Does the autonomic nervous system play a role in the development of insulin resistance? A study on heart rate variability in first-degree relatives of Type 2 diabetes patients and control subjects.

AIMS: To investigate dysregulation of the autonomic nervous system as a potential mechanism for early insulin resistance in the development of Type 2 diabetes. METHODS: Thirteen healthy individuals with first-degree relatives with Type 2 diabetes (R) were compared with 14 control subjects without family history of diabetes (C), matched for age, body mass index and sex. An oral glucose tolerance test and a hyperinsulinaemic euglycaemic clamp were performed. Analysis of heart rate variability during rest, controlled breathing, an orthostatic manoeuvre and a standardized physical stress (cold pressor test (CPT)), were used to evaluate the activity of the autonomic nervous system. RESULTS: Fasting blood glucose, HbA1c and serum insulin were similar in the R and C groups. The M-value, reflecting insulin sensitivity, did not differ significantly between the groups. Total spectral power and high-frequency power were lower in R during controlled breathing (P = 0.05 and P = 0.07, respectively), otherwise there were no significant differences between R and C in heart rate variability. However, low-frequency (LF)/high-frequency (HF) spectral power ratio during CPT, reflecting sympathetic/parasympathetic balance, was negatively associated with insulin sensitivity (r = -0.53, P = 0.006). When all subjects were divided into two groups by the mean M-value, the low M-value group displayed an overall higher LF/HF ratio (P = 0.04). HF power was lower in the low M-value group during controlled breathing and CPT (P = 0.01 and P = 0.03, respectively). CONCLUSION: An altered balance of the parasympathetic and sympathetic nervous activity, mainly explained by an attenuated parasympathetic activity, might contribute to the development of insulin resistance and Type 2 diabetes.

Heart rate variability in athletes: relationship with central and peripheral performance.

PURPOSE: To investigate relationships between heart rate variability (HRV) and peripheral and central performance measures, 17 cross-country (X-C) skiers and seven canoeists were studied before and after a training period of 7 months. METHODS: For the skiers and canoeists respectively, leg and arm peak torque (Tq), time to peak torque (TiTq), and total work (Wrk) were measured in an isokinetic dynamometer. Maximal oxygen uptakes (VO(2max)) were obtained from treadmill tests. Power spectral analysis of HRV was performed on electrocardiographic recordings in the resting supine position and after a tilt to yield power in the low-frequency (0.04--0.15 Hz) and high-frequency (0.15--0.45 Hz) components of HRV. RESULTS: The change in normalized LF-variability in standing (Delta LFnT) correlated (P < 0.01) with the changes in TiTq (r = 0.63), max lactate (r = -0.63), and VO(2max) (r = -0.53). The change in absolute LFT was inversely correlated with the change in Tq. Subjects who improved VO(2max) were characterized by consistently higher high-frequency and total HRV than subjects with deteriorated aerobic capacity (P < 0.05). CONCLUSION: The results suggest that improved measures of both peripheral and central (aerobic) work capacities were associated with a reduction of low-frequency HRV in the tilted position. High-frequency and total HRV did not change in proportion with changes in muscle performance or aerobic capacity, but the ability to further improve VO(2max) with training in these already fit subjects seemed to depend on their average levels of these HRV measures, interpreted to reflect parasympathetic activity.

Pre- and post-season heart rate variability in adolescent cross-country skiers.

To investigate the effects on cardiac autonomic control after a competitive cross-country skiing season, 9 females and 8 males, 16-19 years old, performed tilt-table heart rate variability (HRV) recordings and incremental treadmill tests before (August), and after (April the following year) the most intensive period of training and competition. Spectral analysis of HRV showed increased total variability at rest and reduced low frequency variability in the tilted position (LFtilt) at the second test (P<0.05). The female subgroup showed consistently higher high frequency (HF) and total heart rate variability than males. Total run time (RunT) increased from 18.5+/-1.9 min to 19.4+/-1.7 min (mean+/-SD) in the entire group (P<0.05), while VO2max only showed a non-significant increase (0.05

Cardiac autonomic imbalance in an overtrained athlete.

PURPOSE: In order to investigate overtraining-related adaptations in the autonomic nervous system, cardiac autonomic activity was examined in a junior cross-country skier who presented with reduced performance in competitions, early breathlessness during training sessions, and accumulated central fatigue. METHODS: Power spectral analysis of heart rate variability (HRV) was performed before, when overtrained (OT), and after recovery (Rec). RESULTS: In the overtrained state, high frequency (HF) and total powers in the lying position were higher compared with before and after. In normalized units, the increased HF in OT was even more prominent and clearly higher than in any control subject, and it was reversed in Rec. Resting heart rate was slightly reduced in OT and returned to baseline in Rec. CONCLUSIONS: The shift toward increased heart rate variability, particularly in the HF range, together with a reduced resting heart rate suggest a cardiac autonomic imbalance with extensive parasympathetic modulation in this athlete when overtrained.

Endoscopic transthoracic sympathicotomy affects the autonomic modulation of heart rate in patients with palmar hyperhidrosis.

BACKGROUND: Palmar hyperhidrosis has been associated with an increased activity of the sympathetic nervous system. The objective of this study was to assess the immediate and long-term effects of endoscopic transthoracic sympathicotomy on the autonomic modulation of the heart rate in patients with palmar hyperhidrosis. METHODS: Power spectrum analysis of heart rate variability in the lying position and after passive tilt to the upright position was performed in thirteen patients the day before and after sympathicotomy. A follow-up recording was performed in ten patients approximately six months later. Recordings from 26 healthy subjects were used as a reference group. FINDINGS: The patients had a tendency to higher power of the low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF; above 0.15 Hz) components than controls in the upright position. After sympathicotomy LF power was reduced, but HF power was unchanged. At follow-up LF power remained at a lower level, but now HF power was reduced. INTERPRETATION: Patients with palmar hyperhidrosis have a sympathetic overactivity but also a compensatory high parasympathetic activity. Sympathicotomy results in an initial sympathovagal imbalance with a parasympathetic predominance, which is restored on a long-term basis.

Short-term overtraining: effects on performance, circulatory responses, and heart rate variability.

PURPOSE AND METHODS: Nine elite canoeists were investigated concerning changes in performance, heart rate variability (HRV), and blood-chemical parameters over a 6-d training camp. The training regimen consisted of cross-country skiing and strength training, in total 13.0+/-1.6 h, corresponding to a 50% increase in training load. RESULTS: Time to exhaustion (RunT) decreased from 19.1+/-1.0 to 18.0+/-1.2 min (P < 0.05). VO2max and max lactate (La(max)) both decreased significantly (P < 0.05) over the training period (4.99+/-0.97 to 4.74+/-0.98 L x min(-1) and from 10.08+/-1.25 to 8.98+/-1.03 mmol x L(-1) respectively). Heart rates (HR) decreased significantly at all workloads. Plasma volume increased by 7+/-7% (P < 0.05). Resting cortisol, decreased from 677+/-244 to 492+/-222 nmol x L(-1) (P < 0.05), whereas resting levels of adrenaline and noradrenaline remained unchanged. The change between tests in RunT correlated significantly with the change in HRmax (r = 0.79; P = 0.01). There were no group changes in high or low frequency HRV, neither at rest nor following a tilt. CONCLUSIONS: The reduced maximal performance indicates a state of fatigue/overreaching and peripheral factors are suggested to limit performance even though HRmax and La(max) both were reduced. The reduced submaximal heart rates are probably a result of increased plasma volume. HRV in this group didn't seem to be affected by short-term overtraining.

Autonomic cardiovascular regulation in patients with obstructive sleep apnoea: a study based on spectral analysis of heart rate variability.

The aim of this study was to assess the function of the autonomic nervous system in patients with obstructive sleep apnoea syndrome (OSAS). The study was designed as a cross-sectional case-control study. Fifty-one patients were included, and the findings were compared with those in 66 controls. Spectral analysis of heart rate variability (HRV) during supine rest, during controlled breathing and after tilting was performed in each patient and control case. The patients performed overnight sleep recordings the night before the HRV recordings. Individuals with an apnoea-hypopnoea index (AHI) above 20 were regarded as OSAS patients and those with AHI lower than 20 as snorers. Differences in HRV and blood pressure between patients and controls were analysed by multiple linear regression with age, body mass index and sex as independent variables. During free and controlled breathing there was a significant decrease in indices reflecting vagal modulation, indicating parasympathetic dysfunction in OSAS patients compared with controls. The mid-frequency component was also significantly reduced in OSAS patients after tilting but not in the lying position. This may be related to the parasympathetic dysfunction, but could also indicate a decreased sympathetic reserve capacity. We found no significant relation between AHI and indices of vagal modulation in the patient group. Our findings show an autonomic dysfunction in patients with OSAS. The dysfunction involves the parasympathetic system, and may be related to the increased cardiovascular mortality and malignant arrhythmia described in OSAS.

The long-term outcome of retropubic urethrocystopexy (sutures and fibrin sealant) and pubococcygeal repair.

BACKGROUND: To evaluate the results of retropubic urethrocystopexy (with sutures and fibrin sealant) and pubococcygeal repair five to seven years postoperatively. MATERIALS AND METHODS: Thirty women with genuine stress urinary incontinence were subjected to retropubic urethrocystopexy (n=30) and 15 women to pubococcygeal repair (n= 15). The preoperative assessment included both subjective and objective methods. The results evaluated three months, one year and five to seven years after the surgical treatment. RESULTS: One year after surgery 71% of the women in the urethrocystopexy group reported that they were continent, compared with only 43% five to seven years after surgery. In the pubococcygeal repair group 80% were continent at one-year follow-up, compared with 60% at the long-term follow-up. According to pad test 79% of the women in the urethrocystopexy group had ceased leaking urine at minimal activity and 64% at maximal activity five to seven years after surgery. However, in the pubococcygeal repair group the corresponding percentage was 71% under both conditions. Intravesical pressure and Body Mass Index increased significantly in the whole group but urethra conductance and maximal urine flow decreased only in the urethrocystopexy group five to seven years after the surgical treatment. CONCLUSIONS: Accurate assessment of the results of any surgical treatment of stress urinary incontinence is difficult. During long term follow-up period significant changes may occur among the women, e.g. menopause and increase of Body Mass Index both predisposing to urinary incontinence.

Spectral analysis of heart rate variability in patients with irritable bowel syndrome.

BACKGROUND: Autonomic dysfunction, both adrenergic and cholinergic, has been associated with the irritable bowel syndrome (IBS). The accuracy of the methods in use, however, has been limited by the need for active co-operation by the patients, with consequent difficulties in standardization. The aim of this study was to investigate the function of the autonomic nervous system in patients with IBS by using spectral analysis of the heart rate variability, an accurate method depending very little on patient cooperation. METHODS: Eighteen patients with IBS were compared with 36 sex- and age-matched controls. Spectral analysis of heart rate variability was performed to quantify sympathetic and parasympathetic nerve activity. RESULTS: The patients with IBS had significantly higher sympathetic activity than controls (P = 0.005). There was no significant (P = 0.308) increase in parasympathetic activity. There were no significant differences in heart rate or blood pressure between the patients and controls. CONCLUSION: Spectral analysis of heart rate variability has been used to assess the function of the autonomic nervous system in patients with IBS. IBS patients have significantly increased symphathetic activity, whereas parasympathetic activity does not differ from that of controls.

Impact of autonomic neuropathy on circulatory instability during liver transplantation for familial amyloidotic polyneuropathy.

BACKGROUND: Circulatory instability with severe hypotension frequently complicates liver transplantation in patients with familial amyloidotic polyneuropathy. Autonomic dysfunction is found early in the course of the disease by analysis of beat-to-beat heart rate variability (HRV). The aim of the present study was to investigate the impact of autonomic neuropathy on intraoperative circulatory instability during liver transplantation for familial amyloidotic polyneuropathy. METHODS: Twenty-two patients were evaluated at the Department of Medicine, Umea University Hospital, by spectral analysis of HRV and later received liver transplants at Huddinge University Hospital. The low-and high-frequency bands obtained by spectral analysis of HRV in the supine and upright positions, respectively, were used as representative of sympathetic and parasympathetic activity. Circulatory instability during transplantation was defined as a fall in systolic arterial blood pressure below 70 mmHg for more than 5 min during the preanhepatic phase. RESULTS: Both arrhythmia preventing spectral analysis of HRV and a sympathetic variability peak below 2.5 mHz2 were significantly more common among patients with intraoperative circulatory instability (P=0.03 and 0. 004, respectively). A diminished increase in pulse rate when tilting the patients from the supine to the upright position was also more pronounced among patients with circulatory instability (P<0.05). CONCLUSIONS: The majority of patients who will develop circulatory instability with a pronounced fall in arterial blood pressure can be identified by Poincare plots of R-R intervals and spectral analysis of HRV. A low sympathetic peak or arrhythmia precluding spectral analysis of HRV is significantly related to operative circulatory instability.

Assessment of autonomic nerve function in acute intermittent porphyria; a study based on spectral analysis of heart rate variability.

OBJECTIVES: To assess the function of the autonomic nervous system in patients with acute intermittent porphyria by spectral analysis of the heart rate variability. DESIGN: A cross-sectional case-control study. SETTING: Patients were examined at the Primary Health Care Centre, Arjeplog and at Umeå University Hospital, where the controls were also examined. SUBJECTS: Twenty-three patients with acute intermittent porphyria verified by DNA analysis and 92 healthy controls were included. MAIN OUTCOME MEASURES: The mid-frequency band power after tilting was used to evaluate sympathetic function, and the high frequency band power during controlled breathing at 12 breaths min-1 and the mid-frequency band power during controlled deep breathing at 6 breaths min-1 were used to evaluate parasympathetic function. RESULTS: There was no evidence of sympathetic dysfunction in the patients. The mid-frequency band power during controlled deep breathing at 6 breaths min-1 was significantly (P = 0.02) lower in the patient group. CONCLUSIONS: Our findings indicate a parasympathetic dysfunction in patients with acute intermittent porphyria. This may be causally related to sudden cardiac death and the life-threatening arrhythmias which have been observed in this disorder.

Cold induced vasospasm in replanted digits: a comparison between different methods of arterial reconstruction.

Nineteen patients each of whom had had a single digit replanted were examined after replantation. The arterial reconstruction had been done with long grafts (n = 10) or short grafts or no graft (n = 9). The effect of local or whole body cooling on the replanted and uninjured opposite digits was monitored (9-46 months after the replantation), and the patients were given a questionnaire (9-95 months after replantation) designed to explore the development of their cold related symptoms in relation to time. All patients were troubled by cold intolerance, and improvement occurred in only 60% of the cases. Pathological (vasospastic) arterial reactions to cold measured as finger systolic pressure, were less common after replantation with long grafts. Perceived cold intolerance was significantly more pronounced in the group of patients (60%) who had evidence of cold induced arterial spasm in the replanted finger.

Grip strength of the human hand--measurements on normal subjects with a new hand strength analysis system (Hastras).

This study describes a method of acquiring data from healthy and non-injured men that can be used as reference data when measuring the grip strength of the human hand using newly developed, PC-based hand strength analysis equipment--'Hastras'. Hastras can be used for continuous measurement and recording of force when the subject grips a sensor with maximum power. Computerized analysis of the force signal gives information about maximum force, fatigue, area and rise (force/s). The statistical analysis of the measurements on 81 subjects are consistent with earlier published data from other hand strength equipment. It is concluded that Hastras gives easy processing and storage of data, and also a detailed analysis of grip function.

von Willebrand factor and fibrinolytic variables are differently affected in the insulin resistance syndrome.

OBJECTIVES: To test whether von Willebrand factor, a new cardiovascular risk factor, belongs to the group of risk factors forming part of the insulin resistance syndrome. DESIGN: A population-based, age-stratified, cross-sectional study. SETTING: A primary health care centre. SUBJECTS: All subjects aged 35, 45, 55, and 65 years in Norsjö municipality (n = 265) were invited, and 68% (82 males, 93 females) entered and completed the study. RESULTS: von Willebrand factor did not correlate with any measured lipid, anthropometric, or glucose metabolism variable. The higher levels of cardiovascular risk factors found in the subgroup of patients with electrocardiographical signs of ischaemic heart disease did not confound this result. CONCLUSION: von Willebrand factor plasma concentration is unrelated to the metabolic factors involved in the insulin resistance syndrome. Thus, it may be difficult to reduce elevated von Willebrand factor levels by conventional non-pharmacological cardiovascular high-risk intervention schemes.

Arterial spasticity and cold intolerance in relation to time after digital replantation.

Cold induced arterial vasospasm was studied in ten patients with single digit replantation, by measuring finger systolic pressure at different finger temperatures. Each patient was examined three times; within 2 weeks of surgery, after 1 year and after 3 years. The replantations were performed using long arterial and venous grafts. Cold-related vasospasm is established during the first year after trauma, and thereafter seems to be persistent. It is concluded that the subjective cold tolerance, which affects all patients after digital amputation regardless of whether replantation is performed or not, is partly due to vasospasm. It is less pronounced in patients without pathological vasospasm in the replanted digit. Cold intolerance is likely to decrease during the first 2 years after replantation, but not to disappear completely.

Urodynamics in women with stress incontinence before and after surgery.

Pad test, cystometry and analysis of micturition were performed in 36 women with stress incontinence before and a year after operation with either retropubic urethrocystopexy (n = 22) or pubococcygeal repair (n = 14). There was no difference in the subjective cure rate between the two groups of women (77% and 79%, respectively). The pad test 1 year after operation showed that 59% of the women in the urethrocystopexy group and 43% of the women in the pubococcygeal repair group had stopped leaking urine. The bladder volume had increased in both groups and the intravesical pressure of the bladder filled to the maximum had increased in the pubococcygeal repair group. The functional length of the urethra, intravesical pressure at maximal urine flow, maximal urine flow rate and urethral conductance were not affected by either operation. Pad test was a more accurate test for an objective evaluation of urine leakage before operation than were the urodynamic investigation or continence tests.

Oesophageal dysfunction in familial amyloidosis with polyneuropathy.

Sixteen patients with familial amyloidosis and polyneuropathy (FAP) and 14 health subjects underwent oesophageal manometry. Six of the patients had a severe oesophageal dysmotility with almost completely abolished propulsive pressure waves on swallowing in the lower 2/3 of the oesophagus. Ten patients had moderate dysfunction with reduced propulsive pressure wave amplitudes. Neostigmine increased the pressure wave amplitudes in healthy subjects but less so in the FAP patients. Scopolamine (Scopyl)-terbutaline (Bricanyl) almost abolished the propulsive pressure waves in healthy subjects and all patients in the lower 2/3 of the esophagus. Oesophageal distensibility, tested by inflating a rubber balloon in the oesophagus, was similar in FAP patients and healthy subjects. Thus, it is unlikely that amyloid deposits in the mucosal wall increased the oesophageal stiffness. An autonomic, predominantly vagal, denervation probably explains the disturbed function.

Heart-rate variation: what are we measuring?

Many methods have been proposed during the last two decades for the assessment of autonomic nervous system function by quantification of the heart-rate variation (HRV). Relatively little has been written about the HRV in relation to physiological models of the heart-rate regulation. The integral pulse frequency model (IPFM) is a simple model that describes the genesis of heartbeats under the influence of the autonomic nervous system. By comparing simulated HRV data generated with the IPFM model with data from healthy volunteers we found similarities indicating that the model accurately reflects real data. Furthermore, we found a considerable difference between HRV measurements based on beat-by-beat heart-rate and measurements based on the heartbeat interval. Our results suggest that the commonly used electrocardiographic RR interval representation of heart-rate variation might possess an inherent nonlinear, mean heart-rate-dependent property indicating that analysis directly based on RR intervals can give biased results with respect to the underlying autonomic activity. The conclusions embrace all measurements of variation that are directly based on RR intervals including simple indices as well as higher-level quantification such as spectral analysis.

Factors that influence the incidence of brachial oedema after treatment of breast cancer.

Six factors that may increase the likelihood of swelling of the arm after treatment of breast cancer were investigated in 136 patients who had undergone treatment. The highest incidence of oedema was among patients who had received radiotherapy in high doses with few fractions to the axilla (60%), and in patients with a history of one or more infections in the arm on the operated side (89%). Overweight, oblique surgical incision, infection in the arm, and radiotherapy correlated with arm swelling. The age of the patient and whether the operation had been done on the dominant or non-dominant side correlated less with the incidence of oedema.

Increased plasminogen activator inhibitor and tissue plasminogen activator levels in subjects with electrocardiographic abnormality indicative of ischaemic heart disease: a cross-sectional study in Norsjö, Sweden.

The plasma levels of tissue plasminogen activator (tPA) antigen concentration and plasminogen activator inhibitor (PAI) activity were measured in a random sample of 260 subjects, 30, 40, 50, or 60 years of age. Electrocardiographic Q, ST and/or ST-T changes, suggestive of definite or possible ischaemic heart disease (IHD), were found in 21% of the 50-year-old and 37% of the 60-year-old subjects. As compared to subjects lacking such signs, plasma tPA and PAI levels were significantly increased in the 60-year-old group, and PAI tended to be increased in the 50-year-old group. Previous case-control studies, usually performed at specialized centres and liable to sampling biases, have suggested an association between increased PAI levels and ischaemic heart disease. This cross-sectional population study provides independent data that patients with electrocardiographic signs of IHD have increased levels of both PAI and tPA antigen.