Burst emergence of intracellular Ca2+ waves evokes arrhythmogenic oscillatory depolarization via the Na+-Ca2+ exchanger: simultaneous confocal recording of membrane potential and intracellular Ca2+ in the heart.

Intracellular Ca(2+) waves (CaWs) of cardiomyocytes are spontaneous events of Ca(2+) release from the sarcoplasmic reticulum that are regarded as an important substrate for triggered arrhythmias and delayed afterdepolarizations. However, little is known regarding whether or how CaWs within the heart actually produce arrhythmogenic membrane oscillation because of the lack of data confirming direct correlation between CaWs and membrane potentials (V(m)) in the heart. On the hypothesis that CaWs evoke arrhythmogenic oscillatory depolarization when they emerge synchronously and intensively in the heart, we conducted simultaneous fluorescence recording of intracellular Ca(2+) ([Ca(2+)](i)) dynamics and V(m) of ventricular myocytes on subepicardial surfaces of Langendorff-perfused rat hearts using in situ dual-view, rapid-scanning confocal microscopy. In intact hearts loaded with fluo4/acetoxymethyl ester and RH237 under perfusion with cytochalasin D at room temperature, individual myocytes exhibited Ca(2+) transients and action potentials uniformly on ventricular excitation, whereas low-K(+)-perfused (2.4 mmol/L) hearts exhibited CaWs sporadically between Ca(2+) transients without discernible membrane depolarization. Further [Ca(2+)](i) loading of the heart, produced by rapid pacing and addition of isoproterenol, evoked triggered activity and subsequent oscillatory V(m), which are caused by burst emergence of CaWs in individual myocytes. Such arrhythmogenic membrane oscillation was abolished by ryanodine or the Na(+)-Ca(2+) exchanger inhibitor SEA0400, indicating an essential role of CaWs and resultant Na(+)-Ca(2+) exchanger-mediated depolarization in triggered activity. In summary, we demonstrate a mechanistic link between intracellular CaWs and arrhythmogenic oscillatory depolarizations in the heart. Our findings provide a cellular perspective on abnormal [Ca(2+)](i) handling in the genesis of triggered arrhythmias in the heart.

Generation of reentrant arrhythmias by dominant-negative inhibition of connexin43 in rat cultured myocyte monolayers.

AIMS: Alteration of connexin43 (Cx43)-mediated intercellular communication is known to promote susceptibility to ventricular tachyarrhythmias. However, the precise mechanism of the altered Cx43 responsible for arrhythmogenesis remains unclear. We sought to understand changes in impulse propagation of ventricular myocytes under dominant-negative (DN) inhibition of Cx43 in the development of arrhythmias. METHODS AND RESULTS: Intercellular communication was inhibited in confluent monolayers of neonatal rat cultured myocytes by an adenoviral vector-mediated gene transfer for DNCx43-fused red fluorescence protein (RFP). A high-resolution, macro-zoom fluorescence imaging system was used to visualize both the fluo4- and RFP-fluorescence intensities as measures of Ca2+ transient propagation and distribution of DNCx43 inhibition, respectively, in the myocyte monolayers. DNCx43 inhibition of the monolayers resulted in not only a significant slowing of Ca2+ transient propagation velocity, but also a preferential emergence of spiral-wave reentrant arrhythmias elicited by rapid pacing. Detailed observations on the development of spiral waves revealed that the gene-transferred myocyte monolayers exhibited regional slowing of propagation and subsequent generation of wave break, resulting in reentrant arrhythmias. Furthermore, DNCx43-RFP-transferred monolayers showed higher fluorescence intensity of RFP at the break point than at the surrounding myocardium, indicating a culprit role of DNCx43 inhibition in the genesis of spiral reentry. CONCLUSION: The present results indicate that regional heterogeneity in gap-junctional communication promotes, in addition to slowing of conduction velocity, susceptibility to reentrant tachyarrhythmias.

Infectious ductal aneurysm after coil embolization in an infant.

We report a case of ductal aneurysm after transcatheter coil embolization in an infant. The aneurysm was asymptomatic and was not detected until it ruptured during surgical intervention. We suspect that the aneurysm was induced by methicillin-resistant Staphylococcus aureus infection, as the resected aneurysmal wall was severely infiltrated by inflammatory cells and the patient had recurrent methicillin-resistant Staphylococcus aureus infection. We recommend remaining on guard against formation of a ductal aneurysm after coil embolization, especially in patients with associated recurrent bacteremia.

In situ Ca2+ dynamics of Purkinje fibers and its interconnection with subjacent ventricular myocytes.

Purkinje fibers play essential roles in impulse propagation to the ventricles, and their functional impairment can become arrhythmogenic. However, little is known about precise spatiotemporal pattern(s) of interconnection between Purkinje-fiber network and the underlying ventricular myocardium within the heart. To address this issue, we simultaneously visualized intracellular Ca(2+) dynamics at Purkinje fibers and subjacent ventricular myocytes in Langendorff-perfused rat hearts using multi-pinhole type, rapid-scanning confocal microscopy. Under recording of electrocardiogram at room temperature spatiotemporal changes in fluo3-fluorescence intensity were visualized on the subendocardial region of the right-ventricular septum. Staining of the heart with either fluo3, acetylthiocholine iodide (ATCHI), or di-4-ANEPPS revealed characteristic structures of Purkinje fibers. During sinus rhythm (about 60 bpm) or atrial pacing (up to 3 Hz) each Purkinje-fiber exhibited spatiotemporally synchronous Ca(2+) transients nearly simultaneously to ventricular excitation. Ca(2+) transients in individual fibers were still synchronized within the Purkinje-fiber network not only under high-K(+) (8 mM) perfusion-induced Purkinje-to-ventricular (P-V) conduction delay, but also under unidirectional, orthodromic P-V block produced by 10-mM K(+) perfusion. While spontaneous, asynchronous intracellular Ca(2+) waves were identified in injured fibers of Purkinje network locally, surrounding fibers still exhibited Ca(2+) transients synchronously to ventricular excitation. In summary, these results are the first demonstration of intracellular Ca(2+) dynamics in the Purkinje-fiber network in situ. The synchronous Ca(2+) transients, preserved even under P-V conduction disturbances or under emergence of Ca(2+) waves, imply a syncytial role of Purkinje fibers as a specialized conduction system, whereas unidirectional block at P-V junctions indicates a substrate for reentrant arrhythmias.

New "right side median" approach for postoperative re-coarctation of the aorta.

Anatomic repair of postoperative recurrent coarctation of the aorta is surgically difficult using the conventional lateral approach. Therefore, we have developed a new approach to the stenotic aorta through a median sternotomy, involving division of the superior vena cava and left caudal displacement of the heart. This approach facilitates extensive dissection and mobilization of the descending aorta in the posterior mediastinum behind the heart and also facilitates direct anastomosis of the aortic arch and the descending aorta after resection of the stenosis. This approach is useful for anatomic repair of postoperative recurrent coarctation of the aorta and other posterior mediastinal procedures.

"Bay window" technique for the arterial switch operation of the transposition of the great arteries with complex coronary arteries.

BACKGROUND: The success of arterial switch operations for transposition of the great arteries largely depends on faultless coronary translocation and subsequent sufficient myocardial perfusion. However, in patients with complex coronary artery anatomy, coronary translocation is often difficult to perform by conventional surgical techniques alone. Therefore we developed the "bay window" technique as a useful adjunct in patients with complex coronary arteries undergoing concomitant coronary translocation and arterial switch operation. Early and midterm results of this technique are described. METHODS: Between September 2001 and February 2002, 4 patients with transposition of the great arteries with complex coronary arteries underwent arterial switch operation. The ages of the patients at the time of operation ranged from 8 to 52 days. Great arterial relationships were anteroposterior in 2 patients, right-oblique in 1, and side-by-side in 1. One patient also had ventricular septal defect. Coronary arterial patterns were as follows: absent left main trunk in 1 patient, short left main trunk in 1, and short right main trunk in 1. Both coronary arterial orifices were resected as a tall U-shaped cuff. The inferior half of the coronary cuff was sewn into a J-shaped incision on the pulmonary stump. The superior half of the coronary cuff was folded down inside to form a bay window channel. RESULTS: No coronary events occurred (ie, inclusive of coronary stenosis, myocardial infarction, and coronary death). Postoperative echocardiogram demonstrated normal ventricular wall motions in all 4 patients. CONCLUSIONS: The bay window technique is an innovative and simple surgical adjunct for translocating complex coronary arteries.