Activation of purinergic receptors by ATP induces ventricular tachycardia by membrane depolarization and modifications of Ca homeostasis

Cardiac myocytes are continuously exposed to extracellular nucleotides secreted by the myocytes themselves, nerve terminals, or platelets and other blood cells during coronary perfusion, and the concentrations of such extracellular nucleotides are known to increase during cardiac ischemia and hypoxia. The effects of the extracellular nucleotides ATP, ADP, UTP, and adenosine on ventricular arrhythmogenic properties were explored in 36 Langendorff-perfused mouse hearts using monophasic action potential recording. Extracellular nucleotides induced arrhythmic phenomena in form of ectopic activity and ventricular tachycardia in a potency order of ATP (n = 7) > ADP (n = 5) > UTP (n = 3) ≈ adenosine (n = 3). The purinergic receptor antagonists suramin and pyridoxal phosphate-6-azo(benzene-2,4-disulphonic acid) reduced the incidence of ATP-triggered arrhythmias. In isolated ventricular myocytes, ATP induced sustained increases in diastolic Ca²⁺ and triggered multiple Ca²⁺ waves, which were inhibited by suramin but not by the L-type Ca²⁺ channel antagonist nifedipine. In whole-cell patch clamp experiments, extracellular ATP induced two distinct types of inward currents, which were inhibited by suramin and PPADS, suggesting activation of P2X receptors. ATP also induced delayed after-depolarizations and ectopic action potentials in current clamped ventricular myocytes. In conclusion, extracellular ATP activates purinergic receptors and induces arrhythmic activity through modifications of Ca²⁺ homeostasis and an activation of depolarizing membrane currents.     

Effect of adenosine and adenosine-5'-triphosphate on atrioventricular conduction in patients

This study was carried out to further elucidate the effects of adenosine and adenosine-5'-triphosphate (ATP) on atrioventricular (AV) conduction in patients. Adenosine (0.24 mg/kg) and ATP (0.28 mg/kg) were administered intravenously to 37 patients undergoing intracardiac electrophysiologic evaluation. Both adenosine and ATP depressed AV conduction by lengthening the atrial to His bundle (AH) interval. The effects of adenosine and ATP after rapid intravenous bolus administration were fast in onset (15 +/- 0.5 and 15 +/- 1.5 s, respectively), but transient in duration (10.5 +/- 0.5 s for ATP and 17 +/- 3 s for adenosine). Although muscarinic blockade with 0.04 mg/kg atropine shortened the AH interval from a control value of 123 +/- 12 to 74 +/- 4 ms, it did not modify the effects of adenosine or ATP, or both (that is, latency and duration of the effects were not significantly different from before atropine administration). In contrast, aminophylline, a competitive antagonist of adenosine, completely prevented the effects of adenosine and ATP. Aminophylline alone also shortened the AH interval from a control value of 98 +/- 9 to 74 +/- 9 ms. This decrease was blocked by propranolol (0.1 mg/kg), whereas propranolol did not influence the ability of aminophylline to antagonize the effects of adenosine or ATP, or both. Thus, the catecholamines released by aminophylline are unlikely to account for the ability of aminophylline to antagonize the effects of adenosine and ATP. In conclusion, these findings indicate that intravenously administered adenosine and ATP are equally effective in producing AV block that is antagonized by aminophylline but not by atropine.     

The content of erythrocyte 2,3 diphosphoglycerate and adenosine-5'-triphosphate in myelomatosis and leukaemia.

Ery-DPG and thus the oxygen-releasing capacity of haemoglobin increases in meylomatosis and in chronic myelocytic and lymphocytic leukaemia at decreased concentrations of haemoglobin, to the same extent as in other types of anaemia. Consequently the need for blood transfusions is less than assumed in these disorders. Ery-ATP is considerably increased in chronic myelocytic leukaemia, the values correlating positively with the 'activity' of the disease. This finding can probably be used for diagnostic and prognostic purposes.     

Transient complete atrioventricular block provoked by ventricular pacing in a patient with nonsustained ventricular tachycardia.

A 75-year-old woman with complete left bundle branch block underwent electrophysiological study (EPS) to assess the conduction in the His-Purkinje conduction system and to further investigate the electrical instability in the ventricle, which was suggestive by the findings of nonsustained ventricular tachycardia in ambulatory monitoring. Transient complete atrioventricular (AV) block was provoked by ventricular pacing, and the intracardiac recordings proved that the site of AV block was distal to the His bundle. This phenomenon was not related to the rate or the duration of the ventricular pacing. The transient impairment of the conduction appeared to be due to the fatigue phenomenon in the His-Purkinje system.     

Effects of ethanol on adenosine 5'-triphosphate-gated purinergic and 5-hydroxytryptamine receptors

This report of the proceedings of a symposium presented at the 2005 annual meeting of the Research Society on Alcoholism highlights the actions of ethanol on purinergic (P2XRs) and 5-hydroxytryptamine3 (5-HT3Rs) receptors. Both P2XRs and 5-HT3Rs, are modulated by pharmacologically relevant concentrations of ethanol, with inhibition or stimulation of P2XR subtypes and stimulation of 5-HT3Rs, respectively. With regard to ethanol-modulatory actions, these 2 distinctly different receptor classes have been studied to a much lesser extent than other LGICs. The organizers and chairs were Daryl L. Davies and Tina K. Machu. John J. Woodward discusses the molecular pharmacology and physiology of P2XRs and 5-HT3Rs and sets the stage for a detailed investigation into the ethanol sensitivity of these channels by the invited speakers. Daryl L. Davies discusses the results from recent electrophysiological studies conducted in his and Dr. Woodward's laboratories, highlighting the actions of ethanol on P2XR subtypes. Jiang-Hong Ye discusses results from recent studies using loose-patch and whole-cell recordings on purinergic receptors expressed on neurons from the ventral tegmental area (VTA) in rats. Tina K. Machu discusses electrophysiological studies conducted in her and Dr. David Lovinger's laboratories on nonpore lining residues of the second transmembrane domain (TM2) of the 5-HT3A receptor. Li Zhang presents data demonstrating that F-actin cytoskeletons play a critical role in 5-HT3 receptor clustering in hippocampal neurons. Collectively, the presentations provided strong evidence that P2X and 5-HT3 receptors are important targets for ethanol action.     

Mitral subannular left ventricular aneurysm. A case presenting with ventricular tachycardia.

A young African immigrant presented with ventricular tachycardia in association with two mitral subannular left ventricular aneurysms. Although an unusual finding, the recognition of such aneurysms is important as prophylactic measures may prevent complications. Furthermore, they are a surgically treatable cause of heart failure and arrhythmias.     

Idiopathic left ventricular aneurysm presenting with ventricular tachycardia. A case report

Left ventricular aneurysm presenting with ventricular tachycardia was observed in a 48 year old man. Aetiological investigation was negative. The differences between aneurysm and diverticulum and the aetiologies of aneurysms are discussed. The treatment of the arrhythmias caused by this condition is discussed with the help of a review of the literature.     

Dispersion of the monophasic action potential duration in patients with polymorphic ventricular tachycardia.

The mechanism of polymorphic ventricular tachycardia (PMVT) remains unclear. To investigate the electrophysiologic mechanism of PMVT, monophasic action potentials (MAPs) were recorded with a contact electrode technique from right ventricular sites during sinus rhythm and right ventricular pacing. MAPs were obtained from 6 patients with PMVT (PMVT group) and 11 patients without PMVT (control group). The duration from the onset of the upstroke to 90% repolarization of the MAP (MAPD90) during right ventricular pacing at both pacing cycle lengths of 600 and 400 ms was significantly longer in the PMVT group than in the control group (332+/-60 ms vs 279+/-33 ms [P < .005] and 276+/-32 ms vs 229+/-23 ms [P < .0001], respectively). Dispersion of the MAPD90 in sinus rhythm was significantly larger in the PMVT group than in the control group (52.5+/-34.6 ms vs 26.1+/-12.0 ms [P < .005]), and dispersion of the MAPD90 during right ventricular pacing at both pacing cycle lengths of 600 and 400 ms was also significantly larger in the PMVT group than in the control group (86.0+/-44.2 ms vs 37.4+/-28.6 ms [P < .005], and 48.8+/-19.3 ms vs 27.1+/-7.1 ms [P < .05], respectively). Dispersion of repolarization time (activation time plus MAPD90) at a pacing cycle length of 600 ms was longer in the PMVT group than in the control group (104.3+/-38.9 ms vs 49.4+/-31.2 ms [P < .05]). These results suggest that the patients with PMVT have a greater regional dispersion of ventricular repolarization time and that the heterogeneity of ventricular repolarization may play an important role in the genesis of PMVT.     

Monophasic action potentials in a patient with multiform ventricular tachycardia without QT prolongation.

A 41 year old woman had multiform ventricular tachycardia without QT prolongation. Monophasic action potentials were recorded from the right ventricle during the attacks of multiform ventricular tachycardia and effective refractory periods were examined at the same sites. There was no abnormal hump to suggest early afterdepolarisation in the monophasic action potentials, but there was dispersion of the effective refractory period in the right ventricle (80 ms). Stimulation from the right ventricular apex, where the effective refractory period was shortest, reproducibly induced multiform ventricular tachycardia. Two weeks after admission, when her condition was stable, multiform ventricular tachycardia could not be induced and the dispersion of the effective refractory period in the right ventricle was 20 ms.     

Treatment of ventricular tachycardia using endocavitary fulguration. 5 years' experience with 53 cases

53 patients, between the ages of 14 and 76 years, presented a ventricular tachycardia which was treated by the fulguration method. 19 resulted from a complication of an old myocardial infarction, 15 from a right arrhythmogenic ventricular dysplasia, 8 from a dilated myocardiopathy. 10 patients presented idiopathic tachycardias: 3 originated in the infundibulum of the right ventricule and 7 from the left ventricle. One case originated from a surgical scar of the infundibulum. These tachycardias were continuous or occurred daily in half of the cases, or presented monthly recurrences. 1 to 17 shocks were delivered at each session, 143 on the right, 112 on the left and 2 transseptal. Four patients died from haemodynamic deterioration prior to the shock. The other 49 patients are considered as clinical successes. Three died within the first three months of low cardiac output without any recurrence of the tachycardia. 26 did not longer present any recurrent tachycardia and were not given any preventive anti-arrhythmic treatment. 19 developed recurrence or could be triggered off again, but the anti-arrhythmic medications which were ineffective, become effective. One female patient again developed slavos of ventricular tachycardia after a few months. Seven patients died 4 to 18 months after fulguration, and three presented a sudden death. They belong to the group with medically treated recurrences. This technique is a major factor in the therapeutic strategy of ventricular tachycardias, either used alone or associated with a pharmacological treatment.     

Successful transseptal catheter electrical ablation of sustained ventricular tachycardia of possible intramuscular origin.

Low-energy electrical ablation at 100 joules was attempted via a catheter in a patient with sustained ventricular tachycardia (VT) refractory to drug therapy. The patient was a 17-year-old woman who had undergone complete surgical correction of a double outlet right ventricle at the age of 9. The first episode of VT appeared at the age of 17. It was refractory to procainamide and lidocaine and it was sustained until termination with direct countershock. Two different QRS morphologies of VT were documented in the electrophysiologic study and one was identical to the VT observed in the clinical course. Conventional drug therapy failed to prevent induction of VT and catheter electrical ablation was attempted. The earliest activation site during the clinical episode of VT was localized to the right ventricular side of the interventricular septum (site 14-15), but pacing from this site resulted in a slightly different QRS morphology from that of VT. At the left ventricular side of this site (site 2), pacing during VT resulted in a QRS morphology identical to that of VT but the electrogram of this site did not precede the onset of the surface QRS complex. From these findings, the origin of VT was considered to be in the muscular layer of the interventricular septum. The method of transseptal shock using two catheters was applied and direct countershock at 100 joules successfully ablated the VT.