Delayed preconditioning-mimetic actions of nitroglycerin in patients undergoing exercise tolerance tests

Article

关键词: NITRIC-OXIDE SYNTHASE;    MYOCARDIAL-ISCHEMIA;    CONSCIOUS RABBITS;    LATE-PHASE;    TRANSDERMAL NITROGLYCERIN;    ANGINA-PECTORIS;    STABLE ANGINA;    AMLODIPINE;    MECHANISM;    ATENOLOL;   

DOI  :  10.1161/CIRCULATIONAHA.104.515445

来源: SCIE

【 摘 要 】

Background - Nitroglycerin ( NTG) induces delayed preconditioning ( PC)- mimetic effects in animal models and in humans during coronary angioplasty. We tested the hypothesis that NTG mitigates ischemia and enhances functional capacity during an exercise tolerance test ( ETT) in patients with coronary artery disease. Methods and Results - Twenty- eight patients with stable angina and ischemia documented by a stress test were randomized in a double- masked, crossover design to receive a titrated intravenous infusion of NTG or normal saline over 4 hours. At 24 to 28 hours after study medication infusion, each patient underwent 2 ETTs separated by a 1- week washout period. Compared with control patients, pretreatment with NTG was associated with a dose- dependent increase in exercise duration averaging 40 seconds ( 412 +/- 19 versus 372 +/- 24 seconds, P = 0.014) and an improvement in ECG manifestations of ischemia, as shown by a decrease in maximal ST- segment depression ( 1.84 +/- 0.14 versus 1.63 +/- 0.13 mm, P = 0.011), sum of ST- segment depressions in 12 leads ( 7.64 +/- 1.01 versus 6.61 +/- 0.83 mm, P = 0.027), and time to resolution of ST- segment depression ( 229 +/- 30 versus 207 +/- 28 s, P = 0.018). These benefits occurred despite an increase in myocardial workload after NTG, as indicated by a higher peak rate- pressure product ( 24 492 +/- 1054 versus 22 536 +/- 1019 mm Hg/ min, P = 0.015). Conclusions - NTG produces a late PC- mimetic effect that mitigates the ECG manifestations of ischemia during exercise and improves exercise capacity. To our knowledge, this is the first study to demonstrate that NTG can alleviate exercise- induced ischemia 24 hours after its administration, long after the hemodynamic effects have subsided. The finding that nitrate- induced late PC ameliorates a common manifestation of coronary artery disease has potentially significant implications for the management of this disorder and for the design of clinical trials.

【 授权许可】

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