Modulation of Interval–Force Dependence of Rat Papillary Muscle at Acute and Course Exposure of Amiodarone

Sergey Afanasiev,Sergey Popov,Dina Kondratyeva,Roman Batalov

doi:10.4236/pp.2012.33046

Abstract

Change of interval–force dependence of rat papillary muscles at acute and course use of amiodarone was investigated. Methods. The experiments were performed on isolated papillary muscles of Wistar rats. The extrasystolic (0,2-1,5 s), postextrasystolic contractions and post-rest (4-60 s) reactions of rat left papillary muscles perfused Krebs-Henseleit solution with amiodarone (1 μM) and papillary muscles of rat treated amiodarone in dose 20 mg/kg/day for 14 days were investigated. Results. It has been found that both acute and course use of amiodarone decreases the amplitude of extrasystolic contraction. At the same time, only acute use of amiodarone leads to additional enhancement of potentialtion of contractile response at extrasystolic impulse and performance of post-rest test. Conclusion was made, that both acute and course use of amiodarone decreases excitability of cardiomyocytes but only at course use this antiarrythmic drug increases effective refractory period of myocardium. Acute exposure of amiodarone is accompanied with change of functional state of cardiomyocyte sarcoplasmatic reticulum.

Highlights

Amiodarone is the most effective antiarrythmic drug in therapy of life-threaten ventricular tachyarrhytmias and in comparison with other antiarrythmic preparation has low proarrhytmic activity [1,2]
Inotropic Reaction of Papillary Muscle on Investigation carried out by us showed that stimulation of papillary muscles of intact myocardium with extraordinary electric pulse in 0.2 s after beginning of regular cycle did not caused appearance of extrasystoles, duration of regular contraction-relaxation cycle was increased
That electric stimulation pulse appeared in the 3rd phase of action potential leads to lengthening of action potential plateau in which time additional quantity of external calcium ions enters into myoplasm of cardiomyocytes which are accumulated in SR and take part in the first postextrasystolic contraction-relaxation cycle [10,12,13]

Summary

Introduction

Amiodarone is the most effective antiarrythmic drug in therapy of life-threaten ventricular tachyarrhytmias and in comparison with other antiarrythmic preparation has low proarrhytmic activity [1,2]. Amiodarone is able to inhibit partially sodium and potassium channels as well as to block β-adrenoceptors It is reputed, that this antiarrhytmic drug shows high antiarrhytmic efficiency owing to this properties. Amiodarone effect on electric properties of membrane is defined to a large extent by duration of its use. It may have important significance at clinical use of the drug. Short-term use of amiodarone leads to decreasing of Na+-K+-ATPase activity [6] and particulate blockade of incoming sodium and calcium currents that is accompanied with suppression of Na+-K+-dependent conductivity and excitability of membranes [7]. Chronic use of amiodarone influences on expression of ion channel genes [5] This property of amiodarone can lead to “antiarrhytmic” remodeling of cardiomyocytes. One of intracellular structure responsible for regulation of calcium homeostasis in heart cells is sarcoplasmic reticulum

Methods

Results

Conclusion