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Influence of oxidative stress on the development of collateral circulation in total coronary occlusions

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Abstract

Objectives

The purpose of this study was to investigate whether the levels of total antioxidant capacity (TAC), total peroxide and oxidative stress index (OSI) are associated with the development of collaterals in total coronary occlusions.

Design and methods

Our study group contained 176 consecutive men patients with single-vessel TCO, 94 of whom had poorly developed coronary collateral, while 82 had well-developed coronary collateral. TAC and total peroxide concentration were measured of plasma. The ratio of TAC to total peroxide was accepted as an indicator of oxidative stress.

Results

The values of total peroxide and OSI in the Group I were significantly lower than that in Group II (p < 0.001, for both). TAC levels were significantly higher in patients with poorly developed collaterals than in well-developed collateral group (p < 0.001). OSI values were also significantly different among the Rentrop class-0, -1, -2 and -3 (ANOVA p < 0.001). We found significant correlations between collaterals score and TAC, total peroxide and OSI levels (p < 0.001 for all). In multiple linear regression analysis, total peroxide and OSI were independent predictors of collaterals score (p = 0.006 and p < 0.001 respectively).

Conclusion

This study clearly demonstrates that the level of OSI is independently and positively associated with the presence of collateral circulation in total coronary occlusion patients.

Introduction

Free radicals and oxidants are produced in metabolic and physiological processes [1]. Their effects are controlled by exogenous and endogenous antioxidants. If the quantity of free radicals exceeds the capacity of the antioxidant defense mechanisms, oxidative stress occurs. Oxidative stress alters normal endothelial function, supporting proinflammatory, prothrombotic, proliferative, and vasoconstrictor mechanisms that support the atherogenic process [2], [3], [4], [5].

Coronary collateral vessels recruitment and growth are adaptive responses to severe coronary artery disease, providing an alternative source of blood supply to ischemic myocardium [6]. Numerous studies have demonstrated that collateral circulation in patients with coronary artery occlusion is associated with age [7], diabetes mellitus [8], hypercholesterolemia [9], physical activity [10], [11], heparin [12], nitrates [13], [14] and serotonin blocker [15]. However, the data regarding effects of oxidant and antioxidant status on development of coronary collaterals is controversial. A prior study indicates that treatment with antioxidant attenuated increases in collateral blood flow [16], but another study demonstrated that antioxidants inhibit collateral development in response to myocardial ischemia [17].

Blood contains many antioxidant molecules that prevent and/or inhibit harmful free radical reactions [2]. Plasma concentrations of antioxidants can be measured separately in the laboratory, but these measurements are time-consuming, labour-intensive and costly. Since antioxidative effects of antioxidant components of plasma are additive, the measurement of total antioxidant capacity (TAC) reflects the antioxidative status of plasma [18]. We evaluated the total antioxidative status of plasma using a more recently developed measurement method by Erel [18]. In this method, TAC against especially potent free radical reactions, which strongly lead to oxidative damage of biomolecules such as lipids, proteins and DNA, is measured. Hydrogen peroxide and other derivatives of peroxides, producing physiologically and increasing in some conditions, diffuse into plasma. Here, antioxidant components of plasma overwhelm them, and they are simultaneously consumed [19]. We evaluated total oxidative status of plasma by measuring total peroxide level.

In this study, we tested whether TAC, total peroxide and oxidative stress index (OSI) play a critical role in coronary collateral development in patients with total coronary artery occlusion.

Section snippets

Patient population

The patient population section in “Methods” was rearranged as follows:

Between March 2003 and March 2005, 10 350 consecutive patients who underwent a coronary angiography at our institution and a Special Medical Center were enrolled in a registry. Six hundred fifty of the 10 350 patients had single-vessel TCO artery disease at coronary angiography with no other significant coronary artery stenosis. Because the multi-vessel coronary disease had significant influence on the development of

Results

Demographic and clinical characteristics of patients with Rentrop's coronary collateral classifications 0 and 1 (n = 94) and Rentrop's coronary collateral classifications 2 and 3 (n = 84) are shown in Table 1. Age of patients with poorly developed collaterals tended to be higher than that of patients with well-developed collaterals, but this difference did not reach the significance level. Risk factors and medications are similar between the two groups (Table 1).

The oxidant and antioxidant status

Discussion

In this study, we have studied the role of the OSI, using measurements of total peroxide as an indicator of oxidative stress and using measurements of TAC as an indicator of antioxidant capacity, on the coronary collateral circulation in patients with TCO. The present investigation provides some insights into coronary collateral development. Development of coronary collateral in patients with TCO is more related to oxidants than antioxidants. Plasma total peroxide and OSI are independent

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