254. Diadenosine polyphosphates are potential mediators of post-operative contraction in human coronary artery bypass grafts

Background: Coronary microvascular function (Mcor )h as emergingimplicationsinclinicaldiagnosis, risk-stratification and prognosis of patients. Its comprehensive assessment requires information on endothelium-dependent and -independent coronary responses. Coronary flow reserve (CFR), a commonly used index for Mcor, is derived from ratio of maximal hyperemic (often achieved with a non-specific vasodilator, adenosine) to basal coronaryflow.Wehypothesizedthatadenosine-derivedCFRmay not adequately interrogate the endothelium-dependent component of the coronary microvasculature. Methods/Results: A thermodilution technique (using intracoronary pressure wire) was employed to sequentially compare CFR (hyperemia achieved with adenosine—140 Ag/kg/ml via femoral vein) with % change in coronary flow in response to the endothelial agonist substance-P (endothelium-dependent response—20pmol/min intra-coronary infusion for 2 min) in 56 unobstructed coronary arteries of patients undergoing angioplasty to an adjacent vessel. Mean (T SD) age of patients was 65 T 10 years (55% male–18% diabetic). Mean CFR was 2.9 T 1.3 and substance-P induced change in blood flow 22.2 T 17.4%. There was no correlation between CFR and coronary endothelial response (r = 0.1, P = 0.2). We then studied the relationship between CFR/coronary endothelial response and established clinical markers of endothelial dysfunction. There was a strong correlation between coronary endothelial response and patient’s Framingham Risk Score [FRS—a surrogate marker for cardiovascular risk factor clustering; hence an indirect measure of endothelial dysfunction (ED)—P = � 0.5, P < 0.0001], but no correlation between CFR and FRS (P = 0.01, P = 0.7). Diabetic patients had greater coronary ED than non-diabetics (P = 0.001). CFR was not influenced by diabetes in this patient cohort (P = 0.4). Conclusion: Adenosine-derived CFR may not adequately interrogate the endothelium-dependent component of the coronary microvasculature. We propose that information on both CFR and coronary endothelial function is required to comprehensively assess Mcor.