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Echo-dipyridamole stress test evaluation of isosorbide-5-mononitrate efficacy and tolerance in patients with coronary heart disease: interplay with sympathetic activity.

Abstract：

:In 22 patients with stable myocardial ischemia, we prospectively studied the short- and long-term effects of isosorbide-5-mononitrate (5-ISMN) on dipyridamole-induced myocardial ischemia, the ability of dipyridamole-stress echocardiography to evaluate nitrate tolerance, and the role of activation of the neurohumoral system in nitrate tolerance development, assessed by modifications of catecholamines plasma levels and heart rate variability. After brief treatment with 5-ISMN, dipyridamole-stress echocardiography was negative in 19 of 22 patients (p < 0.001 vs. placebo). During the sustained phase, dipyridamole-stress echocardiography was positive after both placebo and active drug (p = NS vs. placebo). Heart rate variability showed significantly higher values in power of the low frequency (LF) band and low- to high-frequency ratio (L/H), as well as significantly lower values of the power of the high-frequency (HF) band (all p < 0.001) during brief but not during sustained administration of 5-ISMN. Norepinephrine plasma levels were significantly higher (p < 0.001) during short-term 5-ISMN administration but not during the sustained phase. Our results indicate that short-term administration of 5-ISMN antagonizes dipyridamole-induced myocardial ischemia and show the loss of antiischemic efficacy in 95% of patients during sustained treatment, demonstrating that dipyridamole-stress echocardiography is a useful tool to assess the presence of nitrate tolerance. Spectral analysis of heart rate variability and norepinephrine values confirm that brief nitrate administration increases sympathetic activity, a possible crucial trigger event in the development of nitrate tolerance, whereas prolonged nitrate treatment is not associated with prolonged neurohumoral activation.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Longobardi G,Ferrara N,Leosco D,Abete P,Iannuzzi GL,Acanfora D,Furgi G,Nicolino A,Pinna G,Rengo F

doi

10.1097/00005344-200007000-00007

subject

Has Abstract

pub_date

2000-07-01 00:00:00

pages

50-5

issue

eissn

0160-2446

issn

1533-4023

journal_volume

pub_type

临床试验,杂志文章,随机对照试验

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Echo-dipyridamole stress test evaluation of isosorbide-5-mononitrate efficacy and tolerance in patients with coronary heart disease: interplay with sympathetic activity.