title: Cilnidipine, an N+L-type dihydropyridine Ca channel blocker, suppresses the occurrence of ischemia/reperfusion arrhythmia in a rabbit model of myocardial infarction.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagai
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Xue-Hai
authors.initials: XH
authors.lastname: Chen
authors.forename: Ningyuan
authors.initials: N
authors.lastname: Wang
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uno
authors.forename: Chuanjiang
authors.initials: C
authors.lastname: Lu
authors.forename: Yu
authors.initials: Y
authors.lastname: Misao
authors.forename: Hirohito
authors.initials: H
authors.lastname: Onogi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Rumi
authors.initials: R
authors.lastname: Maruyama
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; C065927:cilnidipine; D009638:Norepinephrine