[The antianginal effects of a new delayed-release formulation of diltiazem in patients with stable angina pectoris: its evaluation by the ergometry test and dynamic electrocardiogram]. / Effetti antianginosi di una nuova formulazione ritardo di diltiazem nei pazienti con angina pectoris stabile: valutazione mediante test ergometrico ed elettrocardiogramma dinamico.

The antianginal efficacy and duration of action of slow-release (SR) diltiazem were evaluated in 12 patients with stable angina. Patients underwent maximal symptom limited bicycle exercise testing and 24-hour Holter monitoring at the end of 1-week placebo run-in phase and after 1-month therapy with either placebo or SR-diltiazem (120 mgs bid) using a placebo controlled, double-blind, randomized cross-over trial. No concomitant antianginal therapy, except sublingual nitroglycerin, was allowed during the trial. Exercise testing was performed 3 and 12 hours after drug administration. Blood samples were obtained for the determination of diltiazem plasma concentrations. After diltiazem administration, peak exercise duration increased significantly in comparison both with placebo and the run-in phase: from 292 +/- 48 to 378 +/- 113 s at 3 hours and from 286 +/- 59 to 366 +/- 109 s 12 hours after drug administration. Similarly, ST depression time increased from 240 +/- 59 to 374 +/- 123 s at 3 hours and from 231 +/- 57 to 332 +/- 123 s 12 hours after diltiazem. No significant changes of heart rate, blood pressure and double product were detected. Diltiazem plasma concentrations averaged, respectively, 175 +/- 86 pg/ml and 109 +/- 43 pg/ml 3 and 12 hours after its administration. No correlation was found between plasma concentrations and antianginal effects of diltiazem. At 24 hours Holter monitoring, SR-diltiazem induced a significant decrease of mean heart rate with a reduction in the number and duration of ischemic episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

[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]. / 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.

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)