Distinct types of non-cholinergic pedunculopontine neurons are differentially modulated during global brain states.

The pedunculopontine nucleus (PPN) is critically involved in brain-state transitions that promote neocortical activation. In addition, the PPN is involved in the control of several behavioral processes including locomotion, motivation and reward, but the neuronal substrates that underlie such an array of functions remain elusive. Here we analyzed the physiological properties of non-cholinergic PPN neurons in vivo across distinct brain states, and correlated these with their morphological properties after juxtacellular labeling. We show that non-cholinergic neurons in the PPN whose firing is not strongly correlated to neocortical activity are highly heterogeneous and are composed of at least three different subtypes: (1) "quiescent" neurons, which are nearly silent during slow-wave activity (SWA) but respond robustly to neocortical activation; (2) "tonic firing" neurons, which have a stationary firing rate that is independent of neocortical activity across different brain states; and (3) "irregular firing" neurons, which exhibit a variable level of correlation with neocortical activity. The majority of non-cholinergic neurons have an ascending axonal trajectory, with the exception of some irregular firing neurons that have descending axons. Furthermore, we observed asymmetric synaptic contacts within the PPN arising from the axon collaterals of labeled neurons, suggesting that excitatory, non-cholinergic neurons can shape the activity of neighboring cells. Our results provide the first evidence of distinct firing properties associated with non-cholinergic neuronal subtypes in the PPN, suggesting a functional heterogeneity, and support the notion of a local network assembled by projection neurons, the properties of which are likely to determine the output of the PPN in diverse behavioral contexts.

Increased risks of circulatory diseases in late pregnancy and puerperium.

We studied a nationwide Swedish cohort with 654,957 women who had 1,003,489 deliveries from 1987 through September 1995 to assess late pregnancy and puerperal risks of circulatory diseases. We used standardized incidence rate ratios to calculate relative risks [with 95% confidence intervals (CIs)]. Compared with unexposed (nonpregnant and early pregnant) women, relative risks of venous thrombosis and pulmonary embolism during the third trimester were 6.7 (95% CI = 5.7--7.8) and 2.7 (95% CI = 1.7--4.2), respectively. Around delivery (from 2 days before to 1 day after delivery), the relative risks of all assessed circulatory diseases were dramatically increased: venous thrombosis, 115.1 (95% CI = 96.4--137.0); pulmonary embolism, 80.7 (95% CI = 53.9--117.9); subarachnoid hemorrhage, 46.9 (95% CI = 19.3--98.4); intracerebral hemorrhage, 95.0 (95% CI = 42.1--194.8); cerebral infarction, 33.8 (95% CI = 10.5--84.0); and myocardial infarction, 27.0 (95% CI = 0.6--180.0). During the rest of the first 6 weeks postpartum, the risks declined but were still substantially increased for all diseases, with the exception of subarachnoid hemorrhage. The results suggest that the increased risk for circulatory diseases related to pregnancy is mainly confined to a few days around delivery.

Tall or short? Twenty years after preeclampsia exposure in utero: comparisons of final height, body mass index, waist-to-hip ratio, and age at menarche among women, exposed and unexposed to preeclampsia during fetal life.

Women exposed to preeclampsia during fetal life have lower risk of breast cancer, compared with unexposed women, possibly through fetal programming. Hypothetically, preeclampsia exposure could affect well-known risk factors for breast cancer, such as pubertal development or adult anthropometry. Women born in a defined geographic area of Sweden from 1973 through 1978, with verified preeclampsia exposure (n = 230) and nonexposure (n = 359) during fetal life, answered questions about anthropometric measures, smoking, parity, and age at menarche in a telephone interview in early adulthood. Compared with unexposed offspring, female offspring of women who had preeclampsia were lighter and shorter for gestational age, but in young adulthood there were no differences in height, body mass index, waist-to-hip ratio, or age at menarche. When analyzing the effects of other maternal and fetal characteristics, the results indicate that approximately 50% of the variance in final height was explained by parental heights and birth length for gestational age. Young-adult body mass index was weakly associated with maternal body mass index, maternal smoking, and birth weight for gestational age, which together explained 12% of the variance. Neither of the assessed maternal or fetal characteristics were significantly associated with age at menarche or waist-to-hip ratio. These data indicate that neither adult anthropometry nor age at menarche is in the causal pathway between intrauterine preeclampsia exposure and the reduced risk of breast cancer.

Genetic effects on the liability of developing pre-eclampsia and gestational hypertension.

Genetic factors are known to be important in the etiology of pre-eclampsia and possibly also gestational hypertension, but the degree of genetic influence has not been quantified. To estimate the genetic and environmental effects on the liability of developing pre-eclampsia and gestational hypertension, we cross-linked the population-based Swedish Twin Register and the Swedish Medical Birth Register. We included female twin pairs with known zygosity, both of whom gave birth in Sweden from 1973 through 1993; in all 917 monozygotic and 1,199 dizygotic twin pairs. For pre-eclampsia, the estimates of heritability and nonshared environmental effect were 0. 54 (95% confidence interval 0-0.71) and 0.46 (0.29-0.67), respectively; corresponding estimates for gestational hypertension were 0.24 (0-0.53) and 0.76 (0.47-1.00), respectively. When considering both diseases as a single entity (pregnancy-induced hypertensive diseases), the heritability estimate was 0.47 (0.13-0. 61). These results suggest that genetic factors are important in the development of pre-eclampsia as well as gestational hypertension. The heritability estimates can be of importance when planning genetic linkage studies. In efforts to identify women with elevated risk of developing pre-eclampsia during pregnancy, a question about family history of pre-eclampsia should be included.

A comparison of the incidence of the oculocardiac and oculorespiratory reflexes during sevoflurane or halothane anesthesia for strabismus surgery in children.

UNLABELLED: We examined changes in the cardiorespiratory system of small children during surgical correction of strabismus with a laryngeal mask airway and spontaneous respiration with sevoflurane or halothane inhaled anesthesia. Fifty-one children, 1-7 yr old, having outpatient strabismus correction were randomized to sevoflurane (S) or halothane (H) in 66% nitrous oxide at 1.3 minimum alveolar concentration. Children breathed spontaneously through a laryngeal mask airway and were not pretreated with anticholinergics. The oculocardiac reflex (OCR), defined as a 20% decrease in heart rate (HR) from baseline, dysrhythmias, or sinoatrial arrest concomitant with ocular muscle traction occurred less frequently with sevoflurane than with halothane (S 38%, H79%, P = 0.009). The baseline HR was higher with sevoflurane (S 114 +/- 13 bpm, H 101 +/- 15 bpm, P = 0.002). The lowest HR occurred with halothane (S 95 +/- 22 bpm, H 73 +/- 19 bpm, P = 0.001). The incidence of dysrhythmias was higher in the halothane group (S 4%, H 42%, P = 0.004). Reductions in minute ventilation and PETCO(2) accompanied OCRs. Airway irritability was present with halothane only (S 0, H 3). Eleven children, of whom the majority had received halothane, required measures to correct SpO(2) < 95% or PETCO(2) > 60 mm Hg during maintenance anesthesia (S 11%, H 32%). Sevoflurane may be a more suitable anesthetic than halothane for operations involving traction on the ocular muscles with spontaneous respiration in children because of reduced incidence of OCR, airway irritability, and ventilatory disturbances. IMPLICATIONS: Some children experience a sudden slowing of the heart and impaired breathing when the surgeon pulls on the eye muscles during squint operations under anesthesia. Sevoflurane, a recently developed anesthetic vapor, may reduce this problem when compared with the established vapor halothane.

Comparison of risk factors for preeclampsia and gestational hypertension in a population-based cohort study.

The objective of this study was to evaluate and compare risk factor patterns in association with preeclampsia and gestational hypertension. The data were collected from The Swedish Medical Birth Register and include all nulliparas aged 34 years or less who gave birth at the University Hospital of Uppsala, Sweden, during 1987-1993. Of these 10,666 women, 4.4% developed gestational hypertension, and 5.2% developed preeclampsia. The following risk factors were significantly associated with increased risk of preeclampsia: type 1 diabetes (odds ratio = 5.58, 95% confidence interval 2.72-11.43), gestational diabetes (odds ratio = 3.11, 95% confidence interval 1.61-6.00), and twin birth (odds ratio = 4.17, 95% confidence interval 2.30-7.55). The positive associations between these variables and the risk of gestational hypertension were weaker and nonsignificant. Compared with underweight women (body mass index < 19.8), obese women (body mass index > 29) had increased risks of both gestational hypertension (odds ratio = 4.85, 95% confidence interval 1.97-11.92) and preeclampsia (odds ratio = 5.19, 95% confidence interval 2.35-11.48). Significantly lower risks of preeclampsia and gestational hypertension were observed for women born outside Nordic countries and in association with maternal smoking and summer birth. The similarities in risk factor patterns may indicate similarities in the biologic mechanisms underlying the two conditions.

Atracurium induced vasodilatation is not mediated by histamine in the isolated femoral artery of the rabbit.

Atracurium causes a decrease in systemic vascular resistance (SVR) and mean arterial blood pressure (MAP) which has been ascribed to histamine release. However, histamine receptor blockade does not prevent these decreases completely. The hypotensive side effects of atracurium may not only be caused by histamine. In this study we examined the vasoactive effects of atracurium with and without histamine receptor blockade in an isolated femoral artery preparation of the rabbit. We also investigated whether vasodilatation caused by atracurium depends on the presence of endothelial cells. Tyrode perfused, rabbit femoral arteries were constricted with noradrenaline (NA) to +/- 70% of their passive diameter. Endothelial function was checked with acetylcholine (ACh). The vessels were divided into two groups. In both groups the responses to histamine (1.0-10(-6)M) and atracurium (3.2-10(-5)M) were determined. In group one (n = 5), the histamine and atracurium responses were repeated during histamine receptor blockade. In group two (n = 5), the diameter responses to histamine and atracurium before and after endothelium removal were compared. Also, some vessel segments (n = 5) were histologically prepared and examined for mast cells. The vasodilatory responses to atracurium both with and without histamine receptor blockade were the same. Removal of endothelium caused an increase in the histamine response, while the dilating response to atracurium remained constant. We conclude that in the isolated femoral artery of the rabbit, atracurium induces, vasodilatation that is not mediated by histamine release and cannot be prevented with histamine receptor blockade. The mechanism of atracurium induced dilation is independent of the endothelium and is located in the smooth muscle cell.

Noninvasive continuous blood pressure measurement during anaesthesia: a clinical evaluation of a method commonly used in measuring devices.

The objective of the study was assess the utility during anaesthesia of noninvasive continuous blood pressure measurement techniques which use intermittent oscillometric blood pressure measurement for their calibration. The assessment was performed by comparing noninvasive blood pressure with intra-arterial blood pressure. The noninvasive blood pressure measurement device used for evaluation was the NCAT N-500 which uses tonometry for its continuous measurements. Fifteen patients were studied. In 10 patients the intra-arterial blood pressure curve (IBP) was recorded from the radial artery (radial artery group), and in 5 patients it was recorded from the brachial artery (brachial artery group). In all patients the oscillometrically calibrated tonometric blood pressure (OTBP) was recorded from the other arm. To discriminate between calibration dependent measurement error and tonometric measurement error, the OTBP signal was recalibrated against the IBP signal to get the intra-arterial calibrated tonometric pressure curve (ITBP). OTBP-IBP reflected the overall measurement error, ITBP-IBP the error of the tonometric measurement, and OTBP-ITBP the calibration dependent measurement error. According to criteria formulated in the discussion the accuracy and agreement of the ITBP-IBP measurements were clinical acceptable. Accuracy and agreement of OTBP-IBP and of OTBP-ITBP were not clinical acceptable. Correlation of dynamic behavior was lower for OTBP than for ITBP. A significant effect of site difference between calibration measurements and continuous measurements was not found. It is concluded that the approach of continuous noninvasive blood pressure measurement based on the combination of two different measurement methods, in which the continuous method is calibrated by the oscillometric method, lead to clinical unacceptable accuracy and agreement in the patient group studied.

Effects of epidural analgesia and atropine on heart rate and blood pressure variability: implications for the interpretation of beat-to-beat fluctuations.

Cardiovascular variables such as heart rate, arterial blood pressure, stroke volume and the shape of electrocardiographic complexes all vary beat-by-beat. This variability occurs because of the dynamic response of cardiovascular regulatory systems to perturbations in cardiovascular function. We applied spectral analysis to the effects of sympathetic vasomotor blockade by epidural analgesia and parasympathetic blockade of the heart by atropine on the beat-to-beat variability of heart rate and blood pressure in humans. High-frequency fluctuations in heart rate (+/- 0.2 Hz) are caused by respiratory induced fluctuations of blood pressure, mediated by the vagus nerve. Low-frequency fluctuations (0.06-0.12 Hz) are related to sympathetic baroreflex control of vasomotor activity and heart rate. In our study, even partial parasympathetic blockade of the heart by atropine decreased the power in the high and low frequency heart rate fluctuations. There were no significant changes in blood pressure fluctuations in either frequency range. Sympathetic blockade by epidural analgesia decreased only low-frequency fluctuations of both heart rate and blood pressure. From a cardiovascular model and our experimental results we support the view that high frequency fluctuations in heart rate are due to the vagal response to blood pressure fluctuations caused by respiration and that the fluctuations around 0.1 Hz in both heart rate and blood pressure have their origin in the sympathetic baroreflex control loop of vasomotor activity.

Effects of thiopentone, etomidate and propofol on beat-to-beat cardiovascular signals in man.

Analysis of beat-to-beat fluctuations of heart rate and blood pressure is a promising new approach to the clinical diagnosis and management of alterations in cardiovascular regulation. We investigated the effects of three induction agents on beat-to-beat heart rate and blood pressure fluctuations in man. Beat-to-beat fluctuations were analysed by spectral analysis. Two spectral areas are of main interest. One area is centred on the respiratory frequency and shifts with changes in respiratory rate (High Frequency area). These high frequency fluctuations in heart rate are caused by respiratory-induced blood pressure fluctuations, mediated by the vagus nerve through the baroreflex mechanism. Variability in the Low Frequency area, which occurs between 0.06 and 0.12 Hz is considered to be related to haemodynamic fluctuations due to the sympathetic baroreflex control loop of vasomotor activity and heart rate. Results from our study indicate that thiopentone, etomidate and propofol show considerable differences in their effects on beat-to-beat variability of heart rate and blood pressure. These differences can be explained by their specific effects on the cardiovascular system.

Noninvasive continuous blood pressure measurement: a clinical evaluation of the Cortronic APM 770.

The Cortronic APM 770 (Cortronic, Ronkonkoma, NY) is a commercial device that claims to measure blood pressure noninvasively and continuously with the use of a standard blood pressure cuff. The aim of our study was to assess the performance of the continuous-mode blood pressure readings of the Cortronic during anesthesia and surgery. We recorded blood pressure in 5 patients bilaterally. An interaarterial pressure (IAP) curve was recorded from 1 arm and the Cortronic pressure curve (CPC) was recorded from the other. For statistical analysis the period between 2 Cortronic recalibrations was defined as the intercalibration interval. The duration of these intervals ranged from 20 to 0.5 minutes. Four paired samples were drawn from each interval. The first sample in an interval represented the recalibration blood pressure; the other samples represented the continuous blood pressure. A total of 1,232 samples were taken, of which 308 were recalibration. The median of the differences and the 2.5th and 97.5th percentile limits of agreement were determined. Their respective values for diastolic and systolic recalibration measurements were 5, -17, and 34 mm Hg, and 6, -12, and 38 mm Hg. Their values for continuous measurements were 4, -23.5, and 32 mm Hg, and 6, -30, and 70 mm Hg. Changes in CPC were evaluated against changes in the corresponding IAP by plotting them in 4-quadrant graphs. In these graphs the Spearman rank correlations were between r = -0.17 and r = 0.01. We observed opposite CPC and IAP trends on 24 occasions during this study. We performed a simple simulation study to better understand the measurement method of the Cortronic.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial and His-Purkinje conduction times during isoflurane anaesthesia in humans.

The effect of isoflurane 2.0 MAC on human atrioventricular conduction time was studied. A non-invasive recording system for the detection of His-Purkinje potentials based on signal averaging techniques was used. Recordings were made in 15 patients before and after induction with isoflurane. We were able to measure atrial (P-H) and His-Purkinje (HPS) conduction times in 11 patients. Mean (+/- SEM) P-H conduction time decreased from 101.8 +/- 5.3 to 89.3 +/- 3.3 ms (P less than 0.01). HPS conduction times did not change significantly. Heart rate increased significantly from 86.7 +/- 4.2 to 94.9 +/- 4.7 beats min-1 (P less than 0.05). Systolic blood pressure decreased from 117.3 +/- 4.6 to 94.1 +/- 4.7 mmHg (P less than 0.05). It is concluded that the effects of isoflurane on supraventricular conduction time in humans depend on interactions of several different mechanisms.

Effects of halothane on the conduction system of the heart in humans.

The effects of 2.0 MAC halothane on atrioventricular conduction times in humans were studied. A real-time recording system for the detection of surface His-Purkinje potentials based on signal averaging techniques was used. Recordings were made in 23 patients before and after the administration of halothane. In 18 patients we were able to measure atrial (P-H) and His-Purkinje (H-V) conduction times (78%). A small but statistically significant decrease in P-H conduction times from 115.3 +/- 3.9 (SEM) to 110.8 +/- 4.2 ms was found (P less than or equal to 0.01). H-V conduction times did not change significantly. Heart rates decreased significantly from 87.6 +/- 2.6 to 74.8 +/- 2.5 beats/min (P less than or equal to 0.01). Systolic blood pressures decreased from 118.9 +/- 3.7 to 103.6 +/- 4.2 mm Hg. It is concluded that the decrease in heart rate and the decrease in atrial conduction time caused by halothane can be explained by interactions of several different mechanisms. The specific combination of slowing heart rate and a decrease of atrial conduction time provides a possible explanation for atrial arrhythmias during the administration of halothane.

Median nerve evoked potentials during propofol anaesthesia.

Median nerve somatosensory evoked potentials (SSEP) were studied in 10 ASA I patients during general anaesthesia with propofol, vecuronium and fentanyl after premedication with diazepam. N14 and N20 latencies, central conduction time (CCT) and corresponding interpeak amplitudes were assessed at induction, after intubation, during steady state, at re-commencement of spontaneous breathing and during early recovery. Data were compared with pre-induction values. Median nerve SSEP were reproducible throughout the procedure and wave forms were suitable for assessment of neurological disorders. Intra-individual changes were considerable for latencies and amplitudes.

Skin pulse wave monitoring during lumbar epidural and spinal anesthesia.

The effectiveness of pulse wave monitoring of the big toes was compared with loss of cold discrimination to determine the onset of nerve blockade during lumbar epidural and spinal anesthesia. Forty-seven patients scheduled for elective urologic or lower extremity operations were assigned to one of three groups. Group 1 (15 patients) received epidural mepivacaine 1.5% with epinephrine; group 2 (12 patients), epidural bupivacaine 0.5%, and group 3 (20 patients), spinal bupivacaine 0.5%. In the epidural groups, the mean time to onset of increases in pulse wave amplitude was less than half the mean time to onset of decrease in cold discrimination (P less than 0.05). In patients given spinal anesthesia, there was no significant difference. The pulse wave monitor seems to be a sensitive and objective detector of early anesthetic effect during spinal and epidural anesthesia.

Infusion of vecuronium controlled by a closed-loop system.

Closed-loop control of neuromuscular blockade, using a semi-continuous infusion of vecuronium, is described. In 28 patients, the average neuromuscular transmission was between 13 and 17% of control. Requirements for vecuronium averaged 1.1 micrograms kg-1 min-1 (0.8-1.5 micrograms kg-1 min-1), being in the same range as for repeated bolus injections. No side effects were observed. After the infusion was stopped recovery was rapid. Only three patients required induced reversal of blockade.