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


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 microg.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 (WBeta), 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 WBeta. There was a good correlation (r=0.87) between the two. The decrease in WBeta 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 micromol/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.
Bin
Jian-Ping
JP
Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.
Doctor
Allan
A
Lindner
Jonathan
J
Hendersen
Edward M
EM
Le
D Elizabeth
DE
Leong-Poi
Howard
H
Fisher
Nicholas G
NG
Christiansen
Jonathan
J
Kaul
Sanjiv
S
D000818:Animals; D001783:Blood Flow Velocity; D001785:Blood Gas Monitoring, Transcutaneous; D001809:Blood Viscosity; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis / Q000502:physiology*; D018056:Hemorheology / Q000187:drug effects; D008833:Microcirculation; D017202:Myocardial Ischemia / Q000188:drug therapy*; D009569:Nitric Oxide; D005996:Nitroglycerin / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption
D006454:Hemoglobins; C103574:S-nitrosohemoglobin; D009569:Nitric Oxide; D005996:Nitroglycerin; D010100:Oxygen