, age-matchedmen (mean age=66±1·2 years). Heart rate variability testing involvedsubjects lying supine for 25 min during which subjects’ breathing was paced andmonitored (7·5 breaths min^?1). Heart rate variability was assessedthrough time series analysis (HRV_ts) of the interbeat interval. Results indicated thattrained older men (3·55±0·21 l min^?1) hadsignificantly (P<0·05) greater VO _2maxthan that of control subjects (2·35±0·15 l min^?1).Also, trained older men (52±1·8 beats min^?1) hadsignificantly (P<0·05) lower supine resting heart rate than that of controlsubjects (65±4·2 beats min^?1). HRV_ts at highfrequencies was greater for trained men (5·98±0·22) than for untrainedmen (5·23±0·32). These data suggest that regular aerobic exercise inolder men is associated with greater levels of HRV_ts at rest.     

Atrial natriuretic peptide concentrations in umbilical cord plasma from pre-eclamptic women

Summary. Atrial natriuretic peptide (ANP) was measured in arterial and venous umbilical cord plasma at the time of delivery by cesarean section in pre-eclamptic (n= 7) and normal women (n= 6). In addition venous samples were obtained from pre-eclamptic (n= 7) and normal pregnant women (n= 7) near term. ANP plasma levels were higher in pregnant women with pre-eclampsia than in normal pregnant women (27·9±4·4 [mean±SEM] and 14·1 ±2·5 pmol 1^-1, respectively, P<0·05). Immediately after delivery plasma ANP in pre-eclamptic mothers was 66·7 ± 12·8 pmol 1^-1 compared to 13·9 ±2·2 pmol 1^-1 in normal mothers (P<0·01). However, in the pre-eclamptic group the levels of ANP in arterial and venous umbilical cord plasma (19·5 ±4·2 and 16·7±4·3 pmol 1^-1 respectively) were significantly (P<0·01) lower than ANP levels in arterial and venous cord plasma (39·6 ± 1·0 and 31·1±4·2 pmol 1^-1, respectively) from normal mothers. It is concluded that the increased ANP plasma level in pre-eclamptic women originates from a maternal source. In addition, since the ANP level is lower in cord plasma than in maternal plasma in pre-eclampsia, fetoplacental volume homeostasis may also be changed in pre-eclampsia.     

The effect of a very low-calorie diet-induced weight loss on the severity of obstructive sleep apnoea and autonomic nervous function in obese patients with obstructive sleep apnoea syndrome

The aim of this study was to examine the effect of a very low-calorie diet (VLCD)-induced weight loss on the severity of obstructive sleep apnoea (OSA), blood pressure and cardiac autonomic regulation in obese patients with obstructive sleep apnoea syndrome (OSAS). A total of 15 overweight patients (14 men and one woman, body weight 114 ± 20 kg, age 52 ± 9 years, range 39–67 years) with OSAS were studied prospectively. They were advised to follow a 2·51–3·35 MJ (600–800 kcal) diet daily for a 3-month period. In the beginning of the study, the patients underwent nocturnal sleep studies, autonomic function tests and 24-h electrocardiograph (ECG) recording. In addition, 15 age-matched, normal-weight subjects were studied. They underwent the Valsalva test, the deep-breathing test and assessment of heart rate variability at rest. The sleep studies and autonomic function tests were repeated after the weight loss period. There was a significant reduction in weight (114 ± 20 kg to 105 ± 21 kg, P<0·001), the weight loss being 9·2 ± 4·0 kg (range 2·3–19·5 kg). This was associated with a significant improvement in the oxygen desaturation index (ODI4) during sleep (31 ± 20–19 ±18, P<0·001). Before the weight loss the OSAS patients had significantly higher blood pressure (150 ± 18 vs. 134 ± 20, P<0·05, for systolic blood pressure, 98 ± 10 vs. 85 ± 13, P<0·05, for diastolic blood pressure) and heart rate (67 ± 10 beats min^?1 vs. 60 ± 13, P<0·05) at rest than the control group. They had also lower baroreflex sensitivity (4·7 ± 2·8 ms mmHg^?1 vs. 10·8 ± 7·1 ms mmHg^?1, P<0·01). During the weight reduction, the blood pressure declined significantly, and the baroreflex sensitivity increased by 49%. In conclusion, our experience shows that weight loss with VLCD is an effective treatment for OSAS. Weight loss improved significantly sleep apnoea and had favourable effects on blood pressure and baroreflex sensitivity that may have prognostic implications.     

Autonomic neuropathy precedes cardiovascular dysfunction in rats with diabetes

Background Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ‐ and NA‐treated animals, using modern spectral estimation technique. Design An autoregressive process was performed to each detrended signal of heart rate and systolic blood pressure measured in the 4‐ and 8‐week STZ‐NA rats with anaesthesia. The power of low‐frequency and high‐frequency oscillations was automatically quantified with each spectral peak by computing the residuals. The closed‐loop baroreflex gain was estimated using the square root of the ratio between heart rate and systolic blood pressure powers in the low‐frequency band. Results Compared with the age‐matched controls, both the 4‐ and 8‐week STZ‐NA diabetic rats had significantly decreased low‐frequency oscillations of heart rate but not systolic blood pressure variability, showing a decline in baroreflex gain (0·451 ± 0·060 and 0·484 ± 0·056 vs. 1·196 ± 0·064 ms mmHg^?1, P < 0·05). On the other hand, the low frequency–high frequency power ratio of the heart period was also diminished in the two diabetic groups, indicating a shift in sympatho‐vagal balance of the heart control (0·472 ± 0·109 and 0·504 ± 0·090 vs. 1·857 ± 0·336, P < 0·05). Conclusions The cardiac autonomic dysfunction in the absence of any significant changes in vascular dynamics, 4 but not 8 weeks after induction of type 2 diabetes, suggests that the diabetic autonomic neuropathy may precede arterial stiffening and cardiac hypertrophy in the STZ‐ and NA‐treated rats.     

Interactions of stress hormones on lipid and carbohydrate metabolism in man with partial insulin deficiency

Abstract. The metabolic responses to 4-h infusions of adrenaline (3 μg kg^-1 h^-1) and cortisol (10 mg m^-2 h^-1 for 2 h followed by 5 mg m^-2 h^-1 for 2 h), separately and in combination, have been studied in six healthy subjects with concurrent somatostatin infusion (250 μg h^-1). A combined infusion of adrenaline, cortisol, glucagon (180 ng kg^-1 h^-1) and somatostatin has also been studied. Somatostatin plus adrenaline and somatostatin plus cortisol resulted in hyperglycaemia (at 240 min, somatostatin plus adrenaline 11·4 ± 0·4 mmol l^-1, P < 0·001; somatostatin plus cortisol 6·7 ± 0·3 mmol l^-1, P < 0·05; somatostatin alone 4·9 ± 0·4 mmol l^-1). No synergistic effect on blood glucose was seen with adrenaline and cortisol together. When glucagon was added, blood glucose rose more rapidly than without glucagon (9·3 ± 0·4 mmol l^-1v. 7·2 ± 0·5 mmol l^-1 at 45 min, P < 0·001), but plateau values were similar. Plasma NEFA levels were raised by somatostatin plus adrenaline (0·55 ± 0·04–1·82 ± 0·11 mmol l^-1 at 60 min). Somatostatin plus cortisol had no more effect on plasma NEFA than somatostatin alone. During the combined infusion of somatostatin plus adrenaline plus cortisol, a synergistic effect on plasma NEFA was observed (2·30 ± 0·11 mmol l^-1 at 60 min, P < 0·01 v. somatostatin plus adrenaline). This occurred despite a small escape of insulin secretion. The lipolytic actions of adrenaline are potentiated by elevated circulating cortisol levels in insulin-deficient man. Glucagon does not modify this response, but accelerates the development of hyperglycaemia.     

Can geometric indices of heart rate variability predict improvement in autonomic modulation after resistance training in chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) is associated with autonomic dysfunctions that can be evaluated through heart rate variability (HRV). Resistance training promotes improvement in autonomic modulation; however, studies that evaluate this scenario using geometric indices, which include nonlinear evaluation, thus providing more accurate information for physiological interpretation of HRV, are unknown. This study aimed to investigate the influence of resistance training on autonomic modulation, using geometric indices of HRV, and peripheral muscle strength in individuals with COPD. Fourteen volunteers with COPD were submitted to resistance training consisting of 24 sessions lasting 60 min each, with a frequency of three times a week. The intensity was determined as 60% of one maximum repetition and was progressively increased until 80% for the upper and lower limbs. The HRV and dynamometry were performed at two moments, the beginning and the end of the experimental protocol. Significant increases were observed in the RRtri (4·81 ± 1·60 versus 6·55 ± 2·69, P = 0·033), TINN (65·36 ± 35·49 versus 101·07 ± 63·34, P = 0·028), SD1 (7·48 ± 3·17 versus 11·04 ± 6·45, P = 0·038) and SD2 (22·30 ± 8·56 versus 32·92 ± 18·78, P = 0·022) indices after the resistance training. Visual analysis of the Poincare plot demonstrated greater dispersion beat-to-beat and in the long-term interval between consecutive heart beats. Regarding muscle strength, there was a significant increase in the shoulder abduction and knee flexion. In conclusion, geometric indices of HRV can predict improvement in autonomic modulation after resistance training in individuals with COPD; improvement in peripheral muscle strength in patients with COPD was also observed.     

A comparison of two methods of heart rate variability assessment at high altitude

Heart rate variability (HRV) is a useful index of autonomic function and has been linked to the development of high altitude (HA) related illness. However, its assessment at HA has been undermined by the relative expense and limited portability of traditional HRV devices which have mandated at least a minute heart rate recording. In this study, the portable ithlete^? HRV system, which uses a 55 s recording, was compared with a reference method of HRV which utilizes a 5 min electrocardiograph recording (CheckMyHeart^?). The root mean squares of successive R‐R intervals (RMSSD) for each device was converted to a validated HRV score (lnRMSSD × 20) for comparison. Twelve healthy volunteers were assessed for HRV using the two devices across seven time points at HA over 10 days. There was no significant change in the HRV values with either the ithlete (P = 0·3) or the CheckMyHeart^? (P = 0·19) device over the seven altitudes. There was also a strong overall correlation between the ithlete^? and CheckMyHeart^? device (r = 0·86; 95% confidence interval: 0·79–0·91). The HRV was consistently, though non‐significantly higher with ithlete^? than with the CheckMyHeart^? device [mean difference (bias) 1·8 l; 95% CI ?12·3 to 8·5]. In summary, the ithlete^? and CheckMyHeart^? system provide relatively similar results with good overall agreement at HA.     

The effect of different exercise‐testing protocols on atrial natriuretic peptide

The aim of this study was to examine and to compare alterations in the secretion of atrial natriuretic peptide (ANP) during different exercise‐testing protocols in moderately trained men. Fifteen healthy male physical education students were studied (mean age 22·3 ± 2·5 years, training experience 12·3 ± 2·5 years, height 1·80 ± 0·06 m, weight 77·4 ± 8·2 kg). Participants performed an initial graded maximal exercise testing on a treadmill for the determination of VO_2max (duration 7·45–9·3 min and VO_2max 55·05 ± 3·13 ml kg^?1 min^?1) and were examined with active recovery (AR), passive recovery (PR) and continuous running (CR) in random order. Blood samples for plasma ANP concentration were taken at rest (baseline measurement), immediately after the end of exercise as well as after 30 min in passive recovery time (PRT). The plasma ANP concentration was determined by radioimmunoassay (RIA). The results showed that ANP plasma values increased significantly from the rest period to maximal values. In the short‐term graded maximal exercise testing the ANP plasma values increased by 56·2% (44·8 ± 10·4 pg ml^?1 versus 102·3 ± 31·3 pg ml^?1, P<0.001) and in the CR testing the ANP levels increased by 29·2% (44·8 ± 10·4 pg ml^?1 versus 63·3 ± 19·8 pg ml^?1, P<0.001) compared to the baseline measurement. Moreover, the values of ANP decreased significantly (range 46·4–51·2%, P<0.001) in PRT after the end of the four different exercise modes. However, no significant difference was evident when ANP values at rest and after AR and PR were compared. It is concluded that the exercise testing protocol may affect the plasma ANP concentrations. Particularly, short‐term maximal exercise significantly increases ANP values, while the intermittent exercise form of active and passive recovery decreases ANP concentrations.     

Lower limb vascular conductance and resting popliteal blood flow during head‐up and head‐down postural challenges

This study hypothesized that central and local reflex mechanisms affecting vascular conductance (VC) through the popliteal artery compensated for the reduction in muscle perfusion pressure (MPP) to maintain popliteal blood flow (PBF) during head‐down tilt (35? HDT), but not in head‐up tilt (45? HUT). Resting measurements were made on 15 healthy men in prone position to facilitate the access to the popliteal artery, on two separate days in random order during horizontal (HOR), HDT or HUT. In each body position, the body was supported, and the ankles were maintained in relaxed state so that there was no muscle tension, as with normal standing. Popliteal blood flow velocity and popliteal arterial diameter were measured by ultrasound, and PBF was calculated. MPP was corrected to mid‐calf from measured finger cuff pressure, and VC was estimated by dividing PBF by MPP. The MPP in HDT (48 ± 2 mmHg) was ~100mmHg less than in HUT (145 ± 2 mmHg). PBF was similar between HOR (51 ± 18 ml min^?1) and HDT (47 ± 13 ml min^?1), but was lower in HUT (30 ± 9 ml min^?1). VC was different between HDT (1·0 ± 0·3 ml min^?1 mmHg^?1), HOR (0·6 ± 0·2 ml min^?1 mmHg^?1) and HUT (0·2 ± 0·1 ml min^?1 mmHg^?1). In conclusion, the interactions of central and local regulatory mechanisms resulted in a disproportionate reduction of VC during HUT lowering PBF even though MPP was higher, while in HDT, increased VC contributed to maintain PBF at the same level as the HOR control condition.     

Reduced cerebral oxygen–carbohydrate index during endotracheal intubation in vascular surgical patients

Brain activation reduces balance between cerebral consumption of oxygen versus carbohydrate as expressed by the so‐called cerebral oxygen‐carbohydrate‐index (OCI). We evaluated whether preparation for surgery, anaesthesia including tracheal intubation and surgery affect OCI. In patients undergoing aortic surgery, arterial to internal jugular venous (a‐v) concentration differences for oxygen versus lactate and glucose were determined from before anaesthesia to when the patient left the recovery room. Intravenous anaesthesia was supplemented with thoracic epidural anaesthesia for open aortic surgery (n = 5) and infiltration with bupivacaine for endovascular procedures (n = 14). The a‐v difference for O₂ decreased throughout anaesthesia and in the recovery room (1·6 ± 1·9 versus 3·2 ± 0·8 mmol l^?1, mean ± SD), and while a‐v glucose decreased during surgery and into the recovery (0·4 ± 0·2 versus 0·7 ± 0·2 mmol l^?1, P<0·05), a‐v lactate did not change significantly (0·03 ± 0·16 versus ?0·03 ± 0·09 mmol l^?1). Thus, OCI decreased from 5·2 ± 1·8 before induction of anaesthesia to 3·2 ± 1·0 following tracheal intubation (P<0·05) because of the decrease in a‐v O₂ with a recovery for OCI to 4·6 ± 1·4 during surgery and to 5·6 ± 1·7 in the recovery room. In conclusion, preparation for surgery and tracheal intubation decrease OCI that recovers during surgery under the influence of sensory blockade.     

Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy

Background: Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood. Methods and results: We studied 99 patients with IDC (age 54 ± 1 years, left ventricular ejection fraction (EF) 40 ± 1%, maximum oxygen uptake (VO₂max) 20 ± 1 ml kg^?1 min^?2, mean ± SEM) by using ¹²³I‐metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)‐ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)‐6 and N‐terminal B‐type natriuretic peptide (NT‐proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL‐6 (r = 0·42, P<0·001 and r = ?0·31, P<0·01) and NT‐proBNP (r = 0·48, P<0·001 and r = ?0·40, P<0·001). During a median follow‐up of 4·1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter–defibrillator). In these patients, MIBG washout was higher (53 ± 4 versus 40 ± 2%, P = 0·01) and H/M ratio lower (1·38 ± 0·04 versus 1·51 ± 0·02, P = 0·01) than in patients without an event. Conclusions: In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.     

Progressive central hypovolaemia in man—resulting in a vasovagal syncope?

Summary. Hypotensive functional haemorrhage induced by venous pooling of blood in the legs has been reported to be characterized by a vasovagal reaction. In the present study these observations were extended by determination of the hormonal profile developed during progressive central hypovolaemia and an emotionally induced vasovagal syncope. In six subjects venous pooling resulted in normotensive central hypovolaemia, in one subject hypotensive central hypovolaemia was induced, and one subject experienced an emotionally induced vasovagal syncope. During normotensive central hypovolaemia heart rate increased from 58 ± 4 to 76 ± 4 beats min^-1 (P<0·05) and cardiac output fell from 6·1 ± 0·4 to 4·1 ± 0·21 min^-1. Pulse pressure and central venous pressure decreased from 64 ± 4 to 53 ± 4 mmHg, and from 8 ± 2 to 3 ± 2 mmHg, respectively. Adrenalin and noradrenalin increased from 87 ± 10 to 120 ± 20 pg/ml and from 196 ± 33 to 370 ± 50 pg/ml, respectively. Angiotensin II increased from 13 ± 4 to 36 ± 6 pg/ml and aldosterone from 63 ± 9 to 180 ± 27 pg/ml. In hypotensive central hypovolaemia the decrease in mean arterial pressure was accompanied by a decrease in heart rate and increments in the plasma concentrations of pancreatic polypeptide, indicating increased vagal activity and β-endorphin, while plasma noradrenalin was unchanged. In emotionally induced syncope heart rate decreased to cardiac arrest for 13 s, associated with increments in the plasma concentrations of pancreatic polypeptide and β-endorphin. It is concluded (1) that normotensive functional haemorrhage in man is associated with increased sympathetic activity and (2) that the qualitatively similar observations obtained during an emotionally and a hypovolaemic-induced hypotensive episode indicate that the hypotensive functional haemorrhage is characterized by a vasovagal reaction.     

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.