Orthostatic intolerance and the postural tachycardia syndrome: genetic andenvironment pathophysiologies

Orthostatic intolerance is a common problem for inbound space travelers. Th ere is usually tachycardia on standing but blood pressure may be normal, lo w or, rarely, elevated. This condition is analogous to the orthostatic into lerance that occurs on Earth in individuals with orthostatic tachycardia, p alpitations, mitral valve prolapse, and light-headedness. Our studies durin g the Neurolab mission indicated that sympathetic ner-ve traffic is raised in microgravity and that plasma norepinephrine is higher than baseline supi ne levels but lower than baseline upright levels. A subgroup of patients wi th familial orthostatic intolerance differ from inbound space travelers in that they have an alanine-to-to-proline mutation at amino acid position 457 in their norepinephrine transporter gene. This leads to poor clearance of norepinephrine from synapses, with consequent raised heart rate. Clinical f eatures of these syndromes are presented.