Postural Fall In Blood Pressure Research Articles

New autonomic and sensory neuropathy with loss of adrenergic sympathetic function and sensory neuropeptides

A 30-year-old woman with longstanding dizziness was found to have a severe postural fall in blood pressure and a reduced skin axon-reflex flare response. Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma noradrenaline, adrenaline, dopamine, and dopamine beta hydroxylase were undetectable. Skin biopsy specimens showed loss of tyrosine hydroxylase and neuropeptide Y (markers of adrenergic sympathetic fibres) and of substance P and calcitonin gene-related peptide (sensory neuropeptides). A sural nerve biopsy specimen showed severe depletion of unmyelinated fibres. The constellation of losses were compatible with nerve growth factor (NGF) deprivation, which was confirmed on assay. This new syndrome may be explained by loss of trophic action of NGF.

Diabetic autonomic neuropathy

One of the earliest manifestations of diabetic neuropathy is denervation of the cardiovascular system; loss of heart rate variability may have a prevalence as high as 21.5% in diabetic patients, and declines at 1 beat/min/year, which is 3 times faster than in normal subjects. The cause of this neuropathy is unknown: attempts at decreasing the excess quantities of sorbitol, glucose and fructose in nerve tissue have lead to little functional improvement in man. Nerve ischaemia and immunological damage have stimulated increased interest lately, the latter particularly because of the structural homology of nerve growth factor and insulin. Symptoms from autonomic neuropathy are rare. When present they may well be intermittent, but never remit; they rarely progress or become disabling. One uncommon consequente of loss of sympathetic vascular tone is postural hypotension. This may result from failure of splanchnic vasoconstriction on standing. Food and insulin can greatly exacerbate the postural blood pressure fall. Reduced vascular tone in the neuropathic foot leads to increased arterio-venous shunt flow. The local reflex control of this shunt flow is also abnormal: paradoxical vasoconstriction occurs in response to local skin heating and postural reflexes are reduced. This high shunt flow together with its abnormal vascular control may be important in the pathogenesis of neuroarthropathy and foot ulceration. The prognosis of patients with autonomic neuropathy is better than previously reported. Abnormal heart rate variability alone is of no prognostic value. The presence of symptoms, in particular postural hypotension, significantly reduces survival. The majority of deaths however, result from concurrent renal disease and macrovessel atheroma.

Potassium Supplementation in the Treatment of Idiopathic Postural Hypotension

We studied the effects of potassium supplementation (60 mmol/day) and matching placebo on the postural blood-pressure fall in ten elderly patients with symptomatic idiopathic postural hypotension in a double-blind, randomized cross-over trial. There was a significant decrease in the orthostatic fall in systolic blood pressure (SBP 33 +/- 5 mmHg to 16 +/- 9 mmHg, p less than 0.01) and in supine SBP (162 +/- 7 to 150 +/- 7 mmHg, p less than 0.01) between placebo and potassium phases. Supine diastolic and erect blood pressures were unchanged, though pulse rate showed a greater orthostatic increase (7 +/- 3 beats/min to 14 +/- 2 beats/min, p less than 0.05) following potassium therapy. No significant changes were seen in intracellular electrolytes, plasma renin activity, aldosterone levels or body weight. Seven patients reported symptomatic improvement with potassium, but none during the placebo phase. Potassium therapy was well tolerated and may be a successful and safe method of treating idiopathic postural hypotension.

AUTONOMIC DYSFUNCTION AT DIFFERENT AMBIENT TEMPERATURES IN INFANTS AT RISK OF SUDDEN INFANT DEATH SYNDROME

Autonomic function was assessed by measuring the heart rate and blood pressure responses to a change from the horizontal to upright posture at various ambient temperatures in four groups of infants aged 8-12 weeks: 30 infants who had suffered a well-defined unexplained apparent lifethreatening event (ALTE); 8 infants who had suffered a cyanotic attack; 24 healthy infants with a sibling who had died from sudden infant death syndrome (SIDS); and 17 healthy infants. Autonomic dysfunction was uncommon in the control group; no infant showed an abnormal heart rate response to postural change (R to R interval maximum/ minimum ratio less than 1·0) and a postural fall in blood pressure of greater than 10% occurred in only 1 infant. In contrast, in the ALTE group 9 of 26, 9 of 30, and 4 of 22 infants showed an abnormal heart rate response and 20 of 26, 14 of 30, and 10 of 22 a greater than 10% fall in blood pressure on postural change at 20°C, 25°C, and 30°C, respectively. 1 ALTE infant died of SIDS 14 h after showing an RR max/min ratio of 0·8 and a postural fall in blood pressure of 11% and 14% at 20°C and 30°C. Autonomic function testing should become part of the clinical evaluation of infants at high risk of a sudden unexpected death.

The time course and diurnal variation of postural hypotension in diabetic autonomic neuropathy.

Nine diabetic patients (age range 23-67y) with autonomic neuropathy and symptomatic postural hypotension were studied. The time course of the postural drop in blood pressure (BP) was documented firstly at 0900h, prior to breakfast and insulin, and secondly in the afternoon. Seven patients were symptomatic in the morning but only one in the afternoon. The systolic nadir in the morning was lower (p less than 0.02) than in the afternoon. The mean systolic pressure in the first 3 min after standing was no different in the afternoon but it was lower in the 2nd (p less than 0.05), 3rd (p less than 0.02), and 4th (p less than 0.02) 3-min intervals in the afternoon. The time taken to reach the systolic nadir was variable, ranging from 1-12 min. It is concluded that the assessment of the postural fall in BP may be underestimated if measured immediately after standing or if it is measured in the afternoon.

Oesophageal function in diabetes mellitus and its association with autonomic neuropathy.

We have evaluated oesophageal function in 34 diabetics and in 16 non-diabetic controls by a timed bolus transit method derived from dynamic oesophageal scintiscans (water transit time: WTT) and barium swallow. The diabetics were screened for autonomic neuropathy using standard cardiovascular responses and 10 patients were classified as abnormal. WTT was significantly prolonged in autonomic neuropaths compared with other diabetics (p less than 0.01) and controls (p less than 0.001). Abnormal peristalsis on barium swallow was seen more frequently in autonomic neuropaths (9/10) than in other diabetics (11/24, p less than 0.002). WTTs from all diabetic patients correlated with abnormal heart rate responses at rest (Rs = - 0.49, p less than 0.005), on deep inspiration (Rs = -0.48, p less than 0.005), and on standing (Rs = -0.39, p less than 0.025) but not with the Valsalva manoeuvre. A weaker correlation was found between the postural fall in blood pressure (Rs = 0.3, p less than 0.05). Diabetics with autonomic neuropathy frequently have asymptomatic oesophageal dysfunction which may result from a vagal neuropathy in view of its association with abnormalities of vagally mediated cardiovascular responses.

Urinary electrolyte excretion and orthostatic response of blood pressure and plasma renin activity in children with postural hypotension before and after treatment with Dihydergot.

Na and K metabolism, and orthostatic response of blood pressure and plasma renin activity (PRA) were studied in six children, aged 10 to 15 years, with postural hypotension before and after treatment with Dihydergot (DHE). All abnormal findings which we had already observed in children with postural hypotension (i.e. low fractional excretion of filtered Na in spite of low PRA, extremely high PRA on fainting, great postural fall in blood pressure, and so on) improved on treatment with DHE. This suggests that these abnormal physiological findings found in children with postural hypotension may result from increased venous pooling which can be reduced by DHE. Consequently, DHE seems an excellent drug to treat postural hypotension from the physiological point of view.

Immediate cardiovascular responses to oral prazosin--effects of concurrent beta-blockers.

Initiation of prazosin therapy may be complicated by the first-dose response of acute postural hypotension and tachycardia. The effects of beta-blocker on the responses to oral prazosin were studied in eight normotensive men. After 1 mg oral prazosin there was a marked postural fall in blood pressure to a lowest mean standing systolic pressure of 88 +/- 7 mm Hg (mean +/- SD), associated with a tachycardia of 117 +/- 13 bpm, and an increase in mean plasma norepinephrine concentration to 9.6 +/- 7.9 nmole/l. There was a linear relationship (r = 0.93) between plasma prazosin concentration and hypotensive effect. Concurrent propranolol 80 mg or primidolol 100 mg (a cardioselective beta-blocker) increased the severity and duration of the postural hypotensive response, with lowest mean systolic blood pressure (BP) of 79 +/- 7 and 75 +/- 9 mm Hg. There was no effect on the orthostatic release of norepinephrine but there was attenuation of the postural tachycardia. Concurrent beta-adrenergic blocking therapy, selective or nonselective, intensifies the immediate postural hypotensive response to the initial dose of prazosin.

Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications.

Cardiovascular effects of diabetic autonomic neuropathy include postural hypotension, resting tachycardia, and, possibly, painless myocardial infarction. Involvement of cardiovascular reflexes in diabetes can be assessed using simple noninvasive tests: the Valsalva maneuver, beat-to-beat heart rate variation, the heart rate response to standing, postural fall in blood pressure, and the sustained handgrip test. Tests of parasympathetic function appear to be abnormal more frequently and earlier in cardiac autonomic involvement, whereas sympathetic damage usually occurs later and is associated with clinical symptoms. When test results are abnormal, in association with symptoms suggestive of autonomic neuropathy, the prognosis is grave. Some sudden deaths that occur may be due to abnormal autonomic reflexes.

PRESSOR AMINES AND MONOAMINE-OXIDASE INHIBITORS FOR TREATMENT OF POSTURAL HYPOTENSION IN AUTONOMIC FAILURE: Limitations and Hazards

The short-term effects of pressor amines were investigated in four patients with postural hypotension caused by autonomic failure. In supine patients p-tyramine alone or with a monoamine-oxidase inhibitor produced pronounced supine hypertension without abolishing the symptoms associated with a postural fall in blood-pressure. Phenylephrine or ephedrine maintained a normal blood-pressure on standing but caused supine hypertension. Thus the effects of p-tyramine with or without a monoamine-oxidase inhibitor were unpredictable and did not include relief of postural hypotension. Phenylephrine or ephedrine had some beneficial effect, but since all these drugs influence standing pressure only at the expense of pronounced supine hypertension, alternative therapy must be sought.

Peripheral motor nerve function in diabetic autonomic neuropathy.

Motor conduction velocity was measured in the median, ulnar and common peroneal nerves of 32 diabetics with clinical features of autonomic neuropathy. The responses to the Valsalva manoeuvre and sustained handgrip, and the postural fall in blood pressure were used to assess the integrity of the autonomic nervous system. Abnormalities in the three autonomic function tests were significantly correlated with the forearm conduction velocity of the ulnar nerve, the conduction velocity and motor latency of the common peroneal nerve, and the H reflex. These results show that, in diabetics with autonomic neuropathy, abnormalities in the autonomic nervous system parallel changes in the peripheral nerves. Any diabetic with peripheral neuropathy should be examined for evidence of autonomic nervous system involvement.