Abstract 3933: Local Cytokine Release is Increased in Less Mature Collateral Arteries and Reflects Collateral Arterial Oxygen Pressure in Man
Background: The molecular background of the maturation of the human collateral circulation in response to coronary narrowings is poorly understood, particularly because of the complexity to evaluate coronary collateral growth in-vivo. Local sampling of collateral blood in patients could provide valuable insights in this process. We sought to determine metabolic parameters and plasma cytokine profiles in the human coronary collateral circulation in relation to collateral maturation.
Methods and Results: We used a Proxis® proximal embolic protection device (St. Jude Medical) to perform blood sampling directly from the coronary collateral circulation in 60 patients with non-total (n=25) or total coronary occlusions (n=35). Coronary collateral flow index (CFI) was assessed by intracoronary pressure measurements. Oxygenation and lactate content was measured as well as 30 cytokines potentially involved in collateral artery growth, using a custom-made multiplex assay. Oxygen gradient between systemic and collateral arterial correlated inversely with CFI (R=−0.63, p<0.001). No rise in lactate or change in pH was found in collateral blood. Locally increased plasma levels were found for bFGF, Eotaxin, MIF, MCP-1, VEGF and TGFbeta, while SCF was significantly decreased. The highest cytokine gradients were found in patients with the least developed collateral circulation. The majority of cytokines correlated more strongly with pO2 extraction across the collateral bed than with CFI.
Conclusion: Upregulation of cytokines at the site of coronary collateralization and in collateral vessels with enhanced oxygen gradient between systemic and collateral arterial blood demonstrate increased inflammatory activity in arteries where oxygen delivery is insufficient. Less pronounced cytokine gradients in collateral arteries in CTOs indicate reduced arteriogenic activity in these vessels. Determining oxygen gradient may be a more sensitive tool for the assessment of the functional capacity of the collateral circulation in patients than measurements of CFI.