Perinatal and maternal outcomes in planned home and obstetric unit births in women at 'higher risk' of complications: secondary analysis of the Birthplace national prospective cohort study.

OBJECTIVE: To explore and compare perinatal and maternal outcomes in women at 'higher risk' of complications planning home versus obstetric unit (OU) birth. DESIGN: Prospective cohort study. SETTING: OUs and planned home births in England. POPULATION: 8180 'higher risk' women in the Birthplace cohort. METHODS: We used Poisson regression to calculate relative risks adjusted for maternal characteristics. Sensitivity analyses explored possible effects of differences in risk between groups and alternative outcome measures. MAIN OUTCOME MEASURES: Composite perinatal outcome measure encompassing 'intrapartum related mortality and morbidity' (intrapartum stillbirth, early neonatal death, neonatal encephalopathy, meconium aspiration syndrome, brachial plexus injury, fractured humerus or clavicle) and neonatal admission within 48 hours for more than 48 hours. Two composite maternal outcome measures capturing intrapartum interventions/adverse maternal outcomes and straightforward birth. RESULTS: The risk of 'intrapartum related mortality and morbidity' or neonatal admission for more than 48 hours was lower in planned home births than planned OU births [adjusted relative risks (RR) 0.50, 95% CI 0.31-0.81]. Adjustment for clinical risk factors did not materially affect this finding. The direction of effect was reversed for the more restricted outcome measure 'intrapartum related mortality and morbidity' (RR adjusted for parity 1.92, 95% CI 0.97-3.80). Maternal interventions were lower in planned home births. CONCLUSIONS: The babies of 'higher risk' women who plan birth in an OU appear more likely to be admitted to neonatal care than those whose mothers plan birth at home, but it is unclear if this reflects a real difference in morbidity. Rates of intrapartum related morbidity and mortality did not differ statistically significantly between settings at the 5% level but a larger study would be required to rule out a clinically important difference between the groups.

Assessment of von Willebrand disease as a risk factor for primary postpartum haemorrhage.

It is not clear whether von Willebrand disease (VWD) is associated with an increased risk of postpartum haemorrhage (PPH). We assessed the effect of VWD on PPH in a case-control study. Logistic regression was used to test for differences in the odds of PPH in deliveries to women with and without VWD, before and after adjustment for known risk factors. A total of 62 deliveries in 33 women with VWD were compared with controls matched for age, year of delivery and parity. Primary PPH was observed in 12/62 (19.4%) deliveries in women with VWD and 16/124 (12.9%) controls. The unadjusted odds ratio (OR) for VWD as a risk factor for PPH was 1.62 (95% CI 0.75-3.49, P = 0.22). After adjustment for other risk factors for PPH, the OR for VWD as a risk factor for PPH was 1.31 (95% CI 0.48-3.60, P = 0.60). PPH was observed in 7/24 (29%) deliveries in women known prepregnancy to have VWD. The unadjusted odds for VWD as a risk factor for PPH in this group was significantly greater than the control group (OR 2.78 (95% CI 1.03-7.49) P = 0.043) and remained significant after adjusting for other significant risk factors (OR 3.41 (95% CI 1.07-10.9) P = 0.038). VWD in itself may not be a significant risk factor for PPH, however, women known to have VWD predelivery may represent an at risk sub-group.

Systematic review of dermoscopy and digital dermoscopy/ artificial intelligence for the diagnosis of melanoma.

BACKGROUND: Dermoscopy improves diagnostic accuracy of the unaided eye for melanoma, and digital dermoscopy with artificial intelligence or computer diagnosis has also been shown useful for the diagnosis of melanoma. At present there is no clear evidence regarding the diagnostic accuracy of dermoscopy compared with artificial intelligence. OBJECTIVES: To evaluate the diagnostic accuracy of dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis and to compare the diagnostic accuracy of the different dermoscopic algorithms with each other and with digital dermoscopy/artificial intelligence for the detection of melanoma. METHODS: A literature search on dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis was performed using several databases. Titles and abstracts of the retrieved articles were screened using a literature evaluation form. A quality assessment form was developed to assess the quality of the included studies. Heterogeneity among the studies was assessed. Pooled data were analysed using meta-analytical methods and comparisons between different algorithms were performed. RESULTS: Of 765 articles retrieved, 30 studies were eligible for meta-analysis. Pooled sensitivity for artificial intelligence was slightly higher than for dermoscopy (91% vs. 88%; P = 0.076). Pooled specificity for dermoscopy was significantly better than artificial intelligence (86% vs. 79%; P < 0.001). Pooled diagnostic odds ratio was 51.5 for dermoscopy and 57.8 for artificial intelligence, which were not significantly different (P = 0.783). There were no significance differences in diagnostic odds ratio among the different dermoscopic diagnostic algorithms. CONCLUSIONS: Dermoscopy and artificial intelligence performed equally well for diagnosis of melanocytic skin lesions. There was no significant difference in the diagnostic performance of various dermoscopy algorithms. The three-point checklist, the seven-point checklist and Menzies score had better diagnostic odds ratios than the others; however, these results need to be confirmed by a large-scale high-quality population-based study.

Does miscarriage in an initial pregnancy lead to adverse obstetric and perinatal outcomes in the next continuing pregnancy?

OBJECTIVE: To explore pregnancy outcomes in women following an initial miscarriage. DESIGN: Retrospective Cohort Study. SETTING: Aberdeen Maternity Hospital, Aberdeen, Scotland. POPULATION: All women living in the Grampian region of Scotland with a pregnancy recorded in the Aberdeen Maternity and Neonatal Databank between 1986 and 2000. MAIN OUTCOME MEASURES: (A) Maternal outcomes: Pre-eclampsia, antepartum haemorrhage, threatened miscarriage, malpresenation, induced labour, instrumental delivery, Caesarean delivery, postpartum haemorrhage and manual removal of placenta. (B) Perinatal outcomes: preterm delivery, low birth weight, stillbirth, neonatal death, Apgar score at 5 minutes. METHODS: Retrospective cohort study comparing women with a first pregnancy miscarriage with (a) women with one previous successful pregnancy and (b) primigravid women. Data were extracted on perinatal outcomes in all women from the Aberdeen Maternity and Neonatal Databank between 1986 and 2000. RESULTS: We identified 1561 women who had a first miscarriage (1404 in the first trimester and 157 in the second trimester), 10 549 who had had a previous live birth (group A) and 21 118 primigravidae (group B). The miscarriage group faced a higher risk of pre-eclampsia (adj OR 3.3, 99% CI 2.6-4.6), threatened miscarriage (adj OR 1.7, 99% CI 1.5-2.0), induced labour (adj OR 2.2, 99% CI 1.9-2.5), instrumental delivery (adj OR 5.9, 99% CI 5.0-6.9), preterm delivery (adj OR 2.1, 99% CI 1.6-2.8) and low birthweight (adj OR 1.6, 99% CI 1.3-2.1) than group A. They were more likely to have threatened miscarriage (adj OR 1.5, 99% CI 1.4-1.7), induced labour (adj OR 1.3, 99% CI 1.2-1.5), postpartum haemorrhage (adj OR 1.4, 99% CI 1.2-1.6) and preterm delivery (adj OR 1.5, 99% CI 1.2-1.8) than group B. CONCLUSION: An initial miscarriage is associated with a higher risk of obstetric complications.

Evaluation of cardiac risk in dental patients.

Patients with cardiac disease, cardiac symptoms and related co-morbidities are increasingly being encountered in dental practice. Current methods of medical risk assessment can however be problematic. This paper represents a multi-speciality consensus on how to identify patients that may be more at risk of an adverse cardiac event occurring perio-operatively i.e. during or in the first few weeks after a dental procedure. Drawing on guidelines for surgery and the available literature, we present on an algorithm which aims to inform dental practitioners' decisions about which patients can be managed in primary care and which should be considered for assessment by a dental specialist together with a methodology thereof.

Premature coronary artery disease and early stage chronic kidney disease.

A 30 year old asymptomatic male with stage 3 chronic kidney disease (CKD) secondary to Focal Segmental Glomerulosclerosis was found to have features of CKD associated cardiomyopathy including left ventricular hypertrophy (LVH) and focal sub-endocardial scarring on cardiac magnetic resonance imaging. There was also a significantly raised CT coronary calcium score and evidence of non-flow limiting coronary artery disease (CAD) on a CT coronary angiogram. Early stage CKD is a major risk factor for cardiovascular risk causing myocardial hypertrophy and fibrosis and coronary artery atheroma. Cardiovascular risk begins to increase from an eGFR of around 75ml/min/1.73m2. The pathophysiology of cardiovascular disease in CKD is under investigation but to date, treatment options are limited. Blood pressure control and statins have the strongest supportive evidence.

Platelet and coagulation activation markers in myeloproliferative diseases: relationships with JAK2 V6I7 F status, clonality, and antiphospholipid antibodies.

BACKGROUND AND OBJECTIVES: Patients with myeloproliferative disease (MPD) have an increased risk of thrombosis. We studied markers of platelet and coagulation activation in a large cohort of patients with MPD (n = 118) and related this to Janus Kinase 2 (JAK2) V617 F mutation status, a marker of clonality, and the presence of antiphospholipid antibodies (APA), all of which have been associated with thrombosis in MPD. METHODS: D-dimer, thrombin-antithrombin complexes (TAT), prothrombin fragments 1 + 2 (F(1+2)), soluble E-selectin (sE-selectin), and soluble P-selectin (sP-selectin) levels were compared between patients and hypertensive controls (n = 127). Assays for lupus anticoagulant (LA), anticardiolipin antibodies (ACA), antibeta2 glycoprotein 1 antibodies (anti-beta(2)GP1), and antiprothrombin antibodies (alpha-Pro) were also performed. The JAK2 V617F mutation status was determined in the cohort using amplification refractory mutation system (ARMS) polymerase chain reaction. Disease clonality was determined in 54 patients using the HUMARA assay. RESULTS: sP-selectin was significantly increased in patients with MPD (P

The treatment of coronary artery disease in patients with chronic kidney disease.

Premature cardiovascular disease is the largest cause of mortality, and a major cause of morbidity, in patients with chronic kidney disease (CKD). Patients with end-stage kidney disease (ESKD) are at extreme risk, but cardiovascular event rates are increased even in early CKD. There is little controlled trial evidence on which to base treatment, as most therapeutic trials have excluded CKD patients. Current treatment strategies are therefore based upon small prospective studies or retrospective analyses of controlled trials and registry data. It is thus unclear whether CKD patients benefit from modern secondary preventive treatments in the same manner as patients with normal renal function. There is a need for randomized trials to identify effective drugs to prevent and treat coronary artery disease in CKD. Revascularization by CABG in CKD has been widely reported in registry data to provide better results than medical treatment or angioplasty. Recent angioplasty data in patients with CKD, however, show improving results, and the risks of CABG in CKD remain high. It is not clear which revascularization technique has a better outcome in patients 'equally suitable' on angiographic criteria for either procedure. The high rate of late adverse cardiovascular events after both CABG and angioplasty accentuates the need for effective secondary preventive therapy disease in these high-risk patients.

Large-displacement, hydrothermal frictional properties of DFDP-1 fault rocks, Alpine Fault, New Zealand: Implications for deep rupture propagation.

The Alpine Fault, New Zealand, is a major plate-bounding fault that accommodates 65-75% of the total relative motion between the Australian and Pacific plates. Here we present data on the hydrothermal frictional properties of Alpine Fault rocks that surround the principal slip zones (PSZ) of the Alpine Fault and those comprising the PSZ itself. The samples were retrieved from relatively shallow depths during phase 1 of the Deep Fault Drilling Project (DFDP-1) at Gaunt Creek. Simulated fault gouges were sheared at temperatures of 25, 150, 300, 450, and 600°C in order to determine the friction coefficient as well as the velocity dependence of friction. Friction remains more or less constant with changes in temperature, but a transition from velocity-strengthening behavior to velocity-weakening behavior occurs at a temperature of T = 150°C. The transition depends on the absolute value of sliding velocity as well as temperature, with the velocity-weakening region restricted to higher velocity for higher temperatures. Friction was substantially lower for low-velocity shearing (V < 0.3 µm/s) at 600°C, but no transition to normal stress independence was observed. In the framework of rate-and-state friction, earthquake nucleation is most likely at an intermediate temperature of T = 300°C. The velocity-strengthening nature of the Alpine Fault rocks at higher temperatures may pose a barrier for rupture propagation to deeper levels, limiting the possible depth extent of large earthquakes. Our results highlight the importance of strain rate in controlling frictional behavior under conditions spanning the classical brittle-plastic transition for quartzofeldspathic compositions.

Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?

BACKGROUND: Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the effect on adverse vascular events is unknown. We hypothesized that in patients with chronic renal failure, a condition associated with both hyperhomocysteinemia and atherosclerosis, treatment with folic acid would improve endothelial function. METHODS AND RESULTS: In a prospective, double-blind protocol, 100 patients (mean age 62 years, 67 men) with predialysis chronic renal failure were randomized to 5 mg folic acid or placebo daily for 12 weeks. Endothelial function was assessed by measuring (1) endothelium-dependent dilation of the brachial artery, (2) combined serum nitrite/nitrate concentrations, and (3) plasma von Willebrand factor concentration. Baseline characteristics of the 2 groups were similar. At the end of the study, both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [mean (95% CI) 39.0 (29.8 to 51.0) versus 7.7 (6.6 to 8.9) microg/L and 739 (613 to 891) versus 220 (184 to 262) microg/L, respectively; both P<0.001]. Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [15.1 (14.1 to 16.2) versus 20.1 (18.2 to 22.2) micromol/L; P<0.001], there were no significant differences in endothelium-dependent dilation, combined serum nitrite/nitrate concentrations, or plasma von Willebrand factor concentration between the 2 groups. CONCLUSIONS: High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure. This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia.

Suppression of inflammation in primary systemic vasculitis restores vascular endothelial function: lessons for atherosclerotic disease?

BACKGROUND: Chronic inflammatory rheumatic disorders are associated with excess cardiovascular mortality. This may result from arteriosclerosis following inflammatory damage to the vessel wall by vasculitis. Our hypothesis that vasculitis results in arteriosclerosis by causing vascular endothelial dysfunction was tested in patients with primary systemic necrotizing vasculitis (SNV). METHODS AND RESULTS: Endothelial function was assessed in cross-sectional and longitudinal studies of patients with primary SNV by measuring flow-mediated, endothelium-dependent brachial artery vasodilatation. These patients exhibited marked endothelial dysfunction compared with controls. Remission induction in patients with active primary SNV restored endothelial function. CONCLUSIONS: Endothelial function is significantly impaired in adults with primary SNV, supporting the hypothesis that premature arteriosclerosis in chronic inflammatory rheumatic disorders results from endothelial dysfunction secondary to vasculitis. Normalization of endothelial function after the treatment of primary SNV suggests that early suppression of disease activity in chronic inflammatory rheumatic disorders may reduce long-term vascular damage. The role of inflammation in atheroma formation is increasingly appreciated; this work raises questions regarding the potential for anti-inflammatory therapy in atherosclerosis itself.

A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease.

OBJECTIVES: This study was designed to determine the effects of folic acid therapy on endothelial function in patients with coronary artery disease (CAD). BACKGROUND: Hyperhomocysteinemia, a risk factor for CAD, may cause atherosderosis by oxidative endothelial injury. Folic acid reduces plasma homocysteine, but the effect on adverse vascular events is unknown. METHODS: In a double-blind placebo-controlled trial, 90 patients (mean age [range] 63 [46 to 79] years, 79 men) with CAD were randomized to either folic acid 5 mg or placebo daily for 12 weeks. Endothelial function was assessed by measuring: 1) flow-mediated endothelium-dependent dilation (EDD) of the brachial artery; 2) combined serum nitrite/nitrate (NOx) concentrations and; 3) plasma von Willebrand factor (vWF) concentration. RESULTS: At the end of the study, plasma homocysteine was lower in the folic acid group compared with the placebo group (mean [95% confidence interval] 9.3 (8.5 to 10.1) vs. 12.3 [11.3 to 13.4] micromol/l, p < 0.001). Although there were no significant differences in EDD, serum NOx or plasma vWF between the two groups, there was a greater increase in EDD from baseline in the folic acid group compared to placebo (1.2 [0.7 to 1.8] vs. 0.4 [-0.3 to 1.1]%, p = 0.07). CONCLUSIONS: Folic acid reduced plasma homocysteine and was associated with a trend toward improved endothelial function in patients with CAD. The absence of an unequivocally positive result may have been due to inadequate sample size or chance. This reinforces the need for the results of large randomized controlled trials before the implementation of routine folic acid supplementation.

The effect of running velocity on footstrike angle--a curve-clustering approach.

Despite a large number of studies that have considered footstrike pattern, relatively little is known about how runners alter their footstrike pattern with running velocity. The purpose of this study was to determine how footstrike pattern, defined by footstrike angle (FSA), is affected by running velocity in recreational athletes. One hundred and two recreational athletes ran on a treadmill at up to ten set velocities ranging from 2.2-6.1 ms(-1). Footstrike angle (positive rearfoot strike, negative forefoot strike), as well as stride frequency, normalised stride length, ground contact time and duty factor, were obtained from sagittal plane high speed video captured at 240 Hz. A probabilistic curve-clustering method was applied to the FSA data of all participants. The curve-clustering analysis identified three distinct and approximately equally sized groups of behaviour: (1) small/negative FSA throughout; (2) large positive FSA at low velocities (≤ 4 ms(-1)) transitioning to a smaller FSA at higher velocities (≥ 5 ms(-1)); (3) large positive FSA throughout. As expected, stride frequency was higher, while normalised stride length, ground contact time and duty factor were all lower for Cluster 1 compared to Cluster 3 across all velocities; Cluster 2 typically displayed intermediate values. These three clusters of FSA - velocity behaviour, and in particular the two differing trends observed in runners with a large positive FSAs at lower velocities, can provide a novel and relevant means of grouping athletes for further assessment of their running biomechanics.

Automated cardiopulmonary resuscitation using a load-distributing band external cardiac support device for in-hospital cardiac arrest: a single centre experience of AutoPulse-CPR.

BACKGROUND: Poor quality cardiopulmonary resuscitation (CPR) predicts adverse outcome. During invasive cardiac procedures automated-CPR (A-CPR) may help maintain effective resuscitation. The use of A-CPR following in-hospital cardiac arrest (IHCA) remains poorly described. AIMS & METHODS: Firstly, we aimed to assess the efficiency of healthcare staff using A-CPR in a cardiac arrest scenario at baseline, following re-training and over time (Scenario-based training). Secondly, we studied our clinical experience of A-CPR at our institution over a 2-year period, with particular emphasis on the details of invasive cardiac procedures performed, problems encountered, resuscitation rates and in-hospital outcome (AutoPulse-CPR Registry). RESULTS: Scenario-based training: Forty healthcare professionals were assessed. At baseline, time-to-position device was slow (mean 59 (±24) s (range 15-96s)), with the majority (57%) unable to mode-switch. Following re-training time-to-position reduced (28 (±9) s, p<0.01 vs baseline) with 95% able to mode-switch. This improvement was maintained over time. AutoPulse-CPR Registry: 285 patients suffered IHCA, 25 received A-CPR. Survival to hospital discharge following conventional CPR was 28/260 (11%) and 7/25 (28%) following A-CPR. A-CPR supported invasive procedures in 9 patients, 2 of whom had A-CPR dependant circulation during transfer to the catheter lab. CONCLUSION: A-CPR may provide excellent haemodynamic support and facilitate simultaneous invasive cardiac procedures. A significant learning curve exists when integrating A-CPR into clinical practice. Further studies are required to better define the role and effectiveness of A-CPR following IHCA.

Variability in cardiac MR measurement of left ventricular ejection fraction, volumes and mass in healthy adults: defining a significant change at 1 year.

OBJECTIVE: Variability in the measurement of left ventricular (LV) parameters in cardiovascular imaging has typically been assessed over a short time interval, but clinicians most commonly compare results from studies performed a year apart. To account for variation in technical, procedural and biological factors over this time frame, we quantified the within-subject changes in LV volumes, LV mass (LVM) and LV ejection fraction (EF) in a well-defined cohort of healthy adults at 12 months. METHODS: Cardiac MR (CMR) was performed in 42 healthy control subjects at baseline and at 1 year (1.5 T Magnetom® Avanto; Siemens Healthcare, Erlangen, Germany). Analysis of steady-state free precession images was performed manually offline (Argus software; Siemens Healthcare) for assessment of LV volumes, LVM and EF by a single blinded observer. A random subset of 10 participants also underwent repeat imaging within 7 days to determine short-term interstudy reproducibility. RESULTS: There were no significant changes in any LV parameter on repeat CMR at 12 months. The short-term interstudy biases were not significantly different from the long-term changes observed at 1 year. The smallest detectable change (SDC) for LVEF, end-diastolic volume, end-systolic volume and LVM that could be recognized with 95% confidence were 6%, 13 ml, 7 ml and 6 g, respectively. CONCLUSION: The variability in CMR-derived LV measures arising from technical, procedural and biological factors remains minimal at 12 months. Thus, for patients undergoing repeat annual assessment by CMR, even small differences in LV function, size and LVM (which are greater than the SDC) may be attributed to disease-related factors. ADVANCES IN KNOWLEDGE: The reproducibility and reliability of CMR data at 12 months is excellent allowing clinicians to be confident that even small changes in LV structure and function over this time frame are real.

Hyperhomocysteinaemia and vascular disease.

The amino-acid homocysteine plays a crucial role in cell metabolism. It participates in the remethylation pathway enabling maintenance of adequate cellular levels of methionine or is catabolized by transsulphuration. A number of hereditary defects in the enzymes involved in homocysteine metabolism and acquired deficiencies in the vitamin cofactors of these enzymes are associated with the development of hyperhomocysteinaemia. The association between high circulating homocysteine levels and premature vascular thrombosis is well established in individuals with hereditary homocystinuria. There is now good epidemiological evidence that mild hyperhomocysteinaemia is an independent risk factor in the development of arterial disease and venous thrombosis although the causes of the elevated plasma homocysteine are unclear. A good candidate is homozygosity for the common thermolabile variant of methylenetetrahydrofolate reductase but the evidence for a causative association is conflicting. A number of in vitro effects of homocysteine on vascular endothelium, platelets and coagulation have been described which may predispose to vascular disease but the exact in vivo mechanisms remain to be elucidated. Dietary folate supplementation may normalize homocysteine in hyperhomocysteinaemic individuals and modify the risk of vascular disease.

Nitric oxide and cardiac autonomic control in humans.

Cardiac autonomic control is of prognostic significance in cardiac disease, yet the control mechanisms of this system remain poorly defined. Animal data suggest that nitric oxide (NO) modulates cardiac autonomic control. We investigated the influence of NO on the baroreflex control of heart rate in healthy human subjects. In 26 healthy male volunteers (mean age, 23+/-5 years), we measured heart rate variability and baroreflex sensitivity during inhibition of endogenous NO production with N(G)-monomethyl-L-arginine (L-NMMA) (3 mg/kg per hour) and during exogenous NO donation with sodium nitroprusside (1 to 3 mg/h). Increases from baseline (Delta) in high-frequency (HF) indexes of heart rate variability were smaller with L-NMMA in comparison to an equipressor dose of the control vasoconstrictor phenylephrine (12 to 42 microg/kg per hour): Deltaroot mean square of successive RR interval differences (DeltaRMSSD)=23+/-32 versus 51+/-48 ms (P<0.002); Deltapercentage of successive RR interval differences >50 ms (DeltapNN50)=5+/-15% versus 14+/-12% (P<0.05); and DeltaHF normalized power=-2+/-7 versus 9+/-8 normalized units (P<0.01), respectively. Relative preservation of these indexes was observed during unloading of the baroreflex with sodium nitroprusside compared with a matched fall in blood pressure produced by a control vasodilator, hydralazine (9 to 18 mg/h): DeltaRMSSD=-8+/-8 versus -24+/-15 ms (P<0.001); DeltapNN50=-6+/-11% versus -15+/-19% (P<0.01); DeltaHF normalized power=-7+/-13 versus -13+/-11 normalized units (P<0.05), respectively. The change in cross-spectral alpha-index calculated as the square root of the ratio of RR interval power to systolic spectral power in the HF band (although not alpha-index calculated in the same way for the low-frequency bands or baroreflex sensitivity assessed by the phenylephrine bolus method) was attenuated with L-NMMA compared with phenylephrine (Delta=4+/-8 versus 14+/-15 ms/mm Hg, respectively; P<0.02) and with sodium nitroprusside compared with hydralazine (Delta=-7+/-6 and -9+/-7 ms/mm Hg, respectively; P<0.05). In conclusion, these data demonstrate that NO augments cardiac vagal control in humans.

Modulation of cardiac autonomic control in humans by angiotensin II.

Angiotensin II (Ang II) exerts an inhibitory action on vagal activity in animals and may also facilitate sympathetic activity. The object of this study was to compare autonomic activity resulting from equivalent steady-state baroreflex activation during intravenous Ang II infusion with that resulting from a control infusion of phenylephrine. Eight healthy subjects aged 22 to 34 years were studied in a single-blind, randomized, prospective crossover study. Autonomic activity was determined by computer analysis of RR interval variability in the time and frequency domains. Despite equal experimental hypertension with Ang II and phenylephrine infusion, at peak infusion rates the mean RR interval was significantly shorter with Ang II (983 +/- 179 milliseconds; mean +/- SD) than with phenylephrine (1265 +/- 187 milliseconds, P < .01). The variability of RR intervals was not significantly different, but the variability (median interquartile difference) of RR interval successive differences was significantly lower with Ang II (66 milliseconds) than with phenylephrine (104 milliseconds, P < .02). Power spectral analysis revealed the power of the 0.25-Hz component in normalized units to be significantly smaller during Ang II infusion (20.5 +/- 12.7 U) than during phenylephrine (38.2 +/- 14.7 U, P < .05), whereas the power of the 0.1-Hz component was significantly greater during Ang II infusion (67.8 +/- 17.1 U) than phenylephrine (38.8 +/- 20.3 U, P < .05). Measures of vagal modulation of heart rate were significantly attenuated, and sympathetic modulation appeared to be increased during Ang II infusion compared with control phenylephrine infusions. These observations may underlie reports of increased vagal activity during angiotensin-converting enzyme inhibitor therapy.