Published Online
on May 22, 2006

A more recent version of this article appeared on May 30, 2006

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Submitted on August 12, 2005
Revised on March 27, 2006
Accepted on March 31, 2006

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, and 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.).

^* To whom correspondence should be addressed. E-mail: kauls{at}ohsu.edu.

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.

Key words: nitroglycerin • microspheres • oxygen • nitric oxide

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