Ectopic automaticity induced in ventricular myocytes by transgenic overexpression of HCN2.

Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) are expressed in the ventricles of fetal hearts but are normally down-regulated as development progresses. In the hypertrophied heart, however, these channels are re-expressed and generate a hyperpolarization-activated, nonselective cation current (Ih), which evidence suggests may increase susceptibility to arrhythmia. To test this hypothesis, we generated and analyzed transgenic mice overexpressing HCN2 specifically in their hearts (HCN2-Tg). Under physiological conditions, HCN2-Tg mice exhibited no discernible abnormalities. After the application of isoproterenol (ISO), however, ECG recordings from HCN2-Tg mice showed intermittent atrioventricular dissociation followed by idioventricular rhythm. Consistent with this observation, 0.3 µmol/L ISO-induced spontaneous action potentials (SAPs) in 76% of HCN2-Tg ventricular myocytes. In the remaining 24%, ISO significantly depolarized the resting membrane potential (RMP), and the late repolarization phase of evoked action potentials (APs) was significantly longer than in WT myocytes. Analysis of membrane currents revealed that these differences are attributable to the Ih tail current. These findings suggest HCN2 channel activity reduces the repolarization reserve of the ventricular action potential and increases ectopic automaticity under pathological conditions such as excessive ß-adrenergic stimulation.

Five cases of aconite poisoning: toxicokinetics of aconitines.

Aconite poisoning was examined in five patients (four males and one female) aged 49 to 78 years old. The electrocardiogram findings were as follows: ventricular tachycardia and ventricular fibrillation in case 1, premature ventricular contraction and accelerated idioventricular rhythm in case 2, AIVR in case 3, and nonsustained ventricular tachycardia in cases 4 and 5. The patient in case 1 was given percutaneous cardiopulmonary support because of unstable hemodynamics, whereas the other patients were treated with fluid replacement and antiarrhythmic agents. The main aconitine alkaloid in each patient had a half-life that ranged from 5.8 to 15.4 h over the five cases, and other detected alkaloids had half-lives similar to the half-life of the main alkaloid in each case. The half-life of the main alkaloid in case 1 was about twice as long as the half-lives in the other cases, and high values for the area under the blood concentration-time curve and the mean residence time were only observed in case 1. These results suggest that alkaloid toxicokinetics parameters may reflect the severity of toxic symptoms in aconite poisoning.

[Transient arrhythmia disclosing major glycine poisoning during hysteroscopy]. / Trouble transitoire du rythme cardiaque révélateur d'une intoxication majeure à la glycine au cours d'une hystéroscopie.

We report the case of a 41-year-old ASA I patient who experienced during endometrial resection a transient idioventricular cardiac rhythm with hypotension related to a major glycine intoxication. The total volume of absorbed irrigating fluid was over six liters when these clinical signs occurred. The biological data were as following: Na = 89 mmol.L-1, Cl = 60 mmol.L-1 and osmolarity = 215 mOsm.L-1. Simultaneously, the glycine concentration in the plasma was 54.6 mmol.L-1, i.e 160 times higher than the normal value. The clinical course was unremarkable except vomiting. The treatment included only the administration of a diuretic agent, as the correction of the disorder took place spontaneously. The paucity of clinical symptoms when compared to the severity of the biological disorders explain why preventive measures are essential in this type of surgery.

Accelerated idioventricular rhythm associated with propranolol treatment in a child.

Accelerated idioventricular rhythm (AIVR) is a ventricular arrhythmia most commonly seen in adults with underlying cardiac disease. It is important to establish the diagnosis when it occurs to differentiate this benign phenomenon from dangerous ventricular tachycardia. We present the case of a healthy child who developed episodes of AIVR associated with propranolol treatment. Her 24-hour electrocardiography recording showed AIVR with difference between sinus and ventricular beats. The arrhythmia resolved with the discontinuation of propranolol, and eventually the case was in sinus rhythm. This patient is the first case of AIVR associated with propranolol treatment in the literature.

Idioventricular rhythm: hypervagotonia associated with placebo.

We report a case of hypervagotonia manifested by idioventricular rhythm in a healthy, athletic man who participated in a Phase I study of an investigational calcium-channel blocker. Upon breaking the study's double-blind study code, it was discovered that the subject had received placebo. We discuss this unusual finding and the implications of including athletic subjects in safety/tolerance studies.