QT Interval Prolongation and Torsades de Pointes Unmasked by Intracoronary Acetylcholine Administration

Intracoronary acetylcholine administration, which was performed to exclude vasospasms, unmasked an abnormal QT interval prolongation and initiated torsades de pointes in a patient with normal QT interval at rest.     

Megakaryocytic Maturation is Regulated by Maintaining a Balance Against Cytokine Induced-cell Proliferation: Steel Factor Retards Thrombopoietin-induced Megakaryocytic Differentiation While Synergistically Stimulating Mitogenesis; Hematopoiesis

Using a factor-dependent cell line MO7ER, which contains a stably transduced human erythropoietin (EPO) receptor gene in human megakaryoblastic cell line MO7e and which resulted in concomitant expression of EPO receptor, c-Mpl and c-Kit, we investigated the biological effects of these cytokines in terms of cell growth and differentiation. Thrombopoietin (TPO), EPO and Steel factor (SLF) all stimulated MO7ER cell proliferation in a dose-dependent manner. Combined stimulation of cells with SLF plus either TPO or EPO resulted in striking synergistic enhancement of MO7ER cell growth as compared with each cytokine alone, whereas combination of TPO plus EPO showed only an additive effect on cell proliferation. With regards to cell differentiation, either TPO or EPO treatment induced enhancement of platelet glycoprotein (GP) IIb/IIIa and GPIb expression. SLF induced GPIIb/IIIa and GPIb expression, but the effect was much weaker than that of EPO or TPO. However, addition of SLF to either TPO- or EPO- containing cultures (which induced potent mitogenesis in MO7ER cells) resulted in suppression of these megakaryocyte specific antigens. Addition of low-dose cytosine arabinoside (Ara-C)(1 to 10 ng/ml) enhanced TPO- or EPO- induced megakaryocytic differentiation in MO7ER cells while mildly suppressing cell growth. Treatment the cells with low-dose Ara-C plus TPO plus SLF overrode the proliferative enhancing effects of SLF and induced GPIIb/IIIa and GPIb expression as efficient as TPO alone. Retardation of TPO-induced megakaryocytic maturation was also observed in normal murine bone marrow cells by combined stimulation with TPO and SLF as assessed by the numbers of acetylcholinesterase staining-positive cells and megakaryocyte nuclear polyploidy. These results suggest that megakaryocytic maturation is, at least in part, regulated by countering cytokine-induced cell proliferation.     

Right Atrial Compartmentalization Using Radiofrequency Catheter Ablation for Management of Patients with Refractory Atrial Fibrillation

INTRODUCTION: Atrial fibrillation (AF) is often refractory to antiarrhythmic drugs, and patients who are intolerant of AF may require the maze operation for cure. As a less invasive alternative, a catheter-based, right atrial compartmentalization procedure was evaluated. METHODS AND RESULTS: Twelve patients with AF refractory to Class I and III antiarrhythmic drugs were studied. Four linear right atrial radiofrequency ablations were performed, from superior to inferior vena cava in the posterior wall and interatrial septum, anteriorly from the superior vena cava to the tricuspid annulus through the appendage, and across the tricuspid valve-inferior vena cava isthmus. The radiofrequency catheter was dragged along each line three to four times, until the atrial electrogram amplitude decreased by 75% and there was bidirectional conduction block in the tricuspid valve-inferior vena cava isthmus. One complication occurred: sinus node dysfunction requiring a pacemaker. Eight patients were discharged from the hospital on no antiarrhythmic drugs, and four were discharged on previously ineffective antiarrhythmic drugs. Total duration of follow-up was 21.3 +/- 11.2 months. Four patients discharged on previously ineffective antiarrhythmic drugs had no recurrence of AF. One patient discharged off antiarrhythmic drugs had no recurrence of AF. Seven patients discharged off antiarrhythmic drugs had recurrent AF by 12.6 +/- 13.0 months (median 6, range 1 to 39); 3 of these 7 responded to previously ineffective antiarrhythmic drugs without further AF and 4 did not. Thus, 8 of 12 patients (67%) had suppression of AF after ablation on previously ineffective medication or no medication. CONCLUSION: Right atrial compartmentalization may alter the substrate for AF, thus improving the efficacy of previously ineffective antiarrhythmic drugs. Because it is relatively safe, it may be a reasonable adjunctive intervention to maintain sinus rhythm in patients with drug-refractory AF.