Terminal vessel hyperperfusion despite organ hypoperfusion in familial dysautonomia

Abstract

Patients with familial dysautonomia (FD) exhibit orthostatic hypotension as well as recumbent hypertension. In addition, during dysautonomic crises, patients have hypertensive blood pressure that is presumed to be secondary to episodic vasoconstriction, as well as swollen hands that are presumed to be secondary to vasodilatation. This discrepancy in vascular control is poorly understood, yet may provide insight into the pathophysiology of autonomic crises. To evaluate the pathological mechanisms of overall blood flow and end-organ perfusion, we assessed resting and post-ischaemic limb and skin blood flow in FD patients. In groups of 15 FD patients and 15 controls, we measured resting and post-ischaemic forearm blood flow using venous occlusion plethysmography, and superficial skin blood flow using laser Doppler flowmetry. At rest, arterial inflow was averaged from eight venous occlusion measurements and expressed as percentage volume change/min. Post-ischaemic plethysmographic inflow was determined from the peak influx during the first venous occlusion following 3 min of ischaemia. Transcutaneous forearm partial pressures of oxygen and carbon dioxide were monitored continuously. At rest, plethysmographic limb perfusion was lower in FD patients than in controls, while skin blood flow did not differ between the two groups. After ischaemia, hyperperfusion of the forearm and hand was less pronounced in FD patients than in controls, while skin blood flow was significantly higher in patients than in controls. Partial pressures of O(2) and CO(2) did not differ between the two groups. We conclude that the reduced overall limb perfusion in patients with FD is due to hypertension-induced structural changes to vessel walls, with an increase in resistance vessel rigidity. The exaggerated post-ischaemic skin perfusion in FD patients seems to be due to deficient sympathetic innervation of precapillary vessels and arteriovenous shunts and to denervation hypersensitivity of intradermal small nerve fibres. Both the reduced limb perfusion and the dysfunctional end-organ blood supply in FD patients are likely to be major contributors to the vasomotor instability observed in these subjects, particularly during periods of stress.

Effect of physical countermaneuvers on orthostatic hypotension in familial dysautonomia

“…The increase in cardiac output was presumably due to compression of splanchnic veins and arterioles, thus mobilizing the abdominal reservoir of blood and enhancing the venous return of blood to the heart [12]. The increased total peripheral resistance during squatting is consistent with findings in other patients with autonomic failure [5] and was probably a mechanical effect, because FD patients have impaired reflex peripheral vascular responses [7,17,18]. Since an absent peripheral vasoconstriction is the most important contributor to orthostatic hypotension in FD [7], we might expect that any maneuver that increases total peripheral resistance -like squattingwould be particularly valuable in these patients.…”

Head and Neck Cooling Decreases Tympanic and Skin Temperature, But Significantly Increases Blood Pressure

“…The laser probe emits a divergent narrow band light at a wavelength of approximately 780 nm with an intensity Յ0.8mW. 10 The volume measured in the skin is a hemisphere with an approximate radius of 1 mm. 10 However, the instrument does not measure perfusion in absolute values (mlϫmin…”

“…10 We recorded respiratory frequency using calibrated 2-belt chestabdomen inductance plethysmography (Respitrace Calibrator, Ambulatory Monitoring, Inc,) with 1 belt at the level of maximal thoracic and the other at maximal abdominal respiratory excursions. 11 Skin blood flow (SBF) was monitored at the right index finger pulp and the left cheek using laser Doppler flowmetry (Perimed).…”

Fludrocortisone in patients with familial dysautonomia

“…1). Over the entire study period, there was a significant difference in overall survival among the group on fludrocortisone alone, the group on fludrocortisone and midodrine, and the group on neither drug (logrank χ 2 = 30.69, p < 0.001 (median survival time for patients on fludrocortisone alone: 32.8 years; for patients on both drugs, 37.9 years; for patients on neither drug: 22 Fig. 2 presents the curves for the three groups; note cumulative survival is poorest when neither drug is used.…”