Abnormalities in reflex control of the circulation in familial dysautonomia: Effects of changes in posture on venous and arterial constriction in normal subjects and in patients with dysautonomia

Abstract

This study was designed to elucidate the mechanisms responsible for the severe orthostatic hypotension and other impairments of circulatory regulation that occur in patients with familial dysautonomia. The effects of changes in posture and of immersing the hand in ice water on the dynamics of the arterial and venous beds of the forearm and on total peripheral vascular resistance were compared in five patients with dysautonomia and in eight normal subjects. Forearm blood flow was measured with a strain gauge plethysmograph, and venous tone was determined by an acute venous occlusion technic, in which increment changes of forearm venous pressure and volume were related. In normal subjects, tilting to a 45 degree head-up position did not alter arterial pressure, decreased forearm blood flow (−47 per cent) and cardiac output (−15 per cent), and increased venous tone (+53 per cent), forearm vascular resistance (+88 per cent) and total vascular resistance (+19 per cent). In contrast, in patients with dysautonomia, forearm blood flow and venous tone remained unchanged, whereas arterial pressure fell (−47 per cent), as did cardiac output (−33 per cent), forearm vascular resistance (−24 per cent) and total vascular resistance (−21 per cent). The reflex elevations of arterial resistance and venous tone which occurred during cold stimulation in normal subjects also were absent in the patients with dysautonomia. It is concluded that reflex venous and arteriolar constriction are necessary for the normal maintenance of cardiac output and arterial pressure in the upright position, and that the absence of these reflexes in patients with dysautonomia is responsible for the marked impairment of their postural adjustments, leading to syncope, a hallmark of the disease.