Coronary endothelial function: The impact of aging in a matched study group with normal coronary arteries

Make Kelm Julius Rath, P&a Kleinbongard, Tienush Rassaf, Michael Preik, Bodo E. Strauer, Universitatsklinikum Diisseldorf, Diisseldorf, Germany Background: Nitric oxide (NO) has been shown to dilate vessels and to inhibit platelet function, both effects highly desirable during percutaneous intervention (PCI) in patients with coronary artery disease (CAD). Whether or not NO applied directly into human coro- nary circulation exerts biological effects is unknown so far. Therefore, the aims of our study were: (i) to develop a method for reproducible production of sterile solutions con- taining authentic NO, (ii) to find a save mode of intracoronary (ic.) application, and (iii) and to characterize potential dilatory effects in conduit and resistance coronary arteries. Methods: Changes in coronary blood flow (CBF) were quantified by quantitative coro- nary angiography (QCA) and intracoronary Doppler guide wares (ICD) in 13 patients with- out flow limiting CAD after application of either saline controls, aqueous NO solutions (NO.1 -6 wmol), adenosin (ADO, 2.4mg/min) or tsosorbiddinitrate (ISDN, 0.3 mg) in ran- dom order. Results: NO dilated epicardial arteries I” a dose-dependent manner up to lo+_1 %, equiv- alent to that seen upon ISDN. In parallel average peak velocity (APV) increased from 21 to 51+4 cm/s. Thus NO dilated coronary microvasculature to almost the same degree as seen after infusion of adenosine, whereas ISDN increased APV only slightly. Conse- quently. coronary blood flow increased according to the following rank order: NO and ADO > ISDN, whereas saline controls ware without effect. NO induced increases in CBF lasted much longer than expected from Its biochemical life span in human blood. Heart rate or blood pressure remained unaffected. Conclusions:Aqueous NO solutions can be applied directly into human coronary circu- lation and dilate uniformly epicardial