Rate-dependent and antiarrhythmic reentrant tachycardia (AVNRT) effects of simvastatin in isolated rabbit atrioventricular nodal model

Background and purpose: Several previous studies have shown the direct and indirect effects of statins on supraventricular and ventricular arrhythmia. The purpose of the present study is to determine (1) whether Simvastatin modifies the rate-dependent properties of the AV node, (2) to what extent such changes are related to effect of Simvastatin on the basic properties of AV nodal conduction and refractoriness. Materials and methods: AV nodal refractoriness (AVERP & AVFRP) and rate dependency protocols Fatigue and Facilitation were used to assesse the electrophysiological properties of AV node. We used an isolated perfussed rabbit with AV nodal preparation in one group (N=8). The stimulation protocols were carried out during control phase and in the presence of various concentrations of Simvastatin (0.5 , 0.8 , 1, 3 ,10 μm). Results: Simvastatin in concentration-dependent manner successfully prolonged effective and functional nodal refractory period (AVERP & AVFRP). Also an increase in Wenckebach cycle length was observed. Simvastatin in high concentration (3,10 μm) increases the arrhythmia threshold. Various concentrations of simvastatin increased fatigue, but it reached to significant level only at 30 μM. Conclusion: Simvastatin has potential anti-AVNRT effects by elevating arrhythmia threshold and prolongation of nodal refractoriness

Age-dependent dynamic electrophysiological field potential behavior of atrioventricular node during experimental AF in rabbit

Introduction: Electrophysiological studies have demonstrated a relationship between aging and atrioventricular (AV) nodal conduction and refractoriness. The aim of the present study was to determine the effects of nodal aging on dynamic AV nodal field potential recording during atrial fibrillation (AF) in rabbit. Methods: Two groups of male New Zealand rabbits (neonatal 2-week-olds and adult 12-week-olds, n=14 each group) were used in this study. Field potential recordings were executed by silver electrodes with a diameter of 100 μM. Pre-defined stimulation protocols of AF, zone of concealment (ZOC) and concealed conduction for determination of the electrophysiological properties of the AV-node were separately applied in each group. Results: Results of the study showed that mean ventricular rate (HH) during atrial fibrillation was smaller in the neonatal compared to the adult group (229.1 ± 8.3 versus 198.6 ± 13.1 msec, respectively). Also ventricular distribution conduction pattern showed two peaks in the adult and one peak in the neonatal group. Analyzing the zone of concealment in different rates and after concealed beat indicated that the zone of concealment in neonates were significantly smaller compared with adult rabbits and increasing zone of concealment, which is accompanied with increasing ventricular rate is abrogated in the neonatal group (5 ± 3.3, 12.2 ± 6.3 msec). Conclusion: The results of this study showed that the electrophysiological protective dynamic behavior of the AV node during atrial fibrillation is smaller in neonates compared to adults. Narrower zone of concealment, abrogation rate dependent trend of the zone of concealment and shorter nodal refractoriness can account for the specific nodal electrophysiological properties of neonatal rabbits

Frequency-dependent anti arrhythmic effects of crataegus monogyna on the extracellular field potential recordings in the rabbit atrioventricular node, an experimental model of AF

Introduction: Despite extensive studies that have been performed on the effects of Crataegus monogyna in cardiovascular diseases, only few investigations have addressed the antiarrhythmic properties of this plant. Aims of the present study were: 1) To determine the protective role of methanolic extract of C. monogyna on the rate-dependent model and the concealed conduction of the AV node. 2) To explore the role of Na+-K+ ATPase in the protective role of C. monogyna Methods: Male New Zealand rabbits (1.5-2kg) were used in all experiments. Stimulation protocols were used to measure basic and rate-dependent AV nodal properties (recovery, atrial fibrilation and zone of concealment) in two groups (N=14). In the first group, all the stimulation protocols were performed before and after the administration of different concentrations of C. monogyna extract (n=7), while in the second group (n=7), all stimulation protocols were carried out in the presence of ouabaine (0.05 μM) and the plant extract. Results: Basic and rate-dependent properties of the AV node were inhibited after the addition of the extract of C. monogyna to Kerebs Henselite solution. At the maximum concentration of C. monogyna (30 mg/l), WBCL cycle length was significantly increased from 156.5±3.4 to 173±5.8 ms and the nodal functional refractory period was prolonged from 164.4±4.1 to 182.7±3.8 ms (P<0.05). Significant decreases of ventricular rhythm were recorded in both selective concentrations of the plant extract. The depressant electrophysiological effect of C. monogyna on the AV node was not abolished by ouabaine, a selective inhibitor of Na+-K+ ATPase enzyme. Conclusion: The results showed a potential anti-arrhythmic and protective effect for C. monogyna. The effect of the plant extract in increasing nodal refractory period and widening of the concealment zone might be the major mechanisms involved. The protective role of C. monogyna was not related to the Na+-K+ ATPase activity

Protective role of cyclosporine on the model simulated the rotational nodal arrhythmia (AVNRT) by using extracellular field potential recordings of isolated atrioventricular-node of rabbit

Introduction: Recent studies have shown acute cardioprotective effects of cyclosporine. The aim of the present study was to determine the protective role of cyclosporine on the model simulated the rotational nodal arrhythmia (AVNRT) by using extracellular field potential recordings of isolated atrioventricular-node (AV-node) of rabbit. Methods: This study was performed on isolated double-perfused AV-node of male New Zealand rabbits (1.5-2.5 kg) in one group (n=7). Basic and rate-dependent stimulation protocols (recovery, facilitation, fatigue) and arrhythmia threshold (index of refractoriness) and % Gap incidence were measured for assessment of electrophysiological properties of the AV- node. All stimulation protocols were repeated in control step and in the presence of various cumulative concentrations of cyclosporine (0.5 - 10 μm). Results: Cyclosporine prolonged the effective refractory period from 114.3±7.9 to 142±7.3 msec at the concentration of 10 μm. It also prolonged the functional refractory period from 162±3.3 to 178.6±5 msec and increased the time of Wenckebach at the concentrations of 5 - 10 μM. Various concentrations of cyclosporine increased fatigue and reached a significant level at 10 μm. Gap incidence was 82%, 16.6% and 20% in the control and treatments with 0.5 and 10 μm of cyclosporine, respectively. Conclusion: Block of MPTP by cyclosporine caused inhibition of basic and rate-dependent properties of atrioventricular node. Cyclosporine, by raising the threshold of arrhythmia, could be possibly considered as an anti- AVNRT drug

Role of histaminegic and calcium channels in the inhibitory effects of hydroalcoholic extract of matricaria recutita L. on isolated rabbit jejunum

Introduction: Considering the long traditional history of anti-inflammatory and anti-spasmodic effects of Matricria spices on the gastrointestinal system, the present study aimed to investigate the role of calcium channels and Histamine receptors in the inhibitory effects of hydroalcoholic dry extract of German chamomile (Matricaria recutita L.) on the isolated rabbit jejunum. Methods: All experiments were done on the isolated jejunum of New Zealand rabbits (1.8-2.5 kg). Dry extract of aerial parts of M. recutita was obtained by the maceration technique. The study was performed on two groups (n=6 in each group). In the first group, the effects of cumulative concentrations of M. recutita (3×10-3-1×10-2 mg/ml) on normal and K+-induced contractions (50 mM) of isolated jejunum were studied. In the second group, the inhibitory role of M. recutita (3 – 13×10-3 mg/ml) was evaluated in the presence and absence of histamine and cetrizine. In the presence and absence of 10 μM certizine, a histamine H1-antagonist, a concentration-dependent inhibitory effect of M. recutita extract in the range of 3-13×10-3 mg/ml was recorded the rabbit jejunum. Results: Results showed that EC50 of M. recutita in the absence and presence of K+ was 6.3×10-3 and 6.5×10- 3mg/ml, respectively. IC50 values for two concentrations of M. recutita (8×10-3 , 1×10-2 ) to abrogated contractive phase of Histamine was 9.55 × 10-6 and 1.57 × 10-6 μM. Cetrizine (10 μM) abolished inhibitory effects of M. recutita (IC50=3.6×10-3), (p< 0.001). Conclusion: Dry extract of matricaria recutita had inhibitory effects on the contractions of isolated rabbit jejunum. Calcium channels and histamine were involved in these antispasmodic effects

Effect of nitric oxide modulation on the basic and rate-dependent electrophysiological properties of AV-node in the isolated heart of rabbit: The role of adrenergic and cholinergic receptors

Introduction: Recent studies showed that nitrergic system have specific modulatory effects on electrophysiological properties of atrioventricular (AV) node. The aim of this study was to determine the effects of nitric oxide (NO) on the electrophysiological properties of isolated rabbit AV node and to investigate the role of adrenergic and cholinergic receptors in the mechanism of its action. Methods: In our laboratory, an experimental model of isolated double-perfused AV-node of rabbits weighing 1.5-2 kg was used. Specific experimental protocols of recovery, Facilitation, Fatigue and Wenckbach were applied in both control and in the presence of the drug. A total number of 35 rabbits were divided randomly into the following groups (n=7): 1) L-Arg (NO donor) (250, 750 and 1000 μmol), 2) L- NAME, a NO synthesis inhibitor (25, 50 and 100 μmol), 3) L-Arg + L- NAME, 4) Nadolol (1 μmol), 5) Atropine (3 μmol). All data were shown as mean ± SE. The level of statistical significance was set at p<0.05. Results: Our results revealed the depressant effect of L-Arg on the basic and rate-dependent electrophysiological properties of AV-node. L- NAME did not deteriorate the effects of L-Arg on the basic and rate-dependent properties, nevertheless, at high concentration (100 μmol) it had a direct inhibitory effect on the AV-node. Nadolol and atropine could prevent the effects of NO on the basic nodal characteristics and the fatigue phenomenon, respectively. Conclusion: Nitergic system can affect basic and rate-dependent electrophysiological properties of the AV-node through adrenergic and cholinergic receptors

Role of nitric oxide on the electrophysiological properties of isolated rabbit atrioventricular node by extracellular field potential during atrial fibrillation

Introduction: The aim of the present study was to determine direct effects of NO modulation on protective electrophysiological properties of atrioventricular node (AV node) in the experimental model of AF in rabbit. Methods: Isolated perfused rabbit AV nodal preparations were used in two groups. In the first group (N=7), LNAME (50μM) was applied. In the second group (N=12), different concentrations of L - argenine (250 μM - 5000 μM) were added to the solution. Programmed stimulation protocols were used to quantify AV nodal conduction time, refractoriness and zone of concealment. AF protocol was executed by software with coupling intervals (ranging from 75–125 msec). Results: L-NAME had depressive effects on basic AV nodal properties. L-Arginine (250μM) had direct inhibitory effects on nodal conduction time, Wenckebach and refractoriness. Significant increases in the number of concealed beats were induced by L-Arginine (500 μM). Number of concealed beats were increased from 700.7±33.7 to 763±21 msec (P<0.05). Trend of zone of concealment prolongation in a frequency-dependent model was abrogated by Larginine (250, 5000 μM). Conclusion: NO at low concentration (in the presence of L-NAME) had facilitatory role on AV nodal properties, but at high concentration (in the presence of L-arginine) enhanced protective role of AV node during AF. Biphasic modulatory role of NO may affect protective behavior of AV node during AF. © 2011, Iranian Society of Physiology and Pharmacology. All rights reserved

Dynamic age-related changes of extracellular field potential of isolated AV-node of rabbit

Introduction: Developmental changes in atrioventricular nodal conduction time and refractoriness have been shown in several studies. Prevalence of atrioventricular nodal reentrant tachycardia (AVNRT) is clearly age-dependent. The purpose of this study was to determine developmental changes of basic and frequency-dependent electrophysiological properties of the atrioventricular node (AV-node) in neonatal and adult rabbits. Methods: In this study, the effects of increasing age on the basic and rate-dependent properties of isolated perfused AV-node were analyzed in neonatal (2-week-old) and adult (12-week-old) New Zealand rabbits. Specific stimulation protocols of recovery, facilitation and fatigue were separately applied in each group (n=7). Unipolar extracellular field potential was recorded by a silver electrode (100 μM). Results: The results showed that the basic nodal properties (ERP, FRP, WBCL and AHmax) were significantly shorter in neonates compared to the adult group. The magnitude of fatigue was also decreased in the neonatal group compared to control (18.9 ±3.3 vs. 11.1 ± 1.2 msec). Time constant of recovery of the adult group was significantly higher than the neonatal group (P<0.05). Conclusion: The results of this study showed that nodal basic and frequency-dependent properties are age-related and different developmental changes of slow and fast pathways are responsible for this behavior and may reveal the grater susceptibility of AVNRT in young adults compared to infants

Modulation of extracellular atrioventricular node field potential pattern and ventricular rhythm by morphine in experimental atrial fibrillation in isolated rabbit heart

Introduction: Endorphins are produced by cardiomyocytes, and exert different effects on the heart. The aim of the present study is to assess morphine effects on extracellular atrioventricular (AV) node field potential pattern and ventricular rhythm of isolated rabbit heart during experimental atrial fibrillation (AF). Methods: Effects of different concentrations of morphine (10, 20, 50 and 100 μM) were assessed by applying basic stimuli protocols involving Wenckebach, recovery, zone of concealment and concealed conduction parameters during experimental atrial fibrillation in isolated rabbit heart. Two-way ANOVA was used to compare the groups. Results: Morphine significantly suppressed basic parameters of AV node. Morphine (100 μM) significantly increased wenckebach index (153.6±3.9 to 169.8±2.9 ms) and functional refractory period (156.9±3.0 to 176.4±3.5 ms) (P 0.05). Conclusion: The present results showed that morphine has concentration-dependent effects on AV node electrophysiological properties. Morphine at low concentrations can decrease nodal conduction and refractoriness of AV node, but in high concentrations causes increased nodal conduction without concealed conduction changes. Dual effects of morphine can explain the unpredictable behavior of heart in cardiac tachyarrhythmias

Acute direct effects of cyclosporine on extracellular field potential of isolated rabbit AV node during experimental atrial fibrillation

Introduction: Previous studies have indicated a relationship between MPTP pore and AV nodal rate-dependent properties. The aim of present study was to determine acute direct effects of cyclosporine on extracellular field potential of isolated rabbit AV node during experimental atrial fibrillation. Methods: In one group of male New Zealand rabbits (1.5-2.5 kg) cumulative concentrations of cyclosporine (0.5 -10 μm) were applied on isolated perfused atrio-nodal preparation (n=7). Extracellular field potential recording was sampled during specific stimulation protocols (recovery, zone of concealment and atrial fibrillation) in the presence of drug on electrophysiological properties of AV-node. Results: Cyclosporine significantly decreased the ventricular rate (HH mean) from 231.8 ± 5.7 to 277.4 ± 14.6 msec and functional refractory period during AF (AF FRP) from 138.3 ± 7.5 to 161.2 ± 10.31 msec in control and treated groups, respectively. Effective refractory period during AF (AF ERP) was significantly decreased by cyclosporine 10 mM compared to control group (p<0.05). Conclusion: Cyclosporine-evoked slowing ventricular heart rate during AF was induced by increasing functional refractoy period and ZOC. A possible mechanism can be through blocking of MPT pores