Change of a beneficial effect into an untoward effect by ischaemia: Effect of quinidine-like drugs on vulnerability to ventricular fibrillation

被引:4
作者
Aupetit, JF [1 ]
Freysz, M [1 ]
Faucon, G [1 ]
Loufoua, J [1 ]
Timour, Q [1 ]
机构
[1] UNIV LYON 1, DEPT MED PHARMACOL, F-69373 LYON 08, FRANCE
关键词
antiarrhythmic drug; disopyramide; lidocaine; flecainide; ventricular fibrillation; myocardial ischemia;
D O I
10.1016/1382-6689(96)00027-0
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
The effects of three quinidine-like drugs, disopyramide, lidocaine and flecainide were investigated in anaesthetized, open-chest pigs on vulnerability to ventricular fibrillation under normal conditions and under myocardial ischaemia conditions. Vulnerability to fibrillation was evaluated by electrical ventricular fibrillation threshold (VFT), measured with 100 ms duration diastolic impulses the intensity of which was increased by steps of 1.0 or 0.5 mA. Impulses were delivered at the rate of 180 beats min(-1). The ventricles were subjected to pacing at the same rate before the VFT determination, particularly throughout periods of ischaemia of increasing duration (30, 60, 90, 120, 150 s), separated by appropriate intervals for reproducibility of the results. Monophasic action potential (MAP) duration and conduction time were monitored in the ischaemic area under pacing. Ischaemia was obtained by complete occlusion of the left anterior descending coronary artery near its origin. The three drugs were i.v. administered in clinical dose range (1.00 mg . kg(-1) plus 0.04 mg . kg(-1). min(-1)). In the absence of ischaemia, they increased almost equally VFT (from about 7 to 10 mA), despite 25% prolongation of conduction time. But, none of them was able to impede the increasingly marked fall of VFT caused by ischaemia: at 30 s, they had already lost any capacity for raising VFT and, beyond this time, they even aggravated its fall which led to spontaneous fibrillation when VFT approached 0 mA. The faster fall of VFT shortened time to onset of fibrillation (20/24 fibrillations for the three drugs at 150 s as against 12/24 in control period), the ischaemia-induced reduction of MAP duration (by 20%) being also hastened and slowing of conduction enhanced, given the addition of the depressant effects of ischaemia and drugs on conduction. Consequently, the antifibrillatory properties normally manifested by the studied drugs are first suppressed, then inverted by ischaemia.
引用
收藏
页码:1 / 7
页数:7
相关论文
共 36 条
[1]   ORAL FLECAINIDE ACETATE FOR THE TREATMENT OF VENTRICULAR ARRHYTHMIAS [J].
ANDERSON, JL ;
STEWART, JR ;
PERRY, BA ;
VANHAMERSVELD, DD ;
JOHNSON, TA ;
CONARD, GJ ;
CHANG, SF ;
KVAM, DC ;
PITT, B .
NEW ENGLAND JOURNAL OF MEDICINE, 1981, 305 (09) :473-477
[2]  
[Anonymous], 1989, NEW ENGL J MED, V321, P406
[3]   DECLINING INCIDENCE OF VENTRICULAR-FIBRILLATION IN MYOCARDIAL-INFARCTION - IMPLICATIONS FOR THE PROPHYLACTIC USE OF LIDOCAINE [J].
ANTMAN, EM ;
BERLIN, JA .
CIRCULATION, 1992, 86 (03) :764-773
[4]  
AUPETIT JF, 1993, N-S ARCH PHARMACOL, V348, P509
[5]   PROFIBRILLATORY EFFECTS OF LIDOCAINE IN THE ACUTELY ISCHEMIC PORCINE HEART [J].
AUPETIT, JF ;
TIMOUR, Q ;
LOUFOUAMOUNDANGA, J ;
BARRALCADIERE, L ;
LOPEZ, M ;
FREYSZ, M ;
FAUCON, G .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1995, 25 (05) :810-816
[6]   ARRHYTHMOGENICITY OF ANTIARRHYTHMIC DRUGS AND INTRAVENTRICULAR-CONDUCTION DISORDERS - POSSIBLE AGGRAVATION BY MYOCARDIAL-ISCHEMIA - STUDY IN THE PORCINE INSITU HEART [J].
AUPETIT, JF ;
TIMOUR, Q ;
LARBRE, JP ;
LOUFOUAMOUNDANGA, J ;
KIOUEH, I ;
LOPEZ, M ;
FAUCON, G .
CARDIOVASCULAR DRUGS AND THERAPY, 1993, 7 (02) :217-223
[7]   INADVERTENT MASSIVE LIDOCAINE OVERDOSE CAUSING TEMPORARY COMPLETE HEART-BLOCK IN MYOCARDIAL-INFARCTION [J].
BADUI, E ;
GARCIARUBI, D ;
ESTANOL, B .
AMERICAN HEART JOURNAL, 1981, 102 (04) :801-803
[8]   ACUTE CORONARY-ARTERY OCCLUSION-REPERFUSION-INDUCED ARRHYTHMIAS IN RATS, DOGS AND PIGS - ANTIARRHYTHMIC EVALUATION OF QUINIDINE, PROCAINAMIDE AND LIDOCAINE [J].
BERGEY, JL ;
NOCELLA, K ;
MCCALLUM, JD .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1982, 81 (02) :205-216
[9]   EFFECT OF DILTIAZEM ON ISCHEMIC MYOCARDIAL DEPOLARIZATION AND EXTRACELLULAR-K+ ACCUMULATION [J].
BLAKE, K ;
CLUSIN, WT .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1986, 127 (03) :261-265
[10]  
BOYETT MR, 1983, J PHYSIOL-LONDON, V342, pP52