Facilitation of reentry by lidocaine in canine myocardial infarction

Fazekas, Tamás; Scherlag, Benjamin J.; Mabo, Philippe; Patterson, Eugene; Lazzara, Ralph

doi:10.1016/0002-8703(94)90123-6

Cited by 14 publications

(12 citation statements)

References 43 publications

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“…In this subacute myocardial infarction group, sustained monomorphic ventricular tachycardia (VT) was inducible by programmed electrical extrastimuli as late as 1-4 days after consecutive LAD ligation before lidocaine administration in one, but in seven dogs after lidocaine. The results show that lidocaine (3 mg/kg) has arrhythmogenic/proarrhythmic action probably due to its depressant effect on moderately sick cardiac tissue 19 . The membrane-stabilizing effect of lidocaine and moricizine in the late phase of myocardial ischemia on the canine model of AMI was confirmed in two international laboratories.…”

Section: Results Of Experiments In International Laboratoriesmentioning

confidence: 94%

“…Modulation of the Class IB and IC AADs due to the high noradrenaline levels in cardiac tissue manifested itself in animal experiments by a high degree of electrical destabilization of cardiac ventricles demonstrable by a decrease in VFT (ref. 10 ), altered course of membrane-action potentials, and an increased tendency toward reentry circuit closure 19 . Sympathetic neural activation can be induced not only by Malliani's reflex but, also, by psychological (emotional) stress, which is why the SNA-mediated "modulation" of the effect of AADs should also be taken into account in psychological stress, as documented in animal experiments.…”

Section: Pathogenesis Of Electrical Destabilization Of Cardiac Ventrimentioning

confidence: 99%

See 1 more Smart Citation

Class I and III antiarrhythmic drugs for prevention of sudden cardiac death and management of postmyocardial infarction arrhythmias. A review

Vrána

Pokorný²,

Marcián³

et al. 2013

BIOMED PAP

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Background. The aim of the present paper is to review the evolution of concepts regarding the use of Class I and III antiarrhythmic drugs (AADs) in myocardial infarction over the past four decades. Methods. Results of animal experiments carried out by the authors and papers published between 1970 and 2012 in journals and the PubMed search system were used. Results. Animal experiments carried out as early as the 1970s showed that Class IB and IC AADs lose their antiarrhythmic effect and electrically destabilize ventricles in the very early phase of myocardial ischemic focus formation. The cause of this is interaction between Class IB and IC AADs as well as Class III AADs with sympathetic neural activation (SNA) of the heart in the early phase of myocardial ischemia. Given the extremely high and uneven distribution of noradrenaline in tissue, SNA results in dispersion of the depolarization and repolarization processes in the ventricles. The clinical sequels of the interaction between the effects of AADs and SNA are as follows: the antiarrhythmic effect of AADs is restored in AMI once SNA has resolved; membrane-destabilization of the ventricles can be restored any time in the presence of randomly occurring SNA not only due to increasing myocardial ischemia but, also, as a result of psychological stress (emotions), and any pre-existing structural heart disease will enhance the pro-fibrillatory effect of a randomly occurring SNA. Conclusions. Despite the above risks, AADs continue to play an irreplaceable role in suppressing post-myocardial arrhythmias and in preventing sudden cardiac death following ICD placement. The risk of AADs' proarrhythmic effect in SNA can be reduced by combining them with beta-blockers. The last recourse when attempting to suppress malignant ventricular tachyarrhythmias is left sympathetic denervation of the heart.

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Section: Results Of Experiments In International Laboratoriesmentioning

confidence: 94%

Section: Pathogenesis Of Electrical Destabilization Of Cardiac Ventrimentioning

confidence: 99%

Class I and III antiarrhythmic drugs for prevention of sudden cardiac death and management of postmyocardial infarction arrhythmias. A review

Vrána

Pokorný²,

Marcián³

et al. 2013

BIOMED PAP

View full text Add to dashboard Cite

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“…It must be noted that several factors, such as tissue condition or the applied concentration of the drug, are responsible for the controversial pro-or antiarrhythmic effects of lidocaine (19,30) and that simulation studies provide a powerful tool for gaining a greater understanding of the underlying mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Exploring the role of pH in modulating the effects of lidocaine in virtual ischemic tissue

Cardona

Trénor

Moltó³

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Lidocaine is a class I antiarrhytmic drug that blocks Na(+) channels and exists in both neutral and charged forms at a physiological pH. In this work, a mathematical model of pH and the frequency-modulated effects of lidocaine has been developed and incorporated into the Luo-Rudy model of the ventricular action potential. We studied the effects of lidocaine on Na(+) current, maximum upstroke velocity, and conduction velocity and demonstrated that a decrease of these parameters was dependent on pH, frequency, and concentration. We also tested the action of lidocaine under pathological conditions. Specifically, we investigated its effects on conduction block under acute regional ischemia. Our results in one-dimensional fiber simulations showed a reduction of the window of block in the presence of lidocaine, thereby highlighting the role of reduced conduction velocity and safe conduction. This reduction may be related to the antifibrillatory effects of the drug by hampering wavefront fragmentation. In bidimensional acute ischemic tissue, lidocaine increased the vulnerable window for reentry and exerted proarrhythmic effects. In conclusion, the present simulation study used a newly formulated model of lidocaine, which considers pH and frequency modulation, and revealed the mechanisms by which lidocaine facilitates the onset of reentries. The results of this study also help to increase our understanding of the potential antifibrillatory effects of the drug.

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“…Animal models of cardiac disease have reliably forecast adverse effects on cardiac physiological function, especially on normal sinus rhythm (e.g., pro-arrhythmogenicity of certain inotropes and anti-arrhythmic agents) [42,88]. Use of experimental models of acute MI, for example, confirmed the clinically observed detrimental effect of class 1B and 1C antiarrhythmic drugs in patients with acute MI vs. beneficial effect of beta-adrenoceptor-blocking agents in that context [89][90][91].…”

Section: Cardiac Toxicity In Animal Modelsmentioning

confidence: 99%

Guidelines for Translational Research in Heart Failure

Lara‐Pezzi

Menasché

Trouvin

et al. 2015

J. of Cardiovasc. Trans. Res.

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Heart failure (HF) remains a major cause of death and hospitalization worldwide. Despite medical advances, the prognosis of HF remains poor and new therapeutic approaches are urgently needed. The development of new therapies for HF is hindered by inappropriate or incomplete preclinical studies. In these guidelines, we present a number of recommendations to enhance similarity between HF animal models and the human condition in order to reduce the chances of failure in subsequent clinical trials. We propose different approaches to address safety as well as efficacy of new therapeutic products. We also propose that good practice rules are followed from the outset so that the chances of eventual approval by regulatory agencies increase. We hope that these guidelines will help improve the translation of results from animal models to humans and thereby contribute to more successful clinical trials and development of new therapies for HF.

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Facilitation of reentry by lidocaine in canine myocardial infarction

Cited by 14 publications

References 43 publications

Class I and III antiarrhythmic drugs for prevention of sudden cardiac death and management of postmyocardial infarction arrhythmias. A review

Class I and III antiarrhythmic drugs for prevention of sudden cardiac death and management of postmyocardial infarction arrhythmias. A review

Exploring the role of pH in modulating the effects of lidocaine in virtual ischemic tissue

Guidelines for Translational Research in Heart Failure

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