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Objectives: This study was undertaken to examine the relation of in vivo low density lipoprotein (LDL) oxidation and other lipid risk factors to coronary reactivity in normal subjects., Background: Experimental studies have shown that oxidized LDL (ox-LDL) particles are injurious to the vascular wall by impairing its normal vasodilator function., Methods: We used noninvasive positron emission tomographic (PET) imaging with intravenous dipyridamole to measure coronary flow reserve, a marker of coronary endothelial and smooth muscle function, in 30 healthy men (mean [+/-SD] age 34.4 +/- 3.2 years). As a marker of in vivo LDL oxidation, the autoantibody titer against ox-LDL was measured by the enzyme-linked immunosorbent assay method., Results: Plasma levels of autoantibody titer against ox-LDL were inversely associated with coronary flow reserve (r = -0.42, p = 0.023). High LDL cholesterol levels (above median > 3.0 mmol/liter) were associated with a low coronary flow reserve only in subjects expressing simultaneously high levels of ox-LDL titer (above median). Subjects with simultaneously high levels of LDL cholesterol and ox-LDL titer had lower coronary flow reserve values than subjects in other groups (3.89 vs. > 5.0 in other groups, p = 0.066)., Conclusions: These data provide evidence for the role of ox-LDL in affecting the coronary reactivity in vivo and support the concept that oxidative modification of LDL particles provides a mechanism by which high LDL concentrations exhibit injurious effects on the coronary vascular bed.

To examine the role of immaturity in the free radical-mediated rate of lipid peroxidation in premature infants, we studied 27 infants [gestational age, 27.1 (SD 2.4) wk; birth weight, 970 (SD 330) g]. Ethane and pentane were quantitated in expired air during the first 18 d of life. During the first 2 postnatal d ethane [24.1 (SEM 7.8) pmol x kg-1 x min-1] and pentane [24.2 (SEM 4.1) pmol x kg-1 x min-1] were stable but increased during d 5 to maxima of 79.1 (15.8) pmol x kg-1 x min-1 and 62.1 (8.1) pmol x kg-1 x min-1, respectively. Maximum ethane and pentane correlated with gestational age (r = -0.42, p = 0.03 and r = -0.52, p = 0.005, respectively) and birth weight (r = -0.38, p = 0.05 and r = -0.59, p = 0.001, respectively). Infants with high maximum expired ethane and pentane (exceeding 40 pmol x kg-1 x min-1) had higher odds of dying or having bronchopulmonary dysplasia than those with low ethane and pentane (odds ratio, 6.5; 95% confidence interval, 1.1 to 38.5; p < 0.05 for ethane and odds ratio, 5.6; 95% confidence interval, 1.1 to 29.3; p < 0.05 for pentane). We conclude that degree of prematurity is the single most important factor explaining free radical-mediated lipid peroxidation in premature infants. A therapeutic intervention to limit the effects of free radicals should be started during the 1st postnatal d in premature infants to be effective.

Peroxidation of human erythrocyte membranes was followed in vitro with head space analysis of ethane and pentane and a thiobarbituric acid assay in a standardized system liberating free oxygen radicals. Simultaneously, the decrease of the membrane palmitic, linoleic, arachidonic and docosahexaenoic acid was monitored. The recoveries of the peroxidation products of the red cell ghost preparations were compared with those obtained by peroxidation of pure fatty acids. Experiments using purified fatty acids revealed that ethane was preferentially produced from docosahexaenoic and linolenic, and pentane from linoleic and arachidonic acids. Thiobarbituric acid-reactive material (TBAR) was produced from each unsaturated fatty acid tested, but the amount was dependent on the number of carbon chain double bonds. During peroxidation of the erythrocyte ghosts, 72% of ethane and 51% pentane were produced during the first 12 h of incubation, whereas TBAR was produced at a constant rate throughout the 36-h test period. Hydrocarbon and TBAR production were similarly inhibited by desferoxamine (at p less than 0.005 and p less than 0.0001, respectively). The total recoveries of ethane, pentane and TBAR exceeded the amount expected by 7.8-, 1.4- and 5.5-fold, respectively. It was concluded that measurement of pentane is a reliable method to monitor lipid peroxidation during oxidative damage of the erythrocyte membrane.

Lipid emulsions for parenteral use are peroxidized during storage, indicating that the amount of the natural vitamin E in the preparations is inadequate. Peroxidation products in the lipid emulsion preparations can induce cell damage in vitro. The parenteral administration of lipid emulsions increases in vivo lipid peroxidation in adult and healthy newborn patients as well as in premature infants, whereas enteral feeding seems to lead to a more balanced accretion of polyunsaturated fatty acids. The use of parenteral lipids has recently been associated with increased morbidity of premature infants. Current opinion favors the view that evolution of the complications is highly influenced by the inferior defense of the premature infants to resist oxidant loads. A novel antioxidant added in the preparations for the intravenous provision of polyunsaturated lipids could be beneficial for such patients.

Lipid peroxidation was measured in 19 very low birth weight infants with respiratory distress syndrome by quantitating ethane and pentane in expired air during the first 5 days postnatally. Despite high levels of inspiratory oxygen, the ethane and pentane output was low within the first 24 hours; thereafter it increased up to 100 and 30 fold, respectively. On days 1 to 3 there was no detectable correlation between lipid peroxidation and fractional inspiratory oxygen. However, on days 4 and 5, lipid peroxidation and fractional inspiratory oxygen showed a significant correlation. Maximal amounts of expired ethane and pentane were significantly higher for patients with a poor outcome (five deaths, six cases of bronchopulmonary dysplasia) than for those with good outcome (eight infants surviving intact) (p less than 0.01). The results imply a role for free oxygen radicals in the pathogenesis of life-threatening complications in the very low birth weight infant.

It has been proposed that ethane and pentane reflect free oxygen radical-induced lipid peroxidation. However, methodological difficulties limit the use of these gases for assessment of free oxygen radical activity. In the present report we describe an improved method for the accurate analysis of picomole quantities (greater than or equal to 1 pmol) of ethane and pentane. They are first quantitatively trapped into an adsorbent and then heat-desorbed directly into a capillary column for gas chromatographic quantitation. During oxidation of linolenic (n-3) and linoleic (n-6) acid, ethane and pentane were formed, respectively. Nonstimulated granulocytes formed pentane. Upon addition of phorbol 13-myristate 12-acetate, the generation of pentane was increased by 540%. Addition of superoxide dismutase plus catalase inhibited lipid peroxidation in both a cell-free system and in isolated cells. The present method is useful in the evaluation of free oxygen radical induced damage.