Thoracic Bioimpedance Research Articles

Liver afferents contribute to water drinking‐induced sympathetic activation in human subjects

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, the so called osmopressor response. We hypothesized that hepatic denervation attenuates water drinking‐induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as drug matched control group. Before and after 500 ml water ingestion, we monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance and obtained venous blood samples for catecholamine analysis. 30–40 minutes after water drinking, plasma norepinephrine had changed 0.0096±0.073 nmol/l in liver and 0.214±0.066 nmol/l in kidney transplant recipients (p<0.05 between groups). While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water‐drinking induced sympathetic activation in human subjects.

Cardiac function and arteriovenous oxygen difference during exercise in obese adults

The purpose of this study was to assess cardiac function and arteriovenous oxygen difference (a-vO(2) difference) at rest and during exercise in young, normal-weight (n = 20), and obese (n = 12) men and women who were matched for age and fitness level. Participants were assessed for body composition, peak oxygen consumption (VO(2peak)), and cardiac variables (thoracic bioimpedance)-cardiac index (CI), cardiac output (Q), stroke volume (SV), heart rate (HR), and ejection fraction (EF)-at rest and during cycling exercise at 65% of VO(2peak). Differences between groups were assessed with multivariate ANOVA and mixed-model ANOVA with repeated measures controlling for sex. Absolute VO(2peak) and VO(2peak) relative to fat-free mass (FFM) were similar between normal-weight and obese groups (Mean ± SEE 2.7 ± 0.2 vs. 3.3 ± 0.3 l min(-1), p = 0.084 and 52.4 ± 1.5 vs. 50.9 ± 2.3 ml kg FFM(-1) min(-1), p = 0.583, respectively). In the obese group, resting Q and SV were higher (6.7 ± 0.4 vs. 4.9 ± 0.1 l min(-1), p < 0.001 and 86.8 ± 4.3 vs. 65.8 ± 1.9 ml min(-1), p < 0.001, respectively) and EF lower (56.4 ± 2.2 vs. 65.5 ± 2.2%, p = 0.003, respectively) when compared with the normal-weight group. During submaximal exercise, the obese group demonstrated higher mean CI (8.8 ± 0.3 vs. 7.7 ± 0.2 l min(-1) m(-2), p = 0.007, respectively), Q (19.2 ± 0.9 vs. 13.1 ± 0.3 l min(-1), p < 0.001, respectively), and SV (123.0 ± 5.6 vs. 88.9 ± 4.1 ml min(-1), p < 0.001, respectively) and a lower a-vO(2) difference (10.4 ± 1.0 vs. 14.0 ± 0.7 ml l00 ml(-1), p = 0.002, respectively) compared with controls. Our study suggests that the ability to extract oxygen during exercise may be impaired in obese individuals.

Selection and collection of multi parameter physiological data for cardiac rhythm diagnostic algorithm development

Automated diagnostic algorithms are used in implantable cardioverter-defibrillators (ICD's) to detect abnormal heart rhythms. Algorithms misdiagnose and improved specificity is needed to prevent inappropriate therapy. Knowledge engineering (KE) and artificial intelligence (AI) could improve this. A pilot study of KE was performed with artificial neural network (ANN) as AI system. A case note review analysed arrhythmic events stored in patients ICD memory. 13.2% patients received inappropriate therapy. The best ICD algorithm had sensitivity 1.00, specificity 0.69 (p<0.001 different to gold standard). A subset of data was used to train and test an ANN. A feed-forward, back-propagation network with 7 inputs, a 4 node hidden layer and 1 output had sensitivity 1.00, specificity 0.71 (p<0.001). A prospective study was performed using KE to list arrhythmias, factors and indicators for which measurable parameters were evaluated and results reviewed by a domain expert. Waveforms from electrodes in the heart and thoracic bio-impedance; temperature and motion data were collected from 65 patients during cardiac electrophysiological studies. 5 incomplete datasets were due to technical failures. We concluded that KE successfully guided selection of parameters and ANN produced a usable system and that complex data collection carries greater risk of technical failure, leading to data loss.

Noninvasive estimation of cardiac output by thoracic bioimpedance: A comparison with doppler echocardiography

Noninvasive estimation of cardiac output by thoracic bioimpedance: A comparison with doppler echocardiography

Acute Cardiovascular Effects of Apelin in Humans

Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure. Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr(1))apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all P<0.0001). Vasodilatation to acetylcholine (P=0.01) but not apelin (P=0.3) or sodium nitroprusside (P=0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all P<0.05). Systemic infusions of (Pyr(1))apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all P<0.01) but increased heart rate only in control subjects (P<0.01). Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure.

Maternal haemodynamics at elective caesarean section: a randomised comparison of oxytocin 5-unit bolus and placebo infusion with oxytocin 5-unit bolus and 30-unit infusion

Background Rapid intravenous injection of oxytocin is associated with marked hypotension secondary to decreased venous return. Reductions in dose and rate of bolus administration have reduced the incidence of cardiovascular side effects, but no study has yet investigated cardiovascular stability when oxytocin is infused for several hours after delivery. This study compared maternal haemodynamics during a 4-h 30-unit oxytocin infusion and during a placebo infusion following caesarean section. Methods Women booked for elective caesarean section were randomised to receive either oxytocin 5-unit bolus and placebo infusion or oxytocin 5-unit bolus and oxytocin 30-unit infusion. Before, during and for 4 h after surgery electrocardiogram, oxygen saturation, systolic and diastolic pressure and heart rate were monitored non-invasively and cardiac index (CI), left ventricular work index (LVWi) and systemic vascular resistance index (SVRi) by thoracic bioimpedance. Results A total of 74 women agreed to haemodynamic measurements. Heart rate, systolic and diastolic pressure, CI, LCWi and SVRi all fell following the onset of spinal anaesthesia, and, with the exception of SVRi, continued to decrease throughout surgery. After delivery of the baby, slow injection of oxytocin 5 units was associated with a temporary rise in CI, LCWi and heart rate, a decrease in SVRi and no change in systolic or diastolic pressure. Thereafter, haemodynamic measures returned to normal over 60 min with no adverse effects apparent from the additional oxytocin infusion. Conclusions An additional oxytocin infusion at elective caesarean section did not adversely affect maternal haemodynamics either during or after surgery.

The cardiovascular effects of normobaric hyperoxia in patients with heart rate fixed by permanent pacemaker

To investigate whether the established reductions in heart rate and cardiac output with hyperoxia in humans are primary effects or secondary to increases in systemic vascular resistance, we paced the hearts of nine patients with permanent pacemakers at a fixed rate when breathing either medical air (inspired O(2) fraction 0.21) or oxygen (inspired O(2) fraction 0.80) in a randomised, double-blind fashion. A thoracic bio-impedance machine was used to measure heart rate, stroke volume and blood pressure and calculate cardiac index and systemic vascular resistance index. Oxygen caused no change in cardiac index (p = 0.18), stroke index (p = 0.44) or blood pressure (p = 0.52) but caused a small (5.5%) increase in systemic vascular resistance index (p = 0.03). This suggests that hyperoxia has no direct myocardial depressant effects, but that the changes in cardiac output reported in previous studies are secondary to changes in systemic vascular resistance.

Comparison of electrical velocimetry and transthoracic thermodilution technique for cardiac output assessment in critically ill patients

The results of studies validating the assessment of cardiac output by pulmonary artery thermodilution and a modified algorithm using thoracic bioimpedance/electrical velocimetry in patients undergoing elective cardiac surgery are conflicting. The present observational study was designed to detect whether electrical velocimetry measurements are comparable to transthoracic thermodilution in septic patients after major general surgery. Cardiac output was assessed simultaneously by thoracic bioimpedance measurement/electrical velocimetry and transthoracic thermodilution technique (PiCCO) in 30 patients with severe systemic inflammatory response syndrome or sepsis with haemodynamic instability being treated in the surgical intensive care unit of an university hospital. Thirty simultaneous measurements were taken with both methods. The Bland-Altman analysis of agreement revealed a bias of -0.3 l min(-1) with a precision of +/-1.9 l min(-1) and wide limits of agreement (-4.1-3.5 l min(-1)). The percentage error was 54%. There was poor agreement between the values of cardiac output estimation by transthoracic thermodilution and those by electrical velocimetry. Electrical velocimetry could not replace invasive monitoring in this trial.

Thoracic impedance vs chest radiograph to diagnose acute pulmonary edema in the ED

Objective We sought to investigate the relationship between thoracic impedance (Zo) and pulmonary edema on chest radiography in patients presenting to the emergency department (ED) with signs and symptoms of acute decompensated heart failure (ADHF). Design This was a prospective, blinded convenience sample of patients with signs and symptoms of ADHF who underwent measurement of Zo with concomitant chest radiography. Attending physicians blinded to the Zo values interpreted the radiographs, categorizing the severity of pulmonary edema as normal (NL), cephalization (CZ), interstitial edema (IE), or alveolar edema (AE). Intergroup comparisons were analyzed with a 2-way analysis of variance (ANOVA), with P < .05 considered statistically significant and reported using 95% confidence intervals (CIs). Setting We enrolled patients (≥18 years) presenting to a tertiary care medical center ED with signs and symptoms consistent with ADHF. Results A total of 203 patients were enrolled, with 27 (14%) excluded because of coexisting pulmonary diseases. The mean Zo values were inversely related to the 4 varying degrees of radiographic pulmonary vascular congestion as follows: NL, 25.6 (95% CI, 22.9-28.3); CZ, 20.8 (95% CI, 18.1-23.5); IE, 18.0 (95% CI, 16.3-19.7); and with AE, 14.5 (95% CI, 12.8-16.2) (ANOVA, P < .04). A Zo less than 19.0 ohms had 90% sensitivity and 94% specificity (likelihood ratio [LR], − 0.1; LR + 15) for identifying radiographic findings consistent with pulmonary edema. Females had an increased mean Zo value compared to males ( P < .03). Conclusion The Zo value obtained via thoracic bioimpedance monitoring accurately predicts the presence and severity of pulmonary edema found on initial chest radiograph in patients suspected of ADHF.

Hemodynamic Changes After Administration of Mannitol Measured by a Noninvasive Cardiac Output Monitor

Mannitol is the most commonly used hyperosmotic agent in neurosurgery. Being an agent that increases intravascular volume by withdrawing water from the brain, it may cause significant changes in stroke volume (SV), cardiac output (CO), systemic vascular resistance and blood pressure. In this study, we monitored the hemodynamic changes in response to a single dose of mannitol by using a noninvasive CO monitor based on the thoracic electrical bioimpedance technique, in patients undergoing craniotomy. Eleven adult patients undergoing elective craniotomy received mannitol 1.0 g/kg 15 minutes before dural opening. The following hemodynamic variables were recorded: heart rate, systolic blood pressure, diastolic blood pressure, SV, CO, and cardiac index. The measurements were made before the administration of mannitol, at 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, and 45 minutes after the termination of the mannitol infusion. Urine output was measured at 10, 20, 30, 40, 50, 60, 90, and 120 minutes after termination of the mannitol infusion. Heart rate values from 25 to 45 minutes were significantly lower compared with the premannitol values (P<0.05). All the postmannitol systolic blood pressure values were significantly lower than the premannitol value (P<0.05). SV increased significantly for 15 minutes after administration of mannitol (P<0.05). SV at 45 minutes was significantly lower than that from 1 to 30 minutes (P<0.05). Cardiac index also showed a similar change with a significant increase at 1 to 10 minutes and a decrease at 40 to 45 minutes compared with 1 to 15 minutes.The rate of urine secretion was higher during the first 10 minutes (40+/-15 mL/kg/ h) than during the rest of the study period. The overall fluid balance at the end of 120 minutes was -370+/-987 mL. In this study using noninvasive measurement of CO by thoracic bioimpedance plethysmography during craniotomy, a single bolus dose of mannitol 1.0 g/kg caused a significant but short duration changes in the hemodynamic variables. The changes in SV, and CO, lasted for only 15 minutes after the infusion.

Comparaison des valeurs de débit cardiaque obtenues à l’aide d’un nouveau système d’impédancemétrie thoracique avec les données du cathéter artériel pulmonaire en postopératoire de chirurgie cardiaque

Thoracic bioimpedance has been proposed for cardiac output (CO) determination and monitoring without calibration or thermodilution (ICG Monitor 862146, Philips Medical System, Philips, Suresnes, France). The accuracy and clinical applicability of this technology has not been fully evaluated in the cardiac surgery setting. We designed this prospective study to compare the accuracy of the ICG Monitor (CO(ICG)) versus pulmonary artery catheter standard bolus thermodilution (CO(PAC)) in patients after cardiac surgery or having benefited from cardiac surgery. Prospective, monocentric. We studied 13 patients in the postoperative period. CO(ICG) and CO(PAC) were determined at the arrival in the intensive care unit and every four hours. Bland-Altman and Critchley and Critchley's analysis were used to assess the agreement between CO(ICG) and CO(PAC). CO(PAC) ranged from 2.6 to 11.0 l/min and CO(ICG) ranged from 1.8 to 11.7 l/min. There was a significant relationship between CO(PAC) and CO(ICG) (r=0.61 ; p<0.001). Agreement between CO(PAC) and CO(ICG) was -0.5+/-1.3 l/min (Bland-Altman analysis). Percentage error between the two methods was 49% (Critchley and Critchley's analysis). We found clinically unacceptable agreement between CO(ICG) and CO(PAC) in this setting. Despite its non invasiveness, this device cannot be recommended for CO monitoring in the postoperative period following cardiac surgery.

Clinical Investigation of noninvasive hemodynamic monitoring using thoracic electrical bio-impedance in critical ill patients

Objective To evaluate the application value of thoracic electrical bioimpedance (TEB)in critical ill patients. Methods 48 patients who stayed more than 24 hours in comprehensive intensive care unit from October 2006 to August 2007 were studied. All patients were examined by TEB and echocardiography si-multeneonsly. The cardiac output ( CO), cardiac index ( CI ), stroke volume ( SV ) and stroke volume index ( SI ) were obtained by TEB and echocardiography. Pearsons relevance analysis was used to investigate the relationship of parameters between TEB andechocardiography. Results A significant high correlation between TEB and ech-ocardiography was found in CO,CI,SV,SI. Conclusion Hemodynamic parameters obtained by TEB are com-pares favorably with echocardiography in critical ill patients. TEB can evaluate the changes of of hemodynamics in critical patients. Key words: Noninvasive hemodynamics; Thoracic dectrical bioimpedance; Echocardiography

Noninvasive Assessment of Cardiac Index in Healthy Volunteers: A Comparison Between Thoracic Impedance Cardiography and Doppler Echocardiography

Thoracic bioimpedance cardiography (ICG) has been proposed as a noninvasive, continuous, operator-independent, and cost-effective method for cardiac output monitoring. In the present study, we compared cardiac index (CI) measurements with ICG (Niccomo device) and transthoracic Doppler echocardiography in resting healthy volunteers undergoing hemodynamic load challenge. Twenty-five healthy volunteers (7 men and 18 women, mean age 36 +/- 6 yr, body surface area 1.75 +/- 0.17 m(2)) were investigated during three experimental conditions: baseline, positive end-expiratory pressure + 10 cm H(2)O and lower body positive pressure by means of medical antishock trousers inflated to 30 cm H(2)O in the abdominal compartment. ICG signal quality was >89% over all sets of measurements. A weak but significant relationship was observed between CI(TTE) and CI(ICG) (r = 0.36; P = 0.002). Agreement between both techniques was 0.94 L x min(-1) x m(-2) (95% CI: 0.77-1.11), limits of agreement were -0.47 to 2.35 L x min(-1) x m(-2), and percentage error was 53%. No statistically significant relationships were found between percent changes in CI(TTE) and CI(ICG) after applications of positive end-expiratory pressure + 10 cm H(2)O (r = 0.21; P = 0.31) and medical antishock trousers (r = 0.22; P = 0.30). Poor correlation and lack of agreement between absolute values of CI measured by ICG and transthoracic Doppler echocardiography were found in resting healthy volunteers. The Niccomo device was also unreliable for monitoring changes in CI during hemodynamic load challenge.

Minimally Invasive Cardiac Output Monitoring in the Perioperative Setting

With advancing age and increased co-morbidities in patients, the need for monitoring devices during the perioperative period that allow clinicians to track physiologic variables, such as cardiac output (CO), fluid responsiveness and tissue perfusion, is increasing. Until recently, the only tool available to anesthesiologists to monitor CO was either a pulmonary artery catheter or transesophageal echocardiograph. These devices have their limitations and potential for morbidity. Several new devices (including esophageal Doppler monitors, pulse contour analysis, indicator dilution, thoracic bioimpedance and partial non-rebreathing systems) have recently been marketed which have the ability to monitor CO noninvasively and, in some cases, assess the patient's ability to respond to fluid challenges. In this review, we will describe these new devices including the technology, studies on their efficacy and the limitations of their use.

Abstract P101: Comparison of Ventilation Rate Measured with Thoracic Bioimpedance and with Capnography during Out-of-Hospital Cardiopulmonary Resuscitation

Objective: To determine the ability of thoracic bioimpedance to measure ventilation rate during cardiac arrest and CPR. Methods: Philips MRx devices monitored 32 patients during out-of-hospital cardiac arrest and CPR. The devices recorded chest compressions with an accelerometer, continuous 1-lead EKG, thoracic bioimpedance, and continuous capnography. Of the 32 files, 4 were not used in this study because of incomplete recording. Two reviewers manually annotated ventilation waveforms independently using Laerdal QCPR software, which also automatically annotated ventilation through the bioimpedance channel. Reviewers manually measured ventilation rate (number of breaths/min) recorded with capnography for each 1 minute epoch, which were matched and compared with those measured through bioimpedance for each patient file (N = 28). A total of 585 1-minute epochs were measured and compared. We assessed intra-class correlation for 2 individual raters for ventilation rates measured with capnography and with annotated bioimpedance to establish inter-user reliability of measurements. Ventilation rate measured with capnography vs. bioimpedance was compared with simple regression. Results: The majority (60%) of ventilation rates measured with capnography and with automated software bioimpedance were within 2 breaths/min of each other. After manual annotation of the bioimpedance channel, 81% of 1-min epochs were within 2 breaths/min of rates measured with capnography. Ventilation rate measured with capnography had good correlation with bioimpedance (r = .82, p &lt; .0001). Inter-rater agreement is estimated to be 0.96 for ventilation rate measured with capnography and 0.93 for rate measured with bioimpedance. Discussion: The software occasionally missed obvious ventilation waveforms and occasionally annotated waveforms obviously caused by chest compressions. Manual review and annotation improved the accuracy of ventilation rates measured with bioimpedance. Approximately 75% to 90% of recordings made with the Philips MRx device are expected to be useful for measurement. Conclusion: Ventilation rate measured with thoracic bioimpedance alone is acceptable using the Philips MRx device. Inter-rater agreement for measurements is excellent.

Sex difference in peak oxygen uptake in prepubertal children

Prepubertal boys’ greater aerobic fitness (peak V ˙ ⁡ O 2 ) has been attributed to their larger lean body mass (LBM); this bestowing a greater heart size and consequent larger maximum cardiac output. No difference in peak arterio-venous (A-VO 2) difference is thought to exist. However other work indicates that boys’ aerobic fitness remains 5% higher even after controlling for differences in LBM. Consequently the purpose of this study was to investigate whether peak V ˙ ⁡ O 2 , heart size, peak cardiac output and peak A-VO 2 difference would be comparable between a group of boys and girls with a similar LBM. A group of 9 prepubertal boys and 9 prepubertal girls with a similar mean LBM (27.0 ± 1.4 boys vs. 27.0 ± 2.0 kg girls) were selected. Left ventricular mass (LVM) and end diastolic volume (LVEDV) were measured using cardiac magnetic resonance imaging. Peak V ˙ ⁡ O 2 was determined on a cycle ergometer following an incremental exercise protocol to exhaustion, and cardiac output was recorded using thoracic bioimpedance. Boys’ peak V ˙ ⁡ O 2 (1.41 ± 0.18 L min −1 vs. 1.23 ± 0.08 L min −1) and A-VO 2 difference (14.8 ± 2.1 mL 100 mL −1 vs. 12.6 ± 1.6 mL 100 mL −1) were significantly ( p < 0.05) higher than girls’ values, but there were no significant sex differences in peak cardiac output (10.0 ± 1.4 L min −1 vs. 9.9 ± 1.40 L min −1), LVM (97 ± 13 g vs. 93 ± 20 g) or LVEDV (77 ± 8 mL vs. 70 ± 13 mL). Central factors of heart size and peak cardiac output are proportional to the LBM of the individual and sex independent. Sex differences in peripheral factors such as muscle fibre type profile, may affect A-VO 2 difference and underlie prepubertal boys’ higher peak V ˙ O 2 .

Cardiovascular changes after achieving constant effect site concentration of propofol

Target controlled infusions of propofol use a pharmacokinetic/pharmacodynamic model to calculate an effect site concentration of the drug. We assessed the cardiovascular stability of 10 healthy patients using non-invasive thoracic bioimpedance and their 'depth' of anaesthesia using the Bispectral index after they had been anaesthetised to a constant effect site concentration of propofol (6.5 min from starting). Each patient had no surgical stimulus and received no intravenous fluid during the study period. The patients also received effect site target controlled remifentanil (steady state 2.5 min from starting) and a bolus of vecuronium to facilitate intubation and ventilation. We mathematically calculated when each measured parameter would reach a state of stability (i.e. with 95% certainty). Heart rate levelled off at 20 min, Bispectral index at 32 min, and cardiac index and mean arterial pressure at 47 min after achieving effect site stability, the final levels being, respectively, 21%, 47%, 14% and 28% lower than those at effect site stability. We conclude that cardiovascular parameters continue to change to a clinically significant degree after achieving a constant effect site concentration of propofol via target controlled infusions.

Using Surface Thoracic Bioimpedance for monitoring patients with risk development of Acute Heart Failure. New experience

Using Surface Thoracic Bioimpedance for monitoring patients with risk development of Acute Heart Failure. New experience

Hormonal Influences on Cardiovascular Norepinephrine Transporter Responses in Healthy Women

Gender differences in human cardiovascular norepinephrine transporter function may be mediated through female sex hormones. We studied 16 healthy eumenorrheic women (25+/-1 years) during the early follicular phase (day 5+/-0) and midluteal phase (day 22+/-0) of the menstrual cycle. In a randomized, crossover, double-blind fashion, subjects ingested 8 mg of the selective norepinephrine transporter inhibitor reboxetine or placebo. We monitored heart rate, blood pressure, and thoracic bioimpedance at rest and during standard autonomic function tests, including head-up tilt. Venous estradiol and progesterone concentrations were higher in the luteal than in the follicular phase but did not differ between placebo and norepinephrine transporter inhibition testing days. On placebo, hemodynamics at rest and in response to different stressors were mostly identical between cycle phases. In the supine position, norepinephrine transporter inhibition increased blood pressure and stroke volume to a greater extent during the follicular than during the luteal phase. Conversely, the increase in heart rate and cardiac output with norepinephrine transporter inhibition was augmented in the luteal compared with the follicular phase. During head-up tilt with norepinephrine transporter inhibition, blood pressure and stroke volume decreased to a greater extent in the follicular than in the luteal phase. The tachycardic response to head-up tilt with norepinephrine transporter inhibition was augmented in the follicular phase. Our study suggests that sex hormones alter the hemodynamic response to norepinephrine transporter inhibition in women. The phenomenon may be explained by an effect of female sex hormones on norepinephrine transporter function, on compensatory cardiovascular responses, or both.

Cardiovascular changes after achieving constant effect site concentration of propofol*

Target controlled infusions of propofol use a pharmacokinetic/pharmacodynamic model to calculate an effect site concentration of the drug. We assessed the cardiovascular stability of 10 healthy patients using non-invasive thoracic bioimpedance and their 'depth' of anaesthesia using the Bispectral index after they had been anaesthetised to a constant effect site concentration of propofol (6.5 min from starting). Each patient had no surgical stimulus and received no intravenous fluid during the study period. The patients also received effect site target controlled remifentanil (steady state 2.5 min from starting) and a bolus of vecuronium to facilitate intubation and ventilation. We mathematically calculated when each measured parameter would reach a state of stability (i.e. with 95% certainty). Heart rate levelled off at 20 min, Bispectral index at 32 min, and cardiac index and mean arterial pressure at 47 min after achieving effect site stability, the final levels being, respectively, 21%, 47%, 14% and 28% lower than those at effect site stability. We conclude that cardiovascular parameters continue to change to a clinically significant degree after achieving a constant effect site concentration of propofol via target controlled infusions.