Incidence of new onset dementia and health care utilization following spine fusions: A propensity score matching analysis.

BACKGROUND: Dementia following spine fusions is not described in the literature. Also, the impact of new onset dementia on long-term health care utilization is not described. The aim of our study was to define the incidence of new onset dementia and its long-term health care utilization in elderly patients. MATERIALS AND METHODS: MarketScan database were queried using the ICD-9/10 and CPT 4th edition, from 2001 to 2019. We included patients≥55 of age who underwent spine fusions with at least 5years follow-up. Outcomes were new onset dementia (>6months after the procedure) length of stay (LOS), discharge disposition, hospital readmissions, outpatient services, and medication refills. RESULTS: Of 45,129 patients who underwent spine fusions, 1283 patients (2.84%) were diagnosed to have new onset dementia. There was no difference in the reoperation rates among the dementia and non-dementia cohort at 1-, 2- and 5-years following the index procedure. Patients in the dementia cohort incurred higher number of hospital readmissions up to 5-years after the index procedure. In terms of combined index procedure and post-discharge utilization payments, significant differences were noted among the dementia vs. non-dementia cohorts at 5-years ($126,628 vs. $77,098), following the index procedure. CONCLUSION: Elderly age, higher comorbidities, Medicare insurance, multilevel lumbosacral fusions were identified as risk markers for developing dementia following spine fusions. Dementia resulted in significantly higher health care utilization with no increased rate of reoperations for up to 5-years following the index procedure.

Influence of endogenous angiotensin II on control of sympathetic nerve activity in human dehydration.

Arterial blood pressure can often fall too low during dehydration, leading to an increased incidence of orthostatic hypotension and syncope. Systemic sympathoexcitation and increases in volume regulatory hormones such as angiotensin II (AngII) may help to maintain arterial pressure in the face of decreased plasma volume. Our goals in the present study were to quantify muscle sympathetic nerve activity (MSNA) during dehydration (DEH), and to test the hypothesis that endogenous increases in AngII in DEH have a mechanistic role in DEH-associated sympathoexcitation. We studied 17 subjects on two separate study days: DEH induced by 24 h fluid restriction and a euhydrated (EUH) control day. MSNA was measured by microneurography at the peroneal nerve, and arterial blood pressure, electrocardiogram, and central venous pressure were also recorded continuously. Sequential nitroprusside and phenylephrine (modified Oxford test) were used to evaluate baroreflex control of MSNA. Losartan (angiotensin type 1 receptor (AT1) antagonist) was then administered and measurements were repeated. MSNA was elevated during DEH (42 +/- 5 vs. EUH: 32 +/- 4 bursts per 100 heartbeats, P = 0.02). Blockade of AT1 receptors partially reversed this change in MSNA during DEH while having no effect in the control EUH condition. The sensitivity of baroreflex control of MSNA was unchanged during DEH compared to EUH. We conclude that endogenous increases in AngII during DEH contribute to DEH-associated sympathoexcitation.

[Diagnostic and preoperative staging of endometrial carcinoma with transvaginal sonography--a review]. / Diagnostik und präoperatives Staging des Endometriumkarzinoms mittels transvaginaler Sonographie--eine Ubersicht.

Endometrial carcinoma is the most common malignant tumor of the female genital tract. The major non-invasive diagnostic method is ultrasound. Endometrial thickness (double layer) is measured by transvaginal sonography. The cut-off value in patients with postmenopausal bleeding is still controversial, although in patients with endometrial thickness below 4 mm (or 5 mm respectively), malignancy can be excluded with high probability. If the endometrium measures more than 4 mm (or more than 5 mm respectively) or the patient presents with continuous bleeding, hysteroscopy and curettage should be performed in order to obtain histologic diagnosis. Sonographic findings like structure and demarcation of the endometrium increase diagnostic specificity only when combined with the measurement of endometrial thickness. Measuring the fluid within the uterine cavity does not seem to be useful in differentiating malignant from benign disorders. The extent of surgery depends on the preoperative estimation of the tumor stage which is particularly important for elder patients with increased morbidity. Transvaginal sonography has not been widely accepted to predict the depth of myometrial invasion or cervical infiltration. Although promising studies exist, additional examinations have to be done in order to determine the role of transvaginal sonography beside other methods (CT, MRT). This article on transvaginal ultrasound reviews current data on the method's capacity to identify endometrial cancer and to diagnose the depth of invasion.

Relationship between muscle sympathetic nerve activity and systemic hemodynamics during nitric oxide synthase inhibition in humans.

Large interindividual differences exist in resting sympathetic nerve activity (SNA) among normotensive humans with similar arterial pressure (AP). We recently showed inverse relationships of resting SNA with cardiac output (CO) and vascular adrenergic responsiveness that appear to balance the influence of differences in SNA on blood pressure. In the present study, we tested whether nitric oxide (NO)-mediated vasodilation has a role in this balance by evaluating hemodynamic responses to systemic NO synthase (NOS) inhibition in individuals with low and high resting muscle SNA (MSNA). We measured MSNA via peroneal microneurography, CO via acetylene uptake and AP directly, at baseline and during increasing systemic doses of the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). Baseline MSNA ranged from 9 to 38 bursts/min (13 to 68 bursts/100 heartbeats). L-NMMA caused dose-dependent increases in AP and total peripheral resistance and reflex decreases in CO and MSNA. Increases in AP with L-NMMA were greater in individuals with high baseline MSNA (PANOVA<0.05). For example, after 8.5 mg/kg of L-NMMA, in the low MSNA subgroup (n=6, 28+/-4 bursts/100 heartbeats), AP increased 9+/-1 mmHg, whereas in the high-MSNA subgroup (n=6, 58+/-3 bursts/100 heartbeats), AP increased 15+/-2 mmHg (P<0.01). The high-MSNA subgroup had lower baseline CO and smaller decreases in CO with L-NMMA, but changes in total peripheral resistance were not different between groups. We conclude that differences in CO among individuals with varying sympathetic traffic have important hemodynamic implications during disruption of NO-mediated vasodilation.

Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans.

In humans, sympathetic nerve activity (SNA) at rest can vary several-fold among normotensive individuals with similar blood pressures. We recently showed that a balance exists between SNA and cardiac output, which may contribute to the maintenance of normal blood pressures over the range of resting SNA levels. In the present studies, we assessed whether variability in vascular adrenergic responsiveness has a role in this balance. We tested the hypothesis that forearm vascular responses to noradrenaline (NA) and tyramine (TYR) are related to SNA such that individuals with lower resting SNA have greater adrenergic responsiveness, and vice-versa. We measured multifibre muscle SNA (MSNA; microneurography), arterial pressure (brachial catheter) and forearm blood flow (plethysmography) in 19 healthy subjects at baseline and during intrabrachial infusions of NA and TYR. Resting MSNA ranged from 6 to 34 bursts min(-1), and was inversely related to vasoconstrictor responsiveness to both NA (r = 0.61, P = 0.01) and TYR (r = 0.52, P = 0.02), such that subjects with lower resting MSNA were more responsive to NA and TYR. We conclude that interindividual variability in vascular adrenergic responsiveness contributes to the balance of factors that maintain normal blood pressure in individuals with differing levels of sympathetic neural activity. Further understanding of this balance may have important implications for our understanding of the pathophysiology of hypertension.

Balance between cardiac output and sympathetic nerve activity in resting humans: role in arterial pressure regulation.

Large, reproducible interindividual differences exist in resting sympathetic nerve activity among normotensive humans with similar arterial pressures, resulting in a lack of correlation between muscle sympathetic nerve activity (MSNA) and arterial pressure among individuals. Although it is known that the arterial pressure is the main short-term determinant of MSNA in humans via the arterial baroreflex, the lack of correlation among individuals suggests that the level of arterial pressure is not the only important input in regulation of MSNA in humans. We studied the relationship between cardiac output (CO) and baroreflex control of sympathetic activity by measuring MSNA (peroneal microneurography), arterial pressure (arterial catheter), CO (acetylene uptake technique) and heart rate (HR; electrocardiogram) in 17 healthy young men during 20 min of supine rest. Across individuals, MSNA did not correlate with mean or diastolic blood pressure (r<0.01 for both), but displayed a significant negative correlation with CO (r=-0.71, P=0.001). To assess whether CO is related to arterial baroreflex control of MSNA, we constructed a baroreflex threshold diagram for each individual by plotting the percentage occurrence of a sympathetic burst against diastolic pressure. The mid-point of the diagram (T50) at which 50% of cardiac cycles are associated with bursts, was inversely related to CO (r=-0.75, P<0.001) and stroke volume (SV) (r=-0.57, P=0.015). We conclude that dynamic inputs from CO and SV are important in regulation of baroreflex control of MSNA in healthy, normotensive humans. This results in a balance between CO and sympathetically mediated vasoconstriction that may contribute importantly to normal regulation of arterial pressure in humans.

Diabetic dyslipidemia and exercise affect coronary tone and differential regulation of conduit and microvessel K+ current.

Spontaneous transient outward K(+) currents (STOCs) elicited by Ca(2+) sparks and steady-state K(+) currents modulate vascular reactivity, but effects of artery size, diabetic dyslipidemia, and exercise on these differentially regulated K(+) currents are unclear. We studied the conduit arteries and microvessels of male Yucatan swine assigned to one of three groups for 20 wk: control (C, n = 7), diabetic dyslipidemic (DD, n = 6), or treadmill-trained DD animals (DDX, n = 7). Circumflex artery blood flow velocity obtained with intracoronary Doppler and lumen diameters obtained by intravascular ultrasound enabled calculation of absolute coronary blood flow (CBF). Ca(2+) sparks were determined in pressurized microvessels, and perforated patch clamp assessed K(+) current in smooth muscle cells isolated from conduits and microvessels. Baseline CBF in DD was decreased versus C. In pressurized microvessels, Ca(2+) spark activity was significantly lower in DD versus C and DDX (P < 0.05 vs. DDX). STOCs were pronounced in microvessel (approximately 35 STOCs/min) in sharp contrast to conduit cells ( approximately 2 STOCs/min). STOCs were decreased by 86% in DD versus C and DDX in microvessels; in contrast, there was no difference in STOCs across groups in conduit cells. Steady-state K(+) current in microvessels was decreased in DD and DDX versus C; in contrast, steady-state K(+) current in conduit cells was decreased in DDX versus DD and C. We conclude that steady-state K(+) current and STOCs are differentially regulated in conduit versus microvessels in health and diabetic dyslipidemia. Exercise prevented diabetic dyslipidemia-induced decreases in baseline CBF, possibly via STOC-regulated basal microvascular tone.

Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans.

Volume expansion often ameliorates symptoms of orthostatic intolerance; however, the influence of this increased volume on integrated baroreflex control of vascular sympathetic activity is unknown. We tested whether acute increases in central venous pressure (CVP) diminished subsequent responsiveness of muscle sympathetic nerve activity (MSNA) to rapid changes in arterial pressure. We studied healthy humans under three separate conditions: control, acute 10 degrees head-down tilt (HDT), and saline infusion (SAL). In each condition, heart rate, arterial pressure, CVP, and peroneal MSNA were measured during 5 min of rest and then during rapid changes in arterial pressure induced by sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). Sensitivities of integrated baroreflex control of MSNA and heart rate were assessed as the slopes of the linear portions of the MSNA-diastolic blood pressure and R-R interval-systolic pressure relations, respectively. CVP increased approximately 2 mmHg in both SAL and HDT conditions. Resting heart rate and mean arterial pressure were not different among trials. Sensitivity of baroreflex control of MSNA was decreased in both SAL and HDT condition, respectively: -3.1 +/- 0.6 and -3.3 +/- 1.0 versus -5.0 +/- 0.6 units.beat(-1).mmHg(-1) (P < 0.05 for SAL and HDT vs. control). Sensitivity of baroreflex control of the heart was not different among conditions. Our results indicate that small increases in CVP decrease the sensitivity of integrated baroreflex control of sympathetic nerve activity in healthy humans.

Validation of the inflammatory bowel disease questionnaire IBDQ-D, German version, for patients with ileal pouch anal anastomosis for ulcerative colitis.

BACKGROUND AND AIMS: The inflammatory bowel disease questionnaire (IBDQ) is the standard instrument for assessment of health-related quality of life (HRQOL) in patients with inflammatory bowel diseases. It has not been validated for patients with ileal pouch anal anastomosis (IPAA) and ulcerative colitis (UC). METHODS: To determine acceptance (percentage of completed items), reliability (Cronbach's alpha of the IBDQ-D subscales) and convergent validity (correlations of the IBDQ subscales with the questionnaires used for validation) 61 patients with UC (age 52.7 +/- 13.9 years; 47 % female, 53 % male) and IPAA completed the German (Competence Network IBD) version of the Inflammatory Bowel Disease Questionnaire (IBDQ-D), the Short Form Health Survey (SF-36) the Hospital Anxiety and Depression Scale German Version (HADS-D) and the Giessener Symptom List (GBB 24). Face validity was assessed by a physicians' and patients' panel. All 37 patients underwent endoscopy making it possible to differentiate between patients with and without pouchitis (discriminant validity). RESULTS: With 97.7 % completed items the acceptance was high. Cronbach's alpha value for the subscales ranged from 0.71 to 0.93. Missing items covering extraintestinal manifestations of IBD were criticized by patients. The correlation coefficients with comparable subscales of other instruments ranged between 0.41 and 0.76. Patients with clinical pouchitis scored significantly lower in all subscales than patients without pouchitis (p < 0.001). CONCLUSION: The IBDQ-D has good acceptance, reliability, convergent and discriminant validity, but limited face and construct validity in patients with IPAA and UC.

Sympathetic vasodilation in human muscle.

The idea that there might be sympathetic vasodilator nerves to skeletal muscle is an old concept that fits with the archaic 'fight or flight' model of the sympathetic nervous system. Clear evidence for vasodilator nerves to skeletal muscle began to emerge in animals during the 1930s, when stimulation of selected brainstem areas was shown to evoke hypertension, tachycardia and skeletal muscle vasodilation (i.e. the 'defense reaction'). By the 1940s and 1950s this idea was well established and it was shown in animals that the sympathetic dilator nerves to muscles were cholinergic. During this time, circumstantial evidence began to suggest the existence of sympathetic cholinergic vasodilator fibres in human skeletal muscle. In this context, the well- known forearm vasodilator response to mental stress was shown to be atropine-sensitive, and absent after surgical sympathectomy. However, while there was clear histological evidence for sympathetic cholinergic dilator fibres in animal muscle, such evidence was not seen in humans. Additionally, attempts to record from sympathetic dilator fibres human muscle have never demonstrated clear evidence for dilator nerve traffic, and many 'sympathetic dilator' responses are still present after local anaesthetic nerve block. More recently, the skeletal muscle dilator response to sympathoexcitatory manoeuvres in both humans and animals appears to be nitric oxide (NO)-dependent. While there are clearly atropine-sensitive and NO-dependent dilator nerves to skeletal muscles in animals, our current thinking is that most 'sympathetic dilator' responses in human muscle are due to adrenaline or local cholinergic mechanisms acting to stimulate NO release from the vascular endothelium.

Exercise training attenuates coronary smooth muscle phenotypic modulation and nuclear Ca2+ signaling.

Physical inactivity is an independent risk factor for coronary heart disease, yet the mechanism(s) of exercise-related cardioprotection remains unknown. We tested the hypothesis that coronary smooth muscle after exercise training would have decreased mitogen-induced phenotypic modulation and enhanced regulation of nuclear Ca(2+). Yucatan swine were endurance exercise trained (EX) on a treadmill for 16-20 wk. EX reduced endothelin-1-induced DNA content by 40% compared with sedentary (SED) swine (P < 0.01). EX decreased single cell peak endothelin-1-induced cytosolic Ca(2+) responses compared with SED by 16% and peak nuclear Ca(2+) responses by 33% (P < 0.05), as determined by confocal microscopy. On the basis of these results, we hypothesized that sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and intracellular Ca(2+) stores in native smooth muscle are spatially localized to dissociate cytosolic Ca(2+) and nuclear Ca(2+). Subcellular localization of SERCA in living and fixed cells revealed a distribution of SERCA near the sarcolemma and on the nuclear envelope. These results show that EX enhances nuclear Ca(2+) regulation, possibly via SERCA, which may be one mechanism by which coronary smooth muscle cells from EX are less responsive to mitogen-induced phenotypic modulation.

From Belfast to Mayo and beyond: the use and future of plethysmography to study blood flow in human limbs.

Venous occlusion plethysmography is a simple but elegant technique that has contributed to almost every major area of vascular biology in humans. The general principles of plethysmography were appreciated by the late 1800s, and the application of these principles to measure limb blood flow occurred in the early 1900s. Plethysmography has been instrumental in studying the role of the autonomic nervous system in regulating limb blood flow in humans and important in studying the vasodilator responses to exercise, reactive hyperemia, body heating, and mental stress. It has also been the technique of choice to study how human blood vessels respond to a variety of exogenously administered vasodilators and vasoconstrictors, especially those that act on various autonomic and adrenergic receptors. In recent years, plethysmography has been exploited to study the role of the vascular endothelium in health and disease. Venous occlusion plethysmography is likely to continue to play an important role as investigators seek to understand the physiological significance of newly identified vasoactive factors and how genetic polymorphisms affect the cardiovascular system in humans.

Reduced submaximal leg blood flow after high-intensity aerobic training.

This study evaluated the hypothesis that active muscle blood flow is lower during exercise at a given submaximal power output after aerobic conditioning as a result of unchanged cardiac output and blunted splanchnic vasoconstriction. Eight untrained subjects (4 men, 4 women, 23-31 yr) performed high-intensity aerobic training for 9-12 wk. Leg blood flow (femoral vein thermodilution), splanchnic blood flow (indocyanine green clearance), cardiac output (acetylene rebreathing), whole body O(2) uptake (VO(2)), and arterial-venous blood gases were measured before and after training at identical submaximal power outputs (70 and 140 W; upright 2-leg cycling). Training increased (P < 0.05) peak VO(2) (12-36%) but did not significantly change submaximal VO(2) or cardiac output. Leg blood flow during both submaximal power outputs averaged 18% lower after training (P = 0.001; n = 7), but these reductions were not correlated with changes in splanchnic vasoconstriction. Submaximal leg VO(2) was also lower after training. These findings support the hypothesis that aerobic training reduces active muscle blood flow at a given submaximal power output. However, changes in leg and splanchnic blood flow resulting from high-intensity training may not be causally linked.

Differences in K+ current components in mesenteric artery myocytes from WKY and SHR.

Previous studies have documented increased K+ permeability of arterial smooth muscle in hypertension and suggested a role in altered arterial contractile function. To characterize the mechanisms responsible for these alterations, we determined the contribution of K+ current (IK) components to whole cell IK in freshly dispersed myocytes and tetraethylammonium (TEA)-induced contractile responses in mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tetraethylammonium produced a larger tonic contractile response in SHR with a lower threshold compared to WKY (ie, 0.1 v 1 mmol/L), which was due in part to the larger Ca2+ current in SHR. Whole cell IK recorded by perforated patch methods was similar at a holding potential (HP) of -60 mV (IK60), but were larger in SHR when recorded from a HP of -20 mV (IK20). The selective blocker iberiotoxin (IbTX) was used to separate the contribution of voltage- (Kv) and calcium-dependent (KCa) components of IK60. The IK60 and IK20 component inhibited by 100 nmol/L IbTX (ie, KCa) was larger in SHR than in WKY myocytes, whereas the IbTX-insensitive IK60 component (ie, Kv) was larger in WKY. In the presence of IbTX, 1 and 10 mmol/L TEA inhibited a larger fraction of IK60 in SHR myocytes compared with WKY. The activation properties of the TEA-sensitive and TEA-insensitive Kv components determined by fitting a Boltzmann activation function to the current-voltage data, exhibited both group and treatment differences in the half maximal activation voltage (V0.5). The V0.5 of the TEA-sensitive Kv component was more positive than that of the TEA-insensitive component in both groups, and values for the V0.5 of both TEA-sensitive and TEA-insensitive components were more negative in SHR than WKY. These results show that SHR myocytes have larger KCa and smaller Kv current components compared with WKY. Furthermore, SHR myocytes have a larger TEA-sensitive Kv component. These differences may contribute to the differences in TEA contractions, resting membrane potential, Ca2+ influx, and KCa current reported in hypertensive arteries.

Calcium buffering in coronary smooth muscle after chronic occlusion and exercise training.

OBJECTIVE: Exercise promotes "sarcoplasmic reticulum (SR) Ca2+ unloading" in porcine coronary smooth muscle, resulting in decreased agonist-induced Ca2+ release. We studied Ca2+ handling in healthy, non-occluded right coronary artery cells from hearts chronically occluded at the circumflex artery. METHODS: Myoplasmic free Ca2+ (Ca(m)) was assessed with fura-2 in cells from sedentary (n=8) and aerobically exercise-trained (n=6) female Yucatan pigs after 6-month circumflex artery ameroid occlusion (OCC) and in cells from non-occluded, sedentary pigs (SED, n=5). First, Ca influx was induced by 80 mM KCl depolarization (priming step) followed by 5 mM caffeine to elicit maximal Ca2+ release and depletion. The SR was Ca-loaded again by depolarization and then exposed to caffeine after 2- or 11-min recovery to compare SR Ca2+ unloading. RESULTS: Baseline Ca(m), caffeine-induced peak Ca(m), and depolarization-induced maximum Ca(m) were decreased, and depolarization-induced time-to-half-maximum was increased in OCC vs. SED pigs, suggesting a tonic Ca2+ buffering (lowering) effect of occlusion. Exercise did not alter these effects. SR Ca2+ unloading occurred only in SED, as evidenced by decreased caffeine-induced Ca2+ release after 11 min of recovery, and was inhibited by low extracellular Na+. CONCLUSIONS: SR Ca2+ unloading can be demonstrated in coronary smooth muscle from sedentary pigs using a novel SR Ca2+ unloading protocol, and Ca2+ unloading partly depends on Na+-Ca2+ exchange activity. Furthermore, SR Ca2+ unloading in cells from non-occluded right coronary arteries of chronically circumflex-occluded pig hearts was not altered by exercise, perhaps due to enhanced tonic Ca2+ extrusion versus cells from normal, sedentary animals.

Theoretical analysis of phase-matched second-harmonic generation and optical parametric oscillation in birefringent semiconductor waveguides.

We analyze the phase-matching conditions for second-harmonic generation (SHG) and optical parametric oscillation (OPO) in birefringent nonlinear semiconductor waveguides and apply these results to the model system of ZnGeP2 on a GaP substrate. The analyses and numerical results show that phase matching can be achieved for OPO and SHG for reasonable guide thicknesses throughout much of the infrared, indicating significant potential applications for nonlinear birefringent waveguides. For the fundamental mode of a relatively thick guide the region of phase matching and the phase-matching angles are similar to those in bulk material. However, the waveguide has the added flexibility that phase-matched coupling can occur between the various modes of the guide. For example, the phase-matching region for SHG can be considerably extended by coupling the pump into the guide in the fundamental, m = 0, mode and phase matching to the m = 2 mode of the second harmonic. Significantly, the results indicate, among other things, that ZnGeP2 waveguides with harmonic output in the m = 2 mode can be used for efficient SHG from input radiation in the 9.6-10.6-microm region where bulk efficiencies in this wavelength range are too small to be useful.

Cardiac output during exercise by the open circuit acetylene washin method: comparison with direct Fick.

An open-circuit (OpCirc) acetylene uptake cardiac output (QT) method was modified for use during exercise. Two computational techniques were used. OpCirc1 was based on the integrated uptake vs. end-tidal change in acetylene, and OpCirc2 was based on an iterative finite difference modeling method. Six subjects [28-44 yr, peak oxygen consumption (VO(2)) = 120% predicted] performed cycle ergometry exercise to compare QT using OpCirc and direct Fick methods. An incremental protocol was repeated twice, separated by a 10-min rest, and subsequently subjects exercised at 85-90% of their peak work rate. Coefficient of variation of the OpCirc methods and Fick were highest at rest (OpCirc1, 7%, OpCirc2, 12%, Fick, 10%) but were lower at moderate to high exercise intensities (OpCirc1, 3%, OpCirc2, 3%, Fick, 5%). OpCirc1 and OpCirc2 QT correlated highly with Fick QT (R(2) = 0.90 and 0.89, respectively). There were minimal differences between OpCirc1 and OpCirc2 compared with Fick up to moderate-intensity exercise (<70% peak VO(2)); however, both techniques tended to underestimate Fick at >70% peak VO(2). These differences became significant for OpCirc1 only. Part of the differences between Fick and OpCirc methods at the higher exercise intensities are likely related to inhomogeneities in ventilation and perfusion matching (R(2) = 0.36 for Fick - OpCirc1 vs. alveolar-to-arterial oxygen tension difference). In conclusion, both OpCirc methods provided reproducible, reliable measurements of QT during mild to moderate exercise. However, only OpCirc2 appeared to approximate Fick QT at the higher work intensities.

Effects of atropine and L-NAME on cutaneous blood flow during body heating in humans.

We sought to investigate further the roles of sweating, ACh spillover, and nitric oxide (NO) in the neurally mediated cutaneous vasodilation during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured with a laser-Doppler flowmeter. After a rise in core temperature (1. 0 +/- 0.1 degrees C) and the establishment of cutaneous vasodilation, atropine and subsequently the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) were given to the forearm via a brachial artery catheter. After atropine infusion, cutaneous vascular conductance (CVC) remained constant in five of six subjects, whereas L-NAME administration blunted the rise in CVC in three of six subjects. A subsequent set of studies using intradermal microdialysis probes to selectively deliver drugs into forearm skin confirmed that atropine did not affect CVC. However, perfusion of L-NAME resulted in a significant decrease in CVC (37 +/- 4%, P < 0.05). The results indicate that neither sweating nor NO release via muscarinic receptor activation is essential to sustain cutaneous dilation during heating in humans.

Leg free fatty acid kinetics during exercise in men and women.

We previously reported that epinephrine stimulates leg free fatty acid (FFA) release in men but not in women. The present studies were conducted to determine whether the same is true during exercise. Six men and six women bicycled for 90 min at 45% of peak O(2) consumption, during which time systemic and leg FFA kinetics ([9, 10-(3)H]palmitate) were measured. The catecholamine and hormonal responses to exercise were not different in men and women. The baseline systemic and leg palmitate release was 94 +/- 15 vs. 114 +/- 5 micromol/min and 16 +/- 2 and 20 +/- 3 micromol/min, respectively, in men and women [P = nonsignificant (NS)]. Systemic and leg palmitate release increased (both P < 0.001) to 251 +/- 18 vs. 212 +/- 16 micromol/min and 73 +/- 19 vs. 80 +/- 12 micromol/min in men and women, respectively, during the last 30 min of exercise (P = NS, men vs. women). We conclude that the systemic and leg adipose tissue lipolytic response to exercise is not different in nonobese men and women.

Gender and nitric oxide-mediated vasodilation in humans.

BACKGROUND: We compared forearm vasodilator responses between females and males after administration of compounds that stimulate nitric oxide (NO) release, act as NO donors, or are NO-independent. METHODS AND RESULTS: We studied nine premenopausal females and nine age-matched males. Forearm blood flow (FBF) was measured with plethysmography. Graded doses of the endothelial-dependent vasodilators acetylcholine and bradykinin and the endothelial-independent vasodilator sodium nitroprusside were given via a brachial artery catheter to the non-dominant arm. Reactive hyperemia was measured as an index of NO-independent vasodilation. In females estradiol levels were greater, and serum triglycerides were lower, but cholesterol was similar to that of males. FBF responses to all doses of the three drugs were approximately 30% less in females. Females had smaller forearms and lower peak FBF during reactive hyperemia. Blood flow responses to the drugs as a fraction of the peak reactive hyperemia values were similar in females and males. In the females, but not in the males, FBF responses to all three drugs and reactive hyperemia correlated with estradiol levels. CONCLUSIONS: The smaller FBF responses in females were likely due to smaller forearm volume and muscle mass. Estradiol levels are associated with both NO-mediated and non-NO-mediated dilator responses in females.