Clinical use of permanent pacemaker for conversion of intraatrial reentry tachycardia in children.

The use of the implanted atrial-based pacemaker to overdrive postsurgical intraatrial reentry tachycardia (IART) was evaluated in a large group of pediatric patients over a 14-year study period. The authors sought to determine the feasibility of this noninvasive technique in the management of this specialized population and to determine factors associated with successful conversion. They examined 128 manual overdrive attempts performed on 22 consecutive patients. There were 10 patients with post-Fontan repair, 7 with post-Mustard/Senning procedure, and 5 with miscellaneous lesion types. The number of IART episodes for overdrive pacing per patient ranged from 1 to 15. The first overdrive pacing attempt was successful in 63% (14/22) of the patients. The mean IART cycle length was 278 +/- 59 ms. The mean pacing rate for effective conversion of IART was 66 +/- 10% faster than the IART rate. By controlling for repeated measures for individual patients, three factors were found to be independently associated with a successful outcome: (1) lesion type other than Fontan surgery (P = 0.007), (2) lack of acceleration of IART with the overdrive attempt (P < 0.001), and (3) patient use of amiodarone with attempt (P = 0.005). There were three procedural complications: two inadvertent overdrive pacing episodes, and one episode of acceleration of IART cycle length and conduction resulting in need for cardioversion. Manual pacemaker overdrive conversion of IART is a useful adjunct in the management of postsurgical IART in the pediatric population and should be considered as an initial treatment option.

The Akt kinase signals directly to endothelial nitric oxide synthase.

Endothelial nitric oxide synthase (eNOS) is an important modulator of angiogenesis and vascular tone [1]. It is stimulated by treatment of endothelial cells in a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent fashion by insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) [2] [3] and is activated by phosphorylation at Ser1177 in the sequence RIRTQS(1177)F (in the single-letter amino acid code) [4]. The protein kinase Akt is an important downstream target of PI 3-kinase [5] [6], regulating VEGF-stimulated endothelial cell survival [7]. Akt phosphorylates substrates within a defined motif [8], which is present in the sequence surrounding Ser1177 in eNOS. Both Akt [5] [6] and eNOS [9] are localized to, and activated at, the plasma membrane. We found that purified Akt phosphorylated cardiac eNOS at Ser1177, resulting in activation of eNOS. Phosphorylation at this site was stimulated by treatment of bovine aortic endothelial cells (BAECs) with VEGF or IGF-1, and Akt was activated in parallel. Preincubation with wortmannin, an inhibitor of Akt signalling, reduced VEGF- or IGF-1-induced Akt activity and eNOS phosphorylation. Akt was detected in immunoprecipitates of eNOS from BAECs, and eNOS in immunoprecipitates of Akt, indicating that the two enzymes associate in vivo. It is thus apparent that Akt directly activates eNOS in endothelial cells. These results strongly suggest that Akt has an important role in the regulation of normal angiogenesis and raise the possibility that the enhanced activity of this kinase that occurs in carcinomas may contribute to tumor vascularization and survival.