ABSTRACT
Blood pressure in patients with progressive autonomic failure falls during salt restriction or orthostasis. We contrasted the regulation of plasma volume in patients with progressive autonomic failure with that of controls to determine whether hypovolemia contributes to this hypotension. When sitting, the plasma volume (measured from distribution of human serum albumin) was normal. During 1 week of low Na+ intake, patients with progressive autonomic failure lost three times as much body weight as controls; however, changes in plasma volume were strictly comparable. Therefore, the extra fluid lost in the patients must have derived primarily from the interstitial space. During alteration in Na+ intake, mean blood pressure values were closely related to plasma volume in the patients (r = 0.80, p less than 0.01) but not in controls. Changes in plasma volume in the head-up tilt position were assessed from the hematocrit values. During tilting, the blood pressure in controls was unchanged, but their plasma volume fell by 10.3% +/- 1.8% (p less than 0.001). In contrast, the mean blood pressure of the patients with progressive autonomic failure fell by 40 +/- 6 mm Hg; yet, their plasma volume was unchanged. Thus, in progressive autonomic failure, plasma volume measured during sitting is normal, but dynamic regulation of plasma volume during salt restriction or orthostasis is abnormal and hypovolemia is offset by partitioning of interstitial fluid into the plasma. Also, because the blood pressure is unusually dependent on volume, this fluid redistribution could be an important defense against severe hypotension in patients lacking cardiovascular reflex control.
Subject(s)
Multiple Organ Failure/physiopathology , Plasma Volume/drug effects , Sodium/pharmacology , Adult , Aged , Blood Pressure , Body Weight , Diet, Sodium-Restricted , Extracellular Space , Female , Hematocrit , Humans , Hypotension, Orthostatic/etiology , Male , Middle Aged , PostureABSTRACT
UNLABELLED: We showed previously that patients with progressive autonomic failure with multiple system atrophy (MSA) failed to excrete a water load while they were standing, suggesting abnormal postural regulation of vasopressin release. The rise of plasma arginine vasopressin (AVP) with upright posture is modulated by central dopamine and opioid receptors. Patients with MSA may have depletion of brain dopamine and opioid peptides. We measured the plasma levels of AVP in patients with MSA and control subjects during postural stimulation by head-up tilt and the inhibition of this rise in AVP by L-DOPA (dopamine precursor) and naloxone (opiate antagonist). Since L-DOPA and naxolone can alleviate hypotension, we also studied the effects of these agents on orthostatic hypotension. Plasma AVP concentration of normal subjects rose progressively over 90 min of head-up tilt and this postural rise in AVP was abolished by L-DOPA and naloxone. Patients with MSA had similar levels of AVP while horizontal. However, they showed a severely blunted postural AVP response since their levels rose to only 10 per cent of the rise in the normal subjects despite the additional stimulus to AVP secretion of considerable postural hypotension. They also showed no inhibition of AVP secretion by L-DOPA or naloxone. Naloxone did not alter the blood pressure of either group. Although L-DOPA did not change the blood pressure of normal subjects, it lowered it in patients with MSA both while they were horizontal and tilted. IN CONCLUSION: (1) the postural stimulation of AVP release is blunted in MSA; (2) this postural rise in AVP is not inhibited by a dopamine agonist or opioid antagonist in MSA suggesting loss of dopaminergic and opioid pathways involved in AVP release; (3) endogenous opioids do not contribute to orthostatic hypotension in MSA; (4) patients with MSA are supersensitive to the hypotensive effects of an acute L-DOPA infusion.
Subject(s)
Arginine Vasopressin/blood , Autonomic Nervous System Diseases/drug therapy , Hypotension, Orthostatic/drug therapy , Levodopa/therapeutic use , Naloxone/therapeutic use , Aged , Arginine Vasopressin/physiology , Autonomic Nervous System Diseases/therapy , Female , Humans , Hypotension, Orthostatic/therapy , Male , Middle Aged , Physical Stimulation , PostureABSTRACT
Resting ECGs were recorded in 29 patients with angina pectoris before, during and after treatment with prenylamine 180 mg daily. The QT interval became significantly prolonged after one week of treatment. The prolongation persisted as long as therapy was continued, which was up to 6 months. After withdrawal of treatment the QT interval returned to normal within 2 weeks. In this study no serious problems were encountered by those patients in whom the QT interval was prolonged.
