Sympathetic nervous response to ischemia-reperfusion injury in humans is altered with remote ischemic preconditioning.

Sympathetic neural activation may be detrimentally involved in tissue injury caused by ischemia-reperfusion (IR). We examined the effects of experimental IR in the forearm on sympathetic nerve response, finger reactive hyperemia, and oxidative stress, and the protection afforded by applying remote ischemic preconditioning (RIPC). Ischemia was induced in the forearm for 20 min in healthy volunteers. RIPC was induced by applying two cycles, 5 min each, of ischemia and reperfusion to the upper leg immediately before IR. We examined muscle sympathetic nerve activity (MSNA) in the contralateral leg using microneurography, finger reactive hyperemia [ischemic reactive hyperemia index (RHI)], erythrocyte production of reduced gluthathione (GSH), and plasma nitric oxide (NO) concentration. In controls (no RIPC; n = 15), IR increased MSNA in the early and late phase of ischemia (70% at 5 min; 101% at 15 min). In subjects who underwent RIPC (n = 15), the increase in MSNA was delayed to the late phase of ischemia and increased only by 40%. GSH increased during ischemia in the control group (P = 0.05), but not in those who underwent RIPC. Nitrate and nitrite concentration, taken as an index of NO availability, decreased during the reperfusion period in control individuals (P < 0.05), while no change was observed in those who underwent RIPC. Experimental IR did not affect RHI in the control condition, but a significant vasodilatory response occurred in the RIPC group (P < 0.05). RIPC attenuated ischemia-induced sympathetic activation, prevented the production of an erythrocyte marker of oxidative stress and the reduction of NO availability, and ameliorated RHI.

Sympathetic activation and endothelial dysfunction in polycystic ovary syndrome are not explained by either obesity or insulin resistance.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrine condition underpinned by insulin resistance and associated with increased risk of obesity, type 2 diabetes and adverse cardiovascular risk profile. Previous data suggest autonomic imbalance [elevated sympathetic nervous system (SNS) activity and decreased heart rate variability (HRV)] as well as endothelial dysfunction in PCOS. However, it is not clear whether these abnormalities are driven by obesity and metabolic disturbance or whether they are independently related to PCOS. PARTICIPANTS AND METHODS: We examined multiunit and single-unit muscle SNS activity (by microneurography), HRV (time and frequency domain analysis) and endothelial function [ischaemic reactive hyperaemia index (RHI) using the EndoPAT device] in 19 overweight/obese women with PCOS (BMI: 31·3 ± 1·5 kg/m(2), age: 31·3 ± 1·6 years) and compared them with 21 control overweight/obese women (BMI: 33·0 ± 1·4 kg/m(2), age: 28·2 ± 1·6 years) presenting a similar metabolic profile (fasting total, HDL and LDL cholesterol, glucose, triglycerides, insulin sensitivity and blood pressure). RESULTS: Women with PCOS had elevated multiunit muscle SNS activity (41 ± 2 vs 33 ± 3 bursts per 100 heartbeats, P < 0·05). Single-unit analysis showed that vasoconstrictor neurons were characterized by elevated firing rate and probability and incidence of multiple spikes (P < 0·01 for all parameters). Women with PCOS also had impaired endothelial function (RHI: 1·77 ± 0·14 vs 2·18 ± 0·14, P < 0·05). HRV did not differ between the groups. CONCLUSION: Women with PCOS have increased sympathetic drive and impaired endothelial function independent of obesity and metabolic disturbances. Sympathetic activation and endothelial dysfunction may confer greater cardiovascular risk in women with PCOS.

Serum uric acid and the relationship with subclinical organ damage in adults.

AIMS: Elevated serum uric acid (SUA) is often present in conditions associated with increased cardiovascular risk yet it is not recognized as a marker of risk. We evaluated whether SUA was associated with evidence of early markers of cardiovascular risk factor including subclinical early organ damage, sympathetic tone and metabolic profile in a healthy population with a high prevalence of obesity. MATERIAL AND METHODS: Data from 281 patients (175 women and 106 men, mean age: 35.5 ±â€Š0.8 years, mean BMI: 33.2 ±â€Š0.5 kg/m) were retrieved from a database. All participants were healthy, nonsmoker and free of medication. Available data included metabolic profile, muscle sympathetic nervous activity (MSNA, microneurography), endothelial function (pulse amplitude tonometry, augmentation index), estimated glomerular filtration rate (eGFR) and echocardiography. RESULTS: With participants grouped into sex-adjusted tertiles of SUA, those in the third tertile of SUA had increased waist circumference, worse metabolic profile (fasting glucose, total cholesterol, triglycerides and HDL), elevated MSNA, decreased endothelial function, increased augmentation index and decreased eGFR compared with those in the first tertile of SUA. In multiple regression analysis adjusted for age, sex, BMI and ethnicity, SUA was independently associated with waist circumference, low-density lipoprotein, triglycerides, augmentation index, MSNA and eGFR, providing a combined adjusted R = 0.599 or 60% of the overall variance. CONCLUSION: In a healthy population with a high proportion of obesity, SUA is associated with measures of metabolic, end-organ damage and sympathetic tone indicating the potential value of SUA as a marker of early cardiovascular disease development.

Elevated sympathetic activity, endothelial dysfunction, and late hypertension after repair of coarctation of the aorta.

BACKGROUND: There is a high prevalence of late hypertension after coarctation repair. The relative contribution of elevated sympathetic tone and endothelial dysfunction to its development is unknown. This study aims to investigate the neural profile of coarctation patients including muscle sympathetic nerve activity testing to directly measure sympathetic nervous activity. METHODS: Twenty-three patients aged ≥18years with a coarctation repair underwent measurements of clinic and 24-h blood pressures, muscle sympathetic nerve activity, sympathetic and cardiac baroreflex functions, digital endothelial function, and ambulatory arterial stiffness index. Median age at repair was 1.2months (interquartile range: 0-9months). Patients were compared to 17 healthy matched controls. RESULTS: After 26±5years, 6% (1/18) and 44% (8/18) suffered clinic hypertension and prehypertension, respectively. On 24-h blood pressure monitoring, 15% (3/20) and 20% (4/20) had hypertension and prehypertension, respectively. Coarctation patients had elevated muscle sympathetic nerve activity compared with controls (49.6±24.9 vs. 29.9±14.0 bursts/100 heartbeats, p=0.02), dampened sympathetic baroreflex function (-2.2±2.1 vs. -7.0±5.6 bursts/100heartbeats·mm·Hg-1, p=0.007), normal cardiac baroreflex function (41.9±30.4 vs. 35.7±21.1ms·mm·Hg-1, p=0.6), endothelial dysfunction (pulse amplitude tonometry ratio: 0.39±0.32 vs. 0.81±0.50, p=0.004), and increased ambulatory arterial stiffness index (0.46±0.15 vs. 0.29±0.17, p=0.008). CONCLUSION: After coarctation repair patients have increased muscle sympathetic nerve activity, dampened sympathetic baroreflex response, endothelial dysfunction, and increased ambulatory arterial stiffness index, all of which may contribute to the development of late hypertension.