Resolution of abnormal body surface maps in children with atrial septal defect after intracardiac repair.

INTRODUCTION: The genesis of repolarization abnormalities of ECG waveforms in atrial septal defect (ASD), which typically is characterized by right ventricular (RV) volume overload, has not been explored, particularly in association with postoperative hemodynamic improvement. The aim of this study was to evaluate the effects of reduced RV overload after ASD closure on depolarization and repolarization abnormalities on body surface maps (BSMs). METHODS AND RESULTS: BSMs of 14 children with ASD were recorded preoperatively and at early postoperative (1-6 months) and late postoperative (>9 months) stages. BSMs of 31 age-matched healthy children were studied as normal controls. Before intracardiac repair, QRS isopotential maps of children with ASD showed delayed RV breakthrough and subsequent rightward enlargement of the positive area with a maximum shifting to the right. Delayed conduction of the RV, particularly at the outflow tract area, was noted. The preoperative QRST isointegral maps exhibited the two-maximum pattern reflecting repolarization abnormality. The delayed appearance of breakthrough and delayed RV conduction on the QRS isopotential maps persisted from the preoperative to the late postoperative stage, whereas the two-maximum pattern on the QRST isointegral maps normalized to the one-dipole pattern at an early stage after repair. CONCLUSION: Abnormal repolarization parameters in ASD patients showed rapid improvement postoperatively, despite the persistence of depolarization abnormalities. Therefore, the two-maximum pattern on the QRST isointegral maps indicates a primary T wave change due to hemodynamic RV volume overload.

Changes in body surface potential distributions induced by isoproterenol and Na channel blockers in patients with the Brugada syndrome.

BACKGROUND: The characteristics of unique ECG findings in the Brugada syndrome have not been well explained. METHODS: To clarify their characteristics and mechanisms, body surface maps (BSM) were recorded from patients with the Brugada syndrome (13 cases; a mean age of 48 years) before and after administration of isoproterenol (ISP) or Na channel blockers (12 cases). RESULTS: ST elevation in V1-V3 was decreased by 0.1 mV or more after ISP infusion in 8 of 11 cases and elevated after Na channel blockers in 8 of 12. In ventricular activation time (VAT) isochronal map, delayed conduction was noted on upper anterior chest in 11 and on anterior left chest in two. Delayed conduction areas were decreased by ISP and expanded by Na channel blockers. QRST isointegral map showed normal findings in baseline with minimal changes after ISP or Na channel blockers. Activation recovery interval (ARI) isochronal map showed prolonged area on upper anterior chest in baseline, being reduced by ISP and expanded by Na channel blockers. ARI dispersion (ARI-d), defined as difference between the maximum and minimum value of ARI, was larger in Brugada patients than that of normal subjects in baseline, and decreased after ISP and increased after Na channel blockers. CONCLUSION: ST elevation in the Brugada syndrome is primarily caused by abnormality in depolarization rather than in repolarization. BSM can provide better information to clarify a mechanism of ECG changes adding its diagnostic value for this unique syndrome.

Nitric oxide-dependent modulation of the delayed rectifier K+ current and the L-type Ca2+ current by ginsenoside Re, an ingredient of Panax ginseng, in guinea-pig cardiomyocytes.

1 Ginsenoside Re, a major ingredient of Panax ginseng, protects the heart against ischemia-reperfusion injury by shortening action potential duration (APD) and thereby prohibiting influx of excessive Ca2+. Ginsenoside Re enhances the slowly activating component of the delayed rectifier K+ current (IKs) and suppresses the L-type Ca2+ current (I(Ca,L)), which may account for APD shortening. 2 We used perforated configuration of patch-clamp technique to define the mechanism of enhancement of IKs and suppression of I(Ca,L) by ginsenoside Re in guinea-pig ventricular myocytes. 3 S-Methylisothiourea (SMT, 1 microm), an inhibitor of nitric oxide (NO) synthase (NOS), and N-acetyl-L-cystein (LNAC, 1 mm), an NO scavenger, inhibited IKs enhancement. Application of an NO donor, sodium nitroprusside (SNP, 1 mm), enhanced IKs with a magnitude similar to that by a maximum dose (20 microm) of ginseonside Re, and subsequent application of ginsenoside Re failed to enhance IKs. Conversely, after IKs had been enhanced by ginsenoside Re (20 microm), subsequently applied SNP failed to further enhance IKs. 4 An inhibitor of guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microm), barely suppressed IKs enhancement, while a thiol-alkylating reagent, N-ethylmaleimide (NEM, 0.5 mm), clearly suppressed it. A reducing reagent, di-thiothreitol (DTT, 5 mm), reversed both ginsenoside Re- and SNP-induced IKs enhancement. 5 I(Ca,L) suppression by ginsenoside Re (3 microm) was abolished by SMT (1 microm) or LNAC (1 mm). NEM (0.5 mm) did not suppress I(Ca,L) inhibition and DTT (5 mm) did not reverse I(Ca,L) inhibition, whereas in the presence of ODQ (10 microm), ginsenoside Re (3 microm) failed to suppress I(Ca,L). 6 These results indicate that ginsenoside Re-induced IKs enhancement and I(Ca,L) suppression involve NO actions. Direct S-nitrosylation of channel protein appears to be the main mechanism for IKs enhancement, while a cGMP-dependent pathway is responsible for I(Ca,L) inhibition.

Electrophysiological effects of ginseng and ginsenoside Re in guinea pig ventricular myocytes.

Panax ginseng is a folk medicine with various cardiovascular actions; however, its underlying mechanisms of action are not well known. In the present study, we examined the effects of ginseng and its main component, ginsenoside Re, on action potentials and membrane currents recorded from isolated guinea pig ventricular myocytes with the whole-cell patch clamp technique. Ginseng (1 mg/ml) shortened the action potential duration in a rate-dependent manner. Ginseng depressed the L-type Ca2+ current (I(Ca-L)) in a mode of both tonic block and use-dependent block, and enhanced the slowly activating component of the delayed rectifier K+ current (I(Ks)). Ginsenoside Re 3 microM exhibited similar electrophysiological effects to those of 1 mg/ml ginseng, but of slightly smaller magnitude. Inhibition of I(Ca,L) and enhancement of I(Ks) by ginsenoside Re appear to be one of the main electrophysiological actions of ginseng in the heart, although contributions from other ingredients should be considered.

Involvement of local anesthetic binding sites on IVS6 of sodium channels in fast and slow inactivation.

Local anesthetics (LAs) block Na(+) channels with a higher affinity for the fast or slow inactivated state of the channel. Their binding to the channel may stabilize fast inactivation or induce slow inactivation. We examined the role of the LA binding sites on domain IV, S6 (IVS6) of Na(+) channels in fast and slow inactivation by studying the gating properties of the mutants on IVS6 affecting LA binding. Mutation of the putative LA binding site, F1579C, inhibited fast and slow inactivation. Mutations of another putative LA binding site, Y1586C, and IVS6 residue involved in LA access and binding, I1575C, both enhanced fast and slow inactivation. None of the mutations affected channel activation. These results suggest that the LA binding site on IVS6 is involved in slow inactivation as well as fast inactivation, and these two gatings are coupled at the binding site.

Ion channel remodeling in cardiac hypertrophy is prevented by blood pressure reduction without affecting heart weight increase in rats with abdominal aortic banding.

This study investigates changes in the messenger RNA (mRNA) expression levels of HCN2 and HCN4 encoding rat If channels; ClC-3, a candidate gene for swelling-activated Cl- channel, and pICln, a regulatory subunit of Cl- channels in rat hypertrophied heart induced by banding the abdominal aorta. The mRNA expression levels were quantified with competitive reverse transcription polymerase chain reaction methods. Plasma renin activity, blood pressure, and heart weight increased. HCN2, HCN4, and ClC-3 mRNA levels decreased in the early phase after banding, whereas they increased in the late phase; pICln mRNA levels did not change at any stage. Administration of candesartan, an angiotensin II receptor blocker, prevented cardiac hypertrophy, but amlodipine, a Ca2+ channel blocker, did not prevent it, whereas both drugs lowered blood pressure. Changes in mRNA levels of HCN2, HCN4, and ClC-3 were alleviated by both candesartan and amlodipine, and these levels of the treated groups were not different from those in the sham control group. This study is the first to demonstrate changes in mRNA levels of HCN2, HCN4, and ClC-3 in cardiac hypertrophy induced by abdominal aortic banding. The data further suggest that the changes in channel mRNA levels were prevented by blood pressure reduction without affecting heart weight increase in this model.

Moving dipole analysis of normal and abnormal ventricular activation by magnetocardiography.

The current source during ventricular excitation of the in situ heart has not been well characterized. We analyzed current dipoles of ventricular excitation by magnetocardiography (MCG) in 16 healthy subjects and 10 patients with the Wolff-Parkinson-White syndrome or premature ventricular contraction. Single current dipoles were estimated by MCG with the spatial position, direction, and strength in the initial 40 ms of QRS (moving dipole analysis). In 12 of the 16 healthy subjects, the origin of current dipoles moved consecutively from the initial position with the increase in the peak strength at 30 ms of QRS. In the other 4 healthy subjects, dipoles moved discontinuously jumping to the right-anterior thorax at 17.8 ms (mean). In abnormal ventricular excitation, the dipoles remained in the initial position with little movement, smaller strength of dipole than that of normal with a delayed peak time. The moving dipole analysis can be applied to determine spatial distribution of normal and abnormal excitation sources at the initial phase of ventricular depolarization in the in situ heart.