No abstract

Gap junctions (gjs) are increasingly recognized as playing a significant role in seizures. We demonstrate that different types of gap junctional blocking agents reduce the duration of evoked seizure-like primary afterdischarges (PADs) in the rat in vitro CA1 hippocampal pyramidal region, following repetitive tetanization of the Schaffer collaterals. Intracellular acidosis, which is known to block gap junctional communication, decreased the PADs, whereas alkalinization increased the PADs. Cellular excitability was not significantly depressed as determined by input/output relations recorded before and during perfusion of the gj blockers blockers carbenoxolone and sodium propionate. There was a small decrease following 1-octanol perfusion and a large decrease following NH4Cl application. Carbenoxolone diminished PAD duration, but increased neuronal excitability in whole-cell recordings. After robust PADs were established, the expression of several gj proteins including connexins (Cxs) 26, 32, 36, and 43, as measured by Western blotting, was unchanged, although the level of nonphosphorylated Cx43 was decreased. Our data support the concept that blocking gap junctional communication is an anticonvulsant mechanism.

Background-Previous studies suggested a high incidence of congestive heart failure in patients with single and/or systemic right ventricles. The corresponding risk in an adult population is unknown. Methods and Results-A cohort of 188 consecutive adult patients with single or systemic right ventricles was prospectively assessed with gated radionuclide angiography (nϭ135) or 2D echocardiography (nϭ188) and followed up clinically. Clinical assessment showed 82.4% of the patients were in New York Heart Association class I or II, 13.3% were in class III, and 4.3% were in class IV. Heart failure occurred in 22.2% of patients with transposition of the great arteries and a Mustard procedure, 32.3% of patients with congenitally corrected transposition of the great arteries, and 40% of Fontan-palliated patients. Symptomatic patients had significantly lower anaerobic thresholds (10.3Ϯ2.8 versus 13.2Ϯ4.8 mL · kg Ϫ1 · min