Monophasic action potentials

MAP Macrophage-activating 6ctor MAO Monoamine oxidase MAP Monophasic action potential... 

It is customary today to classify anti arrhythmic drugs according to their mechanism of action. This is best defined by intracellular recordings that yield monophasic action potentials. In the accompanying figure, the monophasic action potentials of (A) slow response fiber (SA node) and (B) fast Purkinje fiber are shown. For each description that follows, choose the appropriate drug with which the change in character of the monophasic action potential is likely to be associated... 

I88-E89. The answers arc 188-g 189-b. (Hardman, pp 858-859, 864-865.) It is widely accepted that anti arrhythmic drugs are best classified according to their electro physio logic attributes. This is best accomplished by relating the effects of the different drugs to their actions on Na and Ca channels, which are reflected by changes in the monophasic action potential. Amiodarone blocks Na, Ca, and K currents and markedly prolongs repolarization, particularly in depolarized cells. Hecainide is related... 

Monophasic Action Potential in Anesthetized Guinea Pigs. Epicardia monophasic action potential recording using suction/contact pressure electrodes are emplaced, allowing simultaneous measurement of ECG and heartrate. 

Bunaftine (21) is a naphthalenecarboxamide derivative, that has been developed as an antiarrhythmic agent. The compound exhibits both Class I and Class III electrophysiological effects. Fenici and co-workers studied bunaftine in patients with paroxysmal atrial tachyarrhythmia and recorded right atrial monophasic action potentials [72]. A mean increase of 18% in atrial repolarization time and an increase in monophasic APD during pac-... 

Figure 16.3 Schematic representation of monophasic action potentials (MAP) recorded in the isolated rabbit heart system, showing MAP duration changes Triangulation with APD60 prolongation (a) and triangulation with APD60 shortening (b). Triangulation is...

Monophasic action potential. Glycerin/ ethanol extract of the fresh leaf, administered intragastrically to dogs at a dose of 30 mg/kg, increased duration of ventricular monophasic action potential (16%) . Mutagenic activity. Ethanol (100%) extract of the fresh leaf, on agar plate, was active on Salmonella typhimurium T1530 . Natural-killer cell enhancement. Fixed oil of embryos, administered orally to adults, was inactive . Nonsaponifiable fraction of fruit fixed oil and seed oil, administered to rats at a dose of 0.3% of diet, were active. The polyphenol stripped seed oil was inactive . 

OEl 65 Occhiuto, F., C. Circosta, A. Gregorio, and G. Busa. Olea europaea L. and oleuropein effects on excito-conduc-tion and on monophasic action potential in anesthetized dogs. Phytother... 

The electrocardiogram can be obtaining using standard limb leads and/or precordial leads. A lead should be selected that is stable over time and that has a sharp demarcation at the end of the T wave to facilitate the measurement of the QT interval duration. One can also position a monophasic action potential electrode catheter through the femoral or carotid artery to obtain endocardial monophasic action potentials (see below Modification of the Method). 

Measurement of the monophasic action potential (MAP) in anesthetized dogs for evaluation of arrhythmogenic activity of drugs was recommended by Usui et al. (1998), Weissenburger et al. (2000). 

A quad-polar electrode catheter is inserted through the left femoral artery and positioned at the noncoronary cup of the aortic valve to record a His bundle electrogram. A bidirectional steerable monophasic action potential (MAP) recording/pacing combination catheter is inserted through the left femoral vein and positioned at the endocardium to obtain MAP signals. The signals are amplified with a DC amplifier. 

Franz MR (1991) Method and theory of monophasic action potential recording. Progress in Cardiovascular Diseases 6 347-368... 

CRITICAL ASSESSMENT OF THE METHOD The Purkinje fiber is a non-contractile tissue, which facilitates electrode positioning and stability. In comparison to the papillary muscle or the monophasic action potential in the intact heart, drug-induced effects on the action potential duration are considerably larger. Whereas this is not necessarily a disadvantage, the model has been viewed as possibly being too sensitive for drug-induced effects on repolarization. 

Franz MR (1994) Bridging the gap between basic and clinical electrophysiology What can be learned from monophasic action potential recordings J Cardiovasc Electrophysiol 5 699-710... 

Rabbits are anesthetized with methohexital and alpha-chloralose and ventilated mechanically. After establishing an intravenous port, the animals receive the alphai-agonist methoxamine at 15 fig/kg/min, a dose that should have only a slight effect on systemic arterial blood pressure. The ECG is measured using standard limb leads and an monophasic action potential... 

The evaluation is based on the incidence of either an overt tachyarrhythmia or the appearance of early after depolarizations in the monophasic action potential. 

In studies by Carlsson (1990) the subsequent administration of clofilium (20.8 pmol/kg) lead to a prolongation of the QTU interval and the monophasic action potential with the appearance of early after depolarizations. This was followed by ventricular arrhythmias in all rabbits. Pretreatment with prazosin (1 mg/kg iv) was able to attenuate the arrhythmia. 

Using an endocardial monophasic action potential recording, the incidence of early after depolarizations can be determined. The catheter (e.g. Franz combination catheter, EPT No. 1650) can be placed through the jugular vein or carotid artery under fluoroscopic guidance. 

Sedgwick ML, Dalrymple I, Rae AP, Cobbe SM. Effects of the new class III antiarrhythmic drug dofetilide on the atrial and ventricular intracardiac monophasic action potential in patients with angina pectoris. Eur Heart J 1995 16(11) 1641-6. 

Yuan S, Wohlfart B, Rasmussen HS, Olsson S, Blomstrom-Lundqvist C. Effect of dofetilide on cardiac repolarization in patients with ventricular tachycardia. A study using simultaneous monophasic action potential recordings from two sites in the right ventricle. Eur Heart J 1994 15(4) 514-22. 

Sedgwick ML, Rasmussen HS, Cobbe SM. Effects of the class III antiarrhythmic drug dofetilide on ventricular monophasic action potential duration and QT interval dispersion in stable angina pectoris. Am J Cardiol 1992 70(18) 1432-7. 

Propafenone is a class 1C antiarrhythmic drug with local anesthetic effects and a direct stabilizing action on myocardial membranes. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (phase O) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions. The diastolic excitability threshold is increased, and the effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. 

In pursuit of a suitable means to evaluate compounds that could possibly cause TdP, Hondegham and colleagues employed a bioassay as a means of assessing the proarrhythmic effects of a host of drugs in the isolated female rabbit hearts using the Langendroff perfusion method (Hondegham et al. 2003). Monophasic action potentials (MAP) measurements were used to determine intravascular conductirai, APD,... 

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