Effects of yohimbine, an α2-adrenoceptor antagonist, on experimental neurogenic orthostatic hypotension

Summary— Yohimbine has been proposed for the treatment of neurogenic orthostatic hypotension; however, no controlled trial has been performed in experimental models of orthostatic hypotension or in patients with autonomic failure. The aim of the present study was to compare the effects of yohimbine (0.05 mg/kg, intravenously [iv]) and placebo (saline) in a new model of neurogenic orthostatic hypotension obtained by sinoaortic denervation (SAD) in chloralose-anaesthetized dogs. Blood pressure, heart rate, noradrenaline plasma levels and systolic blood pressure and heart rate short-term variabilities (calculated on low frequency [40–50 MHz] and high frequency [390–490 MHz] bands) were measured in supine position and after a 10 min 80° head-up tilting. The drugs were administered in a double-blind cross-over randomized fashion. The head-up tilting performed in normal animals increased diastolic blood pressure (+12 ± 4 mmHg), heart rate (+39 ± 12 beats per minute [bpm]), the low frequency band of systolic blood pressure and noradrenaline plasma level, without changing systolic blood pressure or heart rate variability. In SAD dogs, a marked fall in systolic (-80 ± 11 mmHg) and diastolic (-43 ± 4 mmHg) blood pressures was observed within 1 min after placebo, without modification in heart rate, systolic blood pressure and heart rate short-term variabilities and noradrenaline plasma levels. In SAD dogs, yohimbine (0.05 mg/kg, iv) delayed the blood pressure fall elicited by head-up tilting, but failed to modify its magnitude. These results show that, in the model of orthostatic hypotension obtained by SAD, yohimbine, at an α₂-adrenoceptor selective dose (0.05 mg/kg), delays the fall in blood pressure elicited by head-up tilting. The effect of yohimbine can be explained by an increase in sympathetic tone.     

Clonidine but not propranolol decreases plasma neuropeptide Y (NPY) levels

The effects of acute administration of two antihypertensive drugs, clonidine and propranolol, on plasma NPY and catecholamine levels were compared in sinoaortic denervated (a model associated with a marked increase in sympathetic tone and a rise in blood pressure) and normal conscious dogs. Clonidine decreased plasma noradrenaline and NPY concentrations in both groups of animals. Propranolol failed to change plasma noradrenaline and NPY levels in sinoaortic denervated dogs but elicited a decrease in plasma noradrenaline with no change in NPY levels in normotensive animals. The present experiments show that changes in plasma noradrenaline and NPY concentrations are not always simultaneous. The decrease in plasma NPY concentrations could contribute to the sympatholytic effect of clonidine.     

Short-term blood pressure and heart rate variability in congenital central hypoventilation syndrome (Ondine's curse)

The effect of CCHS (congenital central hypoventilation syndrome, or Ondine's curse) on short-term BP (blood pressure) and HR (heart rate) variability was evaluated in 16-year-old subjects presenting a form of CCHS requiring night ventilatory assistance. The 12 patients were compared with 12 age- and gender-matched healthy volunteers. Recordings were obtained during daytime while the subjects were breathing spontaneously. Continuous BP was measured with a Finapres device in the supine, head-up tilt and standing positions. The manoeuvre of actively standing was also analysed. HR levels were elevated in CCHS subjects at supine rest (+23%) with a reduced HR overall variability (-88%). The low- and high-frequency components of HR variability were affected. BP levels were preserved at rest, but the manoeuvres demonstrated a limited capacity to elevate BP. There was no overshoot in BP during the manoeuvre of actively standing, and steady standing BP levels in patients were not higher than supine BP levels as usually observed in healthy controls. The spontaneous baroreflex sensitivity estimated using the sequence technique or the cross-spectral analysis fell in the patients to approx. one-third of the sensitivity estimated in the healthy controls whatever the position. This cardiovascular profile suggests a predominant vagal dysfunction with signs of vagal withdrawal and baroreflex failure, and relative preservation of the cardiac and vascular sympathetic function. It is likely that the impaired ontogeny of the visceral reflexes, considered now to cause CCHS syndrome, includes the baroreceptive pathway and mainly its vagal component.     

Effects of triglycyl-lysine-vasopressin on cardiovascular responses to orthostatic stress

Summary. The influence of triglycyl-lysine-vasopressin (TGLVP) on cardiovascular responses to orthostatic stress was studied. Arterial pressures, heart rate (HR) and stroke volume (SV) were measured in eight healthy males subjected to 20 min 70° head-up tilt. On different days they received either 0·01 mg/kg b.w. of TGLVP or a corresponding volume of 0·9% saline i.v. after 15 min supine rest. After the drug injection, in supine subjects, HR had decreased from 58 to 50 beats min^-1, total peripheral resistance (TPR) was elevated by 29%, systolic (SAP) and diastolic pressure (DAP) had increased by 7 and 8 mmHg, respectively. During tilt, values for HR and SAP were similar with and without TGLVP whereas DAP and MAP were elevated 8 and 7 mmHg, respectively, by the drug. 4–8 min into the tilt, TGLVP caused an 8% sustained curtailment of SV. Both with and without the drug TPR increased by about 30% in response to head-up tilt. Thus, the marked peripheral arteriolar constriction after vasopressin in the supine position was not affected by head-up tilt. Tilting also abolished the drug-induced elevation in SAP, most likely explained by the reduction in SV. Although TPR was markedly increased by TGLVP during head-up tilt, reflected in the behaviour of DAP, the response of SV speaks against any beneficial effect of this drug on orthostatic tolerance in healthy subjects.     

Hemodynamics changes after tilting and the efficacy of preventive drugs

Background: We investigated whether hemodynamics changes during head-up tilt test (HUT) predict the efficacy of preventive drugs in neurally mediated syncope (NMS) patients, in order to clarify the differences between drug responders and nonresponders.
Method: In 402 patients with syncope, we examined HUT. In 66 patients with induced NMS, we administered propranolol when heart rate (HR) > 60 and systolic blood pressure (SBP) > 100 mmHg. When HR ≤ 60 or SBP ≥ 100, we administered disopyramide. After administration of each drug we examined HUT test again.
Results: Propranolol prevented NMS in 9/20 patients (propranolol responder group (pro-res group)). In pro-res group, systolic blood pressure (SBP), diastolic BP (DBP), and total peripheral resistance (TPR) at upright position (UP) before propranolol were significantly increased as compared to those at supine position (SP) (P < 0.05). But in propranolol nonresponder (pro-nonres group) SBP was not increased. After propranolol, DBP and TPR at UP was not increased in pro-nonres group. Propranolol inhibited the increase of low-frequency/high-frequency ratio (LF/HF) after tilting in pro-res group. Disopyramide prevented NMS in 14/32 patients (disopyramide responder group (dis-res group)). In dis-res group, DBP and TPR at UP before disopyramide was significantly increased as compared to that at SP (DBP P < 0.0001, TPR P < 0.05). But in disopyramide nonresponder group (dis-nonres group), DBP and TPR were not increased. After disopyramide, DBP and TPR at SP were significantly increased as compared to that before disopyramide in dis-res group (P < 0.05).
Conclusion: The hemodynamics changes after tilting during HUT predict the efficacy of two preventive drugs for NMS induced by HUT.     

Reflex Inhibition of Renal Sympathetic Nerve Activity during Myocardial Ischemia Mediated by Left Ventricular Receptors with Vagal Afferents in Dogs

The major goal of this investigation was to determine if activation of cardiac receptors during coronary artery occlusion could inhibit efferent renal sympathetic nerve activity. In nine chloralose anesthetized dogs with only carotid (n = 3) or with sinoaortic (n = 6) baroreceptors operative, anterior descending coronary artery (LAD) occlusion resulted in a small decrease in mean arterial pressure (-9.8+/-5.1 mm Hg, NS) and in a significant (P < 0.05) increase in renal nerve activity (24.0+/-4.1%). In these dogs, circumflex coronary artery (Cx) occlusion resulted in greater hypotension (-18.4+/-4.0 mm Hg), and yet no change (1.1+/-9%) in renal nerve activity was noted. Changes in left atrial pressure during LAD and Cx occlusion were not different. In seven dogs with carotid sinus denervation, coronary occlusions resulted in decreases both in arterial pressure and in renal nerve activity which were consistently greater during Cx occlusion. The responses to coronary occlusion in six dogs after sinoaortic deafferentation were similar to those observed with only carotid sinuses denervated. In all experiments, vagotomy abolished the difference in the blood pressure responses and the decreases in renal sympathetic nerve activity during Cx occlusion. Vagotomy also abolished the decrease in nerve activity during LAD occlusion in dogs with carotid or sinoaortic denervation. These data show that Cx occlusion and, to a lesser degree, LAD occlusion resulted in reflex withdrawal of renal sympathetic nerve activity mediated by left ventricular receptors with vagal afferents. The reflex withdrawal of renal nerve activity during Cx occlusion occurred in spite of hypotension and the presence of functioning sinoaortic baroreceptors.     

Achieving haemodynamic baseline values with Finapres in elderly subjects during supine rest

Background: Clear guidelines for the resting time necessary to achieve stable blood pressure (BP) levels are scant in gerontology research. Therefore, we aimed to determine the minimum period required for obtaining haemodynamic baseline values in elderly subjects during supine rest. In addition, we evaluated the effect of cardiovascular morbidity, such as diastolic heart failure, and the effect of complex comorbidity of geriatric patients, on haemodynamic changes during supine rest. Methods: A total of 17 healthy subjects, 18 heart failure patients with normal systolic function and 24 geriatric patients, aged 70 years and more, participated. After an overnight fast, changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR), and stroke volume (SV) were determined by Finapres beat‐to‐beat non‐invasive BP monitoring during a 20‐min supine rest. The procedure was repeated in the healthy subjects and geriatric patients on a second day. Results: Complete BP stabilization was reached in each group within 5 min of supine rest, as SBP remained essentially unchanged and DBP did not change significantly anymore after the fourth minute. In the heart failure patients, HR decreased and SV increased until the twelfth minute of rest. The SBP, DBP, HR, and SV changes during supine rest showed good reproducibility. Conclusions: A span of 5 min of supine rest ensured achievement of reliable and reproducible baseline BP values by Finapres in elderly subjects. However, we recommend at least 12 min of rest to obtain full haemodynamic stability in elderly patients with diminished cardiac compliance and diastolic function.     

Cardiovascular effects of ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel

The objective of this randomized, double-masked, cross-over study was to compare the cardiovascular effects of two glaucoma formulations, ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel. Twenty-four young healthy subjects received for 2 weeks either twice daily 0.5% timolol solution or once daily 0.1% timolol hydrogel. Heart rate (HR), blood pressure, atrio-ventricular conduction (PR interval), corrected QT time (QTc) and heart rate variability (HRV) were measured in supine position and during head-up tilted position. The mean peak concentrations of timolol in plasma were significantly higher after administration of 0.5% aqueous solution than after 0.1% hydrogel. A 0.5% timolol aqueous solution decreased HR on average by 3 bpm in supine position and by 7 bpm in head-up tilted position while no significant effects were observed with 0.1% timolol hydrogel. During tilt test HR was significantly lower after administration of timolol aqueous solution than after timolol hydrogel (mean +/- SD, 77 +/- 11 bpm versus 86 +/- 13 bpm, P < 0.05). Timolol aqueous solution slightly decreased QTc during tilt (5.9 +/- 5.6 ms, P < 0.01). During tilt tests, timolol aqueous solution slightly increased atrio-ventricular conduction (7.2 ms, P = 0.02). No significant differences were found in HRV. These results indicate that in healthy volunteers, ophthalmic 0.5% timolol aqueous solution produces more pronounced cardiac beta-blocking effects than 0.1% timolol hydrogel.     

ACUTE RELEASE OF CATECHOLAMINES ON CIRCULATING BLOOD CELL ADRENOCEPTORS AND METABOLIC INDICES IN DOG

The effects of acute release of endogenous catecholamines on both platelet alpha 2 and leukocyte beta adrenoreceptors and metabolic indices (glucose and free fatty acids) were investigated in dogs by means of a model of neurogenic hypertension following acute sinoaortic denervation (ASAD). Despite the marked increase in catecholamine levels (+4.2-fold for noradrenaline and 16.7-fold for adrenaline, for example, at minute 45 following ASAD) and in glucose plasma levels, and the significant decrease in free fatty acid plasma levels, no change in platelet alpha 2 or leukocyte beta adrenoreceptor binding sites (number as well as affinity) was observed during the whole experiment. It is suggested that the number of platelet alpha 2- and leukocyte beta-adrenoreceptors is not submitted to short-term regulation, at least by endogenous catecholamines in dogs.     

The influence of left lateral position on cardiac output changes after head up tilt measured by impedance cardiography

Background.The value of the impedance cardiography (IC) method formeasuring cardiac output (CO) with the subject in the left lateral positionhas not yet been established. We compared the CO after a 30° head-up tiltwith the subjects in the supine and left lateral position. Methods.Thirty healthy young volunteers were placed in the supine horizontalposition. CO, stroke volume (SV) and heart rate (HR) were measured for fiveminutes using impedance cardiography (NCOMM3, BoMed Medical Manufacturing,Location). Then a 30° head-up tilt was done and the measurements werecontinued for an additional five minutes. After that the subjects were placedin the left lateral horizontal position and the measuring procedure wasrepeated. Results.After the tilt, SV and cardiac index (CI) decreasedand HR increased statistically significantly in the supine and in the leftlateral position. SV and CI also decreased statistically significantly but HRdid not change after the shift from the supine to the left lateral position.Although CI was smaller in the left lateral position, the time course of CIchange after the tilt was identical in the supine and in the left lateralposition. Conclusion.When using the IC method of SV measurement, theabsolute value of the CI changes when moving from the supine to lateralpositions. It is not clear whether this change is physiologic or an artifactof the measurement technique. However, changes in CI in response to a 30degree head up tilt are the same in either position. We conclude that changesin CI can be measured with the IC method in the lateral position.     

Plasma catecholamines, plasma renin activity and plasma aldosterone in tetraplegic man, horizontal and tilted.

1. Plasma catecholamines, plasma renin activity, plasma aldosterone and haematocrit were measured in four subjects with physiologically complete cervical spinal cord transections, before, during and after head-up tilt to 45 degrees for 30 min. Plasma catecholamines were measured in five normal male volunteers in the supine position and after head-up tilt to 45 degrees for 10 min. 2. After 10 min of head-up tilt, the plasma noradrenaline rose 14% in the tetraplegic patients and 115% in the control subjects. These findings indicate a failure of sympathetic activity in response to head-up tilt in the tetraplegic patients, probably caused by interruption of pathways by which the brain normally controls sympathetic outflow. 3. In the tetraplegic patients the resting plasma renin activities were above normal, and rose more quickly and greater on head-up tilt than in published studies of normal subjects. It is likely that the renal baroreceptors are important in the control of renin release. 4. In the tetraplegic patients, there was a late rise in plasma aldosterone which was probably due to the elevation in plasma renin activity.     

Leg crossing with muscle tensing, a physical counter-manoeuvre to prevent syncope, enhances leg blood flow

In patients with orthostatic intolerance, the mechanisms to maintain BP (blood pressure) fail. A physical counter-manoeuvre to postpone or even prevent orthostatic intolerance in these patients is leg crossing combined with muscle tensing. Although the central haemodynamic effects of physical counter-manoeuvres are well documented, not much is known about the peripheral haemodynamic events. Therefore the purpose of the present study was to examine the peripheral haemodynamic effects of leg crossing combined with muscle tensing during 70 degrees head-up tilt. Healthy subjects (n=13) were monitored for 10 min in the supine position followed by 10 min in 70 degrees head-up tilt and, finally, for 2 min of leg crossing with muscle tensing in 70 degrees head-up tilt. MAP (mean arterial BP), heart rate, stroke volume, cardiac output and total peripheral resistance were measured continuously by Portapres. Leg blood flow was measured using Doppler ultrasound. Leg vascular conductance was calculated as leg blood flow/MAP. A significant increase in MAP (13 mmHg), stroke volume (27%) and cardiac output (18%), a significant decrease in heart rate (-5 beats/min) and no change in total peripheral resistance during the physical counter-manoeuvre were observed when compared with baseline 70 degrees head-up tilt. A significant increase in leg blood flow (325 ml/min) and leg vascular conductance (2.9 arbitrary units) were seen during the physical counter-manoeuvre when compared with baseline 70 degrees head-up tilt. In conclusion, the present study indicates that the physical counter-manoeuvre of leg crossing combined with muscle tensing clearly enhances leg blood flow and, at the same time, elevates MAP.     

Increased sensitivity to pressor hormones in central diabetes insipidus

Pressor sensitivities to infusions of arginine vasopressin (AVP), noradrenaline (NA) and angiotensin II (AII), as well as cardiovascular responses to head-up tilt, were assessed in subjects with central diabetes insipidus (CDI) and compared with those in normal control subjects. During incremental i.v. infusions of AVP at 0.2-5.0 pmol min-1 kg-1, mean arterial blood pressure (MABP) rose progressively in CDI subjects only and the rise was significantly greater than that which occurred in control subjects during their final infusion. The pressor effects of incremental i.v. infusions of NA and AII were greater, and the bradycardia associated with NA was more pronounced, in CDI subjects than in controls. Whole body tilt from supine to 45 degrees head-up was associated with increased heart rate and an insignificant rise in MABP in both groups, although a rise in plasma AVP occurred in control subjects only. These results demonstrate that subjects with CDI are more sensitive than control subjects to the pressor effects of NA and AII, and also develop sensitivity to the pressor effects of AVP. Their cardiovascular responses to head-up tilt remain intact. Presumably the increased vascular sensitivity to NA and AII in subjects with CDI is sufficient to compensate for their lack of AVP response during head-up tilt.     

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.     

Autonomic dysfunction in migraineurs

Objective.—To evaluate autonomic function and sympathovagal balance in migraineurs and healthy controls.
Background.—The pathophysiology of migraine is still largely unknown. An imbalance of the autonomic nervous system could explain many of the clinical manifestations of the disorder.
Materials and Methods.—We undertook autonomic function tests in 17 women suffering from migraine (8 with aura) (average age 36 ± 7 years) and 16 healthy women (average age 34 ± 7 years). Autonomic nervous system studies consisted of tests of sympathetic function (the quantitative sudomotor axon reflex test, beat-to-beat blood pressure responses to the Valsalva maneuver, sustained handgrip, cold pressor test, and head-up tilt and tests of parasympathetic function (heart rate responses to deep breathing and the Valsalva maneuver). The data from the tilt test were further evaluated by time-frequency analysis (Wigner distribution).
Results.—Subjects with migraine with aura had a smaller increase of mean blood pressure during phase IV of the Valsalva maneuver ( P <0.05) and a lower blood pressure increment during the handgrip test ( P =0.08); their time-frequency distribution showed reduced power at the nonrespiratory frequencies in the R-R interval at both minutes 1 ( P <0.03) and 5 ( P <0.04) of head-up tilt. Sympathovagal balance (a ratio of spectral power of nonrespiratory frequency variations in blood pressure to that at respiratory frequency variations in the R-R interval) was significantly increased in migraineurs, both with and without aura, by 10 minutes of head-up tilt.
Conclusion.—Subjects with migraine with aura had resting supine sympathetic hypofunction and intact parasympathetic function. With head-up tilt, sympathovagal balance is increased. The dynamic alterations in autonomic nervous system function may contribute to the development of aura in patients with migraine.     

Cardiovascular properties of metkephamid, a delta opioid receptor agonist, in man

Opioid receptors exist in at least three forms: mu, delta and kappa. Agonists at mu receptors produce orthostatic hypotension in man by a mechanism involving a reduction in baroreflex sensitivity. We describe here the cardiovascular properties of metkephamid, a relatively selective delta opioid receptor agonist. Blood pressure, heart rate and plasma noradrenaline concentration were measured over a 7 h period in eight normal young male volunteers in the supine position and after 70 degrees 5 min head-up tilt, after receiving metkephamid (50 mg intramuscularly) or placebo. Metkephamid increased heart rate in the supine position with no change in blood pressure or plasma noradrenaline concentration. This was accompanied by symptoms consistent with an anti-muscarinic anticholinergic effect. Head-up tilt resulted in substantial hypotension after metkephamid with an attenuated change in heart rate and no increase in noradrenaline concentration. We conclude that delta as well as mu opioid receptor agonists can produce orthostatic hypotension with attenuation of heart rate response. Metkephamid possesses anticholinergic properties not seen with mu receptor agonists, suggesting a possible role of delta opioid receptors in cholinergic activity.     

不同体位改变模式对青年人和中年人血流动力学的影响

目的 观察70°倾斜站立和0°～70°重复体位改变对青年和中年健康受试者血流动力学的影响。 方法 选取健康中年受试者24例设为中年组,健康青年受试者23例,设为青年组。2组受试者均完成静态70°倾斜站立位和0°～70°重复体位改变两种体位改变,每种体位测试时间为10 min,测试前、中和后均平卧休息10 min。使用无创运动心排和血压计记录2组受试者休息位、静态70°倾斜站立位和0°～70°重复体位改变时的血流动力学参数,并进行统计学分析。 结果 静态70°倾斜站立位时,2组受试者的HR较组内休息位均显著增高,且青年组静态70°倾斜站立位时的心率（HR）为（84.0±9.5）bpm,显著高于组内0°～70°重复体位改变和中年组同体位,而中年组静态70°倾斜站立位时的HR则显著高于组内0°~70°重复体位,差异均有统计学意义（P＜0.05）。中年组静态70°倾斜站立位和0°～70°重复体位改变时的SV则显著低于组内休息位,差异均有统计学意义（P＜0.05）。2组受试者在静态70°倾斜站立、0°～70°重复体位改变的DBP与组内休息位比较,差异均有统计学意义（P＜0.05）,且中年组3种体位下的DBP均显著高于青年组同体位,差异均有统计学意义（P＜0.05）。青年组受试者在休息位、静态70°倾斜站立位、0°～70°重复体位改变时,男性受试者的每搏量(SV),心排出量(CO)和收缩压(SBP)均显著高于女性同体位,差异均有统计学意义（P＜0.05）。 结论 体位改变时,青年人主要表现为心率增加,中年人则表现为SV降低。0°～70°重复体位改变相对于70°倾斜站立对血流动力学的影响更小,相比之下是一种更安全稳定的训练方法,但长期干预效果还需进一步研究证实。     

Fluoxetine in orthostatic hypotension of Parkinson's disease: A clinical and experimental pilot study

Summary— Recent clinical studies have reported a beneficial effect of fluoxetine, a serotonin reuptake inhibitor, in patients with severe refractory orthostatic hypotension. The present study was undertaken to investigate the effect of fluoxetine in orthostatic hypotension occurring during Parkinson's disease on both blood pressure values and number of clinical symptoms during orthostatic procedure evaluated using a validated clinical rating scale. In a pilot study performed in fourteen patients with idiopathic Parkinson's disease plus orthostatic hypotension, fluoxetine hydrochloride (20 mg orally daily during one month) significantly reduced the fall in systolic blood pressure [-33 ± 21 (SD) mmHg before fluoxetine vs -22 ± 19 mmHg after fluoxetine, P = 0.03] elicited by standing without modifying heart rate. The drug also significantly reduced the number of postural symptoms occurring during the orthostatic procedure [2.9 ± 1.5 (SD) before fluoxetine vs 1.2 ± 1.3 after fluoxetine, P = 0.006]. A similar pattern of response was obtained in an experimental model of neurogenic orthostatic hypotension obtained in chronically sino-aortic denervated dogs submitted to an 80° head-up tilt test procedure under chloralose anaesthesia. Fluoxetine did not change plasma noradrenaline levels. This pilot study suggests a slight but clinically significant effect of fluoxetine on both hemodynamic parameters and clinical symptoms in parkinsonian patients suffering from orthostatic hypotension.     

Cross-spectral analysis of heart rate and blood pressure modulations

The cross-spectral analysis of heart rate (HR) and blood pressure (BP) variabilities provides "amplitude" and "phase" related measures. Compared to the amplitude measure, that is the baroreflex gain, the phase related measure characterizing the time lag between HR and BP oscillations has been studied to a much lesser extent. A population of 103 patients (73 men, 30 women, aged 53 +/- 12, range 20-82 years) referred for the management of coronary artery disease and/or hypertension were studied. In each subject, electrocardiogram and BP recordings were obtained in the supine and sitting positions of 5 minutes of rest (spontaneous respiration), 3 minutes of controlled respiration at 0.1 Hz (slow-controlled respiration), and 3 minutes of controlled respiration at 0.33 Hz (fast-controlled respiration). The frequency of maximum coherence (above the arbitrary threshold of 0.5) of BP and RR interval variabilities was searched between 0.033-0.133 Hz and 0.200-0.400 Hz to obtain baroreflex gain and phase shift in low and high frequency bands, respectively. Mean phase shifts of -79.1 and -67.0 degrees (-2.4 and -2.1 s) were found during slow-controlled respiration in the supine and sitting body positions, respectively. The mean phase shift between systolic BP and RR interval in the low frequency band was found between 83 and -109 degrees for body positions and respiration regimes. The actual baroreflex related time lag between systolic BP and RR variations was found between 3.5 and 5.1 seconds. The study concludes that the appropriate, and not always easy, selection of the frequency of maximum coherence between BP and HR oscillation is crucial for an accurate cross-spectral assessment of baroreflex sensitivity.     

Cardiovascular control and plasma catecholamines during rest and mental stress: effects of posture.

In order to understand the complex autonomic adjustments that occur during the psychological challenges of normal daily life, autonomic responses to psychological stress were studied by evaluating the effects of body posture on various indices of sympathetic and parasympathetic regulation during performance of a psychological task. Twelve male subjects were studied in various postures (supine, sitting and standing), and during performance of the Colour Word Test (CWT) when sitting and then when standing. This procedure was subsequently repeated in reverse order (first standing and then sitting) after 15 min of supine rest. Blood samples for assay of plasma catecholamines were obtained before and during each CWT. Spectral analysis of beat-to-beat variations of heart rate (HR) and blood pressure (BP) was applied in order to obtain non-invasive indices of sympathetic and parasympathetic regulation. HR, diastolic BP, mid-frequency band power (0.07-0.14 Hz) of HR and systolic BP, and plasma adrenaline and noradrenaline concentrations showed significant increases when changing from supine to sitting to standing posture, whereas high-frequency band power (0.15-0.50 Hz) of HR decreased in a posture-dependent fashion. In the sitting position, the CWT caused significant increases in HR, BP and plasma adrenaline levels, and decreased HR and BP variability indices. In the standing posture, the CWT responses differed significantly from those during sitting for HR (a mild decrease during standing), high-frequency band power of HR (decreased more while sitting), high-frequency band power of BP (decreased more while standing), and plasma adrenaline responses (larger during sitting). Posture-related differential effects were observed on indices of sympatho-adrenomedullary activation during performance of a psychological challenge, whereas indices of parasympathetic activity indicated primarily less vagolytic effects when the task was performed in the standing posture. Our findings therefore underline the complexity of the adjustments that occur in neurohumoral and haemodynamic parameters during the psychological challenges of daily life.