PERIPHERAL VASCULAR DISEASES 



1229 



and there may be reflux of blood from the venules 

 into the capillaries. The transient cyanotic reaction 

 in Raynaud's disease is similar to the more nearly 

 permanent cyanosis of acrocyanosis in which second- 

 ary dilatation of capillaries and venules results from 

 arteriolar spasm (3). During the erythematous phase, 

 capillary pulsations may be detected. It should be 

 recalled that in Raynaud's disease the vessels supply- 

 ing the hand (radial and ulnar) are normal and 

 continue to pulsate normally during the crises. 



The main controversy remains concerning the 

 initial basic defect in Raynaud's disease, that is, 

 whether or not it is in the nervous system or in the 

 vessel wall itself. Certainly in advanced stages the 

 easily demonstrable intimal thickening and throm- 

 bosis of the vessels contribute significantly in reducing 

 blood flow. It is probable that a vicious cycle is 

 induced whereby repeated vasospastic attacks cause 

 increasing injury and structural changes in the 

 digital vessels which then become more vulnerable 

 to vasospastic influences (60). Nevertheless, the 

 important pathogenic factors in the early stages are 

 still not known and very little recent definitive 

 research in this area has been reported. 



Some recent studies, however, are of interest. 

 Using chromatography and biologic assay, Peacock 

 (70) determined the concentrations of epinephrine 

 and norepinephrine in the peripheral venous blood 

 collected at the wrist in a group of normal subjects 

 and in a group of patients with primary Raynaud's 

 disease. He found that under warm resting environ- 

 mental conditions, the Raynaud's patients showed a 

 significantly higher blood level of these amines than 

 did the normal subjects. Following sympathetic 

 nervous stimulation by cold, the patients with 

 Raynaud's disease had an increase primarily of the 

 norepinephrine fraction. This increase varied directly 

 with the clinical severity of the disease. Peacock con- 

 sidered the high concentrations of these amines to 

 be due to an abnormality in metabolism of these 

 substances. It was noted that in Raynaud's disease 

 the average digital cutaneous temperature in a room 

 temperature of 20 C ± 5 was 22.3 C compared with 

 30.2 C for the normal subjects. Similar differences 

 had been reported for environmental temperatures 

 as high as 25 C. It was reasoned that over this range 

 of temperature, due to precooling of blood by counter- 

 current flow mechanisms, the intraluminal temper- 

 ature of the blood in the digital arteries of patients 

 with Raynaud's disease was probably considerably 

 lower than that seen in normal control subjects. Thus, 

 it was concluded that the lower temperature inhibited 



enzyme systems which inactivate epinephrine and 

 norepinephrine and that this was responsible for the 

 higher concentrations of the vasoconstrictor sub- 

 stances and the intense peripheral vasoconstriction. 

 In this respect monoamine oxidase activity of digital 

 arteries of two patients with Raynaud's disease was 

 absent, whereas that of two normal subjects was found 

 to be 552 ii\ 2 per g per hour. 



These studies are interesting but many questions 

 remain unanswered. For example, the effect of 

 reduced blood flow per se on the concentrations of 

 amines in the venous blood draining these areas is 

 not known. Concentrations may be greater but the 

 total amount may be the same or less. Further, with 

 respect to these amines, the relative contributions of 

 a) increased amount in stores, b) increased release 

 from stores, c) decreased destruction, d) impeded 

 physical removal, and e ) increased vascular sensitivity- 

 are also unknown. Furthermore, the role played by 

 reduced formation of vasodilator metabolites from 

 cooled tissues [as proposed by Freeman (27, 28) and 

 later by Perkins et al. (71)] in the pathophysiology of 

 Raynaud's disease needs investigation. 



Recently, Mendlowitz & Naftchi (61) have reported 

 observations on digital blood pressure (Gaertner 

 capsule) and digital blood flow (calorimetry) in 20 

 patients with primary or idiopathic Raynaud's 

 disease. The patients were studied at rest, under 

 standardized conditions, before and after vasodilata- 

 tion (reflex vasodilatation) and after vasoconstriction 

 produced by infused /-norepinephrine. After appro- 

 priate calculations, they noted that their patients 

 fell into two groups: /) those with digital vascular 

 obstruction and normal vasomotor tone, and 2) 

 those without obstruction but with heightened vaso- 

 motor tone. Neither group showed increased sensitiv- 

 ity to norepinephrine. Thus, the authors suggested 

 that the digital vasospastic crises in Raynaud's 

 disease could be produced either by vascular obstruc- 

 tion acted upon by normal vasomotor tone, or by 

 heightened vasomotor tone produced by increased 

 sympathetic neural discharge acting on otherwise 

 normal vessels. 



The relationship of these latter findings to those 

 of Lewis (49) and the more recent ones of Peacock 

 (70) is not clear. With reference to the grouping 

 offered by Mendlowitz and Naftchi, it is possible, 

 but not proved, that Lewis was studying patients in 

 the group with vascular obstruction and normal 

 vasomotor tone, whereas Peacock was studying 

 patients in the group without obstruction but with 



