Effect of cutaneous nitroglycerin patches on coronary artery diameter: Issues concerning development of tolerance

AbstractThe coronary dilative and systemic responses to graded doses of intracoronary nitroglycerin were studied in 53 patients undergoing diagnostic coronary arteriography, 43 of whom had received a cutaneous nitroglycerin patch. During coronary arteriography, graded doses of 50, 100 and 200 μg of intracoronary nitroglycerin were given 5 min apart. An arteriogram and hemodynamic measurements were obtained after each dose. In the control group (n = 10) cumulative intracoronary nitroglycerin doses of 50,150 and 350 μg caused an increase in coronary diameter in the left anterior descending artery of 20 ± 4%, 21 ± 3% and 22 ± 7%, respectively, and in the circumflex artery of 18 ± 6%, 23 ± 8% and 18 ± 5% (p < 0.01 versus values in untreated group).In Group 1 (15 patients given a 5 mg/24 h nitroglycerin patch 2 to 12 h before coronary arteriography), the same intracoronary nitroglycerin doses increased the left anterior descending artery diameter by 6 ± 2%, 7 ± 2% and 7 ± 2%, respectively, and the circumflex artery diameter by 3 ± 2%, 3 ± 2% and 1 ± 3%. All values were statistically different from control (p < 0.05). An even more pronounced blunting (p < 0.01) of the coronary dilative response was observed in Group 2 (14 patients given a 15 mg/24 h nitroglycerin patch 2 to 12 h before arteriography). The diameter responses to intracoronary nitroglycerin observed in Group 3 (seven patients given a 5 mg/24 h nitroglycerin patch 24 h before arteriography) and Group 4 (seven patients given a 15 mg/24 h nitroglycerin patch 24 h before arteriography) were not significantly different from those of the control group.The results demonstrate that a nitroglycerin patch administered a few hours before coronary arteriography caused significant coronary artery dilation and that the incremental dilation due to the intracoronary nitroglycerin was small. On the other hand, 24 h after arteriography, the coronary dilative effect of the patch was attenuated (suggesting development of tolerance) and the increment in diameter induced by intracoronary nitroglycerin was much larger

Cibenzoline for treatment of ventricular arrhythmias: A double-blind placebo-controlled study

Cibenzoline, a new class I antiarrhythmic drug, was administered to 24 patients with frequent (> 30/h) premature ventricular complexes. Three patients discontinued the medication because of epigastric distress before repeat ambulatory electrocardiography. Of the remaining 21 patients, 13 responded to 130 mg twice daily by more than 75% suppression of premature ventricular complex frequency and 6 additional patients responded to 160 mg twice daily during an open-label titration phase. Events of ventricular tachycardia (≥3 beats) were totally suppressed in 9 of 10 patients and markedly diminished in the 1 remaining patient. During a doubleblind placebo-controlled crossover phase in 16 patients (21 patients minus 2 nonresponders and 3 who developed side effects), cibenzoline suppressed the number of premature ventricular complexes per 24 hours (4,075 ± 868 to 1,758 ± 1,089, p = 0.02), the number of events of ventricular tachycardia (31 ± 30 to 2 ± 0, p = 0.01) and the number of premature ventricular complex pairs (61 ± 28 to 25 ± 21, p = 0.01). Cibenzoline plasma concentration was 59 to 421 ng/ml in responders and higher (387,758 and 852 ng/ml, respectively) in the three subjects with side effects (right bundle branch block in one, hypotension in one, gastrointestinal upset and central nervous system complaints in one). Cibenzoline plasma concentration correlated with PR interval (r = 0.55, p = 0.0106) and corrected QT interval (r = 0.58, p = 0.0054). Further clinical investigation of this new antiarrhythmic agent is needed

ACE inhibitors for myocardial infarction and unstable angina

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30900/1/0000569.pd