Pathophysiological basis of orthostatic hypotension in autonomic failure

Abstract

Patients with autonomic failure may be seriously incapacitated in activities of daily living due to orthostatic hypotension. Their low blood pressure is ascribed to a defective increase in arterial resistance and an excessive venous pooling upon standing. Effective pharmacological treatment is now available, but may aggravate supine hypertension and have other undesirable effects. Additionally, pharmacological treatment is less successful for hypotension with physical exercise or in warm surroundings (Bannister & Mathias, 1992). Non-pharmacological measures are regarded as a cornerstone in the treatment of orthostatic hypotension. These measures consist of chronic expansion of the extracellular volume or reducing the vascular volume in which pooling occurs (Bannister & Mathias, 1992). The latter includes protective measures like physical countermanoeuvres which can be applied by those patients with no major additional neurological and musculo-skeletal disorders, and external support garments which can be recommended to all patients. We reasoned that selection and use of appropriate protective measures would be facilitated by understanding the fundamental physiological mechanisms that prevent excessive orthostatic pooling in healthy subjects, why these mechanisms fail in patients with autonomic failure, and how these protective measures work. Therefore we reviewed the literature and summarized the available data about the amount and location of venous pooling in patients with autonomic failure and the effectiveness of physical countermanoeuvres and external support garments.

Lower vascular tone and larger plasma volume in Parkinson's disease with orthostatic hypotension

“…A lack of appropriate leg vasoconstriction seems, therefore, to play an important role in the pathophysiology of OH in PD, especially in combination with the lower basal leg vascular resistance in PD ϩ OH. A larger calf volume increase is associated with a larger decrease in venous return and, thereby, can contribute to OH (42). In contrast, during 60°head-up tilt the calf volume increase was lower in PD ϩ OH compared with controls and tended to be lower compared with PD Ϫ OH.…”

“…During orthostatic challenges an immediate drop in blood pressure is sensed by baroreceptors. This increases heart rate, cardiac contractility, and peripheral vascular resistance via an increase in sympathetic outflow and a decrease in vagal-nerve activity (12,42). One previous study measured local vascular resistance of the anterior tibial muscle and subcutaneous tissue of the calf in PD ϩ OH during 45°head-up tilt using the 133-xenon washout method, but did not find a significant increase (5).…”

Reliability of orthostatic beat-to-beat blood pressure tests: implications for population and clinical studies

“…These fluctuations are thought to arise from internal and external sources including changes in neurohormonal activity [25], circulating volume [26], changes in sympathetic and parasympathetic activity [8], and environmental effects [11]. Furthermore the active stand response is under the influence of a number of additional factors including self-selected speed of standing, muscle pump activation [27], movement artefact [16], time of day [28] and other experiment effects (e.g. observer) which are likely to further effect the repeatability of measurements.…”

Identical pattern of cerebral hypoperfusion during different types of syncope

“…For example, changes in systemic vascular resistance and cardiac output are not exclusive compensatory mechanisms. 19,20 A fall in systemic vascular resistance in the splanchnic bed might result in translocation of blood to the venous system and a consequential decrease in cardiac output; thereby these responses may interact in an attempt to prevent syncope. Thus, arteriolar dysfunction might underlie, in part, what the earlier authors 6,14,15 have classified as 'venular dysfunction'.…”

“…Furthermore, arterial BP does not necessarily reflect the cerebrovascular phenomena associated with syncope. 3 A more fundamental issue with this classification system is that it oversimplifies the complex physiology of orthostatic BP regulation: 19,20 (see Discussion). Therefore, the main aim of this study was to provide a comprehensive examination of the cardiorespiratory and cerebrovascular changes associated with the previously reported classification of syncope.…”