Cardiac resynchronization therapy in patients with absent right but persistent left superior vena cava.

Abnormalities of the vena cava system are usually asymptomatic and are found incidentally during pacemaker implantation or catherization. We report a case of dilative cardiomyopathy requiring cardiac resynchronization defibrillator therapy (CRT-D). During the operation, a persistent left superior vena cava with an absent right vena cava was discovered. During open chest surgery, we implanted a CRT-D with epicardial patches and pacing leads, which is a simple technique for safe and reliable biventricular defibrillator therapy in these patients.

G-Protein beta(3)-subunit 825T allele is associated with enhanced human atrial inward rectifier potassium currents.

BACKGROUND: A C825T polymorphism was recently identified in the human gene encoding for the beta(3)-subunit of heterotrimeric G proteins. The 825T allele is associated with a splice variant of Gbeta(3) and enhanced signal transduction. We hypothesized that patients carrying the 825T allele exhibit the modified Gbeta(3) phenotype. The resulting enhancement of signal transduction should be detectable in the Gbetagamma-dimer-mediated acetylcholine-stimulated K(+) current (I(K,ACh)). METHODS AND RESULTS: Seventy patients undergoing cardiac surgery were genotyped for the C825T polymorphism. In right atrial myocytes from these patients, the inward rectifier K(+) currents (I(K1), I(K,ACh)) were studied with the whole-cell patch-clamp technique. Background current I(K1) was measured with depolarizing ramp pulses and quantified as inward current at -100 mV; mean amplitudes were (pA/pF) 4.98+/-0.49 (n=30/93 patients/cells) in patients with CC genotype, 4.25+/-0.36 (n=31/121 patients/cells) with TC, and 7. 46+/-1.14 (n=9/32 patients/cells; P<0.05) with TT. Conversely, mean I(K,ACh), which is maximally activated by carbachol (2 micromol/L), was reduced in patients with TT genotype (pA/pF, 4.30+/-1.33, n=9/27 patients/cells; P<0.05) compared with the other 2 groups (6.56+/-0. 54, n=30/80 and 6.16+/-0.45, n=31/117 patients/cells, for CC and TC genotype, respectively). Essentially similar results were obtained with adenosine (1 mmol/L). CONCLUSIONS: We found an association between the Gbeta(3) 825T allele and amplitude of human atrial I(K1) and I(K,ACh). Increased background current density in TT carriers could shorten action potential duration and may be due to I(K,ACh) being constitutively active in this genotype.

Evidence for Edg-3 receptor-mediated activation of I(K.ACh) by sphingosine-1-phosphate in human atrial cardiomyocytes.

Sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPPC) have been reported to activate muscarinic receptor-activated inward rectifier K(+) current (I(K.ACh)) in cultured guinea pig atrial myocytes with similar nanomolar potency. Members of the endothelial differentiation gene (Edg) receptor family were recently identified as receptors for SPP; however, these receptors respond only to micromolar concentrations of SPPC. Here we investigated the sphingolipid-induced activation of I(K.ACh) in freshly isolated guinea pig, mouse, and human atrial myocytes. SPP activated I(K.ACh) in atrial myocytes from all three species with a similar nanomolar potency (EC(50) values: 4-8 nM). At these low concentrations, SPPC also activated I(K.ACh) in guinea pig myocytes. In contrast, SPPC was almost ineffective in mouse and human myocytes, thus resembling the pharmacology of the Edg receptors. Transcripts of Edg-1, Edg-3, and Edg-5 were detected in human atrial cells. Moreover, activation of I(K.ACh) by SPP was blocked by the Edg-3-selective antagonist suramin, which did not affect basal or carbachol-stimulated K(+) currents. In conclusion, these data indicate that I(K.ACh) activation by SPP and SPPC exhibits large species differences. Furthermore, they suggest that SPP-induced I(K.ACh) activation in human atrial myocytes is mediated by the Edg-3 subtype of SPP receptors.