Work

Studies on antioxidant and lipid lowering effects on human microcirculation

Year: 2002
Type: dissertation
Abstract: In previous work from this laboratory, vital microscopy was successfully\nused to study rnicrocirculatcry effects of hypercholesterolemia in a\nrabbit model. Hypercholesterolemia caused a dramatic depression of the\nblood flow velocity in the conjunctiva microvessels of the rabbits. In\naccordance with the contention that hypercholesterolemia is associated\nwith oxidative stress that is of importance for the microcirculation,\nantioxidants were shown to have a clear preventive effect on the\ncholesterol- induced changes in the microcirculation.\n\nIt was considered to be of interest to study if similar effects by\nhypercholesterolemia and antioxidants might be demonstrated also in human\nmicrocirculation. A technique for computerized video capillary microscopy\nimaging was set up for evaluation of the microcirculation in the\nnailfold. In two of the studies, the flying-spot technique was primarily\nused for measurement of the blood cell flow velocity (CBV). In three of\nthe studies the Capiflow system and the time to peak (TtP) after a brief\narterial occlusion (PRH) were used. According to current concepts, the\nlatter technique is a more reliable assessment. In an evaluation of the\nTtP method, the between-day variation was found to have a coefficient of\nvariation of less than 13%, provided that the mean of at least two\nassessments were used.\n\nSmoking is known to induce a considerable oxidative stress that would be\nexpected to affect the microcirculation. In accordance with this, smoking\na single cigarette caused a 40-50% decrease in microcirculatory blood\nflow velocity in 23 of 24 subjects studied. This change was reduced by\nmore than 50% in the same subjects after intake of 2 g of vitamin C 2 h\nbefore smoking. Interestingly, intake of 1 g of vitamin C was without\neffect. Pretreatment for 2 weeks with N-acetylcysteine (200 mgx3 per day)\nalso significantly reduced the smoking-induced effect on the\nmicrocirculation in a group of healthy volunteers with mixed smoking\nhabits. The preventive effect of Nacetylcysteine was however considerably\nlower than the effect of the high dose of vitamin C.\n\nPlasma apheresis offers a unique possibility to study effects in the\nmicrocirculation of abrupt changes in plasma lipid levels. We studied\nfour patients regularly treated with LDL-apheresis every third week. In\nspite of a reduction of the cholesterol levels by almost 50%, there was\nno obvious change in time to peak at PRH registered prior to apheresis\nand two days later. The smoking- induced effect on TtP did not seem to he\naffected by the LDL-apheresis either. Essentially the same results were\nobtained when measuring the change in the diameter of the brachial artery\n(FMD) as a response to arterial occlusion and nitroglycerin. Thus the\nmethod used for evaluation of the microcirculation and that used for\nevaluation of conduit vessels showed concordant results.\n\nDiabetes is known to be associated with a disturbed endothelial function\nand microcirculation. In a double blind cross over study on 17 patients\nwith type 2 diabetes, microvascular reactivity was found to be markedly\nreduced. Treatment for 2 weeks with a daily dose of 1g x 3 of vitamin C\ndid not significantly improve the vascular reactivity. A slight effect\ncould however be demonstrated in capillary blood flow velocity.\n\nIt is concluded that it is possible to use capillary microscopy for\nevaluation of effects on the microcirculation in the nailfold,\nparticularly in connection with acute studies. Patients with\nhypercholesterolemia and diabetes as well as volunteers inhaling\ncigarette smoke had a disturbed microcirculation, probably related to an\noxidative stress. The most significant effects of antioxidants observed\nin the present work appeared in connection with acute oxidative stress\n(smoking) and a very high dose of the antioxidant (vitamin C).
Source: Figshare
Author: Qing Lu
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W1524731194
Cites: 296
Cited by: 2
Related to: 10