Effects of nitroglycerin on erythrocyte rheology and oxygen unloading - Novel role of S-nitrosohemoglobin in relieving myocardial ischemia

Article

关键词: RED-BLOOD-CELLS;    NITRIC-OXIDE;    FLOW REGULATION;    MEMBRANE FLUIDITY;    CORONARY;    VASODILATION;    NO;    MICROVESSELS;    INHIBITION;    TOLERANCE;   

DOI  :  10.1161/CIRCULATIONAHA.106.627091

来源: SCIE

【 摘 要 】

Background - We hypothesized that nitroglycerin improves O-2 delivery to ischemic tissue by altering erythrocyte rheology and O-2 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 mu g (.) 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 eta), erythrocyte charge (EC) and mobility (EM), regional myocardial O-2 delivery and consumption, and tissue O-2 pressure (Po-2) 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 eta. There was a good correlation (r = 0.87) between the two. The decrease in WB eta was associated with a decrease in EC and an increase in EM (r = 0.83). The nitroglycerin-induced increase in tissue Po-2 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 mu mol/L nitroglycerin or the NO donor SNAP, as compared with control (18.9 +/- 8.8 and 10.5 +/- 6.5 versus 2.6 +/- 0.5 +/- 10(-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 O-2 unloading. These additional microvascular mechanisms may contribute to the powerful antiischemic effects of nitroglycerin, especially during low-flow states.

【 授权许可】

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