Yrsa Bergmann Sverrisdóttir

Two sites for modulation of human sympathetic activity by arterial baroreceptors

1 Peroneal muscle sympathetic nerve activity (MSA), finger blood pressure and cardiac intervals were recorded at rest in 60 healthy subjects, aged 18–71 years. Arterial baroreflex control of MSA was analysed by relating each spontaneous sympathetic burst to the diastolic blood pressure and the cardiac interval of the heart beat during which the burst was generated. The results were expressed as blood pressure/cardiac interval threshold for occurrence of bursts, and as baroreflex sensitivity (i.e. the relationship between diastolic pressure/cardiac interval and burst strength). 2 Significant blood pressure/cardiac interval thresholds were present in all subjects and old subjects had less variability of thresholds than young subjects. In contrast, significant baroreflex sensitivity for diastolic pressure and cardiac interval was present in only 55 and 73 % of the subjects, respectively. There was no age‐related difference in sensitivity. 3 In 40 subjects, two 5 min periods from the same recording were analysed. The number of sympathetic bursts and the threshold for occurrence of bursts were reproducible in all subjects. In contrast, significant baroreflex sensitivity in both periods was present in only 30 % (diastolic pressure) and 40 % (cardiac interval) of the subjects. 4 The results show that the baroreflex mechanisms regulating the occurrence and strength of sympathetic bursts are not identical. We suggest that the modulation occurs at two sites, one which determines whether or not a burst will occur, and another at which the strength of the discharge is determined.

Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disturbance among women of reproductive age and is proposed to be linked with size at birth and increased prevalence of cardiovascular disease. A disturbance in the sympathetic nervous system may contribute to the etiology of PCOS. This study evaluates sympathetic outflow in PCOS and its relation to size at birth. Directly recorded sympathetic nerve activity to the muscle vascular bed (MSNA) was obtained in 20 women with PCOS and in 18 matched controls. Ovarian ultrasonographic evaluation, biometric, hormonal, and biochemical parameters were measured, and birth data were collected. Women with PCOS had increased MSNA (30 +/- 8 vs. 20 +/- 7 burst frequency, P < 0.0005) compared with controls. MSNA was positively related to testosterone (r = 0.63, P < 0.005) and cholesterol (r = 0.55, P = 0.01) levels in PCOS, which, in turn, were not related to each other. Testosterone level was a stronger predictor of MSNA than cholesterol. Birth size did not differ between the study groups. This is the first study to directly address sympathetic nerve activity in women with PCOS and shows that PCOS is associated with high MSNA. Testosterone and cholesterol levels are identified as independent predictors of MSNA in PCOS, although testosterone has a stronger impact. The increased MSNA in PCOS may contribute to the increased cardiovascular risk and etiology of the condition. In this study, PCOS was not related to size at birth.

Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome.

We have recently shown that polycystic ovary syndrome (PCOS) is associated with high muscle sympathetic nerve activity (MSNA). Animal studies support the concept that low-frequency electroacupuncture (EA) and physical exercise, via stimulation of ergoreceptors and somatic afferents in the muscles, may modulate the activity of the sympathetic nervous system. The aim of the present study was to investigate the effect of these interventions on sympathetic nerve activity in women with PCOS. In a randomized controlled trial, 20 women with PCOS were randomly allocated to one of three groups: low-frequency EA (n = 9), physical exercise (n = 5), or untreated control (n = 6) during 16 wk. Direct recordings of multiunit efferent postganglionic MSNA in a muscle fascicle of the peroneal nerve before and following 16 wk of treatment. Biometric, hemodynamic, endocrine, and metabolic parameters were measured. Low-frequency EA (P = 0.036) and physical exercise (P = 0.030) decreased MSNA burst frequency compared with the untreated control group. The low-frequency EA group reduced sagittal diameter (P = 0.001), while the physical exercise group reduced body weight (P = 0.004) and body mass index (P = 0.004) compared with the untreated control group. Sagittal diameter was related to MSNA burst frequency (Rs = 0.58, P < 0.005) in the EA group. No correlation was found for body mass index and MSNA in the exercise group. There were no differences between the groups in hemodynamic, endocrine, and metabolic variables. For the first time we demonstrate that low-frequency EA and physical exercise lowers high sympathetic nerve activity in women with PCOS. Thus, treatment with low-frequency EA or physical exercise with the aim to reduce MSNA may be of importance for women with PCOS.

Firing Properties of Single Muscle Vasoconstrictor Neurons in the Sympathoexcitation Associated With Congestive Heart Failure

BACKGROUND Congestive heart failure (CHF) in humans is associated with a marked sympathoexcitation, including an augmented muscle sympathetic nerve activity (MSNA) in intraneural multiunit recordings. In the present study, single-unit recording was used to evaluate whether the firing properties of individual muscle vasoconstrictor neurons can reveal underlying mechanisms for this increase in MSNA. METHODS AND RESULTS Eight patients with CHF (NYHA class II to IV; left ventricular ejection fraction, 29+/-5%, mean+/-SEM) were studied. In standard multiunit recordings, MSNA burst incidence (bursts/100 heartbeats) ranged from 65% to 100% (88+/-5%). Using selective tungsten microelectrodes, we made recordings from 16 single muscle vasoconstrictor axons. Mean unit firing probability (ie, the percentage of cardiac intervals in which a single axon fired) was 54.5+/-5.2% (range, 21 to 89%), and mean firing frequency was 0.98+/-0.22 Hz (0.14 to 3.86 Hz), both of which were higher than seen previously in healthy subjects (P<0.001). Although single neurons occasionally generated multiple spikes per sympathetic burst, such multiple firing was rare and was not different from that seen in healthy subjects. CONCLUSIONS An increased firing frequency of individual vasoconstrictor neurons is one mechanism for the increased number of multiunit MSNA bursts at rest in CHF. The neurons discharge in more diastoles than in healthy subjects (ie, firing probability is increased), but the likelihood of discharging >1 impulse per sympathetic burst is not increased. Despite the intense multiunit activity at rest, the firing characteristics of individual vasoconstrictor axons indicate a remaining capacity for transient increases of MSNA in CHF.

Low birth size and final height predict high sympathetic nerve activity in adulthood.

Objective Being born small for gestational age (SGA) is associated with insulin resistance, hypertension and increased cardiovascular morbidity/mortality in adulthood. Sympathetic nerve hyperactivity is a well-known risk factor for cardiovascular disease mortality and is proposed to link insulin resistance with hypertension. The objective of this study was to test the hypothesis that sympathetic nerve activity is altered in individuals born SGA. Design A cross-sectional, comparative study of 20 healthy adults (21–25 years old) born SGA (birth weight < −2SD score for healthy newborns) with normal and short stature, and 12 age, gender and body mass index matched individuals, born appropriate for gestational age (AGA) with normal stature. Methods Direct recordings of resting sympathetic nerve activity to the muscle vascular bed (MSA) were obtained from the peroneal nerve posterior to the fibular head. Heart rate, respiration and blood pressure were recorded during the microneurographic session. Results MSA was increased in both groups of young adults born SGA as compared to those born AGA (P < 0.05 and P < 0.005, respectively). In the combined study group MSA was inversely correlated to birth weight, length (r = −0.59, P < 0.001 and r = −0.69, P < 0.0005, respectively) and final adult height (r = −0.58; P < 0.001). Conclusions Being born SGA and achieving a short final height is associated with increased sympathetic nerve traffic. We suggest that the increase in sympathetic nerve traffic in young adults born SGA with normal and short stature may be the link between low birth size, hypertension and cardiovascular morbidity later in life.

Sympathetic Nerve Activity and Insulin in Obese Normotensive and Hypertensive Men

The relationship between resting levels of muscle sympathetic nerve activity (MSA) and blood pressure is a matter of controversy. Body weight has recently been identified as an independent determinant of muscle sympathetic discharge, which may have influenced previous studies focused on MSA and mechanisms of hypertension. In the present study, we measured resting MSA and plasma insulin levels in 18 obese (body mass index, 32 +/- 4 kg/m2) (mean +/- SD), middle-aged (52 +/- 6 years), hypertensive (155 +/- 11/97 +/- 8 mm Hg) subjects and 16 age- and body mass index-matched normotensive control subjects. In the postabsorptive state, resting MSA was similar in the hypertensive and normotensive groups (43 +/- 4 versus 39 +/- 3 bursts per minute, 69 +/- 5 versus 64 +/- 5 bursts per 100 heart beats, P = NS) (mean +/- SEM) and did not correlate with either systolic or diastolic blood pressure. Weak but significant positive correlations were found between resting MSA and both fasting insulin levels (P < .05) and body mass index (P = .05) in hypertensive but not normotensive subjects. There was a strong positive correlation between fasting insulin and body mass index in both normotensive subjects and the entire study group (P < .005). Fasting insulin and body mass index correlated with diastolic blood pressure (P < .05) in the entire study group. In conclusion, a relationship between fasting insulin, body mass index, and blood pressure was confirmed, whereas only a weak correlation was found between MSA and fasting insulin in hypertensive but not normotensive subjects. The fact that MSA was similar in the two groups argues strongly against augmented MSA being important for the maintenance of hypertension, at least in middle-aged, obese men.

Stress-Induced Cardiomyopathy in Sweden: Evidence for Different Ethnic Predisposition and Altered Cardio-Circulatory Status

Background: In this paper, we report about new insights regarding clinical course, long-term outcome, ethnic/genetic predisposition and cardio-circulatory status in the large stress-induced cardiomyopathy (SIC) cohort from Sweden. Methods and Results: We have included 115 consecutive SIC patients between January 2005 and January 2010 at Sahlgrenska University Hospital in Gothenburg. Hemodynamic status and sympathetic nerve activity were evaluated and compared with those of healthy controls. Mean age was 64, and 14% were males. Thirty-day and 3-year mortality was 6 and 10%, respectively. Eleven percent had ischemic heart disease, 3% developed thromboembolic complications, 6% had cardiac arrest and 14% developed cardiogenic shock. The great majority of SIC patients (93%) were ethnic Swedes. In three families, several close relatives developed SIC. Fourteen percent developed two or more episodes of SIC. Hemodynamic evaluation has shown subnormal systemic vascular resistance, 22% lower sympathetic activity and preserved cardiac output in SIC patients. Conclusions: SIC affects both men and women of different ages and is associated with significant short- and long-term mortality. There is a strong signal for the presence of ethnic/genetic predisposition to develop SIC. Sympathetic activity and systemic vascular resistance are lower in SIC patients, suggesting that SIC is a cardio-circulatory phenomenon.

Sympathetic Neural Burst Amplitude Distribution A More Specific Indicator of Sympathoexcitation in Human Heart Failure

BackgroundHuman muscle sympathetic nerve activity (MSNA) is usually measured as the number of pulse-synchronous bursts in multiunit mean voltage recordings. We recently suggested burst amplitude distribution as a more sensitive indicator of altered MSNA in congestive heart failure (CHF). Here, we test whether this distribution can discriminate between different conditions with increased MSNA burst frequency and whether it reflects single vasoconstrictor fiber firing intensity. Methods and ResultsWe analyzed resting multiunit MSNA in 36 CHF patients (24 with mild to moderate CHF, 12 with severe CHF investigated before and after heart transplantation), 14 patients with pituitary deficiency, 25 matched healthy control subjects, and an additional 56 healthy men with a wider age range (21 to 71 years). Pituitary deficiency was associated with increased MSNA burst frequency (60 versus 37 bursts/min in control subjects), equivalent to that in mild to moderate CHF (61 bursts/min). However, burst amplitude distribution in hypopituitary patients (median burst amplitude, 37%) did not deviate from matched control subjects (36%), whereas amplitudes increased with disease severity in CHF (43% in mild to moderate, 52% in severe) and normalized after transplantation (36%). In the larger healthy group, MSNA burst frequency increased with age, and burst amplitude distribution remained unaffected. In 8 CHF patients, single-unit firing frequency showed a close positive relationship to multiunit burst amplitude distribution (r =0.82, P <0.01) but none to burst frequency (r =0.39, P =0.3). ConclusionsMuscle vasoconstrictor fiber activity is better reflected by multiunit MSNA burst amplitude distribution than by burst frequency, at least in CHF. This distribution can discriminate between conditions with increased burst frequency.

Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.

CONTEXT Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. OBJECTIVE To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. DESIGN AND METHODS Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). RESULTS Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. CONCLUSION Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation.

Relative burst amplitude in human muscle sympathetic nerve activity: a sensitive indicator of altered sympathetic traffic.

Microneurographically recorded sympathetic outflow to the human muscle vascular bed is traditionally quantified by identifying pulse-synchronous bursts of impulses in a mean voltage neurogram and expressing them in terms of bursts per minute (burst frequency) or bursts per 100 heart beats (burst incidence). As both these measures show large inter-individual differences in resting healthy subjects, a problem arises when comparing sympathetic traffic in cross-sectional studies, making moderate differences in muscle sympathetic nerve activity (MSA) between groups difficult to identify. Absolute measures of the strength of the sympathetic discharges (burst amplitude or area) can also be evaluated. However, as they critically depend on the proximity of the microelectrode to the recorded fibres, such measures cannot be used for inter-individual comparisons.The aim of the present study was to evaluate the use of relative burst amplitude spectra for quantification of MSA, describing the proportion of small vs large bursts in a neurogram. We recorded MSA in 18 patients with mild to moderate congestive heart failure (CHF) (New York Heat Association functional classes I–IIIA) and 18 matched healthy controls. Sympathetic activity was expressed as burst frequency, burst incidence and burst amplitude spectra. When comparing the traditional burst counts between the groups (presented as the median and 25th–75th percentiles) there was a tendency towards higher MSA in CHF patients, but the difference was not significant (42 (34–52) vs 53 (41–63) bursts/min, 62 (51–78) vs 69 (52–84) bursts/100 heart beats, both ns). Relative burst amplitude spectra, on the other hand, were clearly shifted to the right in the CHF group compared to the control group (median burst amplitudes 42 (34–45) vs 30 (28–35),P=0.0002).Relative burst amplitude spectra thus appear to provide a more sensitive indicator of altered MSA than traditional burst counts. The right-ward shift of these spectra may suggest that sympatho-excitation occurs early in the development of CHF.