ajmaline and Disease-Models--Animal

Concomitant apamin-sensitive small conductance calcium-activated potassium current (I. The purpose of this study was to test the hypotheses that acetylcholine (ACh), the parasympathetic transmitter, activates I. We performed optical mapping in Langendorff-perfused rabbit hearts and whole-cell voltage clamp to determine I. ACh (1 μM) + ajmaline (2 μM) induced J-point elevations in all (6 male and 6 female) hearts from 0.01± 0.01 to 0.31 ± 0.05 mV (P<.001), which were reduced by apamin (specific I. ACh activates ventricular I

Topics: Acetylcholine; Ajmaline; Animals; Arrhythmias, Cardiac; Cholinergic Agonists; Disease Models, Animal; Heart Ventricles; Isolated Heart Preparation; Myocytes, Cardiac; Optical Imaging; Patch-Clamp Techniques; Potassium Channels, Calcium-Activated; Rabbits; Small-Conductance Calcium-Activated Potassium Channels; Sodium Channels; Voltage-Gated Sodium Channel Blockers

J wave syndromes (JWS), including Brugada (BrS) and early repolarization syndromes (ERS), are associated with increased risk for life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently very limited. Here, we evaluate the effects of the natural flavone acacetin.. The effects of acacetin on action potential (AP) morphology and transient outward current (Ito) were first studied in isolated canine RV epicardial myocytes using whole-cell patch clamp techniques. Acacetin's effects on transmembrane APs, unipolar electrograms and transmural ECGs were then studied in isolated coronary-perfused canine RV and LV wedge preparations as well as in whole-heart, Langendorff-perfused preparations from which we recorded a 12 lead ECG and unipolar electrograms. Using floating glass microelectrodes we also recorded transmembrane APs from the RVOT of the whole-heart model. The Ito agonist NS5806, sodium channel blocker ajmaline, calcium channel blocker verapamil or hypothermia (32°C) were used to pharmacologically mimic the genetic defects and conditions associated with JWS, thus eliciting prominent J waves and provoking VT/VF.. Acacetin (5-10 μM) reduced Ito density, AP notch and J wave area and totally suppressed the electrocardiographic and arrhythmic manifestation of both BrS and ERS, regardless of the experimental model used. In wedge and whole-heart models of JWS, increasing Ito with NS5806, decreasing INa or ICa (with ajmaline or verapamil) or hypothermia all resulted in accentuation of epicardial AP notch and ECG J waves, resulting in characteristic BrS and ERS phenotypes. Phase 2-reentrant extrasystoles originating from the RVOT triggered VT/VF. The J waves in leads V1 and V2 were never associated with a delay of RVOT activation and always coincided with the appearance of the AP notch recorded from RVOT epicardium. All repolarization defects giving rise to VT/VF in the BrS and ERS models were reversed by acacetin, resulting in total suppression of VT/VF.. We present experimental models of BrS and ERS capable of recapitulating all of the ECG and arrhythmic manifestations of the JWS. Our findings provide definitive support for the repolarization but not the depolarization hypothesis proposed to underlie BrS and point to acacetin as a promising new pharmacologic treatment for JWS.

Topics: Ajmaline; Animals; Brugada Syndrome; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Electrocardiography; Flavones; HEK293 Cells; Humans; Hypothermia; Myocytes, Cardiac; Pericardium; Phenylurea Compounds; Tetrazoles; Verapamil

We have discovered that the P/Q-type voltage-gated Ca

Topics: Ajmaline; Animals; Calcium Channels; Calcium Channels, L-Type; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation; HEK293 Cells; Humans; Inhibitory Concentration 50; Internal Ribosome Entry Sites; MicroRNAs; Mutation; Receptors, Atrial Natriuretic Factor; Spinocerebellar Ataxias; Transfection; Voltage-Gated Sodium Channel Blockers

This study sought to test the hypothesis that elimination of sites of abnormal repolarization, via epicardial RFA, suppresses the electrocardiographic and arrhythmic manifestations of BrS.. Brugada syndrome (BrS) is associated with ventricular tachycardia and ventricular fibrillation leading to sudden cardiac death. Nademanee et al. reported that radiofrequency ablation (RFA) of right ventricular outflow tract epicardium significantly reduced the electrocardiogram and arrhythmic manifestations of BrS. These authors concluded that low-voltage fractionated electrogram activity and late potentials are caused by conduction delay within the right ventricular outflow tract and that the ameliorative effect of RFA is caused by elimination of this substrate. Szel et al. recently demonstrated that the abnormal electrogram activity is associated with repolarization defects rather than depolarization or conduction defects.. Action potentials (AP), electrograms, and pseudoelectrocardiogram were simultaneously recorded from coronary-perfused canine right ventricular wedge preparations. Two pharmacological models were used to mimic BrS genotype: combination of I. Fractionated low-voltage electrical activity was observed in right ventricular epicardium but not endocardium as a consequence of heterogeneities in the appearance of the second upstroke of the epicardial AP. Discrete late potentials developed as a result of delay of the second upstroke of the AP and of concealed phase 2 re-entry. Epicardial RFA of these abnormalities normalized Brugada pattern and abolished arrhythmic activity, regardless of the pharmacological model used.. Our results suggest that epicardial RFA exerts its ameliorative effect in the setting of BrS by destroying the cells with the most prominent AP notch, thus eliminating sites of abnormal repolarization and the substrate for ventricular tachycardia ventricular fibrillation.

Topics: Action Potentials; Ajmaline; Animals; Arrhythmias, Cardiac; Brugada Syndrome; Disease Models, Animal; Dogs; Electrocardiography; Humans; Pinacidil; Radiofrequency Ablation; Treatment Outcome

The majority of patients with implanted cardioverter defibrillators (ICD) require antiarrhythmic (AR) drugs. ARs may increase defibrillation energy requirements. This study investigated the effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy needs. In 24 isolated rabbit hearts, the 50 and 80% successful defibrillation energy (ED50, ED80) was calculated in four phases: predrug baseline condition (phase 1), and phases 2, 3, and 4 with increasing concentrations of lidocaine, ajmaline, diltiazem (n = 18). Control experiments (n = 6) with only Tyrode's solution infusion indicated that the preparation was stable over time. Defibrillation energy requirements significantly (p < 0.05) increased with all ARs. Low, medium, and high lidocaine concentrations increased ED50 and ED80 to 146, 223, and 312% and 139, 207, and 285%, respectively. Ajmaline increased ED50 and ED80 to 133, 175, and 251% and 135, 208, and 285%, respectively. Diltiazem increased ED50 and ED80 by 175, 236, and 334% and 158, 212, and 286%, respectively. The results of this study demonstrate a dose-dependent increase in defibrillation energy requirements by using lidocaine, diltiazem, and ajmaline. In patients with ICDs, administration of these drugs might cause a critical increase in defibrillation energy requirements, resulting in device failure.

Topics: Ajmaline; Analysis of Variance; Animals; Anti-Arrhythmia Agents; Cardiovascular Agents; Defibrillators, Implantable; Diltiazem; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Countershock; Electrocardiography; Equipment Failure; Female; Heart; In Vitro Techniques; Lidocaine; Male; Rabbits; Ventricular Fibrillation

The effects of a herbal drug, Ajmaloon (Hamdard, India), on the arterial blood pressure, heart rate (HR) and baroreceptor-heart rate reflex were studied in anesthetized rabbits and monkeys. Intravenously administered Ajmaloon produced a dose-dependent hypotensive response in both the species without any significant effect on the heart rate. Only in high doses (200 mg/kg or more). Ajmaloon produced a bradycardia response in rabbits. Even the highest dose (300 mg/kg) of Ajmaloon used in the present investigation did not cause arrhythmia or any other conduction disorder or respiratory distress. Baroreflex SAP-HR curve was shifted to the left of the control following treatment with 100 mg/kg intravenous Ajmaloon in both the species. Loss of tachycardia response to fall in arterial pressure in Ajmaloon treated animals indicated the drug induced suppression of normally existing sympathetic excitatory influence in response to hypotension. Baroreflex regulatory HR response to hypertension remains intact after intravenous administration of 100 mg/kg Ajmaloon, a dose much higher than the prescribed highest oral dose for humans. Intact baroreflex regulation of arterial blood pressure in response to hypertension in Ajmaloon treated mammals suggests that in patients besides lowering the blood pressure. Ajmaloon might not interfere with the normal blood pressure regulatory mechanism through arterial baroreceptors during hypertension.

Topics: Ajmaline; Analysis of Variance; Animals; Baroreflex; Blood Pressure; Bradycardia; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Haplorhini; Heart Rate; Hypertension; Injections, Intravenous; Male; Phytotherapy; Plant Extracts; Plants, Medicinal; Rabbits; Random Allocation; Rauwolfia

Topics: Ajmaline; Animals; Chagas Cardiomyopathy; Disease Models, Animal; Electrocardiography; Rats

The prostaglandins A1, E1, A2, E2 and F2a were comparatively studied for their antiarrhythmic action using the model of strophanthin arrhythmia of narcotized cats. Infusions of prostaglandins A1, E2 and F2a in doses of 1-5 mug/kg/min for 5 min improved the arrhythmias in 63%, 83% and 81% of the animals, respectively, whereas prostaglandin A2 was effective in 44%, and prostaglandin E1 in only 10% of the cats. Prostaglandins A1 and E2 transiently established a sinus rhythm in 54 and 50%, and prostaglandin F2a in 18% of the animals. The injection of 12 mu9/kg prostaglandin F2a brought about improvement of arrhythmia in 70% of the animals, producing a transient sinus rhythm in 40%. With ajmaline as the standard substance in doses of 0.3 mg/kg/min for 5 min produced an antiarrhythmic effect in 50% of the animals, while injection of 1 mg/kg was effective in 60% of the animals. Effects on the vegetative nervous system are discussed as the possible action mechanism of the prostaglandins.

Topics: Ajmaline; Animals; Arrhythmias, Cardiac; Cats; Disease Models, Animal; Female; Male; Prostaglandins; Prostaglandins A; Prostaglandins E; Prostaglandins F; Strophanthins

Experimental studies on BaCl2 induced arrhythmias in unanaesthetized rabbits showed an antiarrhythmic effect of prostaglandins A1, A2, E1, E2 and F2a by infusions of 0,1 to 6,0 mug/kg/min over 3 min. There was a maximum antiarrhythmic effect between 50% and 80%. Ajmaline was similarly effective when given in doses 100-1000 times higher. PGA1 and PGE2 were most effective in this model; the ED50-values of the other PGs were 2-3 times higher. The mode of action of PGs is unknown; the following factors are discussed: the influence on the ionic movements, the negative feedback mechanism on the release of adrenergic transmitter and central nervous effects.

Topics: Ajmaline; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Barium; Disease Models, Animal; Dose-Response Relationship, Drug; Prostaglandins A; Prostaglandins E; Prostaglandins F; Rabbits

Topics: Aconitum; Ajmaline; Animals; Arrhythmias, Cardiac; Biological Transport; Calcium Chloride; Cell Membrane Permeability; Disease Models, Animal; Heart; Ion Exchange; Myocardium; Potassium; Prostaglandins; Rats; Sodium