Could temporary external fixation after reduction of displaced acetabular fractures prevent posttraumatic heterotopic ossification?

OBJECTIVES: To recommend appropriate immobilization after the initial reduction of acetabular displaced fractures in order to minimize the risk of heterotopic ossification formation. DESIGN: Retrospective study of patients treated in our surgical department during the years 2005-2018. MATERIALS AND METHODS: There were 94 patients included in statistical analysis. The factors of injury severity, course of surgery and hospitalization and incidence of complications were recorded. The functional and X-ray results were evaluated at least one year after surgery. RESULTS: The patients were divided into the two groups according to the type of fixation after closed reduction, the external fixation (EF) and the skeletal traction (ST) group. According to the type of fracture there were 33 patients with central displacement and 61 patients with posterior displacement. Ossification grade III. And IV. Occur in 20% of our sample. There was greater incidence of Brooker grade III. And IV. Ossification in the ST group, but statistically insignificant, p = 0.57. There was no statistically significant difference in the occurrence of ossifications regarding the severity of the head injury, p = 0.11, or to the severity of the injury p = 0.54. The combination of posterior displacement and ST results in higher risk for ossifications, specifically in our group at 11.48% compared to the combination of posterior displacement and EF where it is 8.2%. CONCLUSION: Skeletal traction for posterior displaced acetabular fracture appears to be a more risky procedure for the development of ossifications than external fixation.

Phosphorylated and Phosphomimicking Variants May Differ-A Case Study of 14-3-3 Protein.

Protein phosphorylation is a critical mechanism that biology uses to govern cellular processes. To study the impact of phosphorylation on protein properties, a fully and specifically phosphorylated sample is required although not always achievable. Commonly, this issue is overcome by installing phosphomimicking mutations at the desired site of phosphorylation. 14-3-3 proteins are regulatory protein hubs that interact with hundreds of phosphorylated proteins and modulate their structure and activity. 14-3-3 protein function relies on its dimeric nature, which is controlled by Ser58 phosphorylation. However, incomplete Ser58 phosphorylation has obstructed the detailed study of its effect so far. In the present study, we describe the full and specific phosphorylation of 14-3-3ζ protein at Ser58 and we compare its characteristics with phosphomimicking mutants that have been used in the past (S58E/D). Our results show that in case of the 14-3-3 proteins, phosphomimicking mutations are not a sufficient replacement for phosphorylation. At physiological concentrations of 14-3-3ζ protein, the dimer-monomer equilibrium of phosphorylated protein is much more shifted towards monomers than that of the phosphomimicking mutants. The oligomeric state also influences protein properties such as thermodynamic stability and hydrophobicity. Moreover, phosphorylation changes the localization of 14-3-3ζ in HeLa and U251 human cancer cells. In summary, our study highlights that phosphomimicking mutations may not faithfully represent the effects of phosphorylation on the protein structure and function and that their use should be justified by comparing to the genuinely phosphorylated counterpart.

Deceleration thoracic aortic ruptures in trauma center level I areas: a 6-year retrospective study.

OBJECTIVES: This retrospective study aimed to analyze the trend of mortality due to thoracic aortic ruptures caused by deceleration injuries that occurred within the catchment area of Hradec Kralove University Hospital. MATERIALS AND METHODS: The study sample comprised 175 patients who had sustained thoracic aortic ruptures caused by deceleration injuries and were transported to Hradec Kralove University Hospital in 2009-2014. The small proportion of patients enrolled in this retrospective study were diagnosed and treated at the emergency department (ED). However, the overwhelming majority of the sample comprised of patients who died at the accident scene and later underwent an autopsy at the Institute of Forensic Medicine in our hospital. RESULTS: Of 175 patients, 150 underwent an autopsy. Of these, 139 individuals (79%) died at the incident scene, and 11 (6%) were transported to the ED and later died of their injuries. A total of 36 patients were admitted to the hospital; 29 were admitted primary (11 later died), and 7 were transferred. No deaths occurred in the group of secondary admissions. Thus, 31% of all patients hospitalized died following transport to the hospital. Of 175 patients, 15% (or 69% of all hospitalized patients) survived their injuries. Among patients who died as a result of thoracic aortic injury, no unexpected deaths were recorded (i.e., no deaths among patients with survival probability more than 50% = PS > 0.5). CONCLUSION: Our results suggested that the lethality of thoracic aortic injuries might be minimized by transporting triage-positive patients directly to trauma centers. Accurate diagnoses and treatments were supported by admission chest X-rays, a massive transfusion protocol, and particularly, CT angiography, which is not routinely included in primary surveys. An additional prognostic parameter was clinical collaboration between an experienced trauma surgeon, an interventional radiologist, and a vascular or thoracic surgeon.

The predictive value of cardiac morphology for long-term outcome of patients undergoing catheter ablation for atrial fibrillation.

OBJECTIVE: Catheter ablation (CA) is an established therapy for selected patients with atrial fibrillation (AF), but predictors of CA ablation outcome are still not fully elucidated. The aim of the study was to identify structural and morphological parameters from computed tomography (CT) as predictors of successful CA of AF in a single center prospective cohort. METHODS: An analysis of CT scans dedicated to LA evaluation was performed in 99 patients (63 ±â€¯8 years old, 70% males, 59% paroxysmal AF) scheduled for CA of AF. Survival free of atrial fibrillation/flutter/tachycardia at 1- and 3-years was assessed. RESULTS: In overall study population, both 1- and 3-year responders had smaller distance to the first division in left superior pulmonary vein (16.3 ±â€¯5.42 mm vs. 19.1 ±â€¯7.0 mm and 14.9 ±â€¯3.6 mm vs. 18.7 ±â€¯7.0 mm; p < 0.05). One-year responders had larger ostium area of left inferior pulmonary vein (median 236 mm2 [IQR = 97] vs. 222 mm2 [IQR = 71]; p = 0.03) and less acute angle between the interatrial septum and the right superior pulmonary vein (102 ±â€¯20° vs. 95 ±â€¯10°; p = 0.03). Three-years' responders had smaller ostium area of the right superior pulmonary vein (248 ±â€¯94 mm2 vs. 364 ±â€¯282 mm2; p = 0.02). Multivariate Cox regression analysis identified different predictors in paroxysmal and non-paroxysmal AF. For patients with paroxysmal AF, the predictors were angle to right superior pulmonary vein and left superior/inferior pulmonary veins carina thickness with hazard ratios of 0.965 (95%CI 0.939 to 0.992, p = 0.010) and 0.747 (95%CI 0.591 to 0.944, p = 0.015). In patients with persistent AF, the predictors were gender and NYHA stage with hazard ratios of 4.9 (95%CI 1.758 to 13.579, p = 0.002) and 0.365 (95%CI 0.148 to 0.899, p = 0.028) respectively. CONCLUSIONS: The anatomy of LA, especially morphology of pulmonary veins, seems to be one of the predictors of clinical outcome after CA for paroxysmal AF. In non-paroxysmal AF LA anatomy is less relevant in prediction of clinical outcome.

Physical Compatibility of Propofol-Sufentanil Mixtures.

BACKGROUND: Combined infusions of propofol and sufentanil preparations are frequently used in clinical practice to induce anesthesia and analgesia. However, the stability of propofol emulsions can be affected by dilution with another preparation, sometimes leading to particle coalescence and enlargement. Such unwanted effects can lead to fat embolism syndrome after intravenous application. This study describes the physical stability of 5 commercially available propofol preparations mixed with sufentanil citrate solutions. METHODS: Two common markers of emulsion stability were used in this study; namely, the zeta potential and size distribution of the emulsion droplets. Both were measured using dynamic light scattering. The data for the pure propofol preparations and their mixtures with sufentanil citrate solution were compared. RESULTS: The absolute value of zeta potential decreased in 4 of the 5 propofol preparations after they had been mixed with sufentanil citrate. This effect indicates a lowering of repulsive interactions between the emulsion droplets. Although this phenomenon tends to cause agglomeration, none of the studied mixtures displayed a substantial increase in droplet size within 24 hours of blending. However, our long-term stability study revealed the instability of some of the propofol-sufentanil samples. Two of the 5 studied mixtures displayed a continual increase in particle size. The same 2 preparations showed the greatest reductions in the absolute value of zeta potential, thereby confirming the correlation of both measurement methods. The increase in particle size was more distinct in the samples stored at higher temperatures and with higher sufentanil concentrations. CONCLUSIONS: To ensure the microbial stability of an emulsion infusion preparation, clinical regulations require that such preparations should be applied to patients within 12 hours of opening. In this respect, we can confirm that during this period, none of the studied propofol-sufentanil mixtures displayed any physical instability that could lead to particle enlargement; thus, fat embolism should not be a risk after their intravenous application. However, our long-term stability study revealed differences between commercially available preparations containing the same active ingredient; some of the mixtures showed an increase in particle size and polydispersity over a longer period. Although our results should not be generalized beyond the particular propofol-sufentanil preparations and concentrations studied here, they do suggest that, as a general principle, a compatibility study should be performed for any preparation before the first intravenous application to exclude the risk of droplet aggregation.

Multivariate Analysis of Correspondence between Left Atrial Volumes Assessed by Echocardiography and 3-Dimensional Electroanatomic Mapping in Patients with Atrial Fibrillation.

BACKGROUND: Left atrial (LA) enlargement is a predictor of worse outcome after catheter ablation for atrial fibrillation (AF). Widely used two-dimensional (2D)-echocardiography is inaccurate and underestimates real LA volume (LAV). We hypothesized that baseline clinical characteristics of patients can be used to adjust 2D-ECHO indices of LAV in order to minimize this disagreement. METHODS: The study enrolled 535 patients (59 ± 9 years; 67% males; 43% paroxysmal AF) who underwent catheter ablation for AF in three specialized centers. We investigated multivariately the relationship between 2D-echocardiographic indices of LA size, specifically LA diameter in M-mode in the parasternal long-axis view (LAD), LAV assessed by the prolate-ellipsoid method (LAVEllipsoid), LAV by the planimetric method (LAVPlanimetry), and LAV derived from 3D-electroanatomic mapping (LAVCARTO). RESULTS: Cubed LAD of 106 ± 45 ml, LAVEllipsoid of 72 ± 24 ml and LAVPlanimetry of 88 ± 30 ml correlated only modestly (r = 0.60, 0.69, and 0.53, respectively) with LAVCARTO of 137 ± 46 ml, which was significantly underestimated with a bias (±1.96 standard deviation) of -31 (-111; +49) ml, -64 (-132; +2) ml, and -49 (-125; +27) ml, respectively; p < 0.0001 for their mutual difference. LA enlargement itself, age, gender, type of AF, and the presence of structural heart disease were independent confounders of measurement error of 2D-echocardiographic LAV. CONCLUSION: Accuracy and precision of all 2D-echocardiographic LAV indices are poor. Their agreement with true LAV can be significantly improved by multivariate adjustment to clinical characteristics of patients.

Improvement in quality of life after catheter ablation for paroxysmal versus long-standing persistent atrial fibrillation: a prospective study with 3-year follow-up.

BACKGROUND: Changes in quality of life (QoL) after catheter ablation for long-standing persistent atrial fibrillation (LSPAF) are not well described. We sought to compare QoL improvement after catheter ablation of paroxysmal atrial fibrillation (PAF) versus that after LSPAF. METHODS AND RESULTS: A total of 261 PAF and 126 LSPAF ablation recipients were prospectively followed for arrhythmia recurrence, QoL, hospital stay, and sick leave. In PAF versus LSPAF groups, 1.3±0.6 versus 1.6±0.7 procedures were performed per patient (P<0.00001) during a 3-year follow-up. Good arrhythmia control was achieved in 86% versus 87% of patients (P=0.69) and in 69% versus 69% of patients not receiving antiarrhythmic drugs (P=0.99). The baseline QoL was better in the PAF than in the LSPAF group (European Quality of Life Group instrument self-report questionnaire visual analog scale: 66.4±14.2 versus 61.0±14.2, P=0.0005; European Quality of Life Group 3-level, 5-dimensional descriptive system: 71.4±9.2 versus 67.7±13.8, P=0.002). Postablation 3-year increase in QoL was significant in both groups (all P<0.00001) and significantly lower in PAF versus LSPAF patients (visual analog scale: +5.0±14.5 versus +10.2±12.8, P=0.001; descriptive system: +5.9±14.3 versus +9.3±13.9, P=0.03). In multivariate analysis, LSPAF, less advanced age, shorter history of AF and good arrhythmia control were consistently associated with postablation 3-year improvement in QoL. Days of hospital stay for cardiovascular reasons and days on sick leave per patient/year were significantly reduced in both groups. CONCLUSIONS: Patients with LSPAF had worse baseline QoL. The magnitude of QoL improvement after ablation of LSPAF was significantly greater compared with after ablation of PAF, particularly when good arrhythmia control was achieved without the use of antiarrhythmic drugs.

Slow pathway ablation for typical atrioventricular nodal re-entrant tachycardia significantly alters the autonomic modulation of atrioventricular conduction.

PURPOSE: Atrioventricular (AV) conduction turbulence, biphasic dromotropic response of AV node to single ventricular premature contraction (VPC), consists of early shortening and later prolongation of AV conduction intervals due to the direct electrophysiological mechanisms and perturbation in autonomic modulation. We investigated the acute effect of radiofrequency catheter ablation of slow pathway on AV turbulence. METHODS: The electrophysiological study was performed in 18 patients (7 men, mean age 49 ± 15 years) undergoing catheter ablation for AV nodal reentrant tachycardia. The stimulation protocol consisting of series of isolated VPC (coupling interval of 273 ± 23 ms) delivered from right ventricle apex during constant atrial pacing at 100 bpm was performed immediately prior to and 8 ± 4 min after successful slow-pathway ablation. Averaged post-VPCs profiles of AV conduction intervals were analyzed by purpose-written software. The descriptors of AV turbulence, turbulence onset (TOAV), turbulence slope (TSAV), and AV recovery (R AV) were assessed. RESULTS: Slow-pathway ablation suppressed the AV nodal responsiveness to VPC as evidenced by significant reduction of AV turbulence indices: TOAV: -6.4 ± 7.5 % vs. -4.3 ± 6.1 % (p < 0.05); TSAV: 2.0 ± 2.6 ms/RRi vs. 1.0 ± 0.7 ms/RRi (p < 0.05); and R AV: -13.8 ± 7.3 % vs. -6.5 ± 12.7 % (p < 0.05). CONCLUSIONS: Slow-pathway ablation significantly attenuated both vagal and non-autonomic modulation of AV nodal conduction. This effect is likely due to direct thermal injury of AV node associated with the change of properties of AV nodal fast-pathway although specific alteration of peri-AV nodal ganglionated plexi or their neural inputs into the AV node cannot be excluded.

Hemodynamics and autonomic control of heart rate turbulence.

INTRODUCTION: Late heart rate deceleration parallels the increase of systolic blood pressure during heart rate turbulence (HRT) after ventricular premature complexes (VPC). This is consistent with the involvement of baroreflex mechanism. Physiological background of systolic blood pressure dynamics is not known. Enhanced sympathetic activation and nonautonomic post-VPC changes of stroke volume have been speculated on. METHODS AND RESULTS: We studied 28 subjects (aged 56 +/- 11 years; 20 males; 18 normal and 10 abnormal left ventricular (LV) function) with spontaneous occurrence of VPCs. HRT indices and baroreflex sensitivity were analyzed from the ECGs and finger arterial pressure recordings during 30 minutes of spontaneous respiration in supine position. Beat-by-beat stroke volume and peripheral vascular resistance were computed by a nonlinear, self-adaptive model of aortic input impedance (Modelflow, Finapres Medical Systems, Arnhem, The Netherlands). Indices of HRT and baroreflex sensitivity were highly correlated. In patients with preserved LV function, there was no substantial dynamics of stroke volume in the late phase after VPC, while peripheral vascular resistance increased significantly. In patients with impaired LV function, potentiated first sinus beat after VPC triggered transient hemodynamic alternans. Dynamics of peripheral vascular resistance was attenuated and stroke volume was depressed in the late phase after VPC. CONCLUSIONS: Delayed sympathetically mediated vasomotor response to VPC produces systolic blood pressure overshoot. This subsequently induces vagally mediated late heart rate deceleration. Under physiologic conditions, there is no evidence of other hemodynamic and/or mechanical effect outside the autonomic reflex arch. In patients with LV dysfunction, both depressed vagal and sympathetic modulation and, indirectly, enhanced postextrasystolic potentiation account for attenuated HRT.

Relation between actual heart rate and autonomic effects of beta blockade in healthy men.

This study evaluated the effect of beta blockade on cardiac autonomic control and its dependence on heart rate change. The relations between RR interval duration, heart rate variability (HRV), and baroreflex sensitivity (BRS) were studied in 111 healthy men and in 21 male volunteers before and after a 100-mg oral dose of metoprolol. HRV and BRS correlated significantly with mean RR (r = 0.39, r = 0.57). Metoprolol administration increased both mean RR (from 996 to 1,176 ms, p <0.001), BRS from 24 to 36 ms/mm Hg (p = 0.003), and the SD of RR from 61 to 74 ms (p = 0.05). However, metoprolol-induced changes of HRV and BRS became insignificant (p = 0.69 and 0.48) after they were normalized to the same cycle length, suggesting that the improvement of cardiac autonomic control after beta blockade could be explained by a change of heart rate.

Pulse wave analysis during supine rest may identify subjects with recurrent vasovagal syncope.

In the present study, we studied whether analysis of the FAP (finger arterial pressure) waveform during supine rest discriminates subjects with recurrent VVS (vasovagal syncope) from healthy controls. Signal-averaged FAP waveforms (Finapres) were obtained in 32 head-up tilt-test-positive subjects with recurrent VVS (35 +/- 13 years) and in 32 sex- and age-matched healthy controls. The DT (time delay) between the systolic and diastolic peaks of the FAP waveform was measured and large artery SI (stiffness index) was calculated as a ratio of body height and DT. VVS patients had significantly shorter DT compared with controls (303 +/- 31 compared with 329 +/- 18 ms; P < 0.001) and higher SI (5.79 +/- 0.70 compared with 5.20 +/- 0.36 m/s; P < 0.001). The differences were independent of heart rate and blood pressure. SI > 5.45 m/s identified subjects with syncope with a sensitivity of 72% and a specificity of 84%. Age-corrected DT (cDT = DT + age-350) identified subjects with syncope with a sensitivity of 75% and a specificity of 84%. Combined use of cDT <0 ms and SI > 5.45 m/s increased sensitivity and specificity to 81% and 96% respectively. The discriminative power of FAP descriptors improved further when younger subjects were excluded. In subjects aged >30 years (median age), the combination of cDT and SI identified subjects with syncope with a sensitivity of 93% and a specificity of 100%. These results suggest that FAP descriptors during supine rest might be useful in the diagnosis of VVS in middle-aged subjects.

Predictive characteristics of holter-based postinfarction risk stratifiers appear superior to electrophysiological testing.

Prevalent low-frequency (PLF) oscillation of heart rate and turbulence slope (TS) are both powerful postmyocardial infarction (MI) risk factors. Abnormal composite risk stratifier (CRS) was defined as abnormal PLF or abnormal TS when PLF was not analyzable. We compared the predictive power of CRS with the previously published predictive value of conventional electrophysiological (EP) testing based on the presence of nonsustained ventricular tachycardia (NSVT) and inducibility of sustained ventricular tachycardia/fibrillation (VT/VF) during programmed ventricular stimulation (PVS). PLF and TS were calculated from baseline Holter recordings in the placebo population of European Amiodarone Infarction Myocardial Infarction Trial (EMIAT trial) (n = 633; LVEF /= 0.1 Hz and TS

Repeatability of noninvasive surrogates of endothelial function.

We compared the repeatability of 2 ultrasonographic methods for endothelial function assessment at brachial artery-flow-mediated dilation (FMD) and post-ischemic peak blood flow (PBF). Twenty healthy volunteers were examined twice within 10 days; coefficients of variation were 13.8% for PBF and 41.0% for FMD. PBF seems to be superior to FMD in terms of reproducibility. Consequently, smaller noninvasive studies of endothelial function can be designed utilizing PBF compared with FMD.

Prevalent low-frequency oscillation of heart rate: novel predictor of mortality after myocardial infarction.

BACKGROUND: This study evaluates a novel method for postinfarction risk stratification based on frequency-domain characteristics of heart rate variability (HRV) in 24-hour Holter recordings. METHODS AND RESULTS: A new risk predictor, prevalent low-frequency oscillation (PLF), was determined in the placebo population of the European Myocardial Infarction Amiodarone Trial (EMIAT). Frequencies of peaks detected in 5-minute low-frequency HRV spectra were averaged to obtain the PLF index. PLF >or=0.1 Hz was the strongest univariate predictor of all-cause mortality associated with relative risk of 6.4 (95% CI, 3.9 to 10.6; P<10(-12)). In a multivariate Cox's regression model including clinical risk factors, mean RR interval, HRV index, low- and high-frequency HRV spectral power, and heart rate turbulence, PLF was the most powerful mortality predictor, with a relative risk of 4.6 (95% CI, 2.2 to 9.3; P=0.00003). Predictive power of PLF was blindly validated in the population of the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) trial. PLF >or=0.1 Hz was associated with univariate relative risk of 6.1 (95% CI, 2.9 to 12.9; P<10(-5)) for cardiac mortality or resuscitated cardiac arrest. In multivariate Cox's regression model including age, left ventricular ejection fraction, baroreflex sensitivity, mean RR interval, standard deviation of normal RR intervals, low- and high-frequency HRV spectral power, and heart rate turbulence, only left ventricular ejection fraction and PLF were significant predictors, with relative risks of 4.2 (95% CI, 1.5 to 11.7; P=0.007) and 3.6 (95% CI, 1.3 to 10.5; P=0.02), respectively. CONCLUSIONS: An innovative analysis of frequency-domain HRV, which characterizes the distribution of spectral power within the low-frequency band, is a potent and independent risk stratifier in postinfarction patients.

Effect of atorvastatin and fenofibrate on autonomic tone in subjects with combined hyperlipidemia.

This randomized open-label trial investigated whether autonomic cardiovascular control is altered in middle-aged men with combined hyperlipidemia and whether such alterations are affected by short-term, lipid-lowering therapy with atorvastatin and/or fenofibrate. Compared with normolipidemic subjects, untreated subjects with combined hyperlipidemia had several abnormalities of autonomic tone, indicating increased sympathetic tone and decreased baroreflex sensitivity. The alterations in autonomic cardiovascular control were partially reversible by each of the lipid-lowering drugs.

Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia.

BACKGROUND: Combined hyperlipidemia (CH) is an increasingly prevalent risk factor for premature heart disease, and its treatment is troublesome. The aim of this study was to compare the effects of atorvastatin and fenofibrate on nonlipid biochemical risk factors and the low-density lipoprotein (LDL) particle size in subjects with CH. METHODS: Twenty-nine middle-aged men with CH were randomly assigned to open-label therapy with atorvastatin (10 mg daily) or micronized fenofibrate (200 mg daily); they were sequentially treated with both drugs, with crossover of medication after 10 weeks. RESULTS: Atorvastatin was more efficient in the reduction of total cholesterol, whereas fenofibrate was more efficient in the reduction of triglycerides. Only atorvastatin led to a significant reduction of LDL cholesterol and apolipoprotein B. Only fenofibrate increased high-density lipoprotein cholesterol. Neither drug influenced lipoprotein(a). Mean LDL particle size increased both after fenofibrate (3.08%) and atorvastatin (1.77%). Fenofibrate increased serum homocysteine (HCY) by 36.5%. Atorvastatin had no effect on HCY. Only atorvastatin increased fibrinogen by 17.4%. Only fenofibrate reduced C-reactive protein by 51.7%. Neither drug influenced HOMA (homeostasis model assessment) index of insulin resistance. The plasma level of thiobarbituric acid reactive substances, an index of oxidative stress, decreased after both treatments. CONCLUSIONS: Both atorvastatin and fenofibrate had similar beneficial effects on LDL particle size and on oxidative stress. The effects of both drugs on other parameters such as triglycerides, total and high-density lipoprotein cholesterol, fibrinogen, or HCY differed significantly. These differences, together with the risk profile of a patient, should be considered during selection of a particular lipid-lowering modality.

Nitroglycerin induced syncope occurs in subjects with delayed phase shift of baroreflex action.

Nitroglycerin (NTG) administration occasionally leads to syncope due to severe hypotension and bradycardia. This reaction resembles neurocardiogenic syncope but it may occur when the patient is in the supine position. To address the possible role of prevailing autonomic tone and baroreflex control in precipitation of NTG induced syncope, continuous noninvasive blood pressure and an ECG were taken shortly before NTG application in the supine position. Frequency-domain measures of heart rate variability (HRV) and noninvasive indices of baroreflex were compared between subjects who did (n = 6) and did not (n = 41) develop syncope after NTG. Both groups differed only in the phase shift (P(CR)) between oscillations of blood pressure and heart rate during controlled respiration (0.1 Hz). P(CR) was significantly delayed in subjects who developed syncope than in controls (- 99.3+/-14.1 vs -65.5+/-27.0 degrees, P = 0.002). Thus, subjects with prolonged P(CR) are prone to NTG induced syncope because of increased lagging and, consequently, less stable baroreflex control.