The effects of trimetazidine on heart rate variability in patients with slow coronary artery flow.
OBJECTIVE
We sought to examine the effect of trimetazidine (TMZ) on heart rate variability (HRV), endothelin-1 (ET-1), NO, and anginal symptoms in patients with slow coronary artery flow (SCAF).


METHODS
The 48 patients with SCAF (29 women and 19 men; mean age, 52 +/- 9 years) were included in the study. Twenty milligrams TMZ 3 times a day or matched placebo were given randomly in a double-blinded fashion for 4 weeks. Patients were divided into 4 groups as follows: exercise-positive, TMZ-given group (group A, n = 12); exercise-positive, placebo-given group (group B, n = 12); exercise-negative, TMZ-given group (group C, n = 12); and exercise-negative, placebo-given group (group D, n = 12).


RESULTS
After TMZ treatment, HRV parameters, including SD of the all R-R intervals, SD of the averages of R-R intervals in all 5-minute segments of the entire recording, percentage of R-R intervals with more than 50-millisecond variation, and the square root of the mean of the sum of the squares of differences between adjacent R-R intervals, significantly improved both in exercise-positive and exercise-negative groups when compared with baseline. After TMZ treatment, ET-1 and NO levels significantly altered both in exercise-positive and exercise-negative groups when compared with baseline (17.7 +/- 2.7 vs 13.9 +/- 2.8 pg/mL [P = .01] and 18.1 +/- 3.8 vs 14.2 +/- 2.6 pg/mL [P = .01], respectively). After TMZ treatment, NO levels significantly increased in both exercise-positive and exercise-negative groups when compared with baseline (36.4 +/- 5.4 vs 43.3 +/- 6.8 micromol/L [P = .01] and 36.8 +/- 7.8 vs 43.3 +/- 4.8 micromol/L [P = .01], respectively). However, in placebo group, neither HRV parameters nor ET-1 and NO levels altered when compared with baseline. Also, after treatment, a significant correlation was detected between HRV parameters, including SD of the averages of R-R intervals in all 5-minute segments of the entire recording, SD of the all R-R intervals, percentage of R-R intervals with more than 50-millisecond variation, and the square root of the mean of the sum of the squares of differences between adjacent R-R intervals, and NO and ET-1 levels in TMZ group but not placebo.


CONCLUSIONS
Short-term TMZ therapy improved HRV parameters and endothelial products such as ET-1 and NO as well as anginal symptom in patients with SCAF. Improvement in HRV parameters was correlated with ET-1 and NO levels.
Cardiology Department, Faculty of Medicine, Inonu University, Malatya 34300, Turkey.
Ergun
E
Topal
Ramazan
R
Ozdemir
Irfan
I
Barutcu
Yüksel
Y
Aksoy
Isa
I
Sincer
Erdal
E
Akturk
Sengül
S
Cehreli
D001783:Blood Flow Velocity; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects*; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D019332:Endothelin-1 / Q000097:blood; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D012039:Regional Blood Flow; D018709:Statistics, Nonparametric; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D019332:Endothelin-1; D014665:Vasodilator Agents; D009569:Nitric Oxide; D014292:Trimetazidine