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Nitroglycerine (NTG) enhances coronary blood flow to compromised myocardium is important in relieving ischemia. However, the mechanism for this increase in myocardial blood flow (MBF) is not well defined. In small vessels and capillaries, relative blood viscosity plays a very important role in determining myocardial vascular resistance (MVR). MVR reduce is due partly to the increase in negative charge of erythrocyte surface. We therefore hypothesized that the enhancement of nutrient blood flow to zones of myocardial ischemia during NTG is partly secondary to reduced MVR and blood flow viscosity. The latter is affected by the negative charge of erythrocyte surface. Methods 6 dogs with LAD flow-limiting stenosis ( group 1 ) and 6 dogs with LAD flow-limiting stenosis and LCx occlusion(group 2) were studied. At baseline and during intracoronary infusions of NTG (0.3-0.6 μg · kg-1·min-1 ), hemodynamics, MBF (mL·min-1·g-1), whole blood viscosity (WBη, mPa. S), elongation index (EI), eletrophoretic mobility of erythocytes (EME, [ μ. S-1 )/(V. Cm-1 ) ] ) and percent wall thickening (% WT) were determined. MVR was calculated using driving pressure/MBF. Results As compared to baseline, no changes in hemodynamics were seen during NTG. MBF increased and MVR decreased significantly in normal bed, the central 25 % and the entire of stenosed bed (P ＜ 0.05 ), with a decrease in WBη in both group 1 and group 2 dogs (18.6±9.7 % and 19.2±14.5 %, respectively). However, the % decrease in WBη was proportioned to the % increase in MBF or the % decrease in MVR only in the central 25% of stenosed bed ( r =0.87, P ＜0.001 ), but not in the entire stenosed bed and normal bed. EI did not show statistically significant differences between during NTG and at baseline, but EME did increase. And the % decrease in WBη during NTG was related to the % increase in EME ( r =0.83, P =0.01 ). Conclusions NTG reduced myocardial vascular resistance and blood viscosity due to the change of negative charge of erythrocyte surface may, in part, be the mechanism of the enhancement of nutrient blood flow to zones of myocardial ischemia. These results provide additional insights into the complex anti-ischemic effects of NTG.