Altered activities of daily living and decreased work productivity secondary to pain on exposure to old, """"""""cold intolerance,"""""""" are a significant societal burden. A better understanding of the mechanisms of microvascular regulation will provide insight into cold intolerance and aid clinical management. The altered digital microvascular blood flow and cold intolerance seen after trauma or with vascular compromise occlusive, vasospastic, or vaso-occlusive disease) affects millions of people. The cold intolerance of Raynaud's disease and scleroderma preferentially affects woman of childbearing age; black women are affected more often than white women. Surgical peripheral sympathectomy, which appears to improve blood flow by interrupting sympathetic vasoconstrictor innervation, is used when less invasive treatment fails. Paradoxically, digital amputation results in complete sympathectomy and cold intolerance of the replanted digit. The mechanism(s) causing post-replantation vascular thermoregulatory abnormalities is not known, but supersensitivity of digital adrenergic receptors may be a partial explanation. This study hypothesizes that the digital microvascular responses to cold stress following complete sympathectomy differ functionally from those following peripheral sympathectomy. Specifically, the initial vasodilation following complete sympathectomy is replaced by vasoconstriction which results from an increased sensitivity of adrenergic receptors to agonist neurotransmitters. In contrast, this marked supersensitivity of adrenergic receptors does not follow peripheral sympathectomy. To test this hypothesis, a rabbit ear model has been developed in which chronic arterial pressure, auricular blood flow conductance, microvascular perfusion, and microvascular diameters can be monitored in awake, unanesthetized animals pre- and post-sympathectomy and while receptor agonist/antagonists are being manipulated. An acute rabbit ear preparation has also been developed to characterize adrenergic receptor subtypes participating in peripheral microvascular control by direct observation of the microcirculation during application of alpha-1 and alpha-2 agonists and antagonists. Five separate protocols will establish: l) the adrenergic receptor subtypes responsible for control of auricular blood flow, 2) the effect of sympathectomy on auricular conductance and microvascular dimensions, 3) the post-sympathectomy functional changes in receptor sensitivity, and 4) the identification of the receptor subtype having the maximal influence on functional supersensitivity. Together, these experiments will characterize the relationship between the adrenergic system and sympathectomy-related, cold-evoked vascular responses.
