Gender influences in vivo human responses to endotoxin

Gender appears to influence systemic and organ-specific inflammatory sequelae of ischemia-reperfusion and infectious challenge in many animal models. Despite the protection provided by female gender, androgen blockade, and/or estrogen administration in such experimental studies, many questions remain regarding the influence of gender dimorphism upon human responses to injury. We hypothesized that the administration of low-dose lipopolysaccharide (LPS) to otherwise healthy, young adults would provide insights regarding the influence of gender upon physiological and innate immune system responses to a prototypic inflammatory stimulus. To this end, 72 adult subjects (48 men, aged 29 +/- 1.0 years; 24 women, aged 26 +/- 1.0 years) were prospectively evaluated before and after the i.v. administration of LPS (2 ng/kg). All subjects developed symptoms within 1.0 to 1.5 h after LPS, and the men exhibited a greater increase in core temperature (2.1 +/- 0.1 degrees C) compared with the women (1.4 +/- 0.1 degrees C) (P < 0.001). In addition, the men exhibited a greater maximum decrease in mean arterial pressure (-13.0 +/- 1.3 mmHg) compared with the women (-8 +/- 1.3 mmHg) (P < 0.02). The changes in temperature and mean arterial pressure occurred without detectable differences between the male and female cohort responses of circulating white blood cell count and cortisol or cytokine levels. These results suggest that soluble inflammatory mediators generated by in vivo endotoxin activation of the innate immune system are insufficient to explain the resultant gender-specific phenotypic differences observed in young, adult humans.     

Cardiovascular regulation during head-up tilt in healthy 20-30-year-old and 70-75-year-old men

This study compared the heart rate, finger arterial pressure (AP) and electromyographic (EMG) activity of selected anti-gravity muscles during the initial and prolonged phases of orthostatic stress in healthy young and older men. Beat-by-beat recordings of heart rate, finger systolic pressure, diastolic pressure and mean AP were made during supine rest and 5 min of 90 degrees head-up tilt (HUT) in 18 young (23+/-1 years) and 15 older (73+/-1 years) men. The EMG activity of the soleus, tibialis anterior and vastus medialis muscles was recorded. During the first 30 s following 90 degrees HUT (immediate response), the young men exhibited significant (P<0.05) decreases in finger systolic pressure, diastolic pressure and mean AP, followed by a sustained increase in finger AP during the 5 min following 90 degrees HUT (prolonged response). The immediate and prolonged finger AP and diastolic pressure responses were not significantly different (P>0.05) from the values at supine rest for the older men. The mean root mean square EMG activity of the soleus, tibialis anterior and vastus medialis muscles during 90 degrees HUT was not significantly different (P>0.05) from that at supine rest for either group. These results demonstrate that, when compared with healthy older men, young men show larger reductions in finger AP during the initial phase of orthostatic stress. However, during the prolonged phase of orthostatic stress, older men maintain resting finger AP, whereas young men demonstrate a reflex overshoot in finger AP. Finally, differences in lower-limb anti-gravity muscle activation do not account for the contrasting finger AP responses of healthy young and older men.     

Circulatory response to postural change in healthy male subjects in relation to age

The initial heart rate (HR) response evoked by standing up and 70 degrees head-up tilt from the supine resting position, as well as the changes in HR and blood pressure after 1-2 min in the upright position, was analysed in teenage boys (aged 10-15 years) and healthy old men (aged 60-90 years). Standing up induced a characteristic temporary HR increase that lasted 20 s and far exceeded the gradual initial HR rise induced by head-up tilt. The main effect of age on the initial HR transients was a definite diminution of the response. After 1-2 min standing and tilting, young subjects showed a pronounced increase in HR and diastolic pressure with little change in systolic pressure. In contrast, old subjects showed a lesser increase in HR and diastolic pressure and a decrease in systolic pressure. A fall in systolic pressure of greater than 20 mmHg after 1 min of active standing was, however, not observed. It is concluded that the circulatory adjustment to the stress of postural change differs markedly between young and elderly subjects. In healthy old subjects marked postural hypotension appears to be rare.     

Endobronchial adrenaline: should it be reconsidered? Dose response and haemodynamic effect in dogs

BACKGROUND: Tracheal drug administration is a route for drug delivery during cardiopulmonary resuscitation when intravenous access is not immediately available. However, tracheal adrenaline (epinephrine) injection has been recently shown to be associated with detrimental decrease in blood pressure. This was attributed to exaggerated early beta2 mediated effects unopposed by alpha-adrenergic vasoconstriction. We hypothesized that endobronchial adrenaline administration is associated with better drug absorption, which may abolish the deleterious drop of blood pressure associated with tracheal drug administration. OBJECTIVE: To determine haemodynamic variables after endobronchial adrenaline administration in a non-arrest canine model. DESIGN: Prospective, randomized, laboratory study. METHODS: Adrenaline (0.02, 0.05, 0.1 mg/kg) diluted with normal saline was injected into the bronchial tree of five anaesthetized dogs. Injection of 10-ml saline served as control. Heart rate, blood pressure and arterial blood gases were monitored for 60 min after drug instillation. The protocol was repeated after 1 week. RESULTS: Adrenaline at a dose of 0.02 mg/kg produced only a minor initial decrease in diastolic (from 90 +/- 5 to 78 +/- 3 mmHg, P=0.05), and mean blood pressure (from 107 +/- 4 to 100 +/- 3 mmHg, P=0.05), in all dogs. This effect lasted less then 30 s following the drug administration. In contrast, higher adrenaline doses (0.05 and 0.1 mg/kg) produced an immediate increase in diastolic (from 90 +/- 5 to 120 +/- 7 mmHg; and from 90 +/- 5 to 170 +/- 6 mmHg, respectively), and mean blood pressure (from 107 +/- 4 to 155 +/- 10 mmHg; and from 107 +/- 4 to 219 +/- 6 mmHg, respectively). All adrenaline doses resulted in an immediate increase in systolic blood pressure and pulse. Endobronchial administration of saline (control) affected none of the haemodynamic variables. CONCLUSIONS: In a non-arrest model, endobronchial adrenaline administration, as opposed to the effect of tracheal adrenaline, produced only a minor decrease in diastolic and mean blood pressure. We suggest that endobronchial adrenaline administration should be investigated further in a CPR low-flow model when maintaining adequate diastolic pressure may be crucial for survival.     

Effects of enalapril on the cardiovascular response to treadmill exercise in patients with mild to moderate systemic hypertension

The effects of the angiotensin converting enzyme inhibitor enalapril on exercise-induced changes in blood pressure and heart rate were evaluated in 15 patients in the early stages of systemic hypertension. Multistage treadmill exercise was performed before and after eight weeks of enalapril administration, and the results of the two trials were compared. In patients at rest, enalapril decreased systolic blood pressure from 172 +/- 18 to 147 +/- 14 mmHg and diastolic blood pressure from 99 +/- 9 to 88 +/- 8 mmHg (both P less than 0.001). In patients at peak exercise, enalapril decreased systolic blood pressure from 216 +/- 13 to 195 +/- 18 mmHg and diastolic blood pressure from 106 +/- 12 to 99 +/- 12 mmHg (both P less than 0.001). There was also a significant decrease in blood pressure during the recovery period after treadmill exercise. Enalapril reduced heart rate at peak exercise (P less than 0.05), but not at rest or during recovery. Thus enalapril alleviated the response of blood pressure to exercise in hypertensive patients and may help prevent hypertensive complications during daily activities.     

Oral antioxidants and cardiovascular health in the exercise-trained and untrained elderly: a radically different outcome

Both antioxidant supplementation and exercise training have been identified as interventions which may reduce oxidative stress and thus improve cardiovascular health, but the interaction of these interventions on arterial BP (blood pressure) and vascular function has not been studied in older humans. Thus in six older (71+/-2 years) mildly hypertensive men, arterial BP was evaluated non-invasively at rest and during small muscle mass (knee-extensor) exercise with and without a pharmacological dose of oral antioxidants (vitamins C and E, and alpha-lipoic acid). The efficacy of the antioxidant intervention to decrease the plasma free radical concentration was verified via EPR (electron paramagnetic resonance) spectroscopy, while changes in endothelial function in response to exercise training and antioxidant administration were evaluated via FMD (flow-mediated vasodilation). Subjects were re-evaluated after a 6-week aerobic exercise training programme. Prior to training, acute antioxidant administration did not change resting arterial BP or FMD. Six weeks of knee-extensor exercise training reduced systolic BP (from 150+/-8 mmHg at pre-training to 138+/-3 mmHg at post-training) and diastolic BP (from 91+/-5 mmHg at pre-training to 79+/-3 mmHg at post-training), and improved FMD (1.5+/-1 to 4.9+/-1% for pre- and post-training respectively). However, antioxidant administration after exercise training negated these improvements, returning subjects to a hypertensive state and blunting training-induced improvements in FMD. In conclusion, the paradoxical effects of these interventions suggest a need for caution when exercise and acute antioxidant supplementation are combined in elderly mildly hypertensive individuals.     

Orthostatic circulatory control in the elderly evaluated by non-invasive continuous blood pressure measurement

1. Continuous orthostatic responses of blood pressure and heart rate were measured in 40 healthy and active elderly subjects over 70 years of age in order to assess the time course and rapidity of orthostatic cardiovascular adaptation in old age. 2. During the first 30 s (initial phase) the effects of active standing and passive head-up tilt closely resembled those observed earlier in younger age groups. Standing up was accompanied by a drop (mean +/- SD) in systolic and diastolic blood pressures of 26 +/- 13 mmHg and 12 +/- 18 mmHg, respectively, at around 10 s, and a subsequent rise up to 11 +/- 17 mmHg and 8 +/- 6 mmHg above supine values at around 20 s. The drop in blood pressure upon standing was accompanied by a transient increase in heart rate with a maximum of 13 beats/min, followed by a gradual decrease to 7 beats/min above supine levels. These characteristic transient changes were absent upon a passive head-up tilt. 3. After 1-2 min of standing (early steady-state phase) diastolic blood pressure and heart rate increased significantly after active and passive postural changes. On average, for all subjects systolic blood pressure tended to increase from control during 5-10 min standing, reaching a significant difference at 10 min. During standing, the largest increases in systolic blood pressure were found in subjects with the lowest supine blood pressures. 4. In conclusion, for the investigation of orthostatic circulatory responses in elderly subjects the following factors have to be taken into account: active versus passive changes in posture, the timing of the blood pressure reading, and the level of supine blood pressure.     

Haemodynamics of the pressor effect of oral water in human sympathetic denervation due to autonomic failure

Oral water ingestion increases blood pressure in normal elderly subjects and in patients suffering from autonomic failure, but the time course of the haemodynamic changes is not known. We therefore studied 14 subjects with documented sympathetic denervation due to pure autonomic failure, with continuous haemodynamic recordings obtained before and after ingestion of 500 ml of distilled water at room temperature. The time course of changes in values of systolic and diastolic beat-by-beat finger blood pressure, heart rate, stroke volume, cardiac output, ejection fraction and total peripheral resistance were analysed. Systolic blood pressure rose from 115+/-8 mmHg (mean+/-S.E.M.) to 133+/-8 mmHg (P<0.001), and diastolic blood pressure from 64+/-4 to 73+/-4 mmHg (P<0.001), with the pressor response beginning a few minutes after water ingestion, plateauing between 10 and 35 min (peak at 14 min), and returning to baseline at 50 min. Heart rate fell from 71+/-2.5 to 67+/-2 beats/min (P<0.001), and total peripheral resistance increased from 1.31+/-0.19 to 1.61+/-0.24 m-units (P<0.001). There were no significant changes in ejection fraction, stroke volume or cardiac output. This study confirmed a pressor response to oral water in subjects with sympathetic denervation. The temporal profile of the response did not favour reflexly mediated sympathetic activation. As subjects with autonomic failure are prone to salt and water depletion, and since blood pressure is exquisitely sensitive to such changes, it may be that the observed response is due to repletion or restoration of intravascular and extravascular fluid volume.     

Comparative evaluation of captopril and methyldopa monotherapy for hypertension: double-blind study in Indians

A double-blind, parallel-group study was conducted in 41 Indian men and women with hypertension to compare the antihypertensive effects of captopril and methyldopa. Twenty patients received 150 mg of captopril and 21 patients received 750 mg of methyldopa daily. The drugs were administered in three equally divided doses for four weeks. Blood pressure was measured after one, two, and four weeks of therapy. Relevant clinical and biochemical investigations were carried out before and after treatment. Sixteen patients given captopril and 11 given methyldopa responded to therapy. Among the captopril responders, initial mean systolic blood pressure (+/- SE) was 155 +/- 5.0 mmHg and diastolic blood pressure was 105 +/- 2.1 mmHg. These values were reduced to 119 +/- 9.8 and 80 +/- 6.1 mmHg, respectively, after four weeks of therapy. Similarly, among the methyldopa responders, initial mean systolic blood pressure was 180 +/- 7.4 mmHg and diastolic blood pressure was 112 +/- 3.8 mmHg. These values were reduced to 138 +/- 7.0 and 92 +/- 3.8 mmHg, respectively, after four weeks of therapy. The fall in the blood pressure in both groups was highly significant (P less than 0.001). None of the patients in either group had any clinically significant side effects. The results of this study suggest that monotherapy with captopril may be more effective than monotherapy with methyldopa in Indian hypertensives.     

Effect of a high-carbohydrate versus a high--cis-monounsaturated fat diet on blood pressure in patients with type 2 diabetes

OBJECTIVE: To investigate whether blood pressure is different in type 2 diabetic patients on a diet rich in carbohydrates versus a diet rich in cis-monounsaturated fatty acids. Data on the dietary effects on these diets' glucose and lipid metabolism have been previously published. RESEARCH DESIGN AND METHODS: The study compared the effect of feeding 42 type 2 diabetic patients a carefully controlled isoenergic high-carbohydrate (high-carb; 55% energy as carbohydrate, 30% as fat, and 10% as monounsaturated fat) and high-monounsaturated fat (high-mono; 45% energy as fat, 25% as monounsaturated fat, and 40% as carbohydrate) diet for 6 weeks each in a four-center, randomized, cross-over study on blood pressure. Twenty-one patients continued the diet they received during the second phase for an additional 8 weeks. RESULTS: According to repeated-measures ANOVA, blood pressure during the last 3 days of each phase was similar after 6 weeks of the high-carb and high-mono diets (systolic blood pressure: 128 +/- 16 vs. 127 +/- 15 mmHg, P = 0.9; diastolic blood pressure: 75 +/- 7 vs. 75 +/- 8 mmHg, P = 0.7). However, after 14 weeks of the high-carb diet (n = 13), there was a significant increase in blood pressure compared with 6 weeks of the high-mono diet (systolic blood pressure: 132 +/- 13 vs. 126 +/- 11 mmHg, P = 0.04; diastolic blood pressure: 83 +/- 6 vs. 76 +/- 7 mmHg, P = 0.002). After 14 weeks of the high-mono diet (n = 8), the reduction in blood pressure was not significant compared with 6 weeks of the high-carb diet (systolic blood pressure: 118 +/- 14 vs. 121 +/- 16 mmHg, P = 0.4; diastolic blood pressure: 71 +/- 8 vs. 75 +/- 10 mmHg, P = 0.3). CONCLUSION: Although the exchange of carbohydrates with monounsaturated fats may not affect blood pressure in the short term, long-term consumption of a high-carbohydrate diet may modestly raise blood pressure in type 2 diabetic patients.     

Diastolic pressure in type 2 diabetes: can target systolic pressure be reached without "diastolic hypotension"?

The practicality of vigorous lowering of systolic pressure in diabetes to <130 mmHg remains uncertain. Baseline blood pressure data from several recent trials indicate that, in diabetic subjects, there is nearly a fourfold excess in systolic pressure (the difference between baseline pressure and target pressure) over diastolic pressure with respect to the recommended systolic/diastolic target pressure of <130/80 mmHg. Additionally, systolic pressure was 2-3 mmHg higher and diastolic pressure was 1-3 mmHg lower in diabetic hypertensive than in nondiabetic hypertensive individuals, which adds approximately 4 mmHg to pulse pressure and also to the difference between the excess systolic and excess diastolic pressure. We attempted to force (titrate both systolic and excess diastolic pressure) systolic and diastolic blood pressure to <130/85 mmHg based on Joint National Committee VI guidelines in the setting of a clinical practice in 257 diabetic patients. Although target systolic pressure was attained in a third of this cohort, in 57% of the patients, the attained diastolic pressure was 相似文献   

Chronic caffeine administration exacerbates renovascular, but not genetic, hypertension in rats.

The purpose of this study was to determine whether or not caffeine would exacerbate renovascular hypertension. Therefore, we examined the effects of chronic caffeine administration on arterial blood pressure in rats subjected to either unilateral renal artery clipping (2K-1C rats) or sham-operation. Animals in each group were randomly assigned to receive either 0.1% caffeine in their drinking water or normal drinking water, and systolic blood pressure was monitored for 6 wk. Caffeine markedly exacerbated the severity of hypertension in 2K-1C rats and caused histological changes consistent with malignant hypertension. 6 wk after surgery, systolic blood pressure, plasma renin activity, and creatinine clearance in control 2K-1C rats were 169 +/- 5 mmHg (mean +/- SEM), 4.4 +/- 0.5 ng AI X ml-1 X h-1, and 2.9 +/- 0.2 ml/min, respectively; as compared with 219 +/- 4 mmHg, 31.8 +/- 7.8 ng AI X ml-1 X h-1, and 1.4 +/- 0.3 ml/min, respectively, in 2K-1C rats receiving caffeine (all values were significantly different compared with control 2K-1C). Chronic caffeine administration did not alter systolic blood pressure, plasma renin activity, or creatinine clearance in sham-operated rats or spontaneously hypertensive rats. Chronic treatment with enalapril (a converting enzyme inhibitor) prevented the development of hypertension in control 2K-1C rats and caffeine-treated 2K-1C rats; however, withdrawal of enalapril precipitated a rapid rise in systolic blood pressure in caffeine-treated 2K-1C rats, but not in control 2K-1C rats. These experiments indicate that caffeine specifically exacerbates experimental renovascular hypertension and might worsen the hypertensive process in patients with renovascular hypertension.     

Mechanisms of initial blood pressure response to postural change

The influence of supine rest on the blood pressure response to standing and 70 degrees head-up tilt was studied in detail for the first 30 s after the change of posture. Following 20 min of supine rest, the active transition to standing was accompanied by an immediate increase in systolic pressure of 29 +/- 6 mmHg (mean +/- SEM). This was followed by large fluctuations in systolic pressure: to -28 +/- 2 mmHg below control after 7 s and to 22 +/- 2 mmHg above control after 22 s (17 mmHg in excess of the systolic pressure level after head-up tilt). Following 1 min of supine rest, there was no difference in the immediate increase in systolic pressure. However, the magnitude of the subsequent changes was significantly diminished. With head-up tilt the immediate increase in blood pressure was absent and afterwards small changes were found that were also significantly influenced by the period of prior rest. Taken in conjunction with earlier studies, the following mechanisms are suggested. The immediate blood pressure increase resulted from compression of arteries by the contracting postural muscles. The subsequent blood pressure fall was caused by at least two mechanisms: (a) the fall was predominantly of reflex origin, because the immediate pressure increase stimulated the systemic baroreceptors; (b) supine rest possibly augmented the translocation of blood from the thorax which contributed, approx. 5 s from standing, to the reflex fall of blood pressure.     

Decreased large artery distensibility in borderline hypertension is related to increased in vivo low-density lipoprotein oxidation

The present study tested the hypothesis that reduced arterial elasticity seen in hypertension is related to increased oxidation of LDL. Fifteen men with borderline hypertension (BHT), with blood pressure values classified as high normal (systolic blood pressure 130-140 mmHg or diastolic blood pressure 85-89 mmHg) were included. The control group comprised 22 men with normal blood pressure values (<135/80 mmHg) matched for age, body size and LDL-cholesterol level. Distensibility of aorta was measured using magnetic resonance imaging, and distensibility of the common carotid artery using ultrasound. Baseline LDL diene conjugation was used as a marker for ox-LDL. Aortic and carotid distensibilities were lower in the BHT men than in controls (1.4 +/- 0.6 vs. 1.9 +/- 0.6%/10 mmHg, p<0.05 for aortic distensibility; 2.9 +/- 0.9 vs. 3.6 +/- 0.6%/10 mmHg, p<0.05 for carotid distensibility). Ox-LDL was significantly higher in the BHT men than in controls (44 +/-15 vs. 28 +/- 8 micromol/L, p<0.01). In univariate analysis, ox-LDL associated with aortic distensibility (r=-0.43, p<0.05). In multivariate analysis, the differences in distensibilities between the groups disappeared when the values were adjusted for ox-LDL. These data show decreased arterial elasticity and increased LDL oxidation in young men with borderline hypertension, and suggest that oxidative modification of LDL particles may play a pathophysiological role in the development of reduced arterial distensibility in hypertension.     

Circulatory adaptation to orthostatic stress in healthy 10-14-year-old children investigated in a general practice.

1. The magnitude and time course of circulatory adaptation to active standing were investigated in healthy premenarchic girls and boys (n = 24; 10-14 years old) by non-invasive measurement of heart rate and continuous finger blood pressure (Finapres). 2. Four subjects (two girls, two boys) showed presyncopal symptoms after 4-9 min of free standing. 3. In the 20 non-fainting subjects, changes in blood pressure and heart rate upon standing did not differ between girls (n = 10) and boys (n = 10). In the initial phase of standing (first 30 s) systolic and diastolic blood pressures dropped by 22 +/- 14 (mean +/- SD) and 16 +/- 7 mmHg, respectively, at 8 +/- 2 s. Blood pressure subsequently recovered and showed an overshoot in all subjects. The transient drop in blood pressure was accompanied by an increase in heart rate of 40 +/- 7 beats/min. These characteristic transient changes were not observed with passive head-up tilt. During the early steady-state phase (2 min), systolic blood pressure was similar to the supine value and diastolic blood pressure rose by 11 +/- 5 mmHg. Heart rate increased by 25 +/- 11 beats/min. In six of the subjects (three girls, three boys) the increase in heart rate exceeded 30 beats/min (postural tachycardia). Little further changes were observed during prolonged (10 min) standing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Normal fluctuations in pulmonary artery pressures and cardiac output in patients with severe left ventricular dysfunction.

BACKGROUND: One barrier to accurate interpretation of changes in hemodynamic pressures and cardiac output is lack of data about what constitutes a normal fluctuation. Few investigators have examined normal fluctuations in these parameters and none have done so in patients with left ventricular dysfunction. AIMS: To describe normal fluctuations in pulmonary artery pressures and cardiac output in patients with left ventricular dysfunction. METHODS: Hemodynamically stable advanced heart failure patients (N=39; 55+/-6 years old; 62% male) with left ventricular dysfunction (mean ejection fraction 22+/-5%) were studied. Cardiac output and pulmonary artery pressures were measured every 15 min for 2 h. RESULTS: Mean+/-standard deviation fluctuations were as follows: pulmonary artery systolic pressure=7+/-4 mmHg; pulmonary artery diastolic pressure=6+/-3 mmHg; pulmonary capillary wedge pressure=5+/-3 mmHg; cardiac output=0.7+/-0.3 l/min. The coefficient of variation for fluctuations in pulmonary artery systolic pressure was 6.7%, in pulmonary artery diastolic pressure was 9.3%, in pulmonary capillary wedge pressure was 9.2%, and in cardiac output was 7.2%. CONCLUSIONS: Values that vary <8% for pulmonary artery systolic pressure, <11% for pulmonary artery diastolic pressure, <12% for pulmonary capillary wedge pressure, and <9% for cardiac output from baseline represent normal fluctuations in these parameters in patients with left ventricular dysfunction.     

使用骨水泥髋关节假体置换术中骨水泥对患者生命体征的影响

目的研究使用骨水泥在老年人工髋关节假体置换术中对生命体征的影响。方法对2005年1月至2007年9月使用骨水泥人工髋关节置换术治疗股骨颈骨折的93例患者,术中使用骨水泥前后记录收缩压、舒张压及心率,采用自身配对T检验进行统计分析。结果人工髋置换术后,收缩压平均下降14．73mmHg,舒张压平均下降7．69mmHg,差异均有统计学意义（P〈0．01）;心率平均下降1．11次／min,差异无统计学意义（P〉0．05）。结论使用骨水泥髋关节假体置换术中,使用骨水泥后,患者收缩压、舒张压均会下降,因此,人工髋关节置换术治疗股骨颈骨折术中使用骨水泥时需要密切监测血压,予以相应对策,同时严格完善术前准备,可有效应对相关并发症。     

The effects of irbesartan added to hydrochlorothiazide for the treatment of hypertension in patients non-responsive to hydrochlorothiazide alone

AIM: To evaluate the antihypertensive efficacy and safety of adding irbesartan to hydrochloride (HCTZ) in patients not adequately controlled by HCTZ alone. PATIENTS AND METHODS: In this multicenter study, after a single-blind, placebo lead-in period, hypertensive patients received single-blind HCTZ 25 mg once daily. After 4 weeks, 238 patients with seated diastolic blood pressure of 93-110 mmHg continued on HCTZ 25 mg once daily and were randomized to double-blind irbesartan 75 mg once daily or matching placebo for 12 weeks. At week 6, the dosage of irbesartan or placebo was doubled for seated diastolic blood pressure > or = 90 mmHg. RESULTS: At weeks 2, 6, and 12, irbesartan/HCTZ resulted in significantly greater (P<0.01) reductions from baseline in trough seated diastolic and systolic blood pressure compared with placebo/HCTZ. At week 12, the mean reductions in trough seated diastolic and systolic blood pressure were 7.2 mmHg (95%, C.I., 5.1-9.3 mmHg) and 11.1 mmHg (95% C.I., 7.9-14.3 mmHg) greater, respectively, with irbesartan/HCTZ compared with placebo/HCTZ. At week 12, significantly (P < 0.01) more patients were normalized (trough seated diastolic blood pressure < 90 mmHg) with irbesartan/HCTZ (67%) compared with placebo/HCTZ (29%). The frequency of adverse events, serious adverse events, and discontinuations attributed to adverse events was similar in both groups, and there were no clinically relevant changes in serum creatinine, potassium, or any other laboratory parameter. CONCLUSION: Irbesartan was effective and well tolerated when added to a background of HCTZ 25 mg in patients whose blood pressure was not adequately controlled by HCTZ alone.     

Cardiovascular responses to upright tilting in healthy subjects

1. The cardiovascular responses to passive upright tilting were determined in healthy human subjects of various ages using entirely 'non-invasive' techniques. Cardiac output was determined by a single breath method and arterial blood pressure by an automatic sphygmomanometer. 2. Steady-state responses were achieved within 4-6 min from the onset of the tilt and were maintained for at least 15 min. 3. The reproducibilities of the responses to tilting by 60 degrees, expressed as two standard deviations of the differences between responses on two occasions (mean responses in parentheses), were: cardiac output +/- 0.70 (-1.41) litre/min, heart rate +/- 7.6 (+14.7) beats/min, systolic blood pressure +/- 15.5 (+1.0), and diastolic blood pressure +/- 13.1 (+13.6) mmHg. 4. Tilting by 20 degrees resulted in no significant responses but between 20 degrees and 60 degrees responses were linearly related to the angle of tilt. 5. Supine values and responses to tilting by 60 degrees were compared in subjects in four age groups between 20 and 80 years. With increasing age, the supine values of cardiac output declined and those of arterial blood pressures increased. Responses of heart rate, cardiac output and diastolic pressure declined by increasing age. These results, obtained from a healthy population, provide reference values for comparison with individuals who may have deficient postural responses.     

Use of non-invasive finger blood pressure monitoring in the estimation of aortic pressure at rest and during the Mueller manoeuvre

Summary. The aim of this investigation was to evaluate whether reliable estimates of aortic pressure can be derived using non-invasive finger blood pressure monitoring. Finger blood pressure (Ohmeda 2300 Finapres device; Finapres, Englewood, CO) was compared with simultaneous ascending aortic pressure measured with a catheter-transducer system both at rest and during acute negative intrathoracic pressure (the Mueller manoeuvre). Thirty-eight patients aged 17–73 years were studied. All were undergoing routine diagnostic or therapeutic cardiac catheterization. Beat-to-beat values of systolic, diastolic and mean non-invasive finger and invasive aortic blood pressure were measured at rest and factors which might have an influence on the difference between methods were examined. The mean finger-aortic difference was +5 ± 14 mmHg for systolic, -2 ± 7 mmHg for diastolic, -5 ± 8 mmHg for mean and +6 ± 13 mmHg for pulse pressure. In multivariate linear regression analysis, the difference in systolic pressure was related to aortic systolic pressure (standardized coefficient β=-0.33, P= 0.01), heart rate (β= 0.49, P<0.000), age (β=-0.29, P<0.025) and height (β= 0.40, P<0.005). The linear regression equations to derive resting aortic pressures from the non-invasive finger pressure readings had correlation coefficients between 0.83 and 0.87 and standard errors of estimate between 6 and 14 mmHg. During the Mueller manoeuvre, Finapres reproduced average pressure changes reliably compared with intra-aortic pressure. Due to moderate inter-individual variation in the finger-aortic differences the correlation coefficients ranged from 0.83 to 0.93 and the standard errors of estimate from 3 to 6 mmHg. Non-invasive finger blood pressure monitoring could be used to estimate central aortic mean and diastolic blood pressure fairly reliably at rest, but with respect to systolic pressure the variance in finger-aortic difference was marked. The average intra-aortic pressure changes caused by the Mueller manoeuvre were reliably reproduced by the Finapres device.