Exposure to inorganic arsenic is atherogenic and has been suggested as the most probable cause of an endemic peripheral arterial disease known as blackfoot disease (BFD) along the southwestern coast of Taiwan. A study comparing the microcirculatory flow at the big toes measured by laser Doppler flowmetry in 45 seemingly normal men living in the BFD-hyperendemic villages with more than three decades of exposure to high concentrations of arsenic in drinking water with that in a group of 51 men without arsenic exposure suggested the presence of a lower basal microcirculatory flow in the arsenic-exposed subjects at 36°C (32.8 ± 6.0 vs. 67.0 ± 4.3 perfusion units; P < 0.001) and after a hyperthermic test with local skin heating to 42°C (193.2 ± 13.6 vs. 231.1 ± 6.3 perfusion units; P < 0.005). The microcirculatory defect in the seemingly normal subjects living in the BFD-hyperendemic areas was independent of subclinical arterial insufficiency. Abnormal laser Doppler flow was also detected in the normal fingers of eight patients suffering from BFD while compared to four healthy controls (20.3 ± 6.2 vs. 64.3 ± 16.8 perfusion units). Capillaroscopic examination showed significantly disturbed cutaneous microcirculation, including resting, peak and time to peak capillary blood cell velocities in the affected and nonaffected toes and fingers of BFD patients; and increased transcapillary diffusion and interstitial diffusion in clinically normal nailfolds of the fingers of BFD patients. Although intravenous infusion of prostaglandin E1 into BFD patients might increase microcirculatory flow to the viable sites proximal to the gangrenous ulcers of the foot, the effect is probably transient during the treatment period. Endothelial dysfunction, damage to endothelial cells, hypercoagulability, oxidative stress, apoptosis and atherosclerosis caused by arsenic may lead to closure of the capillary beds resulting in lower basal microcirculatory perfusion. It has been recognized that the sensory nerves may play a role in the regulation of microvascular blood flow. Arsenic is neurototoxic and has been shown to preferentially affect the C fibers which are involved in the release of vasodilatory neuropeptides. Damage to the autonomic nervous system and a reduction in vasodilatory substances may lead to an insufficient response regarding dilation of the vessels in response to an increase in skin temperature. Therefore, the interaction between vascular and neurological deficits in arsenic-exposed subjects would lead to defects in microcirculatory flow and eventually to atherosclerosis and peripheral arterial disease.
ASJC Scopus subject areas
- Environmental Science(all)