BEHAVIORAL TREATMENT OF RAYNAUD'S PHENOMENON

我们最近证明了雷诺氏病的血管痉挛发作 尽管数字神经被封锁，但仍可引发疾病，而且局部 降温可增加未发现的α-肾上腺素能反应性 在正常志愿者中。为了更准确地确定该病的病因 原发性雷诺氏病，有必要确定是否 α1受体和/或α2受体的异常 血管痉挛发作所必需的。我们建议 通过动脉内注入一种α1拮抗剂来研究这个问题， 一个alpha2拮抗者，两个拮抗者都在用 环境和局部降温(研究1)。自我们的调查以来 到目前为止使用的合成肾上腺素能药物，重要的是要确定 这种内源性血管收缩化合物参与了雷诺氏病的发作。 由于去甲肾上腺素在外周血管中的效力很高 肾上腺素受体，我们建议研究它在冷却和非冷却条件下的作用。 雷诺病患者和对照组的手指(研究2)。 我们已经发现阿尔法肾上腺素能受体的异常。 雷诺病患者，最近表现为家族性 这种混乱的集合。因为阿尔法肾上腺素能受体 基因控制，我们建议看看这些基因的突变是否 与雷诺病的发生有关(研究5)。 我们已经证明，反馈诱导的血管扩张部分是通过 一种非神经性β-肾上腺素能血管扩张机制 血浆儿茶酚胺的变化。Aβ-肾上腺素能血管扩张剂 与反馈诱导血管扩张具有相同时程的机制 最近在血管内皮细胞上被证实。我们建议 确定血管内皮细胞参与反馈诱导 使用一种特定抑制内皮的化合物进行血管扩张- 介导的血管扩张(研究3)。 尽管关于温度生物反馈的研究很多，但很少有人做过。 与之相关的大脑机制。一种新的磁共振成像(MRI) 该方法允许无创测量脑血流量 极佳的空间和时间分辨率。我们建议测量大脑 体温反馈训练前后磁共振血流的变化 可靠的控制程序(研究4)。

We have recently demonstrated that the vasospastic attacks of Raynaud's disease can be provoked despite digital nerve blockade and that local cooling produces increases in alpha-adrenergic responsiveness not found in normal volunteers. To more precisely determine the etiology of primary Raynaud's disease, it is necessary to determine whether abnormalities of alpha1 receptors, alpha2 receptors, or both are necessary for the occurrence of a vasospastic attack. We propose to examine this question by infusing intraarterially an alpha1 antagonist, an alpha2 antagonist, and both antagonists while provoking attacks with environmental and local cooling (Study 1). Since our investigations have thus far utilized synthetic adrenergic drugs it is important to determine the endogenous vasoconstrictive compound involved in Raynaud's attacks. Since norepinephrine is highly potent at peripheral vascular adrenoceptors, we propose to study its effects in cooled and uncooled fingers of Raynaud's disease patients and controls (Study 2). We have identified abnormalities of alpha-adrenergic receptors in Raynaud's disease patients and have recently demonstrated familial aggregation of this disorder. Since alpha-adrenergic receptors are under genetic control, we propose to see if mutations of these genes are involved in the occurrence of Raynaud's disease (Study 5). We have shown that feedback-induced vasodilation is mediated in part by a nonneural beta-adrenergic vasodilating mechanism and not through changes in plasma catecholamines. A beta-adrenergic vasodilating mechanism having the same time course as feedback-induced vasodilation has recently been demonstrated on vascular endothelium. We propose to determine the involvement of vascular endothelium in feedback-induced vasodilation using a compound that specifically inhibits endothelium- mediated vasodilation (Study 3). Despite much research on temperature biofeedback, little has been done on the brain mechanisms involved. A new MRI (magnetic resonance imaging) method permits the noninvasive measurement of brain blood flow with excellent spatial and temporal resolution. We propose to measure brain blood flow by MRI before and after training in temperature feedback or a credible control procedure (Study 4).