Arrhythmogenicity of antiarrhythmic drugs and intraventricular conduction disorders: Possible aggravation by myocardial ischemia?Study in the porcine in situ heart

Aupetit, Jean‐François; Timour, Quadiri; Larbre, Jean‐Paul; Loufoua-Moundanga, J; Kioueh, I.; Lopez, Michel; Faucon, G

doi:10.1007/bf00878511

Cited by 10 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results obtained from the EFT measurement for evaluating vulnerability to fibrillation are consistent with those of other methods such as the determination of the time to onset of ischaemia‐induced fibrillation (Timour et al , 1991; Aupetit et al , 1993b; Loufoua et al , 1993). Ischaemia both shortens the time to fibrillation in proportion to its severity and hastens the fall of EFT: vulnerability to fibrillation may thus be considered to be inversely correlated to EFT or time to fibrillation.…”

Section: Discussionsupporting

confidence: 83%

“…The increase in mortality in multicentre trials performed in post‐infarction management (CAST, 1989; 1991) has justified this caution. Lastly, experimental studies have confirmed the possible harmful effects of such drugs under conditions of myocardial ischaemia, seen particularly as a reduction in the time to fibrillation (Timour et al , 1991; Aupetit et al , 1993b; Loufoua et al , 1993), almost immediately after their intravenous injection.…”

Section: Discussionmentioning

confidence: 96%

“…In this way, determination of vulnerability to fibrillation can be performed before and after the drug. The assessment of vulnerability to fibrillation by the time to onset of fibrillation before and after Ic antiarrhythmic drugs (fiecainide, propafenone, cibenzoline) has revealed to us a substantial increase with doses equal to or hardly higher than clinical doses (Timour et al , 1991; Aupetit et al , 1993b). However, time to fibrillation, based on fibrillation which spontaneously occurs after coronary occlusion, does not enable the vulnerability to fibrillation throughout the ischaemia period and before ischaemia to be determined.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ischaemia‐induced loss or reversal of the effects of the class I antiarrhythmic drugs on vulnerability to fibrillation

Aupetit

Loufoua-Moundanga

Faucon

et al. 1997

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 In the last decade, a number of clinical observations have questioned the ecacy of certain class I antiarrhythmic drugs against ischaemia-induced ventricular ®brillation. The eects of three drugs of this class, disopyramide (Ia), lignocaine (Ib) and¯ecainide (Ic) on the vulnerability to ®brillation during experimental ischaemia were investigated. 2 The study was carried out in anaesthetized, open-chest pigs (n=8 for each of the drugs, in addition to the control group, n=6). Vulnerability to ®brillation was evaluated by measuring electrical ®brillation threshold (EFT) by means of stepwise increased intensity of wide (100 ms) diastolic impulses applied to the ischaemic tissue at a 180 beats min 71 rate. Monophasic action potential (MAP) duration and conduction time in the ischaemic region were also measured. 3 EFT determinations were performed before and during periods of ischaemia induced by complete occlusion of the left anterior descending coronary artery near its origin. Ischaemic periods of increasing duration (30, 60, 90, 120, 150 s) were induced to determine the electrophysiological changes, of EFT especially, leading to ®brillation. 4 In the absence of ischaemia, all three drugs, administered by intravenous route (1 mg kg 71 plus 0.04 mg kg 71 min 71 ) increased EFT to a similar extent (from approximately 7 to 10 mA), despite a 25% prolongation of conduction time. 5 During ischaemia, none of the drugs prevented the fall in EFT towards 0 mA, resulting in spontaneous ®brillation. After 30 s of ischaemia, they no longer had any capacity for raising EFT and, after 60, 90 and 120 s of ischaemia, the decrease in EFT was exacerbated. This accelerated reduction in EFT shortened the time to onset of ®brillation (after 120 s of ischaemia, 62.5% of ®brillations with ecainide instead of 12.5 under control conditions, 75% instead of 25 with lignocaine and 50% instead of 25 with disopyramide). The reduction in MAP duration due to ischaemia was also signi®cantly accelerated (at 60 s, 178+5 ms instead of 192+4 with¯ecainide, 175+3 ms instead of 194+5 with lignocaine and 180+5 ms instead of 196+3 with disopyramide) and the slowing of conduction was made worse (prolongation of conduction time by 70% instead of 50). 6 In conclusion, the anti®brillatory properties normally manifested by these drugs are ®rst suppressed, then inverted by ischaemia, depending on oxygen debt varying with severity and duration of ischaemia.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ischaemia‐induced loss or reversal of the effects of the class I antiarrhythmic drugs on vulnerability to fibrillation

Aupetit

Loufoua-Moundanga

Faucon

et al. 1997

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The contractile fibers possessing the most negative potential exhibit the most delayed activation. The behavior of bupivacaine resembles that of the IC antiarrhythmic drugs, such as flecainide (21)(22)(23)(24)(25), which depress intraventricular conduction to a great extent on account of a strong influence on sodium channel in moderate doses which have little effect on repolarization. As these drugs have been shown by multicenter, randomized, placebo-controlled trials (26,27) to be likely to increase the incidence of sudden death, instead of decreasing it as expected, similar accidents were possible with bupivacaine.…”

Section: Discussionmentioning

confidence: 99%

Enhancement by ischemia of the risk of cardiac disorders, especially fibrillation, in regional anesthesia with bupivacaine

Freysz

Timour

Bertrix

et al. 1993

Acta Anaesthesiol Scand

View full text Add to dashboard Cite

The impairment of intraventricular conduction by bupivacaine may result in reentrant arrhythmias including ventricular fibrillation. The concentrations responsible for serious accidents are high (5.0 to 8.0 micrograms/ml), but likely to be lowered by myocardial ischemia which gives rise to similar disorders. Therefore we did an electrophysiological study of bupivacaine's effects in an ischemic area of the myocardium. Monophasic action potential (MAP) of the ventricular myocardium was recorded in 30 anesthetized, open-chest pigs. Conduction time and effective refractory period were also measured. Data were obtained during short periods (10-15 s) of pacing at 180 beats/min, but ventricular beats remained governed by the sinus node in the intervals. Ischemia was produced by occluding the left anterior descending coronary artery completely but transiently (up to 8 min), not far from its origin. Comparison was made between the effects of bupivacaine i.v. (n = 10), ischemia (n = 10) and both factors (n = 10). Two min after injection of bupivacaine 2.0 mg/kg (plasma levels 2.0-3.0 micrograms/ml), the duration of MAP was only slightly (7.5-15%) prolonged and its ischemia-induced shortening only slightly attenuated by bupivacaine. At the same time, conduction time was considerably (75-150%) lengthened and its ischemia-induced lengthening enhanced, so that ventricular fibrillation induced by coronary occlusion occurred sooner (about 100 instead of 300 s) in the presence of bupivacaine. Consequently, bupivacaine should be used only with caution in individuals whose myocardium is ischemic or liable to ischemia episodes.

show abstract

Prevention by Calcium Antagonists of Profibrillatory Effects of Class I Antiarrhythmic Drugs in Acute Myocardial Ischemia: Study in Pig Heart In Situ

Bui‐Xuan,

Aupetit,

Freysz

et al. 1997

Pharmacotherapy

View full text Add to dashboard Cite

Class I antiarrhythmic drugs do not decrease, but increase, the risk of ventricular fibrillation in the ischemic myocardium. On the contrary, vulnerability to fibrillation related to ischemia appears to be substantially reduced by calcium antagonists. We assessed whether the calcium antagonist diltiazem (0.50 mg/kg bolus plus 0.02 mg/kg/min infusion) could prevent the profibrillatory effect or even partially restore the antifibrillatory effect of a class I antiarrhythmic drug, flecainide (1 mg/kg bolus plus 0.04 mg/kg/min infusion) in the ischemic myocardium of anesthetized, open‐chest pigs. Ischemia was obtained by completely occluding the left anterior descending coronary artery near its origin. Vulnerability to fibrillation was assessed by electrical fibrillation threshold (EFT), measured with diastolic impulses of 100 msec duration delivered at a rate of 180 beats/minute. Diltiazem did not oppose the rise in EFT induced by flecainide in the absence of ischemia (6.8 ± 1.2 to 9.9 ± 0.9 mA, p<0.001). It limited the fall in EFT observed under the dual influence of ischemia and flecainide (4.2 ± 0.9 vs 1.3 ± 0.6 mA, p<0.001). By reducing calcium entry into myocardial fibers, diltiazem delayed ischemic depolarization, as evidenced by reduced shortening of the monophasic action potential duration from 215 ± 7 to 200 ± 4 msec, instead of 178 ± 6 (p<0.001), and reduced lengthening of intraventricular conduction time from 33 ± 5 to 43 ± 4 msec, instead of 53 ± 4 (p<0.01). Therefore, diltiazem is likely to prevent the loss and even the reversal of the antifibrillatory properties of flecainide due to myocardial ischemia in dosages that do not adversely affect myocardial contractility or atrioventricular conduction to a large extent.

show abstract

Arrhythmogenicity of antiarrhythmic drugs and intraventricular conduction disorders: Possible aggravation by myocardial ischemia?Study in the porcine in situ heart

Cited by 10 publications

References 19 publications

Ischaemia‐induced loss or reversal of the effects of the class I antiarrhythmic drugs on vulnerability to fibrillation

Ischaemia‐induced loss or reversal of the effects of the class I antiarrhythmic drugs on vulnerability to fibrillation

Enhancement by ischemia of the risk of cardiac disorders, especially fibrillation, in regional anesthesia with bupivacaine

Prevention by Calcium Antagonists of Profibrillatory Effects of Class I Antiarrhythmic Drugs in Acute Myocardial Ischemia: Study in Pig Heart In Situ

Contact Info

Product

Resources

About