. Interactions of plasma osmolality with arterial and central venous pressures in control of sympathetic activity and heart rate in humans. Am J Physiol Heart Circ Physiol 289: H2456 -H2460, 2005. First published September 30, 2005 doi:10.1152/ajpheart.00601.2005.-Plasma osmolality alters control of sympathetic activity and heart rate in animal models; however, it is unknown whether physiological increases in plasma osmolality have such influences in humans and what effect concurrent changes in central venous and/or arterial pressures may have. We tested whether physiological increases in plasma osmolality (similar to those during exercise dehydration) alter control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in humans. We studied 17 healthy young adults (7 women, 10 men) at baseline and during arterial pressure (AP) transients induced by sequential injections of nitroprusside and phenylephrine, under three conditions: control (C), after 1 ml/kg intravenous hypertonic saline (HT1), and after 2 ml/kg hypertonic saline (HT2). We continuously measured HR, AP, central venous pressure (CVP; peripherally inserted central catheter) and MSNA (peroneal microneurography) in all conditions. Plasma osmolality increased from 287 Ϯ 1 mosmol/kg in C to 290 Ϯ 1 mosmol/kg in HT1 (P Ͻ 0.05) but did not increase further in HT2 (291 Ϯ 1 mosmol/kg; P Ͼ 0.05 vs. C). Mean AP and CVP were similar between C and HT1, but both increased slightly in HT2. HR increased slightly but significantly during both HT1 and HT2 vs. C (P Ͻ 0.05). Sensitivity of baroreflex control of MSNA was significantly increased vs. C in HT1 [Ϫ7.59 Ϯ 0.97 (HT1) vs. Ϫ5.85 Ϯ 0.63 (C) arbitrary units (au) ⅐ beat Ϫ1 ⅐ mmHg Ϫ1 ; P Ͻ 0.01] but was not different in HT2 (Ϫ6.55 Ϯ 0.94 au ⅐ beat Ϫ1 ⅐ mmHg Ϫ1 ). We conclude that physiological changes in plasma osmolality significantly alter control of MSNA and HR in humans, and that this influence can be modified by CVP and AP. baroreflex; sympathetic nervous system; hydration; plasma volume CHANGES IN HYDRATION ELICIT important alterations in neural mechanisms controlling arterial pressure (AP) via the baroreflex (5, 6, 17). Influences of increased plasma osmolality, which can accompany decreases in volume seen with certain types of dehydration (such as with prolonged exercise), may also interact with changes in volume to alter autonomic mechanisms that have important implications for control of blood pressure in these conditions.Because increased plasma osmolality often accompanies dehydration, physiological responses to hyperosmolality are generally those that would tend to defend plasma volume and AP. In animal models, these have been shown to include sympathoexcitation (2, 7) and decreased urine output (20). Furthermore, hyperosmolality has been shown to alter arterial baroreflex control of both heart rate (HR) and sympathetic activity in rats (1, 7). Such influences of osmolality on baroreflex control mechanisms may also involve osmolality-induced increases in circulating volume-regulatory hormones ...

Delayed threshold for active cutaneous vasodilation in patients with Type 2 diabetes mellitus. J Appl Physiol 100: 637-641, 2006. First published October 6, 2005 doi:10.1152/japplphysiol.00943.2005.-Epidemiological evidence suggests decreased heat tolerance in patients with Type 2 diabetes mellitus (T2DM), but it is not known whether the mechanisms involved in thermoregulatory control of skin blood flow are altered in these patients. We tested the hypothesis that individuals with T2DM have a delayed internal temperature threshold for active cutaneous vasodilation during whole body heating compared with healthy control subjects. We measured skin blood flow using laser-Doppler flowmetry (LDF), internal temperature (T or) via sublingual thermocouple, and mean arterial pressure via Finometer at baseline and during whole body heating in 9 T2DM patients and 10 control subjects of similar age, height, and weight. At one LDF site, sympathetic noradrenergic neurotransmission was blocked by local pretreatment with bretylium tosylate (BT) to isolate the cutaneous active vasodilator system. Whole body heating was conducted using a water-perfused suit. There were no differences in preheating T or between groups (P Ͼ 0.10). Patients with T2DM exhibited an increased internal temperature threshold for the onset of vasodilation at both untreated and BT-treated sites. At BT-treated sites, T or thresholds were 36.28 Ϯ 0.07°C in controls and 36.55 Ϯ 0.05°C in T2DM patients (P Ͻ 0.05), indicating delayed onset of active vasodilation in patients. Sensitivity of vasodilation was variable in both groups, with no consistent difference between groups (P Ͼ 0.05). We conclude that altered control of active cutaneous vasodilation may contribute to impaired thermoregulation in patients with T2DM. temperature regulation; sweating; metabolic disorders IN RECENT YEARS, THE INCIDENCE of Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the United States and other developed countries (24), leading to increasing interest in mechanisms of metabolic, cardiovascular, and neurological dysfunction in this disease. Importantly, dysfunction in some or all of these areas can lead to significant impairment in mechanisms of thermoregulation, which itself can cause increased morbidity and mortality in patients with T2DM. Epidemiological data indicate that individuals with diabetes are at significantly higher risk for heat illness during heat waves compared with the general population (19,20). Although physiological/pathophysiological mechanisms are not well understood, some existing data are consistent with the potential for impaired thermoregulation. For example, diabetic patients with length-dependent peripheral neuropathy exhibit impaired sweating in affected areas (7,14). Furthermore, individuals with diabetes have been shown to have decreased vasodilator responsiveness to pharmacological stimuli in vascular beds, including the skin (3,11,21,22). Such peripheral impairments could lead to a decrease in the ability of the cutaneous vascu...

The assessment of sympathetic denervation to the upper extremities during surgery for hyperhidrosis is essential in predicting postoperative outcome, particularly for endoscopic thoracic chain sympathotomy, a recently described, minimally destructive technique that minimizes postoperative compensatory hyperhidrosis. To test the hypothesis that skin blood flow (SkBF; laser Doppler flowmetry) provides a faster and more reliable indication of denervation than temperature (temp), we prospectively compared palmar SkBF and fingertip temp in 10 patients undergoing endoscopic thoracic chain sympathotomy for essential hyperhidrosis. From baseline to peak values, palmar SkBF (mean +/- SEM) increased 273.3 +/- 24.7 arbitrary units and 252.4 +/- 30.1 arbitrary units, whereas temp increased 0.9 degrees C +/- 0.3 degrees C and 1.5 degrees C +/- 0.6 degrees C on the right and left, respectively. Upon effective sympathotomy of the right thoracic chain, the time to peak SkBF was 43 +/- 13 s, whereas the time to peak temp was 277 +/- 53 s (P <0.001). On the left, the time to peak SkBF was 81 +/- 14 s, and time to peak temp was 305 +/- 34 s (P <0.001). All patients considered the sympathotomy successful. We conclude that laser Doppler SkBF is superior to temp in temporal resolution for assessment of denervation during sympathotomy and that it provides a superior qualitative and quantitative adjunct to monitoring denervation.