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.     

Afferent baroreflex dysfunction and age-related orthostatic hypotension.

1. To test the hypothesis that in apparently healthy elderly subjects with orthostatic hypotension there is afferent baroreflex dysfunction, cardiovascular and neurohumoral responses were measured after separate stimuli which activated baroreceptor (head-up tilt) and non-baroreceptor (cold stress, isometric exercise) afferent pathways. 2. In 15 healthy elderly control subjects blood pressure did not change with 60 degrees head-up tilting and there was a moderate increase in heart rate, whereas in 13 subjects with age-related orthostatic hypotension head-up tilting was associated with a marked fall in blood pressure but a similar heart rate response to that in the elderly control group. In contrast, both groups of subjects had similar blood pressure and heart rate responses to cold stress and sustained isometric exercise. 3. Nine subjects with autonomic neuropathy also showed a marked hypotensive response to head-up tilt, but produced no pressor response to cold stress or isometric exercise. 4. The plasma concentrations of noradrenaline, adrenaline and neuropeptide-Y-like immunoreactivity rose and that of atrial natriuretic peptide fell after head-up tilt in the study population as a whole. There were no significant differences between groups despite the much greater blood pressure drops in the subjects with autonomic neuropathy and in those with age-associated orthostatic hypotension. 5. The aorto-iliac pulse wave velocity index was significantly higher in subjects with age-associated orthostatic hypotension compared with that in control subjects. 6. The pattern of responses to the separate stresses observed in the group with age-associated orthostatic hypotension is characteristic and different from that in the elderly control subjects and the subjects with autonomic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute hemodynamic and humoral effects of metoclopramide on blood pressure control improvement in subjects with diabetic orthostatic hypotension

Metoclopramide (MCP), a dopaminergic antagonist, is effective in postural hypotension, but the mechanisms of action have not been well defined. We studied responses of mean arterial pressure (MAP), heart rate, cardiac output (CO), and total peripheral resistance (TPR) after 5 min of increasing degrees of head tilt (15 degrees to 90 degrees) before and after MCP (20 mg IV) in seven subjects with diabetic postural hypotension. Plasma renin activity (PRA) and plasma aldosterone levels (PA) were determined at each degree of tilt; responses to the cold pressor test were also assessed before and after MCP. Before MCP, the maximal degree of tilt tolerated was 75 degrees, while after MCP four subjects were able to support 90 degrees tilt. At 45 degrees tilt, the decreases in MAP were smaller after than before MCP (-7.6 +/- 3.3 and -28.1 +/- 8.5 mm Hg; means +/- SE). This was associated with responses of TPR to tilt after (from 18.6 +/- 2.6 to 24.0 +/- 3.9 arbitrary units [AU]) but not before (from 22.9 +/- 4.0 to 25.6 +/- 4.5 AU) MCP. Reductions in CO were of the same order before and after MCP. PRA responded to tilt better after than before MCP. Supine PA levels increased with MCP (delta PA = 5.4 +/- 0.7 ng/dl), but its response to tilt was unaltered. There were significant rises in MAP and HR during the cold pressor test after but not before MCP. Our data suggest that vasoconstriction is the main mechanism of MCP improvement in blood pressure response to an orthostatic stimulus in diabetic postural hypotension, possibly because of its antidopaminergic property.     

Orthostatic challenge reveals impaired vascular resistance control,but normal venous pooling and capillary filtration in familial dysautonomia

Patients with familial dysautonomia (FD) frequently have profound orthostatic hypotension without compensatory tachycardia. Although the aetiology is presumed to be sympathetic impairment, peripheral vascular responses to orthostasis have not been assessed. The aim of this study was to evaluate the control of vascular responses to postural stress in FD patients. Measurements of heart rate, blood pressure, cardiac stroke volume and cardiac output (CO), by impedance cardiography, and calf-volume changes, by impedance plethysmography, were taken from nine FD patients and 11 control subjects while supine and during head-up tilt. During leg lowering, we also assessed the venoarteriolar reflex by measuring skin red-cell flux. Head-up tilting for 10 min induced sustained decreases in mean arterial pressure in the FD patients, but not in the controls. Total peripheral resistance (TPR, i.e. mean arterial pressure/CO) increased significantly in the controls (39.8+/-6.8%), but not in the FD patients. Calf-volume changes during tilting, when normalized for the initial calf volume, did not differ significantly between the patients (4.62+/-1.99 ml.100 ml(-1)) and the controls (3.18+/-0.74 ml.100 ml(-1)). The vasoconstrictor response to limb lowering was present in the patients (47.7+/-9.0% decrease in skin red-cell flux), but was impaired as compared with the controls (80.7+/-3.4%) ( P <0.05). The impaired vasoconstriction during limb lowering and absent increase of TPR during tilting confirm that orthostatic hypotension in FD is due primarily to a lack of sympathetically mediated vasoconstriction without evidence of abnormally large shifts in blood volume towards the legs during orthostasis. This may be due, in part, to a preserved myogenic response to increased vascular pressure in the dependent vascular beds.     

Effects of octreotide on experimental neurogenic orthostatic hypotension in anaesthetized dogs

Summary— This paper investigates the effects of octreotide (0.1 mg/kg, subcutaneous) on cardiovascular adaptation during head-up tilt test in an experimental model of neurogenic orthostatic hypotension (OH) obtained by chronic sinoaortic denervation in anaesthetized dogs. Blood pressure (BP), heart rate (HR), spectral variability (Fast Fourier transformation on 512 consecutive points, Δt: 2 Hz) and plasma catecholamine levels were measured in a double blind cross-over randomized study versus placebo, in supine position and during a head-up tilt test (80°, 10 min) in six sinoaortic denervated and six control (normal) dogs. In normal dogs, head-up tilt test significantly increased HR and diastolic blood pressure (DBP). Plasma noradrenaline levels and energy of the low frequency band (40–150 mHz) of systolic blood pressure (SBP) significantly increased whereas the energy of the low frequency band of HR significantly decreased. Placebo and octreotide failed to modify supine and head-up tilt values of the measured parameters (except the value of low frequency band of SBP, which increased after octreotide). In sinoaortic denervated dogs, supine values of BP, HR and plasma noradrenaline levels were significantly higher than in controls whereas the energy of the low frequency spectral band of HR and SBP was similar to controls. Head-up tilt test induced a dramatic decrease in BP. HR, plasma noradrenaline levels and energy of the low frequency band of SBP and HR remained unchanged during head-up tilt tests. Neither supine nor head-up tilt values of these parameters were modified 45 min after octreotide or placebo administration. These results show that sinoaortic denervation is a reproducible model of OH characterized by a lack of activation of sympathetic efferent pathways during head-up tilt tests. Octreotide, at the dose used, remains ineffective to prevent the fall in BP under these experimental conditions.     

Upper limb exercise effect on tilt tolerance during orthostatic training of patients with spinal cord injury

Twelve male patients with traumatic spinal cord injury were randomly divided into a group of six experimental and six control subjects. All subjects were tilted from 0 degree to 70 degrees by 10 degrees increments at five-minute intervals until blood pressure dropped below 70/40, hypotensive symptoms appeared, or 70 degrees of tilt was achieved. The experimental subjects performed 60 active bilateral full-range forearm flexion and extension movements per minute during the first and third minute of each tilt angle. The control patients did not perform upper limb exercises during the same orthostatic training procedure. Blood pressure and pulse rate of all subjects were recorded prior to orthostatic training, during the training at specified intervals and posttraining on each day of testing and training. Total group response was quantitated by indicating the tilting protocol step at which subjects experienced orthostatic hypotension requiring termination of the test. All subjects significantly increased their tolerance of higher tilt angles by using this protocol, but there was no significant difference between the exercise group and nonexercise group with reference to tolerance to progressive vertical tilt (Mann-Whitney U test).     

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.     

Haemodynamic and neurohumoral responses in elderly patients with postural hypotension

Abstract. Haemodynamic and neurohumoral responses to head-up tilt were measured in 28 elderly patients with postural hypotension (EPPH) and 12 healthy elderly subjects (HE). There were no differences in catecholamines between the groups and only noradrenaline increased on tilt ( P < 0.001). Plasma renin activity and aldosterone were similar in HE and EPPH in the supine and tilt positions. In both groups vasopressin increases ( P =0.032), and plasma volume decreases were the same (P=0.673). Supine EPPH had higher heart rates ( P =0.019) but similar cardiac indices ( P = 0.621). Both had similar changes on tilting ( P =0.975 and P =0.341). Stroke volume decrease was higher in HE (35%) than EPPH (23%; P < 0.001). HE showed an increase in peripheral resistance on tilting with no change in EPPH ( P =0.005). EPPH had larger coefficients of variation for all variables. The differences in haemodynamic responses and the similarity of neurohumoral responses during tilting suggest end-organ failure in EPPH with individual variations. Postural hypotension in old age is not a single entity.     

Haemodynamic and neurohumoral responses in elderly patients with postural hypotension

Haemodynamic and neurohumoral responses to head-up tilt were measured in 28 elderly patients with postural hypotension (EPPH) and 12 healthy elderly subjects (HE). There were no differences in catecholamines between the groups and only noradrenaline increased on tilt (P less than 0.001). Plasma renin activity and aldosterone were similar in HE and EPPH in the supine and tilt positions. In both groups vasopressin increases (P = 0.032), and plasma volume decreases were the same (P = 0.673). Supine EPPH had higher heart rates (P = 0.019) but similar cardiac indices (P = 0.621). Both had similar changes on tilting (P = 0.975 and P = 0.341). Stroke volume decrease was higher in HE (35%) than EPPH (23%; P less than 0.001). HE showed an increase in peripheral resistance on tilting with no change in EPPH (P = 0.005). EPPH had larger coefficients of variation for all variables. The differences in haemodynamic responses and the similarity of neurohumoral responses during tilting suggest end-organ failure in EPPH with individual variations. Postural hypotension in old age is not a single entity.     

The effects of lower-extremity functional electric stimulation on the orthostatic responses of people with tetraplegia

OBJECTIVE: To determine whether application of functional electric stimulation (FES) to lower-limb muscles during postural tilting improves orthostatic tolerance in people with tetraplegia. DESIGN: A crossover design. SETTING: A rehabilitation hospital. PARTICIPANTS: Sixteen acute and chronic subjects with tetraplegia (15 men, 1 woman) with complete motor function loss at the C3-7 levels were recruited. Time since injury ranged from 2 to 324 months (mean, 118.9+/-104.2 mo). INTERVENTION: Subjects were tested on a progressive head-up tilting maneuver with and without the application of FES at 0 degrees , 15 degrees , 30 degrees , 45 degrees , 60 degrees , 75 degrees , and 90 degrees continuously for up to 1 hour. FES was administered to 4 muscle groups including the quadriceps, hamstrings, tibialis anterior, and gastrocnemius muscles bilaterally at an intensity that provided a strong, visible, and palpable contraction. This was to produce a muscle pumping mechanism during the tilting maneuver. MAIN OUTCOME MEASURES: Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, perceived presyncope score, and the overall duration of orthostatic tolerance, that is, the time that subjects could tolerate the tilting maneuver without developing severe hypotension or other intolerance symptoms. RESULTS: When the tilt angle was increased, the subjects' SBP and DBP tended to decrease, whereas the heart rate tended to increase in both testing conditions. Adding FES to tilting significantly attenuated the drop in SBP by 3.7+/-1.1 mmHg (P = .005), the drop in DBP by 2.3+/-0.9 mmHg (P = .018), and the increase in heart rate by 1.0+/-0.5 beats/min (P = .039) for every 15 degrees increment in the angle of the tilt. FES increased the overall mean standing time by 14.3+/-3.9 min (P = .003). CONCLUSIONS: An FES-induced leg muscle contraction is an effective adjunct treatment to delay orthostatic hypotension caused by tilting; it allows people with tetraplegia to stand up more frequently and for longer durations.     

Local and central orthostatic sympathetic reflexes in Raynaud's phenomenon

Finger and hand blood flow was measured by 133xenon washout technique during orthostatic manoeuvres in patients with primary Raynaud's phenomenon (PR), Raynaud's phenomenon secondary to generalized scleroderma (GS) and in healthy, cold-tolerant controls. When supine, finger and hand washout rates in PR were significantly elevated over that of controls and GS. A significantly decreased response to a 40-cm lowering of the hand (local vasoconstrictor response) was observed in PR and was found to be normal in GS. During head-up tilting to 45 degrees (central sympathetic stimulation), all three groups showed parallel responses. We conclude that no increased responses on local or central orthostatic sympathetic reflexes were seen in patients with Raynaud's phenomena. A generally increased sympathetic activity as pathophysiological background for the vasospastic attacks is not likely. However, the increased finger 'blood flow' observed in patients with primary Raynaud's phenomenon in the resting condition, which we interpret as a 'hyperaemic' state, might have influenced the orthostatic sympathetic responses.     

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.     

Blood flow in skeletal muscle of tetraplegic man during postural changes

Relative changes in blood flow and vascular resistance in arm and leg muscle during head-up tilt at 45 degrees were studied in eight patients with complete cervical spinal cord transection and in 13 healthy volunteers. Muscle blood flow was measured by the local 133Xe washout method. In forearm muscle kept at heart level blood flow remained constant in the tetraplegic patients during head-up tilt, in contrast to that seen in the normal subjects, where blood flow decreased by 30%. In the dependent leg muscle, head-up tilt caused a decrease in blood flow of 46% and 40% in the patients and normals, respectively. Abolition of the local veno-arteriolar axon reflex, by inducing local counter-pressure to prevent venous distension in the dependent leg muscle, reduced the decrease in blood flow to 24% and 23%, respectively. Thus, the vascular response to head-up tilt differed significantly in forearm muscle between the two groups, whereas no difference was seen in the leg muscle. The absence of the vasoconstrictor response in forearm muscle indicates that postural sympathetic reflexes to this region depend on sympathetic reflexes integrated in centres located rostrally to the spinal cord. The results further suggest that local veno-arteriolar axon reflexes as well as spinal reflexes contribute to the observed vasoconstriction in the leg muscle.     

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.     

Uncoupling protein 2 promoter polymorphism -866G/A affects peripheral nerve dysfunction in Japanese type 2 diabetic patients

OBJECTIVE: To determine genetic predispositions for diabetic polyneuropathy, we investigated the relationship between the -866G/A polymorphism of uncoupling protein (UCP) 2 and neurological manifestations in 197 type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first examined whether UCP2 mRNA had been expressed in the dorsal root ganglion (DRG) in four Long-Evans Tokushima Otsuka rats using RT-PCR and electrophoresis. Genotyping of UCP2 promoter polymorphism -866G/A was then performed in 197 unrelated Japanese type 2 diabetic patients, who were subjected to nerve conduction, quantitative vibratory perception, head-up tilt, and heart rate variability tests, by PCR restriction fragment-length polymorphism. The relationships between UCP2 genotype and various nerve functions were analyzed by uni- and multivariable analysis. RESULTS: Expression of UCP2 mRNA was confirmed in rat DRG. Multiple regression analysis clarified the hypothesis that the G/A + A/A genotype was significantly related to decreased motor nerve conduction velocity and impaired blood pressure maintenance on the head-up tilt test. Multiple logistic regression analysis revealed that the G/A + A/A genotypes are a significant risk factor for sensory nerve conduction slowing and orthostatic hypotension. CONCLUSIONS: UCP2 promoter gene polymorphism -866 G/A was significantly associated with nerve conduction slowing and vasomotor sympathetic functions. These findings suggest that the higher UCP2 activity related to the A allele has an energy-depleting effect on peripheral nerve function in type 2 diabetic patients.     

Cardiovascular reflex responses in patients with unexplained syncope

1. This study was undertaken to determine whether, in a group of patients complaining of recurrent syncopal attacks but with no apparent cause, there was evidence of abnormal cardiovascular reflex control. 2. The steady-state responses of blood pressure, heart rate and cardiac output to head-up tilting were determined in 67 patients using entirely 'non-invasive' methods. In some patients we also studied the immediate response of pulse interval to carotid baroreceptor stimulation by neck suction. 3. Two of the patients developed vasovagal attacks during the 20 min test period of head-up tilting. Eighteen others showed postural hypotension, defined as a fall in blood pressure to outside the limits of two SDS from the mean values of age-related control subjects. 4. Patients who showed postural hypotension had a mean fall in cardiac output significantly larger than that in age-related control subjects. Responses in the nonhypotensive patients did not differ significantly from controls. 5. Stimulation of carotid baroreceptors resulted in significantly smaller responses of pulse interval in the patients defined as having postural hypotension compared with the non-hypotensive patients and with the age-related control subjects. 6. In some of the patients who did not show postural hypotension during the standard test, the duration of tilt was prolonged for up to 1 h. Five out of 26 patients developed vasovagal attacks. All the vasovagal patients showed an initial tachycardia and the response of pulse interval to neck suction was significantly larger than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular response during head-up tilt in chronic fatigue syndrome

This study examined the cardiovascular response to orthostatic challenge, and incidence and mechanisms of neurally mediated hypotension in chronic fatigue syndrome (CFS) during a head-up tilt test. Stoke volume was obtained by a thoracic impedance cardiograph, and continuous heart rate and blood pressure were recorded during a 45-min 70° head-up tilt test. Thirty-nine CFS patients and 31 healthy physically inactive control subjects were studied. A positive tilt, i.e. a drop in systolic blood pressure openface> 25 mmHg, no concurrent increase in heart rate and/or development of presyncopal symptoms, was seen in 11 CFS patients and 12 control subjects (P>0·05). During baseline and the first 5 min of head-up tilt, CFS patients had higher heart rate and smaller pulsatile-systolic area than control subjects (P<0·05). Among subjects who completed the test, those with CFS had higher heart rate and smaller stroke volume (P<0·05) than corresponding control subjects. When comparing those who had a positive test outcome in each group, CFS patients had higher heart rates and lower pulse pressure and pulsatile-systolic areas during the last 4 min before being returned to supine (P<0·05). These data show that there are baseline differences in the cardiovascular profiles of CFS patients when compared with control subjects and that this profile is maintained during head-up tilt. However, the frequency of positive tilts and the haemodynamic adjustments made to this orthostatic challenge are not different between groups.     

Spectrum of autonomic cardiovascular neuropathy in diabetes

OBJECTIVE: Diabetic patients with incapacitating orthostatic hypotension can have either a "hyperadrenergic" or "hypoadrenergic" presentation. Although the latter is related to overt autonomic neuropathy, the former is proposed to be explained by appropriate autonomic responses. We hypothesize, however, that both conditions are part of a spectrum of autonomic dysfunction. RESEARCH DESIGN AND METHODS: We studied 16 consecutive diabetic patients with preserved renal function referred for incapacitating orthostatic hypotension and characterized their autonomic and neurohumoral cardiovascular regulation. RESULTS: Six patients had a hyperadrenergic orthostatic response: systolic blood pressure fell 42 +/- 15 mmHg, heart rate increased 20 +/- 3 bpm, and plasma norepinephrine increased from 340 +/- 80 to 910 +/- 100 pg/ml. Ten patients had a hypoadrenergic response: systolic blood pressure fell 78 +/- 5 mmHg, heart rate increased only 7 +/- 3 bpm, and norepinephrine increased only from 130 +/- 28 to 230 +/- 40 pg/ml. Vagal (sinus arrhythmia, Valsalva ratio) and sympathetic (response to hyperventilation, postprandial hypotension) responses were impaired in both groups, but to a greater extent in the hypoadrenergic group. Notwithstanding severe orthostatic hypotension, the postural increase in plasma renin was blunted in both groups, more so in the hypoadrenergic group. Despite preserved renal function, patients had mild anemia due to impaired erythropoietin release, as seen in primary cases of autonomic failure. CONCLUSIONS: Our results suggest that diabetic patients presenting with hyperadrenergic orthostatic hypotension have an initial stage of autonomic neuropathy, with overtly abnormal vagal function and early signs of sympathetic impairment. Furthermore, altered renin response can contribute to the patients' orthostatic hypotension.     

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.     

Usefulness of Plasma Catecholamines During Head-Up Tilt as a Measure of Sympathetic Activation in Vasovagal Patients

Vasovagal syncope is a common clinical disorder which has been traditionally related to a vasovagal reflex precipitated by an initial excess sympathetic stimulation. We hypothesized that the increase in plasma Catecholamines during head-up tilt is more accentuated in patients with tilt induced vasovagal syncope. To test this hypothesis, plasma Catecholamines were measured in supine posture and during head-up tilt in patients with a history suggestive of vasovagal syncope. Of these, 13 had a normal response to tilt (nonvasovagal group; age 41 ± 19 [SD]years) and 11 had a vasovagal response to tilt (vasovagal group; 39 ± 20 years). In the supine posture at rest, plasma epinephrine and norepinephrine were not significantly different between the nonvasovagal and the vasovagal groups (39 ± 28 ng/L vs 46 ± 38 ng/L, P = 0.5792, 335 ± 158 ng/L vs 304 ± 124 ng/L, P = 0.6007, respectively). Furthermore, the tilt induced changes in plasma epinephrine and norepinephrine were not different between the two groups (20 ± 20 ng/L vs 35 ± 55 ng/L, P = 0.3562, 264 ± 158 ng/L vs 242 ± 205 ng/L, P = 0.7724, respectively) suggesting that differences in the hemodynamic response to tilt are not predictable by the supine levels of circulating plasma Catecholamines, and that the extent of plasma catecholamines increase during tilt does not determine the hemodynamic outcome of the tilt test. Since orthostatic changes of plasma Catecholamines could be influenced by volume factors, we assessed plasma renin activity and aldosterone as surrogates of blood volume. Baseline plasma renin activity and aldosterone were not significantly different between the two groups. We conclude that inasmuch as plasma catecholamines reflect the status of sympathetic activity, our data do not support the hypothesis that accentuation of sympathetic activity precedes necessarily the tilt induced vasovagal syncope. However, one should take in consideration that multiple factors may influence catecholamine levels and catecholamines kinetics. A hyperresponsiveness of β-receptors to Catecholamines in patients with vasovagal syncope may be suggested but needs to be tested.