Cilnidipine, an N+L-type dihydropyridine Ca channel blocker, suppresses the occurrence of ischemia/reperfusion arrhythmia in a rabbit model of myocardial infarction.
Dihydropyridine Ca channel blockers are widely prescribed for the treatment of hypertension and coronary artery diseases, but it remains unknown whether these agents protect against arrhythmias. We investigated whether cilnidipine, an N+L-type Ca channel blocker, reduces the incidences of ventricular premature beats (VPBs) and, if so, via what mechanisms. Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Cilnidipine (0.5 or 1.0 microg/kg/min, i.v.) or saline (i.v.) was administered from 30 min before ischemia to 30 min after reperfusion. Electrocardiogram and blood pressure were monitored and the incidences of VPBs were measured. At 48 h after reperfusion, myocardial infarct was measured. Myocardial interstitial noradrenaline levels were determined before, during and after 30 min of ischemia with cilnidipine (0.5 and 1.0 microg/kg/min) or saline. The incidences of VPBs during ischemia and reperfusion were significantly attenuated in the cilnidipine 0.5 group (15.6 +/- 3.1 and 6.8 +/- 1.9 beats/30 min) and in the cilnidipine 1.0 group (10.4 +/- 4.9 and 3.5 +/- 1.0 beats/30 min) compared to the control group (27.2 +/- 4.5 and 24.2 +/- 3.1 beats/30 min), respectively. Myocardial interstitial noradrenaline levels were significantly reduced in the cilnidipine 0.5 and 1.0 groups compared to the control group during ischemia and reperfusion. The antiarrhythmic effect of cilnidipine may be related to the attenuation of cardiac sympathetic nerve activity. This finding may provide new insight into therapeutic strategies for hypertensive patients with ventricular arrhythmias.
Nagai
Hiroshi
H
Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
Minatoguchi
Shinya
S
Chen
Xue-Hai
XH
Wang
Ningyuan
N
Arai
Masazumi
M
Uno
Yoshihiro
Y
Lu
Chuanjiang
C
Misao
Yu
Y
Onogi
Hirohito
H
Kobayashi
Hiroyuki
H
Takemura
Genzou
G
Maruyama
Rumi
R
Fujiwara
Takako
T
Fujiwara
Hisayoshi
H
D000818:Animals; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D004195:Disease Models, Animal; D006339:Heart Rate; D015994:Incidence; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D011817:Rabbits; D015996:Survival Rate; D013564:Sympathetic Nervous System / Q000378:metabolism; D017180:Tachycardia, Ventricular / Q000453:epidemiology / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000453:epidemiology / Q000517:prevention & control*; D018879:Ventricular Premature Complexes / Q000453:epidemiology / Q000517:prevention & control
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; C065927:cilnidipine; D009638:Norepinephrine