Abstract 2898: Chronic Smoking Impairs Endogenous Coronary Fibrinolytic Function in Women with Angiographically Normal Coronary Arteries
Background: In the human forearm vasculature, cigarette smoking has been shown to impair tissue plasminogen activator (tPA) release induced by bradykinin (BK). However, in women, it is unknown whether smoking impairs endogenous fibrinolysis by reducing the capacity of the coronary endothelium to release tPA. Thus, we assessed whether chronic smoking influenced coronary tPA release in response to BK in 18 women (10 nonsmokers and 8 smokers; mean age 58 ± 4) who had normal coronary angiograms.
Methods: Graded doses of BK (0.2, 0.6, 2.0 μg/min) were infused into the left coronary artery. Coronary blood flow (CBF) of the left anterior descending artery was evaluated by measuring Doppler flow velocity. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS) for measurement of tPA antigen and plasminogen activator inhibitor-1 (PAI-1) antigen. Net coronary release of tPA antigen was determined as a CS-Ao gradient × CBF × [(100−Hematocrit)/100].
Results: Age, coronary risk factors except for smoking status, and baseline coronary diameters and flows were identical in the two groups. Graded doses of BK caused dose-dependent increases in CBF, the CS-Ao gradient, and net tPA release in all subjects. Increases in the CS-Ao gradient induced by BK in smokers were significantly smaller than those in nonsmokers (nonsmokers: 1.6 ± 0.3, 7.4 ± 1.2, 8.5 ± 0.9 ng/ml; smokers: 0.6 ± 0.3, 4.0 ± 0.8, 5.7 ± 1.0 ng/ml, p<0.05). Although the increase in CBF induced by BK did not differ between the two groups (nonsmokers: 102 ± 18, 176 ± 34, 292 ± 43 %; smokers: 78 ± 14, 156 ± 28, 258 ± 33, p=n.s.), net coronary tPA release induced by BK in smokers was significantly lower than that in nonsmokers (nonsmokers: 33 ± 9, 237 ± 35, 358 ± 78 ng/min; smokers: 10 ± 11, 157 ± 26, 229 ± 51 ng/min, p<0.05). With an increase in the dosage of BK, the level of PAI-1 did not change either the Ao or the CS in these two groups.
Conclusion: In women with angiographically normal coronary arteries, chronic smoking impairs coronary release of tPA in response to BK, suggesting that chronic smoking in women may suppress endogenous coronary fibrinolytic function and promote coronary thrombogenesis.