Abstract 19191: A Mouse Model for Coronary Collateral Growth Validated Via Micro-CT and Echo-Contrast

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Abstract

Patients with an undeveloped collateral circulation have a poorer prognosis than those with well-developed collaterals when they have ischemic heart disease. Despite this great importance of the collateral circulation, the underlying mechanism(s) is (are) that are causal for growth are unknown. To enable a more mechanistic interrogation of this problem, we developed a murine model that would enable the use of genetically modified mice to facilitate a better understanding of causal mechanisms. The model involved implantation of a pneumatic snare that is situated around the LAD (open chest surgery during anesthesia). After the mice recovery from the surgery, periodic inflation of the snare occludes the LAD; thus producing episodes of ischemia or repetitive ischemia (RI). Coronary collateral growth was measured by contrast echocardiography (myocardial blood flow) and micro-CT (collateral numbers and structure). Results of coronary collaterals are shown in the Figure 1. Panel A and B showed the micro-CT images. Panel A represents filling of the coronary circulation in a mosue heart during an acute occlusion of the LAD. Note a large area (circumscribed by the white oval) without filling, indicating either a lack of collaterals or vessels too small to be visualized. Panel B shows extensive collateral growth from an mouse subjected to RI. The white filling represents the right coronary artery perfusion territory. Green is the septal circulation and blue is the LAD vasculature. The yellow and purple vessels denote collaterals. Whether these collateral vessels carry perfusion is shown in Panel C, in which blood flow to the collateral zone is represented as the ratio of flow to the collateral and normal zones (CZ/NZ). Note the CZ/NZ flow ratio increases from 0.35 to 0.63 after RI (n=7, p<0.01). We believe this murine model of coronary collateral growth will provide the platform to analyze the mechanisms of coronary collateral growth using genetically modified models.

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