Importance of inpatient hypoglycaemia: impact, prediction and prevention.

Hypoglycaemia is a key barrier to achieving euglycaemic control in people who are hospitalized. Inpatient hypoglycaemia has been linked to adverse clinical outcomes, including mortality and longer stay in hospital. A number of studies have applied mathematical tools and statistical models to predict inpatient hypoglycaemia and identify factors that may result in hypoglycaemic events. Several different approaches have been tested to prevent inpatient hypoglycaemia. These can be categorized as human intervention, computerized methods or application of medical devices. In this review we provide an overview of the epidemiology of inpatient hypoglycaemia and its impact on patients and hospitals. We also discuss the existing methodology used to predict inpatient hypoglycaemia and the limited number of trials performed to prevent inpatient hypoglycaemia. The review highlights the urgent need for evidence-based methods to reduce inpatient hypoglycaemia.

Leptin (rs7799039) and solute carrier family 30 zinc transporter (rs13266634) polymorphisms in Euro-Brazilian pregnant women with gestational diabetes.

Leptin (LEP), a protein that plays a fundamental role in the metabolism of energy reserves, and the solute carrier family 30 A8 zinc transporter (SLC30A8) have been consistently associated with diabetes. Women with gestational diabetes are at moderate risk of developing diabetes type 1 and 2 after pregnancy, in addition to complications to the fetus. We investigated the association of the polymorphisms rs7799039 (LEP) and rs13266634 (SLC30A8) in a case-control study in Euro-Brazilians with gestational diabetes (GDM, N = 134) and healthy pregnant women (control, N = 180). Real-time PCR with fluorescent probes (TaqMan system) was applied to genotyping. All polymorphisms were in Hardy-Weinberg equilibrium. The minor allele frequencies, for healthy and GDM, respectively, for the A-allele (LEP gene rs7799039) were 40.3% (95%CI = 35-45%) vs 36.6% (95%CI = 31-42%), P = 0.345; and for the T-allele (SLC30A8 gene rs13266634) were 27.8% (95%CI = 23-32%) vs 23.5% (95%CI = 18-29%), P = 0.227. Genotype comparisons for both polymorphisms showed no significant difference (P > 0.05). The polymorphisms rs7799039 and rs13266634 were not associated with GDM in the population studied (P > 0.05). The minor allele frequencies for both polymorphisms were similar to those of other Caucasian populations.

Low prevalence of glucokinase gene mutations in gestational diabetic patients with good glycemic control.

Glucokinase (GCK) plays a key role in glucose homeostasis. Gestational diabetes mellitus increases the risk of gestational complications in pregnant women and fetuses. We screened for mutations in coding and flanking regions of the GCK gene in pregnant women with or without gestational diabetes in a Brazilian population. A sample of 200 pregnant women classified as healthy (control, N = 100) or with gestational diabetes (N = 100) was analyzed for mutations in the GCK gene. All gestational diabetes mellitus patients had good glycemic control maintained by diet alone and no complications during pregnancy. Mutations were detected by single-strand conformation polymorphism and DNA sequencing. Thirteen of the 200 subjects had GCK gene mutations. The mutations detected were in intron 3 (c.43331A>G, new), intron 6 (c.47702T>C, rs2268574), intron 9 (c.48935C>T, rs2908274), and exon 10 (c.49620G>A, rs13306388). None of these GCK mutations were found to be significantly associated with gestational diabetes mellitus. In summary, we report a low frequency of GCK mutations in a pregnant Brazilian population and describe a new intronic variation (c.43331A>G, intron 3). We conclude that mutations in GCK introns and in non-translatable regions of the GCK gene do not affect glycemic control and are not correlated with gestational diabetes mellitus.

The functional polymorphisms -429T>C and -374T>A of the RAGE gene promoter are not associated with gestational diabetes in Euro-Brazilians.

The receptor for advanced glycation end products (RAGE or AGER) is a multiligand member of the immunoglobulin superfamily. RAGE is expressed in several tissues, including human myometrium, chorionic villi and placenta. Advanced glycation end products are the best studied ligands of RAGE; they have pro-inflammatory actions in human gestational tissues, increasing oxidative stress and the release of cytokines and prostaglandins. We investigated the association of RAGE gene promoter polymorphisms -429T>C (rs1800625) and -374T>A (rs1800624) with gestational diabetes. A sample of 750 unrelated European origin pregnant Brazilian women were classified as nondiabetic (control group, N = 600) or having gestational diabetes (N = 150) according to American Diabetes Association 2009 criteria. Genotyping was performed by PCR-RFLP. The frequencies of the rare alleles -429C (6.3 versus 9.1%) and -374A (26 versus 30%) were not significantly different between the gestational diabetes patients and healthy pregnant women. Also, the -429T>C and -374T>A polymorphisms were not associated with body mass index, lipid profile, fasting glycemia, HbA1C, or insulin requirement. We found that functional promoter polymorphisms of the RAGE gene were not associated with gestational diabetes or its complications in these Euro-Brazilian patients.

Population Health Management in Diabetes Care: Combining Clinical Audit, Risk Stratification, and Multidisciplinary Virtual Clinics in a Community Setting to Improve Diabetes Care in a Geographically Defined Population. An Integrated Diabetes Care Pilot in the North East Locality, Oxfordshire, UK.

BACKGROUND: Disparities in diabetes care are prevalent, with significant inequalities observed in access to, and outcomes of, healthcare. A population health approach offers a solution to improve the quality of care for all with systematic ways of assessing whole population requirements and treating and monitoring sub-groups in need of additional attention. DESCRIPTION OF THE CARE PRACTICE: Collaborative working between primary, secondary and community care was introduced in seven primary care practices in one locality in England, UK, caring for 3560 patients with diabetes and sharing the same community and secondary specialist diabetes care providers. Three elements of the intervention included 1) clinical audit, 2) risk stratification, and 3) the multi-disciplinary virtual clinics in the community. METHODS: This paper evaluates the acceptability, feasibility and short-term impact on primary care of implementing a population approach intervention using direct observations of the clinics and surveys of participating clinicians. RESULTS AND DISCUSSION: Eighteen virtual clinics across seven teams took place over six months between March and July 2017 with organisation, resources, policies, education and approximately 150 individuals discussed. The feedback from primary care was positive with growing knowledge and confidence managing people with complex diabetes in primary care. CONCLUSION: Taking a population health approach helped to identify groups of people in need of additional diabetes care and deliver a collaborative health intervention across traditional organisational boundaries.

People with Type Diabetes Mellitus (T1DM) self-reported views on their own condition management reveal links to potentially improved outcomes and potential areas for service improvement.

BACKGROUND: The self-management of type 1 diabetes (T1DM) has moved forward in many areas over the last 40 years. Our study asked people with T1DM what is their experience of blood glucose (BG) monitoring day to day and how this influences decisions about insulin dosing. METHODS: An on-line self-reported questionnaire containing 44 questions prepared after consultation with clinicians and patients was circulated to people with T1DM 116 responders provided completed responses. Fixed responses were allocated specific values (e.g. not confident = 0 fairly confident = 1). Multivariate regression analysis was carried out. Only those 5 factors with p-value <0.05 were retained. RESULTS: 59% of respondents were >50 years old and 66% had diabetes for >20 years, with 63% of patients reporting HbA1c results ≤8% or 64 mmol/mol. Findings included; 75% used only 1 m; 56% had used the same meter for ≥3 years; 10% had tried flash monitors; 47% were concerned about current BG level; 85% were concerned about long-term impact of higher BG. 72% of respondents keep BG level high to avoid hypoglycaemia; 25% used ≥7 mmol/L as pre-meal BG target to calculate dose; 65% were concerned they might be over/under-dosing; 83% did not discuss accuracy when choosing meter. However 85% were confident in their meter's performance. The factors that linked to LOWER HbA1c included LESS units of basal insulin (p < 0.001), HIGHER number of daily BG tests (p = 0.008), LOWER bedtime blood glucose (p = 0.009), HIGHER patient's concern over long-term impact of high BG (BG) (p < 0.009 but LOWER patient's concern over current BG values (p = 0.009). The final statistical model could explain 41% of the observed variation in HbA1c. CONCLUSION: Many people still run their BG high to avoid hypoglycaemia. Concern about the longer-term consequences of suboptimal glycaemic control was associated with a lower HbA1c and is an area to explore in the future when considering how to help people with T1DM.

Mitochondria exert a negative feedback on the propagation of intracellular Ca2+ waves in rat cortical astrocytes.

We have used digital fluorescence imaging techniques to explore the interplay between mitochondrial Ca2+ uptake and physiological Ca2+ signaling in rat cortical astrocytes. A rise in cytosolic Ca2+ ([Ca2+]cyt), resulting from mobilization of ER Ca2+ stores was followed by a rise in mitochondrial Ca2+ ([Ca2+]m, monitored using rhod-2). Whereas [Ca2+]cyt recovered within approximately 1 min, the time to recovery for [Ca2+]m was approximately 30 min. Dissipating the mitochondrial membrane potential (Deltapsim, using the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxy-phenyl-hydrazone [FCCP] with oligomycin) prevented mitochondrial Ca2+ uptake and slowed the rate of decay of [Ca2+]cyt transients, suggesting that mitochondrial Ca2+ uptake plays a significant role in the clearance of physiological [Ca2+]cyt loads in astrocytes. Ca2+ signals in these cells initiated either by receptor-mediated ER Ca2+ release or mechanical stimulation often consisted of propagating waves (measured using fluo-3). In response to either stimulus, the wave traveled at a mean speed of 22.9 +/- 11.2 micrometer/s (n = 262). This was followed by a wave of mitochondrial depolarization (measured using tetramethylrhodamine ethyl ester [TMRE]), consistent with Ca2+ uptake into mitochondria as the Ca2+ wave traveled across the cell. Collapse of Deltapsim to prevent mitochondrial Ca2+ uptake significantly increased the rate of propagation of the Ca2+ waves by 50%. Taken together, these data suggest that cytosolic Ca2+ buffering by mitochondria provides a potent mechanism to regulate the localized spread of astrocytic Ca2+ signals.

Suboptimal asthma control: prevalence, detection and consequences in general practice.

Telephone surveys describing suboptimal asthma control may be biased by low response rates. In order to obtain an unbiased assessment of asthma control and assess its impact in primary care, primary care physicians used a 1-page control questionnaire in 50 consecutive asthma patients. Of the 10,428 patients assessed by 354 physicians, 59% were uncontrolled, 19% well-controlled and 23% totally controlled. Physicians overestimated control, regarding only 42% of patients as uncontrolled. Physicians were more likely to report plans to alter the regimens of uncontrolled patients than controlled patients (1.29 versus 0.20 medication changes per patient) doing so in a fashion consistent with guideline recommendations. Of the uncontrolled patients, 59% required one or more urgent care or specialist visits versus 26 and 15% of well-controlled or totally controlled patients, respectively. Patients were more likely to report short-term symptom control when they had not required urgent or specialist care (odds ratio 5.68; 95% confidence interval 4.91-6.58). The majority of asthma patients treated in general practice are uncontrolled. Lack of control can be recognised by physicians who are likely to consider appropriate changes to therapy. A lack of short-term symptom control of asthma is associated with excess healthcare utilisation.

Effect of glycaemic control on complications following cardiac surgery: literature review.

INTRODUCTION: No uniform consensus in the UK or Europe exists, for glycaemic management of patients with Diabetes or pre-diabetes undergoing cardiac surgery. OBJECTIVE: [i] Determine the relationship between glycaemic control and cardiac surgical outcomes; [ii] Compare current vs gold standard management of patients with Diabetes or pre-diabetes undergoing cardiac surgery. METHODS: Searches of MEDLINE, NHS Evidence and Web of Science databases were completed. Articles were limited to those in English, German and French. No date limit was enforced.13,232 articles were identified on initial literature review, and 50 relevant papers included in this review. RESULTS: No national standards for glycaemic control prior to cardiac surgery were identified. Upto 30% of cardiac surgical patients have undiagnosed Diabetes. Cardiac surgical patients without Diabetes with pre-operative hyperglycaemia have a 1 year mortality double that of patients with normoglyacemia, and equivalent to patients already diagnosed with Diabetes. Pre- and peri-operative hyperglycaemia is associated with worse outcomes. Evidence regarding tight glycaemic control vs moderate glycaemic control is conflicting. Tight control may be more effective in patients without Diabetes with pre-/peri-operative hyperglycaemia, and moderate control appears more effective in patients with pre-existing Diabetes. Patients with well controlled Diabetes may achieve comparable outcomes to patients without Diabetes with similar glycaemic control. CONCLUSIONS: Pre / peri-operative hyperglycaemia is associated with worse outcomes in both patients with, and without Diabetes undergoing CABG. This review supports the pre-operative screening, and optimisation of glycaemic control in patients undergoing cardiac surgery. Optimal glycaemic management remains unclear and clear guidelines are needed.

Hydrogen ion concentration is not the sole determinant of muscle metaboreceptor responses in humans.

We examined the effects of exercise conditioning on muscle sympathetic nerve activity (MSNA) during handgrip and posthandgrip circulatory arrest (PHG-CA). Two conditioning stimuli were studied: forearm dominance and bodybuilding. Static handgrip at 30% maximal voluntary contraction followed by PHG-CA led to a rise in MSNA smaller in dominant than in nondominant forearms (99% vs. 222%; P less than 0.02) and in body builders than in normal volunteers (28% vs. 244%; P less than 0.01). Separate 31P NMR experiments showed no effect of dominance on forearm pH but a pH in bodybuilders higher (6.88) than in normal volunteers (6.79; P less than 0.02) during PHG-CA. Our second goal was to determine if factors besides attenuated [H+] contribute to this conditioning effect. If differences in MSNA during exercise were noted at the same pH, then other mechanisms must contribute to the training effect. We measured MSNA during ischemic fatiguing handgrip. No dominance or bodybuilding effect on pH was noted. However, we noted increases in MSNA smaller in dominant than nondominant forearms (212% vs. 322%; P less than 0.02) and in bodybuilders than in normal volunteers (161% vs. 334%; P less than 0.01). In summary, MSNA responses were less during exercise of conditioned limbs. Factors aside from a lessening of muscle acidosis contribute to this effect.

Autonomic pathophysiology in heart failure patients. Sympathetic-cholinergic interrelations.

We conducted this study in an effort to characterize and understand vagal abnormalities in heart failure patients whose sympathetic activity is known. We measured sympathetic (peroneal nerve muscle sympathetic recordings and antecubital vein plasma norepinephrine levels) and vagal (R-R intervals and their standard deviations) activities in eight heart failure patients and eight age-matched healthy volunteers, before and after parasympathomimetic and parasympatholytic intravenous doses of atropine sulfate. At rest, sympathetic and parasympathetic outflows were related reciprocally: heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows. Low dose atropine, which is known to increase the activity of central vagal-cardiac motoneurons, significantly increased R-R intervals in healthy subjects, but did not alter R-R intervals in heart failure patients. Thus, our data document reciprocal supranormal sympathetic and subnormal parasympathetic outflows in heart failure patients and suggest that these abnormalities result in part from abnormalities within the central nervous system.

Six-year longitudinal study of Fasciola hepatica bulk milk antibody ELISA in the dairy dense region of the Republic Ireland.

Completion of the F. hepatica lifecycle is dependent on suitable climatic conditions for development of immature stages of the parasite, and its snail intermediate host. Few investigations have been conducted regarding temporal variations in F. hepatica status in Irish dairy herds. The current study aimed to conduct a longitudinal study examining annual and seasonal trends in bulk milk seropositivity over six years, while also investigating associations with soil temperature, rainfall and flukicide treatment. Monthly bulk milk samples (BTM) were submitted by 28 herds between March 2009 and December 2014. In all, 1337 samples were analysed using a Cathepsin L1 ELISA. Soil temperature, rainfall and management data were obtained for general estimating equation and regression analyses. A general decrease in milk seropositivity was observed over the six year study period and was associated with an increased likelihood of treating for liver fluke (OR range=2.73-6.96). Annual and seasonal analyses of rainfall and F. hepatica BTM status yielded conflicting results. Higher annual rainfall (>1150mm) yielded a lower likelihood of being BTM positive than annual rainfall of <1000mm (OR=0.47; P=0.036). This was most likely due to farmers being more proactive in treating for F. hepatica in wetter years, although a 'wash effect' by high rainfall of the free living stages and snails cannot be ruled out. Higher seasonal rainfall (>120mm), however, was associated with increased ELISA S/P% values (Coefficient=9.63S/P%; P=0.001). Soil temperature was not found to influence F. hepatica to the same extent as rainfall and may reflect the lack of severe temperature fluctuations in Ireland. Flukicides active against both immature and mature F. hepatica were approximately half as likely to record a positive F. hepatica herd BTM status than a flukicide active against only the mature stage of the parasite (OR≅0.45; P<0.01). This study highlights the importance of examining both annual and seasonal F. hepatica data, which can vary significantly. Additionally, it highlights the progress that can be achieved in fluke control by application of a continuous BTM monitoring program.

Global right atrial mapping of human atrial flutter: the presence of posteromedial (sinus venosa region) functional block and double potentials : a study in biplane fluoroscopy and intracardiac echocardiography.

BACKGROUND: Previous studies of atrial flutter have found linear block at the crista terminalis; this was thought to predispose the patient to the arrhythmia. More recent observations, however, have demonstrated crista conduction. We sought to characterize the posterior boundary of atrial flutter. METHODS AND RESULTS: Patients with counterclockwise flutter (n=20), clockwise flutter (n=3), or both (n=5) were studied using two 20-pole catheters. Biplane fluoroscopy determined catheter positions. During counterclockwise flutter, craniocaudal activation occurred along the entire lateral and posterior right atrial walls. Septal activation proceeded caudocranially. In all patients, a line of block was seen in the posteromedial (sinus venosa) right atrium; this was manifested by the presence of double potentials where the upward and downward activations collided. Anatomic location was confirmed by intracardiac echocardiography in 9 patients. In patients with clockwise flutter, the line of block and double potentials were seen in the same location during counterclockwise flutter, but the activation sequence around the line of block was reversed. Pacing near the site of double potentials during sinus rhythm excluded a fixed line of block, and premature atrial complexes demonstrated functional block with manifest double potentials. In 2 patients, posterior ectopy organized to subsequently initiate isthmus-dependent atrial flutter. CONCLUSIONS: (1) A functional line of block is seen at the posteromedial (sinus venosa region) right atrium during counterclockwise and clockwise atrial flutter. (2) All lateral wall right atrial activation can be uniform during flutter, without linear block or double potentials in the region of the crista terminalis. (3) Activation at the site of posteromedial right atrial functional block can organize to subsequently initiate isthmus-dependent atrial flutter.

Effects of quinidine on vascular resistance and sympathetic nerve activity in humans.

OBJECTIVES: The purpose of the present study was to test the hypothesis that intravenous quinidine, unlike procainamide, causes direct vasodilation and reflexly mediated increases in sympathetic nerve activity. BACKGROUND: Intravenous quinidine can cause significant hypotension. Animal experiments have suggested that quinidine blocks alpha-receptors and also relaxes vascular smooth muscle by a nonadrenergic mechanism. In a recent study we showed that intravenous procainamide causes peripheral vasodilation, hypotension and inhibition of sympathetic nerve activity in humans. Intraarterial procainamide, however, did not cause vasodilation. METHODS: Postganglionic muscle sympathetic nerve traffic was recorded from the peroneal nerve at the fibular head with tungsten microelectrodes, and forearm blood flow was measured with venous occlusion plethysmography. Central venous pressure was measured directly. The direct effects of quinidine on vascular resistance were determined with brachial artery quinidine infusions and measurement of ipsilateral forearm blood flow. RESULTS: In eight normal subjects intravenous quinidine (8 mg/kg body weight infused for 27 min) decreased mean arterial pressure from 87 +/- 3 (mean +/- SE) to 83 +/- 3 mm Hg, central venous pressure from 6.3 +/- 0.6 to 5.0 +/- 0.7 mm Hg and forearm vascular resistance from 32.2 +/- 5.5 to 25.3 +/- 4.7 U (all p < 0.05). Heart rate increased from 67 +/- 4 to 77 +/- 5 beats/min and muscle sympathetic nerve activity from 288 +/- 70 to 660 +/- 151 U/min (both p < 0.05). In five subjects intravenous nitroprusside that caused similar hemodynamic effects produced similar increases in sympathetic nerve activity. In eight subjects graded infusions of quinidine into the brachial artery (0.37, 0.74 and 1.48 mg/min) produced dose-dependent decreases in ipsilateral forearm vascular resistance and marked attenuation of forearm vasoconstriction caused by the cold pressor test. CONCLUSIONS: These data show that quinidine, unlike procainamide, causes vasodilation directly and, when given intravenously, is associated with baroreflex-mediated increases in sympathetic nerve activity.

Enhancement of sympathetic nerve activity by single premature ventricular beats in humans.

This is the first systematic study of the effects of ventricular premature beats on sympathetic nerve activity in humans. Microneurographic techniques were used to record efferent sympathetic activity from the peroneal nerve, and an intracardiac electrode catheter was used to introduce ventricular premature beats after every 6 to 10 sinus heartbeats. Studies were performed in eight patients, aged 22 to 74 years (mean 57), undergoing cardiac electrophysiologic studies. Three patients did not have apparent heart disease and five had coronary artery disease. During sinus rhythm, 19 to 93% (mean 42%) of heartbeats were followed by a pulse-synchronous burst of sympathetic activity. Provoked ventricular premature beats had obvious effects on this activity. Premature beats with coupling intervals less than 80% of sinus cycle length were consistently followed by a burst of sympathetic activity, and this activity was greater in amplitude, duration and area (all p less than 0.05) than were burst of such activity during sinus rhythm. The magnitude of this burst of activity increased as the coupling interval of the ventricular premature beat decreased (p less than 0.0001). In contrast, postextrasystolic beats were followed by nearly complete neural silence. These effects were seen in all patients regardless of baseline burst incidence and the presence or absence of heart disease. Total nerve activity per 10 heartbeats was 6,520 +/- 770 U during ventricular extrastimulation and 5,720 +/- 440 U during normal sinus rhythm (difference not significant). It is concluded that single ventricular premature beats provoke fluxes of muscle sympathetic nerve activity in humans, comprising surges of sympathetic activity larger than those occurring during sinus rhythm, followed by neural silence.

Utility of a single-stage isoproterenol tilt table test in adults: a randomized comparison with passive head-up tilt.

OBJECTIVES: This study was conducted to develop a time-efficient tilt table test. BACKGROUND: Current protocols of tilt table testing are quite time-consuming. This study was designed to assess the diagnostic value, tolerance and procedural time of a single-stage isoproterenol tilt table protocol. METHODS: A single-stage isoproterenol tilt table test was compared with the passive tilt table test. The study was prospectively designed in a randomized and crossover fashion. RESULTS: The study population consisted of 111 patients with a history of syncope (mean age 55 +/- 20 years). Of the total, 62 patients (56%; 95% confidence interval, 46% to 65%) had a positive vasovagal response during isoproterenol tilt table testing and 35 (32%; 23% to 41%) during passive tilt table testing (p = 0.002). The mean procedural times of the study population were 11.7 +/- 3.6 min and 36.9 +/- 13.3 min for isoproterenol and passive tilt table testing, respectively (p < 0.001). All patients tolerated single-stage isoproterenol testing. In the 23 control subjects (mean age 34 +/- 11 years), the apparent specificities were 91% (72% to 99%) and 83% (61% to 99%) for passive and single-stage tilt table testing, respectively. CONCLUSIONS: The single-stage isoproterenol tilt table test was more effective in inducing a positive vasovagal response in an adult population than the standard passive tilt table test, and it significantly reduced the procedural time. The increase in positive yield was associated with a moderate decrease in apparent specificity. These observations support the conclusion that single-stage tilt table testing could be a reasonable diagnostic option in patients undergoing syncope evaluation.

Distinct hemodynamic profiles in patients with vasovagal syncope: a heterogeneous population.

OBJECTIVE: The objective was to investigate mechanisms of vasovagal syncope by identifying laboratory techniques that characterize cardiovascular profiles in patients with vasovagal syncope. BACKGROUND: The triggering mechanisms of vasovagal syncope are complex. The patient population is likely heterogeneous. We hypothesized that distinct hemodynamic profiles are definable with provocative maneuvers. METHODS: Three groups of subjects were matched for age and gender: 16 patients with a history of syncope and an inducible vasovagal response during passive tilt table testing (70 degrees, 45 min, group I), 16 with a history of syncope, negative passive tilt table testing but positive isoproterenol tilt table testing (0.05 microg/kg per min, 70 degrees, 10 min, group II), and 16 control subjects. Beat-to-beat hemodynamic functions were determined noninvasively by photo-plethysmography and impedance cardiography. RESULTS: At baseline, hemodynamic functions were not different among the three groups (supine). In response to tilt before any symptoms developed, total peripheral resistance decreased 9% +/- 14% in group I from baseline supine to tilt position but increased 27% +/- 18% in group II and 28% +/- 17% in controls (p < 0.001). Responses to isoproterenol were not significantly different between group II and controls in supine position. In response to tilt during isoproterenol infusion before any symptoms developed, total peripheral resistance decreased 24% +/- 20% in group II and increased 20% +/- 48% in controls (p = 0.002). CONCLUSIONS: Group I patients may have impaired ability to increase vascular resistance during orthostatic stress. The inability to overcome isoproterenol-induced vasodilatation during tilt is important in triggering a vasovagal response in group II patients. These data suggest that the population with vasovagal response is heterogeneous. Distinct hemodynamic profiles in response to various provocative maneuvers are definable with noninvasive, continuous monitoring techniques.

Effects of fludrocortisone on sympathetic nerve activity in humans.

Fludrocortisone reduces plasma norepinephrine in healthy humans, but forearm vascular and pressor responses to norepinephrine are potentiated. The effects of fludrocortisone on sympathetic nerve activity in healthy humans are not known. To investigate these effects we evaluated muscle sympathetic nerve activity, heart rate, and arterial pressure in 11 healthy volunteers during three protocols: (1) before and on day 7 of fludrocortisone (0.4 mg/d) treatment with ad libitum diet (n = 6); (2) before and on day 7 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n = 7); and (3) before and on day 2 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n = 4). Placebo did not alter any parameter.(ABSTRACT TRUNCATED AT 250 WORDS)