Project: Research project

Project Details


The long range goal of the principal investigator is to examine mechanisms
that control peripheral blood flow. This proposal examines the arterial
chemoreflex (sympathoexcitatory), its modulation by the lung mechanoreflex
(sympathoinhibitory) and peripheral vascular effects of hypoxemia in
humans. Our hypotheses are that 1) During hypoxemia (with spontaneous
breathing) sympathetic vasoconstrictor traffic and norepinephrine (NE)
release from nerve terminals is increased, yet adrenergic vasoconstriction
does not occur and forearm vascular resistance decreases. The rise in
plasma NE is attenuated because NE clearance rises during hypoxemia. Using
a tritiated NE infusion technique, we will explore the mechanism of
increased NE clearance during hypoxemia. 2) The forearm vasodilation
observed during hypoxemia is not due to sympathetic neural withdrawal but
may be secondary to cholinergic vasodilation and/or local vasodilator
mechanisms. In experiments with intra-arterial infusion of atropine
(cholinergic blockade) and aminophylline (adenosine receptor blockade) we
will explore the mechanism(s) of vasodilation induced by hypoxemia. 3) The
sympathoinhibitory effect of ventilation is crucial in opposing
sympathoexcitation evoked by hypoxemia. We will measure muscle sympathetic
nerve activity (MSNA, peroneal microneurography) and forearm and skin blood
flow (plethysmography, laser Doppler velocimetry) to examine the effects of
altered breathing with/without simultaneous chemoreceptor stimulation. 4)
Periodic breathing, such as seen in patients with obstructive sleep apnea,
is accompanied by striking hemodynamic oscillations. Marked blood pressure
elevations occur immediately after apnea and may in part be mediated by
hypoxemia or absent lung mechanoreflex activity (apnea). To determine the
role of the sympathetic nervous system in this response, we will measure
MSNA during simulated apnea (voluntary breathholding), and apnea during
sleep (spontaneous). Periodic (Cheyne-Stokes) breathing is also very
common in heart failure, especially during sleep. If in heart failure,
hemodynamic oscillations similar to sleep apnea occur, these intermittent
increases in left ventricular afterload may further impair circulatory
function. To determine whether these reflexes are important in heart
failure, we will perform microneurography studies in these patients.

These studies will be conducted in an active clinical research environment
using a multidisciplinary approach. The findings will provide new insight
into mechanisms of circulatory control and may have important implications
in disease.
Effective start/end date7/1/926/30/97


  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute


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