Abstract
Collateral circulation provides an alternative pathway for coronary blood flow during sudden coronary occlusion. Although interest on coronary collaterals has begun decades before, not until recently it regain its attention in the management of cardiovascular disease. Although several important studies have been done to elaborate the coronary collateral circulation, some
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conflicting opinions on its occurrence and function remain. This thesis aims to elaborate some issues in the occurrence and functional impact of coronary collaterals in coronary artery disease. This thesis comprises literature reviews and clinical observational studies. The literature reviews present the current knowledge on the role of collaterals in coronary artery disease and on the formation of collateral vessels. Clinical observational studies have been done to several cohorts of research populations. In a cohort of 52 patients with total or subtotal chronic coronary occlusion who underwent myocardial perfusion imaging and coronary angiography, we found that presence and extent of coronary collaterals are related to the perfusion of the regional myocardium. Nevertheless, only 27-35% of well developed collaterals provide functional perfusion. In a cohort of 879 male patients with stable coronary artery disease who have been followed for 24 months, the angiographical presence of coronary collaterals is a clinical predictor of cardiovascular prognosis. Furthermore, we studied the relevance of coronary collaterals in acute myocardial infarction. In a group of 187 patients with ST-elevation myocardial infarction (STEMI), we studied the appearance of collaterals during STEMI and found that there is a significant increase of collateral prevalence within hours after infarction. The appearance of angiographic visible collaterals is associated with the duration of occlusion during myocardial infarction. In another cohort of 2529 patients with STEMI, we reevaluated the impact of ischemic time on the post-infarction left ventricular function after treatment with primary percutaneous coronary intervention. We found that the association between ischemic time and post-infarction left ventricular ejection fraction is significant, but weak. In the same cohort of patients, we evaluated the independent impact of collaterals on infarct size and post-infarction left ventricular function. Presence of collaterals in STEMI is associated with decreased infarct size, but not associated with better post-infarction LVEF. We also found that ischemic time have less negative effects on infarct size in patients with collaterals. To study the occurrence of coronary collaterals, we conducted two genetic association studies. In a cohort of 879 patients with coronary artery disease, we examined the association between polymorphism in TNF-α gene and collateral presence. We found that a G to A polymorphisms in the promoter region is associated with collateral presence. In another cohort of 226 patients, we studied the association between polymorphism in MCP-1 gene and collateral presence. We found that polymorphism at position -2518 is associated with collateral presence.
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