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

Jian Ping Bin, Allan Doctor, Jonathan Lindner, Edward M. Hendersen, Dai-Trang (Elizabeth) Le, Howard Leong-Poi, Nicholas G. Fisher, Jonathan Christiansen, Sanjiv Kaul

    Research output: Contribution to journalArticle

    22 Citations (Scopus)

    Abstract

    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 (WBη), 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 WBη. There was a good correlation (r=0.87) between the two. The decrease in WBη 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±0.5×10 -5, P2 unloading. These additional microvascular mechanisms may contribute to the powerful antiischemic effects of nitroglycerin, especially during low-flow states.

    Original languageEnglish (US)
    Pages (from-to)2502-2508
    Number of pages7
    JournalCirculation
    Volume113
    Issue number21
    DOIs
    StatePublished - May 2006

    Fingerprint

    Rheology
    Nitroglycerin
    Myocardial Ischemia
    Erythrocytes
    Oxygen
    Blood Viscosity
    Pathologic Constriction
    Hemodynamics
    S-Nitrosothiols
    Dogs
    Nitric Oxide Donors
    S-nitrosohemoglobin
    Coronary Vessels
    Nitric Oxide
    Pressure

    Keywords

    • Microspheres
    • Nitric oxide
    • Nitroglycerin
    • Oxygen

    ASJC Scopus subject areas

    • Physiology
    • Cardiology and Cardiovascular Medicine

    Cite this

    Effects of nitroglycerin on erythrocyte rheology and oxygen unloading : Novel role of S-nitrosohemoglobin in relieving myocardial ischemia. / Bin, Jian Ping; Doctor, Allan; Lindner, Jonathan; Hendersen, Edward M.; Le, Dai-Trang (Elizabeth); Leong-Poi, Howard; Fisher, Nicholas G.; Christiansen, Jonathan; Kaul, Sanjiv.

    In: Circulation, Vol. 113, No. 21, 05.2006, p. 2502-2508.

    Research output: Contribution to journalArticle

    Bin, Jian Ping ; Doctor, Allan ; Lindner, Jonathan ; Hendersen, Edward M. ; Le, Dai-Trang (Elizabeth) ; Leong-Poi, Howard ; Fisher, Nicholas G. ; Christiansen, Jonathan ; Kaul, Sanjiv. / Effects of nitroglycerin on erythrocyte rheology and oxygen unloading : Novel role of S-nitrosohemoglobin in relieving myocardial ischemia. In: Circulation. 2006 ; Vol. 113, No. 21. pp. 2502-2508.
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    abstract = "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 (WBη), 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 WBη. There was a good correlation (r=0.87) between the two. The decrease in WBη 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±0.5×10 -5, P2 unloading. These additional microvascular mechanisms may contribute to the powerful antiischemic effects of nitroglycerin, especially during low-flow states.",
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    AU - Doctor, Allan

    AU - Lindner, Jonathan

    AU - Hendersen, Edward M.

    AU - Le, Dai-Trang (Elizabeth)

    AU - Leong-Poi, Howard

    AU - Fisher, Nicholas G.

    AU - Christiansen, Jonathan

    AU - Kaul, Sanjiv

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    N2 - 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 (WBη), 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 WBη. There was a good correlation (r=0.87) between the two. The decrease in WBη 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±0.5×10 -5, P2 unloading. These additional microvascular mechanisms may contribute to the powerful antiischemic effects of nitroglycerin, especially during low-flow states.

    AB - 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 (WBη), 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 WBη. There was a good correlation (r=0.87) between the two. The decrease in WBη 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±0.5×10 -5, P2 unloading. These additional microvascular mechanisms may contribute to the powerful antiischemic effects of nitroglycerin, especially during low-flow states.

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