Effect of head-up tilt on neural inspiratory drive in the anesthetized dog

To examine how anesthetized dogs compensate for the diaphragmatic shortening that occurs during head-up tilting, we measured the electroneurogram (ENG) of the C5 phrenic root and the electromyographic (EMG) activity of the parasternal intercostal and transversus abdominis muscles in eight spontaneously breathing animals during postural changes between supine (0 degree) and 80 degrees head-up. Both steady state ENG and EMG activities and first breath responses to tilting from 80 degrees head-up to supine were studied. These experiments have shown that: (1) anesthetized dogs respond to head-up tilting by increasing the neural drive to the costal diaphragm and parasternal intercostals; (2) this response, however, does not occur on the first breath and therefore cannot compensate for the immediate changes in diaphragmatic length; (3) the abdominal muscles, in contrast, show a first breath response to tilting and their activation is primarily responsible for the maintenance of tidal volume. Unlike in humans, increases in neural inspiratory drive in head-up anesthetized dogs are mediated by a chemoreceptive, rather than proprioceptive, feedback mechanism.     

血压与心率基础值对直立倾斜试验阳性结果的影响

目的探讨血压与心率基础值对直立倾斜试验阳性结果的影响。方法不明原因晕厥病人51例,行45min基础直立倾斜试验(head-uptilttest,HUT),阴性病人保持70°倾斜角,直接含服硝酸甘油0.25mg,继续20min试验;HUT阳性病人按晕厥反应类型分为血管抑制型组、心脏抑制型组与混合型组。比较基础血压和基础心率。按血压140/90mmHg与心率(60次/分)为界分别分为高血压组与非高血压组,心率偏慢组与心率正常组。结果HUT阳性组率为62.7%(32/51),其中血管抑制型21例;心脏抑制型5例;混合型6例;阴性19例。HUT阳性组病人的血压与心率基础值与HUT阴性者差异无统计学意义(P>0.05)。晕厥发生率:高血压组62%(8/13),血压正常组63%(24/38),差异无统计学意义;心率偏慢组3/5,心率正常组60%(29/46),差异无统计学意义。结论血压与心率基础值对HUT没有明显影响,不能作为HUT试验阳性的预测指标。     

Effect of passive tilting duration on the outcome of head-up tilt testing

OBJECTIVE: We sought to compare the results of head-up tilt test (HUT) using the most common protocols, namely the Italian and Westminster prolonged by nitroglycerin (modified Westminster) protocols.We also investigated the role of passive tilting duration on HUT outcome. METHODS AND RESULTS: From 478 syncopal patients 306 (64%) individuals showed positive tilting results (HUT+), whereas the remaining 172 (36%) were negative (HUT-). A total of 277 patients were tilted using the Italian protocol (20-min passive tilting), while the remaining 201 underwent the modified Westminster (45-min passive tilting) protocol. Univariate analysis showed significant differences (P < 0.001) in the time for syncope induction and number of HUT+ between the Italian (153/277, 55%) and modified Westminster protocols (153/201, 76%). A reduced rate (P < 0.01) of cardioinhibitory responses was observed in the Italian (16/153, 10%) compared to the modified Westminster (31/153, 20%) protocol.The presence of HUT+ was positively associated with the use of the modified Westminster protocol (76%, P < 0.001) and typical vasovagal history (83%, P < 0.001), and negatively with body mass index (BMI) (P < 0.05) and hypertension (P < 0.01). With the use of the Italian protocol, HUT+ negatively associated with BMI (P < 0.05) and hypertension (P < 0.05), and positively with typical vasovagal history (71%, P < 0.01). With the use of the modified Westminster protocol, HUT+ strongly correlated with typical vasovagal history (78%, P < 0.001), but not with either BMI or hypertension. CONCLUSIONS: The HUT protocol may influence tilting outcome.The modified Westminster protocol seems to be more useful than the Italian protocol for syncope diagnosis, especially to avoid underestimation of the cardioinhibitory responses.     

The influence of age and blood pressure on the hemodynamic and humoral response to head-up tilt

It has been reported that postural hypotension in the elderly is common. However, these studies included institutionalized and more or less disabled persons. Furthermore, postural hypotension may be related to baseline blood pressure. In this study, the influence of age and blood pressure on the hemodynamic and plasma catecholamine responses to orthostatic stress was investigated in young and old normotensive and hypertensive healthy subjects. In normotensive and hypertensive elderly persons, the percentage blood pressure responses during tilt were not significantly different from that seen in young normotensives. We measured a slight decrease of systolic blood pressure and a slight increase of diastolic blood pressure. The hypertensive young patients showed an enhanced diastolic blood pressure response with no fall in systolic blood pressure, in contrast to the normotensive young subjects. Both elderly groups had a lower increase of heart rate than the young subjects. The percentage increase in norepinephrine after tilting was significantly lower in elderly hypertensives than in elderly normotensives and young hypertensives. The presence of hypertension was associated with a decrease in blood pressure, but age had no influence on the change in blood pressure during tilt. In this group of healthy elderly subjects, there was no significant orthostatic hypotension when the blood pressure course of the entire tilt test was taken into account.     

Analysis of head-up tilt test responses in patients suffering from syncope and high blood pressure

We studied the difference in head-up tilt test responses between patients suffering from syncope who had hypertension and those who did not. A total of 338 consecutive patients with syncope underwent head-up tilt testing in our department from January 2003 to October 2004. Of these, 243 did not have hypertension (group A), whereas 95 did (group B). There were significant differences between the groups in age (P=.0001), sex (P=.048), timing of syncope development (P=.0001), and prevalence of diabetes mellitus (P=.0001). The head-up tilt test gave positive results in 168 patients (69.1%) in group A and in 63 (66.3%) in group B (P=.6; NS). There was no significant difference between the groups in the proportion of positive responses that occurred in either the baseline or nitroglycerin-enhanced phase of the test (P=.673; NS), nor in the time to onset of syncope in either phase (P=.69; NS, and P=.28; NS, respectively). However, there was a significant difference in the type of response (vasodepressor response, 33% in group A versus 49% in group B, P=.01). In the multivariate analysis, no independent variable was found to be associated with the result of the head-up tilt test.     

Effect of ovarian steroids on vasopressin secretion

In normally menstruating women plasma vasopressin concentrations vary with the stage of the cycle and are highest at the time of ovulation and lowest at the onset of menstruation. To determine whether this is the result of changes in the circulating concentrations of ovarian steroids, vasopressin concentrations were determined in six postmenopausal women given oestrogen and progestogen. An increase in plasma oestradiol concentrations to 299 +/- 97.8 pmol/l augmented vasopressin release. Administration of medroxyprogesterone did not influence vasopressin concentrations but when given in combination with oestrogen a fall was observed. Thus it appears that ovarian steroids can modulate vasopressin release.     

Combined head-up tilt and lower body negative pressure as an experimental model of orthostatic syncope

INTRODUCTION: The combination of head-up tilt and incremental lower body negative pressure has shown promise in the diagnosis of orthostatic hypotension and neurocardiogenic syncope, although prior methodologies limited conclusions as to the reproducibility of the test. The aim of this study was to assess the efficacy and reproducibility of a protocol combining tilt and stages of incremental lower body negative pressure. METHODS AND RESULTS: Ten volunteers (6 men and 4 women; mean age 21 +/- 1 years) participated in the study, which was composed of three sessions, 1 month apart, each consisting of 60 degrees tilt followed by lower body suction in incremental levels of -10 mmHg for 5 minutes at each level. The primary outcome variable was the time to presyncope. Secondary variables were the levels of heart rate, blood pressure, cerebral blood flow, and end-tidal CO2 at each level of the test. Presyncope could be achieved in all subjects. The mean times to presyncope were 24.6 +/- 1.4 minutes, 26.2 +/- 1.8 minutes, and 31.8 +/- 1.6 minutes and were not different across tests (P = 0.3). Intrasubject variability was assessed by determining the mean average deviation from the mean, which was 3.2 +/- 2.0 minutes. Changes in heart rate, blood pressure, end-tidal CO2, and cerebral blood flow were consistent with repeat testing. CONCLUSION: Lower body negative pressure combined with head-up tilt in a staged protocol can safely and reliably induce presyncope in all normal subjects tested. The test is a potent and reproducible investigational tool for inducing hypotension and transient cerebral hypoperfusion.     

硝酸甘油与异丙肾上腺素直立倾斜试验的直接对比研究

目的 比较舌下含服硝酸甘油和静脉注射异丙肾上腺素直立倾斜试验(head-up tilt test,HUTT)诊断血管迷走性晕(vasovagal syncope,VVS)的价值.方法 30例无晕厥史的健康人与84例不明原因晕厥患者在1周内先后进行基础结合硝酸甘油诱发和基础结合异丙肾上腺素诱发的HUTT,比较两种方法对V...     

Beat-to-beat analysis of pressure wave morphology for pre-symptomatic detection of orthostatic intolerance during head-up tilt

OBJECTIVES: The aim of this study was to noninvasively define the hemodynamic profile characterizing the early response to tilting. BACKGROUND: The mechanisms causing orthostatic intolerance have not been fully elucidated. Usually, patients undergoing tilt test are studied in a time-consuming way. Moreover, the test can cause discomfort to the patient and even be potentially hazardous. METHODS: Nineteen orthostatic intolerant patients (OIP), compared with 22 healthy subjects (HS), performed head-up tilt test while their arterial pressure waveform was noninvasively recorded. We elaborated data using the Pressure Recording Analytical Method to obtain hemodynamic parameters, then analyzing the variables by discriminant analysis. RESULTS: Compared with HS, OIP showed lower stroke volume index (SVI) values even in baseline conditions associated with higher values of systemic vascular resistance (SVR) and heart rate (HR). From the third minute of the tilted position and until symptoms appeared, patients exhibited lower values of blood pressure (BP) and SVI and higher HR values but no difference in SVR. At termination, patients showed a further significant reduction in BP and SVI and a persistent increase in HR. CONCLUSIONS: This investigation underlines: 1) the possibility of beat-to-beat monitoring of hemodynamic changes during tilting; 2) the cardiovascular profile of OIP at rest, characterized by lower SVI and higher SVR and HR; 3) the maladaptive response to postural challenge of OIP mainly identifiable in impaired vascular regulation; and 4) the possibility of detecting parameters that enable prompt identification of the positive response to tiltingin these patients, thus guiding the duration of the test.     

Kappa-opioid modulation of vasopressin secretion in conscious rats.

A series of studies has been performed in the conscious rat to investigate the effect of the intracerebroventricular (i.c.v.) administration of the selective kappa-opioid receptor agonist, U50 488H, on arginine vasopressin (AVP) secretion stimulated by i.c.v. administration of hypertonic NaCl. Similarly, the effect of the i.c.v. administration of morphine and the i.v. administration of naloxone on AVP secretion was investigated. The response of AVP to an i.c.v. injection of hypertonic NaCl was potentiated by naloxone at a dose of 0.4 mg/kg, but a higher dose (1.2 mg/kg) was required to increase the basal plasma concentration of AVP. Prior treatment with U50 488H or morphine attenuated the increase in plasma concentrations of AVP stimulated by i.c.v. injection of hypertonic NaCl from 13.92 +/- 4.44 to 1.22 +/- 0.34 and 1.78 +/- 0.74 pmol/l respectively (n = 7; P less than 0.05). Prior administration of U50 488H also attenuated the potentiating effect of naloxone on AVP secretion stimulated by i.c.v. injection of hypertonic NaCl. These results indicate that basal AVP secretion is under tonic inhibitory control by dynorphin, and that mu- and kappa-opioid receptors mediate an inhibitory influence of endogenous opioids on osmoreceptor-mediated AVP secretion.     

Reproducibility of head-up tilt test in patients with syncope

As the head-up tilt test (HUT) is employed to verify the efficacy of undertaking a treatment, we prospectively evaluated the reproducibility of positive and negative results, as well as that of the response type in 64 consecutive patients (mean age 34.6 ± 22.9 years) with syncope of unknown cause. Two HUTs (60 min, 75° ), separated by an interval of 9.77 ± 8.21 days, were performed on each patient. Positive responses were reproduced in the second HUT in 54.5% of the patients. A greater reproducibility (84.3%) was observed for negative responses. Of the 31 patients with a negative first test, 5 had a positive response during the second HUT. Using a multivariate analysis, no clinical variable correlated with the reproducibility of positive or negative results. Likewise, neither arterial pressure nor heart rate observed during the test were correlated with reproducibility. Of 18 patients who reproduced positive responses, 12 (66.6%) did so with the same response modality. In three patients with documented monomorphic sustained ventricular tachycardia, which was hemodynamically well tolerated, and in one patient with temporal spike wave activity in the electroencephalogram, HUT was also positive. It was concluded that the low reproducibility of HUT limits its usefulness as a tool for evaluating treatment efficacy. The variability of the type of response suggests a common mechanism leading to cardioinhibitory and vasodepressor reactions. A positive result in only the second study shows the rationale of performing two tests when the first one is negative.     

Reproducibility of heart rate variability, blood pressure variability and baroreceptor sensitivity during rest and head-up tilt

OBJECTIVE: Previous studies have indicated moderate-to-poor reproducibility of heart rate variability (HRV) but the reproducibility of blood pressure variability (BPV) and spectral measures of baroreceptor sensitivity (BRS) are not well established. METHODS: We measured normal-to-normal heart beat (RR) interval and finger blood pressure (Finapres) in 14 healthy individuals on three different days. The protocol was 1 h of supine rest and 1 h of 60-degree head-up tilt. Time-series of consecutive 300-s segments as well as 1024-s segments of RR intervals and systolic, diastolic and mean blood pressures were extracted for the assessment of day-to-day and short-term reproducibility. Power spectrum analysis (Fourier) and transfer function analysis was performed. Reproducibility was assessed using the coefficient of variation (CV). The reproducibility of the mean RR interval, mean systolic, diastolic and mean blood pressure was good (CV<10 %). However, there was only moderate-to-poor reproducibility of the spectral parameters of HRV (CV range 18-36%) and BPV (16-44%) and moderate reproducibility of BRS (14-20%). CONCLUSION: Spectral estimates of BRS had only moderate reproducibility although it was better than the spectral estimates of HRV and BPV.     

Predicting outcomes on head-up tilt based on orthostatic hypotension patterns

OBJECTIVE: To assess the frequency of different orthostatic hypotension (OH) patterns in patients having supine hypertension with OH ('SHOH') versus patients with OH and normal supine blood pressure ('OH alone'); and to relate OH patterns with outcomes on head-up tilt. METHODS: Consecutive patients with nonspecific dizziness were studied with a 10-min supine, 30-min head-up tilt test. Supine hypertension was diagnosed when supine systolic blood pressure (SBP) was at least 140 mmHg and/or supine diastolic blood pressure was at least 90 mmHg. OH was defined as SBP reduction of at least 20 mmHg within 3 min of tilt. OH patterns were identified corresponding to SBP time-curves during the initial 5 min of tilt: progressive, sustained and transient patterns. RESULTS: Among 400 patients tested, 31 had 'SHOH' and 39 had 'OH alone'. Frequencies of OH patterns were similar in both groups. The progressive OH pattern predicted symptomatic hypotension, leading to early tilt termination in all 'SHOH' and 88% of 'OH alone' patients. In comparison, tilt was early terminated in 33-48% of patients with sustained OH, transient OH and without OH. Early tilt termination was unrelated to age, gender, magnitude of supine SBP, pulse pressure and nadir SBP within 5 min tilt. CONCLUSIONS: Five minutes of postural challenge permitted assessing OH patterns. Outcome on protracted tilt was related to OH patterns, the worse outcome being likened to progressive OH, both in patients with 'SHOH' and in patients with 'OH alone'. Future studies will show whether OH patterns may serve as guidance for blood pressure therapy in selected patients.     

Effects of naloxone on vasopressin secretion in conscious rats: evidence for inhibitory role of endogenous opioid peptides in vasopressin secretion

The effects of naloxone, an opioid antagonist, on arginine vasopressin (AVP) secretion were examined in conscious unrestrained rats under both basal and stimulated conditions. Intravenous injection of naloxone in a dose of 0.1 mg/kg did not significantly affect the basal plasma AVP level. However, 0.5 or 2.5 mg/kg naloxone significantly raised the basal AVP level in euhydrated rats. Naloxone (0.5 mg/kg) significantly enhanced AVP secretion after 72-h water deprivation. However, the enhancement was more prominent in euhydrated rats than in dehydrated rats. Pretreatment with naloxone (0.5 mg/kg) also significantly prolonged AVP secretion induced by intracerebroventricular injection of angiotensin-II (100 ng). Moreover, naloxone (0.5 mg/kg) significantly increased AVP secretion induced by intracerebroventricular injection of carbachol (10 ng). Naloxone (0.5 mg/kg) altered neither basal blood pressure nor the angiotensin-II-induced pressor response, but augmented the carbachol-induced pressor response. This suggests that facilitation of AVP secretion by naloxone is not due to a reflex mechanism resulting from decreased blood pressure. These results indicate that endogenous opioid peptides exert a tonic inhibitory control on AVP secretion in rats.