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(Circulation. 2006;113:2502-2508.)
© 2006 American Heart Association, Inc.

Coronary Heart Disease

Effects of Nitroglycerin on Erythrocyte Rheology and Oxygen Unloading

Novel Role of S-Nitrosohemoglobin in Relieving Myocardial Ischemia

Jian-Ping Bin, MD; Allan Doctor, MD; Jonathan Lindner, MD; Edward M. Hendersen, BS; D. Elizabeth Le, MD; Howard Leong-Poi, MD; Nicholas G. Fisher, MBBS; Jonathan Christiansen, MD; Sanjiv Kaul, MD

From the Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, Oregon (J.-P.B., J.L., D.E.L., H.L.-P., N.G.F., J.C., S.K.); and the Department of Pediatrics, Washington University, St. Louis, Missouri (A.D., E.M.H.).

Correspondence to Sanjiv Kaul, MD, Division of Cardiovascular Medicine, OHSU, UHN62, 3181 SW Sam Jackson Park Rd, Portland, OR 97239. E-mail kauls{at}ohsu.edu

Received August 12, 2005; de novo received March 16, 2006; revision received March 27, 2006; accepted March 31, 2006.

Background— We hypothesized that nitroglycerin improves O₂ delivery to ischemic tissue by altering erythrocyte rheology and O₂ unloading through an increase in bioactive nitric oxide (NO) content.

Methods and Results— Twelve dogs with resting flow-reducing single-vessel stenosis were studied at rest and during intracoronary infusion of nitroglycerin (0.3 to 0.6 µg · kg^–1 · min^–1). Half the dogs also had occlusion of the remote coronary artery to remove any collateral effects. Systemic and coronary hemodynamics, myocardial blood flow (MBF), whole blood viscosity (WB), erythrocyte charge (EC) and mobility (EM), regional myocardial O₂ delivery and consumption, and tissue O₂ pressure (PO₂) were measured. No changes in systemic hemodynamics were seen with nitroglycerin. Despite flow-limiting stenosis, MBF increased significantly in the central 25% of the ischemic bed, which was associated with an approximately 19% decrease in WB. There was a good correlation (r=0.87) between the two. The decrease in WB was associated with a decrease in EC and an increase in EM (r=0.83). The nitroglycerin-induced increase in tissue PO₂ was disproportionate to the increase in MBF, indicating enhanced O₂ unloading. Erythrocyte S-nitrosothiol content (reflecting mainly S-nitrosohemoglobin) was significantly higher for blood exposed in vitro to 0.1 µmol/L nitroglycerin or the NO donor SNAP, as compared with control (18.9±8.8 and 10.5±6.5 versus 2.6±0.5x10^–5, P<0.05).

Conclusions— The augmented MBF in the ischemic microcirculation during nitroglycerin administration occurs in tandem with increased erythrocyte S-nitrosothiol content, EM, and O₂ unloading. These additional microvascular mechanisms may contribute to the powerful antiischemic effects of nitroglycerin, especially during low-flow states.

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