Correlation of visceral adipose tissue measured by Lunar Prodigy dual X-ray absorptiometry with MRI and CT in older men.

Quantification of abdominal visceral adipose tissue (VAT) is important to understand obesity-related comorbidities. We hypothesized that dual X-ray absorptiometry (DXA) measurements of VAT would correlate with traditional gold standards of magnetic resonance imaging (MRI) and computed tomography (CT) in older men. Deming regression and Bland-Altman plots were used to assess the agreement between VAT measured simultaneously by DXA and MRI (n=95) in a cohort of older males participating in a randomized trial of testosterone replacement for diabetes. We also correlated DXA with single-slice CT (n=102) in a cohort of older males undergoing testosterone deprivation for prostate cancer. Lunar Prodigy DXA scanners using enCORE software was used to measure VAT. DXA VAT volume strongly correlated with MRI VAT volume (r=0.90, P<0.0001) and CT VAT area (r=0.83, P<0.0001). As DXA assesses VAT volume in a smaller compartment than MRI, Bland-Altman analysis demonstrated DXA systematically underestimated VAT by an approximately 30% proportional bias. DXA VAT volume measured by Lunar Prodigy DXA scanners correlate well with gold standard MRI and CT quantification methods, and provides a low radiation, efficient, cost-effective option. Future clinical studies examining the effects of interventions on body composition and regional fat distribution may find DXA an appropriate volumetric method to quantify VAT.

Testosterone levels increase in association with recovery from acute fracture in men.

UNLABELLED: In this longitudinal case-control study, acute fracture was associated with low serum testosterone, which was transient in 43% of men. While assessment of gonadal status is part of the assessment of bone fragility, measurement of testosterone in the early period after fracture may overestimate the prevalence of androgen deficiency. INTRODUCTION: Measurement of circulating testosterone is recommended in the evaluation of bone fragility in men. Since acute illness can transiently decrease circulating testosterone, we quantified the association of acute fracture and serum testosterone levels. METHODS: A case-control study was conducted involving 240 men with a radiologically confirmed minimal trauma fracture presenting to a tertiary referral hospital and 89 age-matched men without a history of minimal trauma fracture serving as controls. Follow-up testosterone levels 6 months after baseline were available for 98 cases and 27 controls. Results were expressed as the median and interquartile (IQR) range. RESULTS: Compared to controls, cases had lower total testosterone [TT, 7.2 (3.5, 10.8) vs 13.6 (10.9, 17.1) nmol/L, p < 0.001]. The 143 cases treated as inpatients had lower testosterone levels than the 97 cases treated as outpatients [TT 4.7 (2.3, 8.1) vs 10.3 (7.5, 12.7) nmol/L, p < 0.001]. Group differences in calculated free testosterone (cFT) were comparable to the group differences in TT. At follow-up, in 98 cases, median TT increased from 6.5 nmol/L (3.2, 8.5) to 9.6 nmol/L (6.9, 12.0) p < 0.0001, and SHBG remained unchanged. Of cases with low testosterone, 43% with TT <10 nmol/L and/or cFT <230 pmol/L at presentation were reclassified as androgen sufficient at follow-up. TT was unchanged in the controls. CONCLUSIONS: Low testosterone levels in men presenting with an acute fracture may, at least in part, be due to an acute, fracture-associated, stress response. To avoid over diagnosis, evaluation for testosterone deficiency should be deferred until recovery from the acute event.

Readmission rates of older patients (age >75 years) discharged within 48 hours of admission to the Acute Medical Unit, Norwich: observational study.

The benefits of specialist geriatric assessment in acute medical units are debated and it is unclear if there is a reduction in readmission rates for older patients with specialist geriatric care compared to general acute medical care. We examined readmission rates for 2414 older patients who had been discharged from the acute medical unit at the Norfolk and Norwich University Hospital, either by acute medicine or older people's medicine (OPM), both of which teams were consultant-led. We found no significant difference in readmission rates between patients discharged by the acute medical team as compared to the OPM team. This finding was robust to a variety of sensitivity analyses, including different lengths of stay, or readmissions at different time intervals. Hence, acute medical teams may be able to achieve similar levels of quality care for older patients to specialist geriatric teams.

Cardiovascular risk and bone loss in men undergoing androgen deprivation therapy for non-metastatic prostate cancer: implementation of standardized management guidelines.

Our objective was to evaluate the effectiveness of implementing standardized guidelines to mitigate metabolic and bone side effects of androgen deprivation therapy (ADT) in men with non-metastatic prostate cancer. We conducted a 2-year prospective cohort study at a tertiary referral teaching hospital. Overall, 236 men (mean age 69.8 ± 7.1) commencing ADT for non-metastatic prostate cancer attended a baseline clinic visit between 2007 and 2011, and 153 men were eligible for follow-up after 2 years of continuous ADT. Of these, 113 men had data available for analysis at 2 years. At baseline, 87% of the men were overweight or obese, 61% had hypertension, 56% had hypercholesterolaemia, 27% prior cardiovascular disease, 11% osteoporosis and 40% osteopaenia. After 2 years of ADT, there was an increase in waist circumference (+2.8 ± 6.3 cm, p = 0.002), and, in men without diabetes, in HbA1c (+0.13 ± 0.34%, p = 0.019). Despite this, due to treatment, there were significant reductions in total cholesterol (-0.35 ± 1.00 mmol/L, p < 0.001), and blood pressure (systolic -7.6 ± 19.3 mmHg; diastolic -4.7 ± 11.6 mmHg, p < 0.001). After 2 years, men not receiving anti-resorptive therapy experienced a significant decline in lumbar spine (-0.042 ± 0.134 g/cm(2) , p = 0.012) and total hip bone mineral density (BMD) (-0.026 ± 0.036 g/cm(2) , p < 0.001), whereas bisphosphonate treatment maintained stable BMD. Prevalence of anaemia increased from 13.8 to 32.5%. Older age independently predicted a greater drop in haemoglobin (p = 0.005). We conclude that a structured approach to assess and treat men undergoing ADT effectively improves cardiovascular risk factors and prevents bone decay. Larger studies are needed to determine effects on cardiovascular outcomes, fracture prevention and survival.

Out with the old, in with the new? Case reports of the clinical features and acute management of two novel designer drugs.

Methoxydine (4-MeO-PCP) and Methoxetamine (3-MeO-2-Oxo-PCE) are both commercially produced designer drugs with structural and biochemical similarities to phencyclidine (PCP). Although phencyclidine toxicity is well documented, its recreational use in present times is rare. With the advent of new designer drugs being available widely through internet sites, Acute Physicians should be aware of the clinical features and management of these potential toxins. We present a case of methoxydine ingestion (which to our knowledge has not been previously documented in any medical journals) and a case of methoxetamine ingestion, and discuss their history, contrasting clinical features and acute management.

Increase in visceral and subcutaneous abdominal fat in men with prostate cancer treated with androgen deprivation therapy.

OBJECTIVE: Androgen deprivation therapy (ADT) for prostate cancer is associated with increases in fat mass and risk of type 2 diabetes; however, the relationship between sex steroid deficiency and abdominal fat distribution remains controversial. DESIGN: We conducted a 12-month prospective observational study at a tertiary referral centre. PATIENTS AND MEASUREMENTS: We investigated changes in abdominal fat distribution and insulin resistance in 26 men (70.6±6.8 years) with nonmetastatic prostate cancer during the first year of ADT. RESULTS: Twelve months of ADT increased visceral abdominal fat area by 22% (from 160.8±61.7 to 195.9±69.7 cm(2) ; P<0.01) and subcutaneous abdominal fat area by 13% (from 240.7±107.5 to 271.3±92.8 cm(2) ; P<0.01). Fat mass increased by 14% (+3.4 kg; P<0.001) and lean tissue mass decreased by 3.6% (-1·9 kg; P<0.001). Insulin resistance (HOMA-IR) increased by 12% (2.50±1.12 to 2.79±1.31, P<0.05). There was no change in fasting glucose or glycated haemoglobin levels. Total testosterone (TT) was inversely associated with visceral fat area independent of oestradiol (E2), but E2 was not associated with visceral fat area independent of TT. Visceral fat area, not TT or E2, was independently associated with insulin resistance. CONCLUSIONS: ADT for prostate cancer results in accumulation of both visceral and subcutaneous abdominal fat. Increased visceral fat area appears more closely linked to testosterone than oestradiol deficiency. Increased insulin resistance may arise secondary to visceral fat accumulation, rather than as a direct result of sex steroid deficiency.

Structural decay of bone microarchitecture in men with prostate cancer treated with androgen deprivation therapy.

CONTEXT: Androgen deprivation therapy (ADT) used in the treatment of prostate cancer reduces bone mineral density (BMD) and predisposes to fractures. The structural basis of the BMD deficit and bone fragility is uncertain. OBJECTIVE AND PATIENTS: We investigated changes in bone microarchitecture in 26 men (70.6±6.8 yr) with nonmetastatic prostate cancer during the first year of ADT using the new technique of high-resolution peripheral quantitative computed tomography. DESIGN AND SETTING: We conducted a 12-month prospective observational study in the setting of a tertiary referral center. RESULTS: After 12 months of ADT, total volumetric density decreased by 5.2±5.4% at the distal radius and 4.2±2.7% at the distal tibia (both P<0.001). This was due to a decrease in cortical volumetric BMD (by 11.3±8.6% for radius and 6.0±4.2% for tibia, all P<0.001) and trabecular density (by 3.5±6.0% for radius and 1.5±2.3% for tibia, all P<0.01), after correcting for trabecularization of cortical bone. Trabecular density decreased due to a decrease in trabecular number at both sites (P<0.05). Total testosterone, but not estradiol, levels were independently associated with total and corrected cortical volumetric BMD at the tibia. CONCLUSIONS: Sex steroid deficiency induced by ADT for prostate cancer results in microarchitectural decay. Bone fragility in these men may be more closely linked to testosterone than estradiol deficiency.

Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes.

AIMS: To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes. METHODS: One hundred and two patients (52 female, 50 male) with Type 1 diabetes aged 20-71 years underwent cross-sectional assessment of biochemical/hormonal markers of bone metabolism, and bone mineral density (BMD) measurement at forearm, hip and spine using dual energy x-ray absorptiometry. BMD data were available for 102 age- and gender-matched population-based control subjects. RESULTS: After adjusting for age and body mass index (BMI), osteopenia and osteoporosis were more common at the spine in males with Type 1 diabetes than in control subjects (P = 0.030). In Type 1 males, after adjustment for age and BMI, BMD, T- and Z-scores at the hip, femoral neck and spine were lower compared with age-matched control subjects (P < or = 0.048). Female Type 1 patients and control subjects had similar BMDs and T- and Z-scores at all sites. On multiple linear regression analysis, which adjusted for the natural logarithm of the sex hormone binding globulin concentration, smoking status and alcohol consumption, and (for women) menopausal status, each of BMI, serum ionized calcium and serum alkaline phosphatase (negatively) were independently associated with BMD at the hip and femoral neck in Type 1 diabetic subjects. CONCLUSIONS: Adult males with Type 1 diabetes have reduced bone density at the hip, femoral neck and spine when compared with age-matched control subjects. Impaired bone formation may occur in Type 1 diabetes.

Natriuretic peptides stimulate the cardiac sodium pump via NPR-C-coupled NOS activation.

Natriuretic peptides (NPs) and their receptors (NPRs) are expressed in the heart, but their effects on myocyte function are poorly understood. Because NPRs are coupled to synthesis of cGMP, an activator of the sarcolemmal Na(+)-K(+) pump, we examined whether atrial natriuretic peptide (ANP) regulates the pump. We voltage clamped rabbit ventricular myocytes and identified electrogenic Na(+)-K(+) pump current (arising from the 3:2 Na(+):K(+) exchange and normalized for membrane capacitance) as the shift in membrane current induced by 100 micromol/l ouabain. Ten nanomoles per liter ANP stimulated the Na(+)-K(+) pump when the intracellular compartment was perfused with pipette solutions containing 10 mmol/l Na(+) but had no effect when the pump was at near maximal activation with 80 mmol/l Na(+) in the pipette solution. Stimulation was abolished by inhibition of cGMP-activated protein kinase with KT-5823, nitric oxide (NO)-activated guanylyl cyclase with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), or NO synthase with N(G)-nitro-L-arginine methyl ester (L-NAME). Since synthesis of cGMP by NPR-A and NPR-B is not NO dependent or ODQ sensitive, we exposed myocytes to AP-811, a highly selective ligand for the NPR-C "clearance" receptor. It abolished ANP-induced pump stimulation. Conversely, the selective NPR-C agonist ANP(4-23) reproduced stimulation. The stimulation was blocked by l-NAME. To examine NO production in response to ANP(4-23), we loaded myocytes with the NO-sensitive fluorescent dye diacetylated diaminofluorescein-2 and examined them by confocal microscopy. ANP(4-23) induced a significant increase in fluorescence, which was abolished by L-NAME. We conclude that NPs stimulate the Na(+)-K(+) pump via an NPR-C and NO-dependent pathway.

Opposing effects of coupled and uncoupled NOS activity on the Na+-K+ pump in cardiac myocytes.

Pharmacological delivery of nitric oxide (NO) stimulates the cardiac Na(+)-K(+) pump. However, effects of NO synthesized by NO synthase (NOS) often differ from the effects of NO delivered pharmacologically. In addition, NOS can become "uncoupled" and preferentially synthesize O(2)(.-), which often has opposing effects to NO. We tested the hypothesis that NOS-synthesized NO stimulates Na(+)-K(+) pump activity, and uncoupling of NOS inhibits it. To image NO, we loaded isolated rabbit cardiac myocytes with 4,5-diaminofluorescein-2 diacetate (DAF-2 DA) and measured fluorescence with confocal microscopy. L-arginine (L-arg; 500 micromol/l) increased DAF-2 DA fluorescence by 51% compared with control (n = 8; P < 0.05). We used the whole cell patch-clamp technique to measure electrogenic Na(+)-K(+) pump current (I(p)). Mean I(p) of 0.35 +/- 0.03 pA/pF (n = 44) was increased to 0.48 +/- 0.03 pA/pF (n = 7, P < 0.05) by 10 micromol/l L-Arg in pipette solutions. This increase was abolished by NOS inhibition with radicicol or by NO-activated guanylyl cyclase inhibition with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. We next examined the effect of uncoupling NOS using paraquat. Paraquat (1 mmol/l) induced a 51% increase in the fluorescence intensity of O(2)(.-)-sensitive dye dihydroethidium compared with control (n = 9; P < 0.05). To examine the functional effects of uncoupling, we measured I(p) with 100 micromol/l paraquat included in patch pipette solutions. This decreased I(p) to 0.28 +/- 0.03 pA/pF (n = 12; P < 0.001). The paraquat-induced pump inhibition was abolished by superoxide dismutase (in pipette solutions). We conclude that NOS-mediated NO synthesis stimulates the Na(+)-K(+) pump, whereas uncoupling of NOS causes O(2)(.-)-mediated pump inhibition.

The effect of taurine depletion on the contractile properties and fatigue in fast-twitch skeletal muscle of the mouse.

Taurine increases force production in skeletal muscle, and taurine levels may fall during exercise. The contractile properties and fatigability of extensor digitorum longus (EDL) muscles depleted of taurine by guanodinoethane sulfonate (GES) treatment were investigated. GES treatment decreased muscle taurine levels to <40% of controls. Peak twitch force levels were 23% of controls in GES treated EDL muscles (p < 0.05), but maximal specific force was unaffected. The force-frequency relationship was examined and significantly less force was produced by the GES treated muscles compared to controls at stimulation frequencies from 50 to 100 Hz (p < 0.05). GES treated EDL muscles exhibited significantly slower rates of fatigue than controls (p < 0.05). In skinned fibres, 20 mM GES had a small but significant effect on force production, indicating that GES may have some minor taurine-like effects. In this study, a fall in taurine levels decreased force output, and increased the endurance of EDL skeletal muscles.

A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention.

OBJECTIVE: The therapeutic effectiveness of diet, exercise, and diet plus exercise for weight loss in obesity was determined. DATA SOURCES: All human research reported in English, published in peer-reviewed scientific journals within the past 25 y was reviewed. STUDY SELECTION: Acceptance criteria (n = 493 from > 700 studies) were that a therapeutic intervention of diet, exercise or diet plus exercise was employed, specifically for weight reduction in obese adult humans and that weight change was reported numerically. Only aerobic exercise studies were included, while drug, hormone and surgical treatments were excluded. DATA EXTRACTION: All data were extracted by the same investigator from the original research report. Except for gender and program type, all extracted data were numerical. DATA SYNTHESIS: ANOVA, with a Newman-Keuls post hoc test, was used to determine differences among programs (P < 0.05). One analysis was performed on the group mean data and one based on effect sizes. Analyses were repeated using initial body weight, initial percent body fat and program length, as covariates. RESULTS: Primarily, subjects aged 40 y have been studied (39.5 +/- 0.4 y, mean +/- s.e.m.) who are only moderately obese (92.7 +/- 0.9 kg, 33.2 +/- 0.5 body mass index (BMI), 33.4 +/- 0.7% body fat); for short durations (15.6 +/- 0.6 weeks). Exercise studies were of a shorter duration, used younger subjects who weighed less, had lower BMI and percentage body fat values, than diet or diet plus exercise studies. Despite these differences, weight lost through diet, exercise and diet plus exercise was 10.7 +/- 0.5, 2.9 +/- 0.4* and 11.0 +/- 0.6 kg, respectively. However, at one-year follow-up, diet plus exercise tended to be the superior program. Effect size and covariate analyses revealed similar program differences. CONCLUSION: Weight loss research over the past 25 y has been very narrowly focused on a middle age population that is only moderately obese, while the interventions lasted for only short periods of time. The data shows, however, that a 15-week diet or diet plus exercise program, produces a weight loss of about 11 kg, with a 6.6 +/- 0.5 and 8.6 +/- 0.8 kg maintained loss after one year, respectively.

Preparation of amorphous boron nitride and its conversion to a turbostratic, tubular form.

Amorphous boron nitride, BN, is obtained from the reaction of B-trichloroborazine, (BCINH)(3), with cesium metal. The amorphous product is converted to a turbostratic form upon heating to 1100 degrees C. Scanning electron microscopy reveals a previously unreported morphology composed of hollow tubular structures. The largest of these appear to be approximately 3 micrometers in external diameter and 50 to 100 micrometers in length. Transmission electron microscopy and selected-area electron diffraction also indicate the tube walls to be turbostratic in nature. The mechanism by which the tubes form is not known, although apparent sites of incipient tube growth have been observed.

Blood pressure and vasoactive hormones with improved glycaemic control in patients with diabetes mellitus.

To assess the effects of improved glycaemic control on arterial pressure and plasma levels of vasoactive hormones, we studied 5 male insulin dependent (Type 1) diabetic patients before and one month after commencement of rigorous control of blood glucose levels. On each occasion, continuous ambulatory intra arterial pressure monitoring for a 10-hour period, together with hourly venous sampling for plasma glucose and vasoactive hormone determinations, was performed under standardised conditions of diet and posture. Mean (+/- SEM) plasma glucose before and after improved glycaemic control was 9.4 +/- 0.3 and 6.6 +/- 0.4 mmol/l respectively (P less than 0.001). There was a small but significant fall in arterial pressure in each patient as well as for the group overall (mean arterial pressure fall 4.8 +/- 1.2 mmHg, p less than 0.01) after improved glycaemic control. The fall in individual (10 hr mean) diastolic arterial pressure levels correlated with concomitant falls in plasma glucose levels (r = 0.92, p less than 0.05) but not with changes in any of the other variables measured.

Hormone, calcium and blood pressure relationships in primary hyperparathyroidism.

The cause of hypertension in primary hyperparathyroidism and its response to corrective surgery remains a matter of controversy. We therefore studied blood pressure, vasoactive hormones and plasma calcium responses to parathyroidectomy in six hypertensive and two normotensive patients with primary hyperparathyroidism. Twenty-four-hour intra-arterial pressure recordings, together with hourly blood sampling for plasma renin activity (PRA), aldosterone, cortisol, catecholamines and calcium levels, were undertaken in each patient before surgery and were repeated under identical conditions 3-6 months after parathyroidectomy. Mean plasma calcium was 3.03 +/- 0.1 before, and 2.35 +/- 0.02 mmol/l after, parathyroidectomy. Changes in arterial pressure were small and variable in individual patients. Group mean arterial pressures before and after surgery were identical. Plasma cortisol and PRA were significantly higher in the hypercalcaemic state (P less than 0.01 and P less than 0.05, respectively) but there was no significant difference in plasma aldosterone or catecholamine levels. No correlations between changes in plasma calcium or parathyroid hormone levels and concomitant changes in plasma concentration of other hormones were observed. Our findings show that correction of primary hyperparathyroidism has no systematic effect on arterial pressure in a heterogeneous group, including some patients with probable background essential hypertension, when evaluated 3-6 months after surgery. Compared with values after corrective surgery, mean levels of PRA and cortisol-but not aldosterone or catecholamines--are elevated in patients with primary hyperparathyroidism. These findings are consistent with an inhibitory effect of raised ionic calcium concentration on the response of the adrenal glomerulosa to angiotensin and adrenocorticotrophic hormone.

Ambulatory pulmonary arterial pressures in humans: relationship to arterial pressure and hormones.

Six healthy volunteers were studied by use of a continuous ambulatory recording technique to document the normal range and variability of pulmonary artery pressure (PAP) and to examine its relationship to systemic arterial pressure (SAP) both at rest and during standardized interventions. Vasoactive hormone levels were measured at frequent intervals. Over 8-10 h of study the mean PAP was 15.7/6.3 mmHg. Parallel changes in PAP and SAP were observed at rest and during exercise and eating. On the contrary, PAP rose and SAP fell with hypoxia, whereas smoking was associated with a rise in SAP but no change in PAP. Sympathetic nervous system activity, as gauged by plasma norepinephrine levels, may have contributed to pressure and heart rate changes during exercise and smoking, but activity of the renin-angiotensin system was not altered by any of the maneuvers. These results provide base-line information on the level of PAP and its variability in healthy volunteers under standardized conditions. Pressures within the systemic and pulmonary circuits change in parallel under some circumstances but move in opposite directions under other conditions.

Endogenous angiotensin-aldosterone-pressure relationships during sodium restriction.

The effects of moderate restriction of dietary sodium and potassium supplementation on plasma levels of renin, angiotensin II, aldosterone, and cortisol and on arterial pressure were studied in 12 patients with mild essential hypertension. To define hormone-blood pressure relationships, venous hormone levels were measured hourly and intra-arterial pressure continuously for 24 hours after 4 to 6 weeks of sodium restriction, 4 to 6 weeks of potassium supplementation, and a similar period of control diet. Our results show that compared with the control diet, moderate sodium restriction was associated with increased levels of aldosterone but no overall change in renin, angiotensin II, or cortisol levels. Further, slopes of regression lines relating log renin and log angiotensin II to aldosterone were increased, as were log cortisol/aldosterone regression lines. On the contrary, regression lines of log renin and log angiotensin II versus arterial pressure were unaltered by sodium restriction. Hormone and blood pressure relationships were not changed by the potassium supplemented diet. Although confirmatory data are needed, our findings suggest that moderate sodium restriction enhances aldosterone responsiveness to endogenous angiotensin II and adrenocorticotropic hormone without diminishing the pressor activity of endogenous angiotensin II. These results may explain in part the disappointingly small hypotensive effect of modest sodium restriction in mild essential hypertension.

Effects of enalapril on clinical status, biochemistry, exercise performance and haemodynamics in heart failure.

The effects of enalapril on clinical well-being, treadmill exercise performance, haemodynamic measurements, hormone levels, and plasma biochemistry in patients with moderate heart failure, were assessed in a 12-week placebo-controlled, double-blind study. Maintenance frusemide and digoxin treatment was continued throughout the study. Compared with placebo, enalapril treatment improved clinical status and increased exercise capacity. The most obvious haemodynamic change was a fall in pulmonary artery wedge pressure and pulmonary artery pressure. Enalapril-induced increases in left-ventricular ejection fraction and cardiac index, and falls in systemic arterial pressure, were small. Of the hormone indices measured, plasma renin activity rose 4-fold, angiotensin II and aldosterone fell slightly, and plasma catecholamines were unaltered by enalapril. Plasma potassium increased on average by 0.3 mmol/L during enalapril therapy. No adverse clinical or biochemical effects were observed. Enalapril has a sustained beneficial action in patients with moderate heart failure.

Syncope in aortic valvular stenosis.

Simultaneous, continuous ambulatory recordings of systemic and pulmonary arterial pressure and heart rate were made in four patients with aortic valvular stenosis (AS) to explore the mechanisms of syncope in the disorder. When compared with six normal volunteers, patients with AS showed a subnormal systemic arterial pressure response to graded submaximal exercise. Three near-syncopal episodes, occurring during abrupt symptom-limited exercise, were associated with simultaneous acute falls in systemic and pulmonary arterial pressure in the absence of cardiac arrhythmia. Acute reflex peripheral arterial and venous vasodilatation, which may be mediated by the effects of sudden changes in left-ventricular pressure on ventricular baroreceptor activity, plays a central role in the exertion-induced syncope of aortic stenosis.