Pathophysiological aspects of peripheral circulatory disorders in the vibration syndrome.

G. Pathophysiological aspects of peripheralcirculatory disorders in the vibration syndrome. Scand J Work Environ Health 13(1987)313-316. A ~eview of current kn?wle~ge on the patho physiological aspects of peripheral circulatory derangements In the hand.-arm. vl~ratlon syn?ro~e IS presented. Hemodynamic measurements indicate that the primary factor In vibration-induced whl.tefinger is an increase in peripheral resistance of finger circulation, present ~fter local and ?e.neral coohng. The reason for this increase is not known, but it is postulated that there IS an ~xcess aff1mt~ for the cf~e~ent receptors of vasoactivesubstances and that this affinity is potentiated during local coohng of the digits,

In attacks of vibration-induced white finger (VWF) the hyperreactivity of the blood vessels of subjects with VWF doe s not seem to be restri cted to locall y appli ed cold stimulus. Reflexivel y induced cold (4), noi se (10), and vibratory stimuli (10) also cause an enhanced vasoconstriction in the affected vessels. It has therefore been proposed that excessive per ipheral vasoconstriction may be produced by augmented vasoconstrictor ner ve tone (10) or by faulty local factors (6,7,11). In the case of the latter possibility the local vasoconstrictor mechanisms aggravate responses of the central output of the sympathetic nervous system (12). Such a situation generally occur s in outdoor workers when the bod y and the vessels of the fingers are coo led sim ultaneously.
Lewis (6) was the first to present the hypothesis that Raynaud' s ph enomenon is cau sed by local fault s, ie, defects in ner ve endings lead ing to excess vasoco nstrictio n when the vessel wall is exposed to cold. Marsha ll et al (7) noticed that, in an attack of VWF, the numbness was more proximal in the fingers than the changes in color. They therefore proposed that in VWF, as in some neurological diseases, injured nerves were the primary reason for Raynaud's phenomenon. In an experim ent on dogs Azuma et al (2) sho wed both in vivo and in vitro that a few hours aft er the termination of vibration the smooth muscles of the vessel wall responded more strongly to noradrenaline than unexposed muscles did . anesthesia . The neurogenic component of the vasomotor acti vity was found to be weaker in the VWF subjects than in referents. However, the authors found no evidence that the myogenic tone of vaso mo tor oscillation in VWF pati ents differed from that of healthy volunteers. The result s therefore suggest that there is damage to the vasomotor nerve s controlling the vessel tone, instead of damage in contracting proteins of the smoo th mu scle. Hen ce local neuropathy, as suggested by the results , may facilitate the "sprouting" of adrenergic receptors on the surface of the smooth muscles in the same manner as surgical sympathectomy produces hypersensitivity of the vessels. H yper sen sitivit y of the vessel wall ma y cause much the same responses to exogenous no xiou s stim uli as does an enhanced central sympathetic ou tflow. Thus different sensory stimuli that have cau sed an excessive vasoconstriction refle xively in the finger circulation of vibration-expo sed workers ultimately ind icat e a control lesion , but the fault ma y be peripheral (10). Moreover, because of the possible fault in the adrene rgic receptors, the subjects with VWF show increased peripheral resistance to normal environmental stimuli and, respectively, show reduced finger skin temperatures and blood flow at normal ambient temperatures (4). In a cold environment the augmented vascular responses may lead to collapse of the vessel wall and thu s pro voke an attack of Raynaud 's phenomenon.
Some other findings indicate that continuous stimulation of the pacinian corpuscles, which are very sensitive to vibration at frequencies of 60 to 700 Hz (10), might lead to continuous acti vation of the autonomic nerv ous system . Acute exposure to vibra tion also triggers a vasoconstriction reflexively in peripheral vessels. The peripheral vasoconstrictor response in the vessels is presumably caused by the acti vation of the autonomic nervous system , since, according to works on isolated animal postal vein, vibration affects smooth muscle tissue by causing vasodilatation . After prolonged stimulation such a repeated vasoconstriction may cause hypertrophy of the medial layer of the muscle wall as an exercise effect and lead to exaggerated vascular response to cold. Similar vascular hyperresponsiveness to noradrenaline, as in cases of VWF, has also been observed in hypertensive rats by Folkow et al (3) in cases in which the muscular layer of the arterioles , and of the arteriovenous shunts, was increased. Distant vibration may also cause changes in cardiovascular reflexes. Even though dist ant vibration may also induce central autonomic dysfunction, these effects of chronic exposure to vibration are still poorly documented.
So far the exact mechanism by which vibration induces a po ssible fault in the mechanisms controlling vessel tone remains to be elucidated. Accordin g to present knowledge it is likely that the fault in VWF might be in the coupling between the nerve and smooth rnus-   314 cle of the vessel at the adrenergic receptor -or, less likely, in the wall lumen ratio at the arteriolar level. Thus there is support for the theory that , in VWF, the fault may be local, in the finger vessels, but the nature and the exact mechanisms of the "excessive vasospasm" must be clarified before any final conclu sions can be drawn .

Hemodynamic aspects of vibration-induced white finger
Hitherto, the importance of the different factors determining blood circulation in patients with VWF has not been understood in detail. There is a well known connection between pressure, flow, and peripheral resistance. Thus flow is inversely related to peripheral resistance and directly related to pressure. The peripheral resistance is dependent on an individual constant (k), the length of the capillary bed (I), the viscosity of the blood (m), and the radius of the lumen of the vessel (r), as described in figure I. Although local mechanisms operating on the vessel wall of the resistance arterioles and capill ary beds may contribute to vasoconstriction (15), the outflow of the sympathetic vasoconstrictor nerves is far more important. Thi s outflow is aimed at the resistance arterioles, precapill ar y sphincters, and arteriovenou s anatomosis (II). According to Pois seuille 's law a slight decrease in the radius causes a powerful increase in the peripheral resistance and results in a reduction in flow, pro vided that the pressure is not chan ged . Thus under physiological conditions, changes in the radius of the vessel lumen provide an effici ent way of controlling skin circulation .
To evaluate possible chan ges in peripheral resistance, invasive measurements are at present more accurate. However, the technical difficulties and size o f measuring devices at pre sent do not allo w the instruments to be placed in digital arteries and arterioles without severely occluding the vessel lumen . Furthermore, finger circulation ca n resist high venou s pressure and still pro vide sati sfactory flow , as during the manipulation of working tool s with a relatively firm grip. Th erefore, the difference in pressure acting as the dri ving force varies greatly in the finger, depending on the changes on the venous side . A monitoring of arterial pressure alone may thus provide biased results.
One possible way to approach the det ermination of the peripheral resistance of the system is to use finger plethysmography with the strain gauge technique (12). In th is kind of approach the circulation is a net result of the combined flow pattern of the arterial and venou s sites (figure 2) and can be measured as peak art erial inflow (5,12). A crude estimation of the pressure difference, the so-called driving force, can be made from a calculation of the difference between finger systolic blood pressure and venou s opening pressure. In this way the finger peripheral resistance that derives from the arterial and venous side can be estimated at different ambient temperatures. This procedure is somewhat different from the usual procedure in which mean arterial pressure and maximal arterial flow is used. Nevertheless, it is extremely difficult, though not impossible, to measure mean arterial pressure noninvasive/y.
Using this approach, Pyykko (12) and Gemne et al (5) determined finger peripheral resistance during local cooling in subjects with and without VWF. The results showed, in fact, that in subjects with VWF the arterial inflow was limited as the result of high peripheral resistance that appeared after local cooling of the fingers. Locally applied cold thus triggered a higher peripheral resistance in the finger vessels of subjects with VWF than in the finger vessels of referents. Furthermore, this increase in peripheral resistance was only partly reduced after the finger nerves were anesthetized (blocking the sympathetic nervous control on the finger vessels) and therefore indicated that an augmentation of local vascular mechanisms is the immediate cause of VWF.
Local exposure to cold affects the alpha-adrenergic receptors and promotes the vasoconstriction induced by the sympathetic nervous system via two different mechanisms, ie, reducing the degradation of transmittor substances and sensitizing the affinity of alphaadrenergic receptors to transmittor substances (15). The slowing of the degradation of transmittor substances is achieved by the inhibition of neuronal uptake, by delayed enzymatic degradation, and by retarded diffusion of noradrenaline. Thus cooling the vessels is an effective way to "prime" an attack in subjects with VWF, in whom presumably the local vascular control mechanism is lesioned. This receptor "priming" effect of cold is allegedly the reason why cold provokes attacks of VWF.
Some studies have demonstrated that subjects with VWF have higher blood viscosity than those without VWF (8). Since blood viscosity also influences peripheral resistance, it seems likely that those subjects with high or pathological viscosity of blood tend to be selected to the group with VWF and that the condition may not be directly caused by hand-arm vibration.
Structural changes have also been found in workers exposed to vibration (14). Intimal thickening and hypertrophy of the medial layer are the most characteristic findings. Since these factors affect the lumen of the digital arteries and reduce the radius of the vessels, they increase peripheral resistance. Nevertheless, no physiological study has yet been able to show any distinct effects on blood circulation which could be explained by structural changes. Therefore, this factor may be a marginal one. However, from the hemodynamic point of view, cooling combined with compression of the skin of the fingers reduces the patency and the length of the finger vessels and results in an increase in peripheral resistance, which may secondarily lead to a reduction in blood flow in VWF. This mechanism may have functional significance in triggering attacks.
Ithas been suggested that exposure to vibration produces "friction" in the skin of the fingers and leads to the formation of subcutaneous callosities (13). The calloused finger pads cause capillary occlusion affecting a part of the capillary bed. This occurrence decreases the blood volume in the capillaries and hence weakens the buffer action to finger circulation during sudden contractions of the finger vessels and therefore leads to an attack of VWF. Substitution of subcutaneous tissue by callosities during prolonged vibration reduces the size of the capillary bed and the apparent length of the vascular bed and also augments peripheral resistance. The hemodynamic significance of this mechanism remains to be elucidated.
An increase in general sympathetic tone induced either by emotional tension or by drugs such as nicotine also favors the outbreak of symptoms (9). A part of the prominent increase in peripheral resistance in subjects with VWF undoubtedly occurs due to central sympathetic output (4). Nevertheless, a pathologically high peripheral resistance during cold has been shown to persist after blockage of the sympathetic nerves to the finger (5), a phenomenon indicating that local factors playa far more important role in the genesis of VWF than do central factors.
During local cooling an increase in venous tone has also been observed in subjects with VWF. The elevated venous tone may increase the venous pressure and retard circulation by reducing the dynamic range of circulation. It has been demonstrated that high venous pressure retards the arterial inflow through the venoarterial reflex. As a net result, changes in the venous side have a powerful effect on peripheral resistance.

Conclusions
Several vascular factors contribute to the generation of an attack of VWF. These factors all cause increased peripheral resistance. An enhancement of blood viscosity may operate in much the same manner as structural changes in the vessel wall and may be a "selecting" factor, rather than an etiologic factor, that favors the worker's becoming a victim of VWF.
An increase in venous tone appears to be an important hemodynamic response which, through the venoarterial reflex and the increased venous flow resistance, "primes" for gross vascular changes on the arterial side. Local cold efficiently affects the vasoconstriction by retarding a reuptake of noradrenaline and by sensitizing the alpha receptors. This occurrence explains why attacks are provoked by cold instead of by mental or emotional stress. The latter factors, however, elevate the central sympathetic outflow and presumably assist the local faulty mechanisms in provoking the attack.