Effect of head-up tilting on systolic time intervals in normal young volunteers.

Systolic time intervals (STI) are sensitive indices of myocardial function. Passive tilting is a rapidly reversible and non-invasive method for inducing cardiovascular stress. The present work was conducted to study the effect of graded head-up tilt (HUT) on STI. 20 male medical students were subjected to 30 degrees, 60 degrees and 80 degrees HUT on a tilting table. ECG, phonocardiogram and carotid pulse were recorded simultaneously on Grass polygraph. Electromechanical systole (QS2), left ventricular ejection time (LVET), pre-ejection period (PEP), PEP/LEVT ratio, heart rate (HR) and corrected STI were determined immediately after and at 1, 2, 3, 4 and 5 min after each angle tilt. HUT produced a decrease in QS2 which was more pronounced at higher angle tilt. LVET decreased after 60 degrees and 80 degrees HUT. PEP and PEP/LVET ratio decreased after each angle tilt. These changes in STI can be explained on the basis of sympathetic stimulation-induced increase in the inotropic state of the heart.     

Effect of pranayam training on cardiac function in normal young volunteers.

Systolic time intervals (STI) are non-invasive and sensitive tests for measuring the ventricular performance. It has been reported that practice of pranayam modulates cardiac autonomic status and improves cardio-respiratory functions. Keeping this in view, the present study was designed to determine whether pranayam training has any effect on ventricular performance as measured by STI and cardiac autonomic function tests (AFT). Twenty four school children were randomly divided into two groups of twelve each. Group I (pranayam group) subjects were given training in nadishuddhi, mukh-bhastrika, pranav and savitri pranayams and practiced the same for 20 minutes daily for a duration of 3 months. Group II (control group) subjects were not given any pranayam training. STI (QS2, LVET and PEP) and AFT (RRIV and QT/QS2) were measured in both the groups at the beginning and again at the end of three months study period. Pranayam training produced an increase in RRIV and a decrease in QT/QS2, suggesting an enhanced parasympathetic and blunted sympathetic activity respectively. QS2, PEP and PEP/LVET increased significantly, whereas LVET was reduced significantly in pranayam group. In contrast, the changes in STI and AFT were much less marked in the control group. Our study shows that three months of pranayam training modulates ventricular performance by increasing parasympathetic activity and decreasing sympathetic activity. Further studies on a larger sample size may illustrate the underlying mechanism(s) involved in this alteration.     

Acute and intermediate cardiovascular responses to zero gravity and to fractional gravity levels induced by head-down or head-up tilt

Determination of early cardiovascular responses to simulated gravity levels between 0 and 1 G will add knowledge of cardiovascular responses to space flight. Cardiovascular responses to 6 hours in a -5 degrees head-down bedrest model of weightlessness (0 G) were compared to those in head-up tilts of +10 degrees, +20 degrees, and +42 degrees (1/6, 1/3, and 2/3 G, respectively). Six healthy young adult males experienced the four angles on separate days. Impedance cardiography was used to measure thoracic fluid index, cardiac output, stroke volume, and peak flow. Although much intersubject variation occurred, the mean thoracic fluid content at -5 degrees decreased during the first hour and remained decreased; 6-hour values were similar to +10 degrees and +20 degrees. Heart rate decreased the first 2 hours for all angles, then increased, converging at 3-4 hours, and reached control by hour 6. Stroke volume decreased for the first 3 hours at -5 degrees, +10 degrees, +20 degrees; values at all four angles converged at hour 3 and increased in unison thereafter. Cardiac output and peak aortic flow reflected the angle at start of tilt; values at all angles converged by the second hour, decreased through the third hour, and increased thereafter. Pulse pressure decreased for the first 3 hours for angles -5 degrees, +10 degrees, and +20 degrees, converged at the fourth hour, and returned to control. Peak flow at +42 degrees was constant for the first 3 hours and increased thereafter. Blood pressure decreased for the first 2 hours, although the greatest decrease occurred at -5 degrees and +42 degrees; thereafter, values at all angles increased in unison and converged at the fourth hour. Total peripheral resistance increased during the first hour at -5 degrees and +20 degrees and decreased from hour 3 to hours 5-6 at the +42 degrees angle. Cardiovascular values were related to tilt angle for the first 2 hours of tilt, but after hour 3 values at all four angles began to converge, suggesting that cardiovascular homeostatic mechanisms seek a common adapted state regardless of effective gravity level (tilt angle) up to 2/3 G.     

Lidocaine and cardiovascular reflex responses to simulated orthostatic stress in normal volunteers.

The interactions of lidocaine with baroreceptor reflexes during simulated orthostatic stress or moderate volume depletion were investigated in healthy volunteers using the lower body negative pressure (LBNP) test. Cardiopulmonary baroreceptors were selectively unloaded at low levels of LBNP (-15 mm Hg) since the central venous pressure (CVP) decreased (-1.4 +/- 0.3 mm Hg) without changes in arterial pressure (AP) and heart rate (HR) but significant increases in forearm vascular resistance (FVR) and plasma noradrenaline (PNA). Cardiopulmonary as well as arterial baroreflexes were both unloaded at higher levels of LBNP (-40 mm Hg) since the CVP (-3.4 +/- 0.4 mm Hg) and systolic AP (-10 +/- 3 mm Hg) decreased whereas FVR, PNA, and plasma renin activity (PRA) increased further (all p less than 0.05). Following lidocaine infusion (serum level of 3.8 +/- 0.2 micrograms/ml), the AP, HR, FVR, and PNA increased and CVP decreased (p less than 0.05). Compared to LBNP performed under saline, lidocaine did not alter the LBNP (-15 mm Hg)-induced changes in cardiovascular and biological parameters but significantly decreased the induced rises in HR, FVR, PNA, and PRA at a LBNP of -40 mm Hg (p less than 0.05). In an additional study, it was also demonstrated that lidocaine significantly decreased the sensitivity of the reflex-mediated bradycardia following phenylephrine injection and attenuated the vasoconstrictor response to the cold pressor test taken as a nonspecific somatic pressor reflex.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of sub-chronic hydrocortisone on responses to amphetamine in normal male volunteers

Rationale Enhancement of dopamine (DA) release by corticosteroids may be of aetiological importance in substance misuse.Objectives To examine the effect of sub-chronic administration of hydrocortisone on the response to amphetamine in healthy male volunteers.Methods Following baseline assessment, 20 volunteers were pretreated for 7 days with 20 mg of hydrocortisone or placebo at 0800 hours and 2000 hours in a double-blind, random order, cross-over design prior to receiving 0.15 mg/kg metamphetamine intravenously. Blood samples for cortisol and prolactin were taken every 15 min. Subjects also underwent tests of neuropsychological function including sustained attention using the rapid visual information processing test (RVIP), which has been shown to be sensitive to changes in DA function.Results Metamphetamine produced a substantial reduction in prolactin levels, and increased subjective mood ratings of "mind-race" and "buzz". Sub-chronic hydrocortisone administration had no effect on these neuroendocrine responses, subjective mood changes or neurocognitive performance on a task of sustained attention (RVIP).Conclusions Despite measurable changes in neuroendocrine and affective functioning in response to metamphetamine, pretreatment with hydrocortisone did not significantly affect any of the variables measured. This suggests that this model of DA function is not affected by this regimen of corticosteroid administration.     

Effect of 60 degrees head-up tilt on systolic time intervals in hypertensive patients

Time course of systolic time interval (STI) variations during 60 degrees head-up tilt (HUT) was studied in 21 patients with essential hypertension and equal number of age-matched control subjects. ECG, Phonocardiogram and carotid pulse were recorded simultaneously on polygraph. Electromechanical systole (QS2), left ventricular ejection time (LVET), pre ejection period (PEP), PEP/LVET ratio and ejection fraction (EF) were determined immediately after and at 1, 2, 3, 4 and 5 min after the tilt. In hypertensive patients, basal values of PEP and PEP/LVET ratio were insignificantly higher whereas LVET and EF were insignificantly lower as compared to the control subjects. 60 degrees HUT produced significant decrease in LVET (P < 0.001) and EF (P < 0.001) and a significant increase in PEP/LVET ratio (P < 0.001) in control subjects. The changes in hypertensive subjects were similar in pattern but statistically insignificant. It is concluded that tilt-induced changes in STIs are blunted in hypertensive patients.     

Effect of sucralfate on ibuprofen absorption in normal volunteers

The effect of the concurrent administration of sucralfate on the absorption of a single dose of ibuprofen was studied in nine normal volunteers using a random crossover design. Each participant received a single 600-mg dose of ibuprofen for the control phase, and a 600-mg dose of ibuprofen following 5 g of sucralfate given in 1-g divided doses for the treatment phase. Blood samples were obtained at regular intervals for 12 hours following the administration of ibuprofen, and pharmacokinetic and statistical analyses were performed. Analysis of time to peak serum concentration, maximum serum concentration, elimination rate constant, and half-life showed no significant difference between the control and treatment phases. Mean total area under the curve for ibuprofen decreased by 11.8% in the treatment phase, but this decrease was not statistically significant. The concurrent administration of sucralfate did not significantly alter the absorption of a single 600-mg dose of ibuprofen in healthy subjects.     

Effect of yoga on exercise tolerance in normal healthy volunteers

Twelve normal healthy volunteers (6 males and 6 females) undergoing yoga training for 90 days were studied for the effect of yoga on exercise tolerance. Their ages ranged from 18 to 28 years. The volunteers were taught only Pranayama for the first 20 days and later on yogic asanas were added. Sub-maximal exercise tolerance test was done on a motorized treadmill by using Balke's modified protocol, initially, after 20 days (Phase-I) and after 90 days of yoga training (Phase-II). Pyruvate and lactate in venous blood and blood gases in capillary blood were estimated immediately before and after the exercise. Minute ventilation and oxygen consumption were estimated before and during the test. Post exercise blood lactate was elevated significantly during initial and Phase-I, but not in Phase-II. There was significant reduction of minute ventilation and oxygen consumption only in males in Phase-I and II at the time when the volunteers reached their 80% of the predicted heart rate. Female volunteers were able to go to higher loads of exercise in Phase-I and II.     

Augmented vasoconstrictor response to head-up tilt in peripheral tissues during beta-receptor blockade

Subcutaneous and skeletal muscle blood flow in the forearm during 30 degrees head-up tilt was studied in 15 healthy subjects before and during treatment with propranolol. Relative blood flow was estimated by the local 133Xe washout technique. Head-up tilt elicited greater vasoconstriction in both tissues during beta-receptor blockade as compared to the pretreatment period. Proximal nerve blockade with lidocaine prevented the vasoconstrictor response in subcutaneous tissue to the tilt. In skeletal muscle injection of a low dose of propranolol had no effect on the vasoconstrictor response to tilt. Therefore, the augmented vasoconstrictor response to head-up tilt during beta-receptor blockade is most probably due to centrally elicited (baroreceptor) and neurogenically mediated impulses to resistance vessels in peripheral tissues and not to "unmasking" of peripheral alpha-receptors.     

Effect of rioprostil on aspirin-induced gastrointestinal mucosal changes in normal volunteers

Rioprostil, a 15-deoxy-16-methyl prostaglandin E1, was evaluated for its effect on aspirin-induced gastrointestinal mucosal changes in normal volunteers. Fifty-six normal male volunteers were evaluated by endoscopy in a double-blind, placebo-controlled study. Aspirin was given at a dose of 975 mg four times per day. Rioprostil was given at doses of 60, 120, and 300 micrograms four times per day. Rioprostil, at both antisecretory and subantisecretory doses, prevented or reduced aspirin-induced injury. Increased stool frequency was the most common side effect and appeared to be a dose-related effect of rioprostil occurring at only antisecretory doses.     

直立倾斜试验在儿童血管迷走性晕厥中的诊断价值

目的　探讨直立倾斜试验对儿童血管迷走性晕厥的诊断价值。方法对２４例不明原因晕厥的患 儿进行基础直立倾斜试验,并以１２名正常儿童作对照,在倾斜过程中动态观察心电图、血压、心率,并进行分析。结 果２４例晕厥患儿中,基础直立倾斜试验阳性１６例,而对照组为０。诊断敏感度为６７％,特异度为１００％,诊断价值 为７８％。１６例阳性反应中,心脏抑制型反应３例（１９％）,表现为心动过缓,血压无变化;血管抑制型反应９例 （５６％）,表现为血压下降,心率加快;混合型反应４例（２５％）,表现为心率、血压均有明显下降。结论基础直立倾斜试验可作为儿童血管迷走性晕厥的一种重要诊断方法。     

Effects of orthostatic self-training on head-up tilt testing and autonomic balance in patients with neurocardiogenic syncope

To investigate the effectiveness and the mechanisms of an orthostatic self-training program for the prevention of neurocardiogenic syncope, 28 patients were treated with an orthostatic self-training program. Syncope was induced by head-up tilt testing (+ 80 degrees for 30 min) in all patients. The onset time of the tilt-induced syncope was 14 +/- 7 min following placement in the upright position. The orthostatic self-training program included standing against a wall without moving twice a day every day for a planned duration of up to 30 min at home. The head-up tilt response was re-evaluated after 24 +/- 6 days based on results of the self-training. In 12 of the 28 patients, the sympathovagal balance was also determined during the head-up tilt test before and after the training with power spectral analysis of heart rate variability using a maximal entropy method. Syncope was not observed in any patient after the training. Although the low frequency/high frequency ratio in the supine position was not different before and after the training, the ratio after 3 min in the upright position after the training decreased significantly compared with that before the training. High-frequency components in the supine and upright positions were not different before and after the training. We concluded that orthostatic self-training significantly improved symptoms in patients with tilt-induced neurocardiogenic syncope. Decreased sympathetic activity in the early stage of the upright position period may play an important role in the mechanisms of this therapy.     

The effect of chronic fluvoxamine on hormonal and psychological responses to buspirone in normal volunteers

We studied the effect of 3 weeks treatment with the selective serotonin reuptake inhibitor (SSRI), fluvoxamine, on hormonal and psychological responses to buspirone, a 5-HT_1A receptor partial agonist which also binds to dopamine receptors, in normal male volunteers. Eleven subjects received buspirone, 30 mg, and placebo before, and in week 3 of fluvoxamine treatment (mean dose 127 mg/day). Placebo and buspirone were given in a balanced order, double-blind. Buspirone significantly elevated plasma prolactin (PRL) and growth hormone (GH) concentrations but had no significant effect on cortisol (CORT) or temperature. Significant psychological effects of lightheadedness, tiredness and difficulty thinking occurred. Fluvoxamine treatment resulted in a nearly 3-fold increase in plasma buspirone with a similar enhancement of the PRL response. In contrast the GH and psychological responses were blunted. The increased buspirone concentrations are likely to be due to inhibition of first pass liver metabolism by fluvoxamine acting on the cytochrome P-450 system. The PRL response is probably mediated by antagonism of pituitary dopamine-D₂ receptors and its enhancement by fluvoxamine treatment may be a pharmacokinetic effect. The blunting of GH and psychological responses suggest that 5-HT_1A receptor function is reduced by chronic fluvoxamine treatment. Received: 15 December 1995/Final version: 29 May 1996     

硝酸甘油倾斜试验药量个体化对试验结果的影响

目的探讨舌下含化硝酸甘油倾斜试验中个体化给药对试验结果的影响。方法设观察组161例按0.3mg/60kg计算,根据体质量大小增减给药量;对照组231例,每例不论体质量大小给硝酸甘油0.3mg舌下含化,比较两组间阳性率、阳性反应类型、阳性患者心律失常和晕厥的发生率。结果阳性率：观察组高于对照组65.84%（106/161）vs42.86%（99/231）,P〈0.01;阳性反应类型：血管抑制型观察组低于对照组32.08%（34/106）vs55.56%（55/99）,P〈0.01,心脏抑制型两组间无显著差异,4.72%（5/106）vs7.07%（7/99）,P〉0.05,混合型观察组明显高于对照组63.21/%（67/106）vs37.37%（37/99）,P〈0.005;心律失常比较：两组间无明显差异,45.28%（48/106）vs43.43%（43/99）,P〉0.05,均以缓慢性心律失常为主,窦性心动过缓观察组40例占37.74%（40/106）,心率小于50次/min者28例,其中窦性停搏8例,对照组32例占32.32%（32/99）,心率小于50次/min者10例,其中窦性停搏2例,观察组交界区逸搏心律的发生率明显低于对照组3.77%（4/106）vs10.10%（10/99）,P〈0.01,窦性停搏的发生率高于对照组7.55%（8/106）vs2.02%（2/99）,P〈0.05;晕厥的发生率高于对照组23.58%（25/106）vs11.11%（11/99）,P〈0.05。结论①个体化用药能明显提高血管迷走性晕厥的敏感性;②个体化用药的阳性反应程度较重,以混合型为主;③阳性反应者均以缓慢性心律失常为主,窦性停搏的发生与硝酸甘油的用量、反应持续的时间和终止试验的速度有关;④严格掌握硝酸甘油的用量,及早发现血压和心率的下降趋势,快速终止试验可避免晕厥和缓慢性心律失常的发生。     

Effect of cimetidine on the pharmacokinetics and pharmacodynamics of enalapril in normal volunteers

The possible effects of cimetidine on the pharmacokinetics and pharmacodynamics of enalapril, a pro-drug requiring hepatic de-esterification to an active angiotensin-converting enzyme (ACE) inhibitor enalaprilat, were assessed in a randomized, crossover study. Cimetidine (400 mg) or placebo was administered orally every 12 h for 3 days and on the day of a single oral administration of enalapril maleate (10 mg) to seven healthy male subjects. Serum ACE, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and alpha-human atrial natriuretic peptide (alpha-hANP) were measured before and 4 h after the enalapril dosing. There were no significant differences in any serum- and urine-derived kinetic parameters of enalapril and enalaprilat, nor in hemodynamics, PAC, or alpha-hANP between the two treatment trials. ACE decreased and PRA increased to a similar extent in the two trials. Serum enalaprilat concentration correlated significantly (p less than 0.001) with percentage of inhibition of ACE activity. The results suggest that the pharmacokinetics and pharmacodynamics of enalapril are unaffected by preadministration of cimetidine. Thus, cimetidine does not appear to alter hepatic esterase activity toward enalapril.     

Role of angiotensin type 2 receptors in human forearm vascular responses of normal volunteers

1. It has been hypothesized that the expression of angiotensin (Ang) II type 2 (AT(2)) receptors may become important in vascular disease; however, the functional existence of AT(2) receptors in normal adult humans remains to be established. 2. Vascular responses to AngII after the administration of the specific AT(2) receptor antagonist PD 123319 were determined in the forearm circulation of normal volunteers. 3. PD 123319 (8 microg/min) did not alter basal forearm blood flow, or forearm blood flow or forearm vascular resistance responses to AngII. 4. These results suggest that AT(2) receptors do not play a significant role in the regulation of forearm blood flow or forearm vascular resistance of normal volunteers, but do not preclude a role for AT(2) receptors in other vascular beds or in patients with cardiovascular disease.     

Effect of intravenous ketanserin on plasma catecholamines and renin activity in normal volunteers

Summary In a placebo controlled, single blind, randomized cross over study catecholamines (CA) and renin activity (PRA) in plasma were measured in 2 female and 4 male healthy volunteers, at rest in the supine position, following a single intravenous injection of 0.15 mg/kg ketanserin (K) and placebo (P, 10 ml saline). K caused a significant increase in the area under the plasma norepinephrine (NE) time curve (AUC_NE) from 13,200 to 18,100 ng × 1^–1 × min for 1 hour after the injection. The area under the plasma epinephrine (E) time curve (AUC_E) was also increased but to a lesser extent; it was significantly elevated from 54 to 68 ng × 1^–1 × min for 1 minute after the injection. Dopamine (DA) and PRA did not show any significant response to ketanserin. Following the P injection, none of the four parameters showed any significant change.     

Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers

Ten healthy subjects received buspirone (30 mg orally) with and without pre-treatment with the 5-HT1A receptor antagonist, pindolol (80 mg over 3 days). Following pindolol treatment the growth hormone and hypothermic responses to buspirone were significantly decreased. There was also a delay in the onset of the prolactin response to buspirone but the total amount of prolactin secretion, calculated as area under the curve, was not significantly reduced. The data suggest that the growth hormone and hypothermic responses to buspirone in humans are mediated by 5-HT1A receptors, but an explanation founded on pharmacokinetic factors cannot presently be excluded. Both this latter possibility and the lack of selectivity of pindolol for 5-HT receptors indicate the need for the further neuroendocrine studies of the mode of action of buspirone, preferably with more selective 5-HT1A receptor antagonists.     

Central cardiovascular responses of histamine and homodimaprit in normal and hypophysectomized rats

Central administration of histamine in conscious rats produced half the pressor response in hypophysectomized rats compared to normal animals. The pressor response was blocked completely by hexamethonium in hypophysectomized rats but not at all in normal rats. Homodimaprit given centrally, gave pressor effects of equal magnitude in both groups. In normal rats, it caused significantly higher blood blood pressure following ganglionic blockade, whereas in hypophysectomized rats hexamethonium did not block the response to homodimaprit. These results, plus previous findings, show that histamine, given centrally, raises blood pressure in normal conscious animals by releasing vasoactive substances from the brain. In hypophysectomized rats it stimulates sympathetic output. Homodimaprit, on the other hand, produces its pressor action by the release of vasoactive substances from the brain both in normal and hypophysectomized animals. A hypothesis is proposed to suggest that parallel neuronal processing occurs in the brain when histamine is given.