Masayuki Yamaura

Expression of Coxsackievirus and Adenovirus Receptor in Hearts of Rats With Experimental Autoimmune Myocarditis

The expression of coxsackievirus and adenovirus receptor (CAR) was dominant in the brains and hearts of mice until the newborn phase. There is no detailed information concerning the relation between the expression of CAR and development of hearts. It is also uncertain whether CAR is able to be induced in adult hearts after cardiac injury. We demonstrated that CAR was abundant in the hearts of newborn rats but was barely detectable in the hearts of adult rats. The expression of CAR in rat hearts with experimental autoimmune myocarditis, which was induced by immunization of purified cardiac myosin, was serially investigated. Active myocarditis was observed from day 15 after immunization. By immunohistochemistry, cardiomyocytes were strongly stained for CAR antibody from days 24 to 42. CAR mRNA was also detected from days 18 to 30 by using reverse transcription-polymerase chain reaction. In the next experiment, the induction of CAR on isolated cardiomyocytes was investigated. CAR was barely detectable in cultured cardiomyocytes by Western blot analysis after isolation. This molecule gradually appeared along with the creation of clusters and beating of cardiomyocytes. Furthermore, the induction of CAR in cultured cardiomyocytes increased after supplement with conditioned medium of rat splenocytes activated by concanavalin A. In conclusion, rat CAR is expressed strongly in the hearts of newborn rats and is suppressed in those of adult rats. The expression of CAR is enhanced during the active phase of experimental autoimmune myocarditis and is induced by inflammatory mediators. CAR may play a role in cell-to-cell contact and adhesion of cardiomyocytes.

Comparison of Arrhythmogenicity of Atrial Pacing at Several Right Atrial Pacing Sites: Evaluation of Canine Atrial Electrograms During Atrial Pacing and Arrhythmogenicity for Atrial Fibrillation

The changes in the duration of atrial electrograms and the appearance of AF during atrial pacing were compared among five atrial pacing sites in dogs to clarify the arrhythmogenicity of atrial pacing at different atrial pacing sites. In seven mongrel dogs (15–20 kg), the right atrial surface was exposed by right thoracotomy. Atrial electrograms were recorded via bipolar electrodes with an interelectrode distance of 1.2 mm at four right atrial sites: (1) the high right atrium (HRA), (2) the mid‐right atrium (MRA), (3) the low right atrium (LRA), and (4) the center of the pectinate muscle (PM). The duration of the atrial electrograms at these four recording sites were measured during atrial pacing with fixed cycle lengths of 200, 150, and 120 ms delivered at five atrial sites: (1) the HRA, (2) the inferior vena cava (IVC), (3) the right atrial appendage (RAA), (4) Bachmans bundle (BB), and (5) the atrial septum (AS). In each dog, the atrial pacing with the 120‐ms cycle length was performed five times at each pacing site to evaluate the in‐ducibility of AF. When AF was induced, the atrial recording site which first showed a fragmented atrial electrogram was considered the initiation site of the AF. AF was induced during 9 of 35 episodes of atrial pacing at the HRA site, 11 of 35 at the IVC site, 5 of 35 at the RAA site. 3 of 35 at the BB site, and none at the AS site. The initiation site of AF was in the HRA site in 11 of 28 episodes of induced AF, in the MRA site in 9 of 28, and in the LRA site in 8 of 28. At each recording site, the shorter the paced cycle length, the longer the duration of the atrial electrogram regardless of the pacing site. During the atrial pacing with the 200‐ms cycle length, the HRA pacing resulted in the shortest duration of the atrial electrogram at each recording site in comparison with the other pacing sites. However, during atrial pacing at the two shorter paced cycle lengths, the duration of the atrial electrogram was shorter during the pacing at the BB or AS sites in comparison with the other three pacing sites, i.e., the HRA, IVC, and RAA sites. These results were the same for all atrial recording sites, but the prolongation of the atrial electrogram was most prominent at the HRA and MRA recording sites, which are most likely initiation sites of the induced AF. In the canine atria, (1) the initiation sites of AF were likely to be the HRA, MRA, or LRA sites in comparison with the PM site; and (2) the atrial pacing at the BB or AS sites was considered less arrhythmogenic for AF than the pacing at the HRA, LRA, or RAA sites.

Effects of the ATP-Sensitive K Channel Opener Nicorandil on the QT Interval and the Effective Refractory Period in Patients with Congenital Long QT Syndrome

Congenital or idiopathic long QT syndrome is characterized by a frequently lethal ventricular arrhythmia called torsades de pointes (TdP) as well as a prolonged QT interval. The long QT interval related to an abnormal gene of the Na+ channel has been shown to be shortened by mexiletine. However, the action of K+ channel openers on the QT interval associated with abnormal genes of the K channel has yet to be studied. Seven patients of five families with long QT syndrome were included in this study, of whom six had syncope and six had documented TdP. Either long QT interval or sudden cardiac death had been observed in family members of all seven patients. At 1 to 3 weeks after admission, when TdP or frequent ventricular arrhythmia had subsided, nicorandil, an ATP-sensitive K channel opener, was administered orally at a dose of 15 mg/day in five patients and at 30 mg/day in the remaining two patients, and the effects were assessed on the third day after drug administration. In four patients, the effective refractory period was measured in the right ventricle before and after administration of K channel opener administration. The QT interval (QTc) prior to administration of the K channel opener was 0.60 +/- 0.09 ms (mean +/- SD) (0.61 +/- 0.10 second(1/2)), which was shortened to 0.54 +/- 0.05 ms (0.55 +/- 0.06 second(1/2)) on the third day of drug administration (P < .05 for both): 10.4 +/- 8.0% (8.6 +/- 5.5%). The QT interval at varying preceding R-R intervals on Holter electrocardiograms showed a shift toward the right as a result of the drug administration. The effective refractory period showed a significant prolongation, 256 +/- 26 ms versus 280 +/- 22 ms before and after drug administration, respectively (P <.05). Intravenous administration of nicorandil resulted in no significant change in heart rate or blood pressure, while QTc showed a tendency to shorten, but nonsignificantly (P = .08). However, a hump on the monophasic action potential was abolished, especially at the long preceding R-R interval induced by premature stimulation of the ventricle. It is concluded that nicorandil shortens the QT interval slightly when administered orally, whereas the effective refractory period shows a slight prolongation. The physiologic and clinical significance of these effects needs to be studied further.

Elevated serum lipoprotein(a) is a risk factor for left atrial thrombus in patients with chronic atrial fibrillation: A transesophageal echocardiographic study

BACKGROUND Patients with chronic atrial fibrillation have an increased risk of thromboembolism. Apoprotein(a) has a structural homology with plasminogen, suggesting that lipoprotein(a) [Lp(a)] may produce thrombogenic effects by modulating the fibrinolytic system. However, the role of Lp(a) level in the formation of left atrial thrombus has not been studied. We sought to evaluate whether Lp(a) is a risk factor for left atrial thrombus in patients with chronic atrial fibrillation. METHODS AND RESULTS The consecutive series of 150 patients (mean age 67 +/- 8 years) with chronic atrial fibrillation underwent transesophageal echocardiography. Left atrial thrombus was diagnosed by transesophageal echocardiography. Clinical, biochemical, and echocardiographic variables were prospectively collected. Univariate analysis showed that patients with left atrial thrombus (n = 29, 19%) had higher frequency of spontaneous echo contrast (93% vs 55%, P <.0001) than patients without left atrial thrombus (n = 121). Patients with left atrial thrombus also had a significantly higher serum concentration of Lp(a) (34.5 +/- 24.1 vs 17.9 +/- 13.5 mg/dL, P <.0001), a larger left atrium (5.4 +/- 0.9 vs 4.8 +/- 0.7 cm, P <.001), and a lower left atrial appendage peak flow velocity (11.1 +/- 5.4 vs 23.5 +/- 14.6 cm/s, P <.0001). Multivariate regression analysis showed that the Lp(a) concentration (P <.0001) was a significant positive predictor and the left atrial appendage peak flow velocity (P =.0125) was a significant negative predictor of left atrial thrombus. Left atrial thrombus was present in 16 (48%) of 33 patients with Lp(a) level >/=30 mg/dL. CONCLUSIONS Elevated serum levels of Lp(a) are strongly associated with left atrial thrombus. These findings suggest that Lp(a) level may be a novel risk factor for left atrial thrombus in patients with chronic atrial fibrillation.

Variable Electrocardiographic Effects of Short‐Term Quinidine Sulfate Administration in Brugada Syndrome

Quinidine, a class I antiarrhythmic agent with blocking property of transient outward current, is a possible candidate for the suppression of ventricular fibrillation in patients with Brugada syndrome; although there is a concern that its ability to these effects may be proarrhythmic. Therefore, we evaluated the effect of quinidine sulfate on ST‐segment elevation in Brugada syndrome. In 8 patients with Brugada syndrome, the magnitude of ST‐elevation at the J‐point (STJ), and the ST‐segment configuration in leads V1–V3, were compared before and on day 2 after the initiation of quinidine administration. In 3 patients, quinidine attenuated STJ by ≥0.1 mV. Of these 3 patients, ST‐segment elevation was normalized in 2 patients, while the ST‐segment configuration was unchanged in another. In another 3 patients, quinidine augmented STJ by ≥0.1 mV without any change of ST‐segment configuration, and the augmentation was returned to baseline after the discontinuation of quinidine. Quinidine exhibited no effect on the ST‐segment in the remaining 2 patients. The favorable effects of quinidine on the ST‐segment tended to be more pronounced in patients with prominent ST‐elevation at baseline. In 1 patient, quinidine was effective in eliminating both ST‐segment elevation and repetitive tachyarrhythmia episodes. In conclusion, the effects of quinidine on ST‐segment elevation were variable. Quinidine may potentially augment the ST‐segment elevation in some patients with Brugada syndrome.

Recovery of the right atrial effective refractory period after cardioversion of chronic atrial fibrillation

The effective refractory period was shorter in patients with than without chronic atrial fibrillation (AF). The effective refractory period was prolonged, and at 12 and 24 hours after cardioversion of AF it was the same as the subjects without AF.