TY - JOUR
T1 - Echo-dipyridamole stress test evaluation of isosorbide-5-mononitrate efficacy and tolerance in patients with coronary heart disease
T2 - Interplay with sympathetic activity
AU - Longobardi, Giancarlo
AU - Ferrara, Nicola
AU - Leosco, Dario
AU - Abete, Pasquale
AU - Iannuzzi, Gian Luca
AU - Acanfora, Domenico
AU - Furgi, Giuseppe
AU - Nicolino, Antonio
AU - Pinna, Giandomenico
AU - Rengo, Franco
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Coronary heart disease
KW - Dipyridamole test
KW - Echocardiography
KW - Heart rate variability
KW - Nitrate tolerance
KW - Sympathetic activity
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M3 - Article
C2 - 10892660
AN - SCOPUS:12944262272
VL - 36
SP - 50
EP - 55
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 1
ER -