[The acute, chronic continuous after treatment and chronic intermittent with a variable therapeutic window (4 and 6 hours) hemodynamic effects induced with transdermal nitroglycerin in patients with congestive heart failure].
The aim of this study was to assess the minimum time interval necessary to avoid the development of tolerance during nitroglycerin patch application. We studied 24 patients, aged 23 to 73 years, with ischemic or idiopathic dilated cardiomyopathy (LV EF less than 0.40) and stable clinical conditions during 30 days before the study. All patients had significant reduction of systemic and pulmonary arterial pressure after sublingual nitroglycerin. After the hemodynamic assessment of the response to the first dose of the nitroglycerin patch, the patients were randomized to 1 of 3 chronic treatment groups: continuous patch application (Group A), intermittent application with 4 hours intervals (Group B), intermittent application with 6 hours intervals (Group C). All patients were studied by right heart Swan-Ganz catheterization; the hemodynamic response to a 10 mg multilayer matrix nitroglycerin patch was assessed before and every hour, in the next 4 hours, after both the first application of the patch and after 1 month of therapy; after chronic intermittent therapy, hemodynamic parameters were also measured 24 hours after drug withdrawal. Hemodynamic parameters were significantly changed after the first nitroglycerin patch application: particularly, mean systemic arterial (MAP), right atrial (RAP) and pulmonary wedge pressures (PWP) declined from 96 +/- 10, 8.9 +/- 1.8 and 20.1 +/- 5 to 81 +/- 6, 4.7 +/- 1.5 and 12.2 +/- 3 mmHg (-15.6, -47.2 and -59.3%, respectively); systemic vascular resistance (SVR) and heart rate (HR) were reduced from 1645 +/- 121 to 1288 +/- 89 dyne.s.cm-5 and from 85 +/- 7 to 81 +/- 7 b/min; lastly, cardiac index (CI), stroke volume (SVI) and stroke work index (SWI) increased from 2.3 +/- 0.3, 28.2 +/- 5 and 28.7 +/- 9 to 2.7 +/- 0.3 l/min/m2, 33.3 +/- 5 ml/min/m2 and 31.5 +/- 8 g.m/m2 (+17.4, 18.1 and 9.7%). After 1 month of either continuous or intermittent patch application with 4 hours intervals, hemodynamic parameters returned to control values with no significant change after patch application. In contrast, after intermittent patch application with 6 hours intervals, a persistent hemodynamic response to nitroglycerin patches was still present.(ABSTRACT TRUNCATED AT 400 WORDS)
Nodari
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Cattedra di Cardiologia, Università degli Studi, Brescia.
Metra
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Gei
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Danesi
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Furloni
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Cuminetti
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Dei Cas
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D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D004341:Drug Evaluation; D004361:Drug Tolerance; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage*; D013997:Time Factors
D003692:Delayed-Action Preparations; D005996:Nitroglycerin
Effetti emodinamici acuti e dopo trattamento cronico continuo, cronico intermittente con finestra terapeutica variabile (4 e 6 ore) indotti dalla nitroglicerina transdermica, in pazienti con insufficienza cardiaca congestizia.