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

Giancarlo Longobardi, Nicola Ferrara, Dario Leosco, Pasquale Abete, Gian Luca Iannuzzi, Domenico Acanfora, Giuseppe Furgi, Antonio Nicolino, Giandomenico Pinna, Franco Rengo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)50-55
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume36
Issue number1
Publication statusPublished - 2000

Keywords

  • Coronary heart disease
  • Dipyridamole test
  • Echocardiography
  • Heart rate variability
  • Nitrate tolerance
  • Sympathetic activity

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Echo-dipyridamole stress test evaluation of isosorbide-5-mononitrate efficacy and tolerance in patients with coronary heart disease: Interplay with sympathetic activity'. Together they form a unique fingerprint.

Cite this