Effects of yutac on new in vivo canine triggered activity arrhythmia models

J Mol Cell Cardiol 22 (Supplement III) (1990) PF52INfiIBITION OF RRPKRFUSION ARRRYTHKtAS BY PRETREATNENT ANGIOTRNSIN CONVERTING RWZYHE INHIBITOR TRANDOLAPRIL

OF PIGS

WITH THE

Cecilia A Muller, Lionel H Opie, Alida M Theron, Helen M Basset, MRC Beart Research Unit, Univ. Cape Town & Groote Schuur Hosp., S. Africa Inhibition of angiotensin converting enzyme (ACE) in the myocardium may theoretically decrease intracellular calcium and thereby prevent reperfusion arrhythmias. Trandolapril (TRAN) is a long-acting ACE TRAN 0.3 mg/kg or inhibitor with marked myocardial tissue specificity. placebo (PLAC) was administered orally once a day for 10 days to pigs Reperfusion of the anterior descending coronary artery (23-27 kg). was allowed after 20 min of total occlusion. ACE activity plasma mu/ml

during reperfusion LV tissue mU/mg protein

50.3 + 10.7 0.649 t 0.080 PLACEBO(n5-9) 0.291 f. 0.035** 'TRAN (n8-11) 8.0 + 2.3* ** P
PF53

Antiarrhythmic

effects

of

ACE-inhibitors

during

myocardial

VFT c-1 % of preCAL

31 + 6 61 + 9*

cardiac output or The PLAC group. may in part be

ischaemia?

R Dietz. T.S. Sueselbeck, 6. Offner and A. Schomig, Oept of Cardiology, 69 Heidelberg, FRG A reductton in the duration of ventricular fibrillation has been observed after reperfusion wrth ACE-inhibitors - a finding of questionable clinical significance. It remained unclear, however whether the incidence and severity of rhythm disturbances could be modulated by ACE-Inhibitors during myocardial ischaemia. In a rat isolated heart preparation reproducrble ventricular tachycardias and ventricular fibrillatron were induced by ligation of the left anterror descendens. The antiarrhythmic effects of the following ACE-inhibitors were tested: captopril (C. 10m5 to 10m3M). enalaprilat (E: 10V5M), lisinopril dihydrat (L: 10e5M). ramiprilat (R: 10-6M)cilazaprilat (CI lo-“M) and zofenoprtl (2: 10e to 10e4M). No protective effect could be observed agatnst ischaemra Induced rhythm disturbances for C.E.L. Ci and R. Only Z caused a dose dependent reduction rn ventricular tachycardias with rates above 400/min (10e6M: from100 % to 75%) rn ventrtcular tachycardias with rates above 800/mm (10e5M, from 74% to 45%) and in ventricular fibrrllatton (lOeM: from 70% to 50%. 10m5: from 70% to 32%). Conclusion: The differential effect of ACE-inhibitors in suppressing cschaemia induced arrhythmias may be related to their potency of inhibiting the cardiac RAS. Only zofenopril which has been shown to produce striking and long lasting inhibition of the cardiac RAS (AJH 2 294-306, 1989) exhibrted a dose-dependent antiarrhythmic effect.

PF54

EFFECTS OF YUTAC ON NEW IN VZVO CANINE TRIGGERED ACTIVITY ARRHYTHMIA MODELS Akihiro Haruno and Keitaro Hashimoto Department of Pharmacology, Yamanashi Medical College,

Yamanashi, Japan

YUTAC is a newly developed class I antiarrhythmic agent and was reported to be effective on digitalis induced-, adrenaline induced-, and two-stage coronary ligation induced-canine spontaneously occurring ventricular arrhythmia models. We investigated whether YUTAC is also effective on our new triggered activity arrhythmia models. Triggered activity induced ventricular arrhythmias were produced during a pause between trains of rapid ventricular stimulation (cycle length; 250 msec, train number; 15) in anesthetized open-chest dog hearts given subtoxic doses of digitalis or adrenaline to the left anterior descending coronary artery. YUTAC suppressed these triggered arrhythmias at doses of 3-30 ug, i.a. Triggered activity is thought to be an important mechanism of generation of arrhythmias, . so YUTAC is expected to become a useful drug for the treatment of various clrmcal arrhythmias. s.73