Abstract-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.
lthough an electrophysiologic study (EPS) is the most reliable method for selecting a suitable treatment for patients with sustained ventricular tachycardia (VT), the effectiveness of antiarrhythmic drugs in preventing VT induction is limited. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Furthermore, clinical VT recurrence has been observed even under EPSguided effective pharmacological therapy and the incidence of such VT recurrence is not low. [3][4][5][6][7][8][9][10][11][12][13][14][15] The reliability of EPS-guided therapy strongly depends on the stimulation protocol and the criteria for the patient response to programmed stimulation at the drug testing. For example, the studies of Mitchell et al, 10,11 which employed some of the most strict criteria for drug efficacy, showed a VT recurrence rate of 15% in 3 years, whereas the ESVEM study, which employed less rigid criteria, showed an arrhythmic event rate >50% in 5 years. 12 This indicates that VT recurrence can be more reliably avoided when stricter criteria are used for the drug assessment in an EPS, although this would reduce the population of patients effectively treated. However, the lowest VT recurrence rate is still 15-20% in 3-5 years. In the present study, electrophysiologic parameters were analyzed in patients with sustained VT who were followed up under treatment with effective antiarrhythmic drugs, which rendered the VT non-inducible, and these parameters were compared between the groups with and without arrhythmic events to identify the electrophysiologic parameters useful for predicting clinical VT recurrence in patients under EPSguided effective pharmacological therapy.
Methods
PatientsThe study population consisted of 77 of 202 consecutive patients with sustained monomorphic VT who underwent an EPS and who met the following criteria: (1) they had had at least one episode of electrocardiographically documented sustained monomorphic VT, (2) at least 1 antiarJpn Circ J 1999; 63: 674 -680 (Received March 3, 1999; revised manuscript received May 26, 1999; accepted June 1, 1999 Although an electrophysiologic study (EPS) is the most reliable method for selecting the treatment for a patient with sustained ventricular tachycardia (VT), VT recurrence may occur even during EPS-guided effective therapy. Electrophysiologic parameters were compared between patients with and without arrhythmic events under EPSguided effective therapy to identify the predictive parameters of VT recurrence during the clinical course. The study population consisted of 77 consecutive patients with sustained VT who were receiving long-term pharmacological therapy that was demonstrated to be effective by the EPS assessment. The VT induction protocol employed 1-3 extrastimuli and rapid ventricular pacing at 2 right ventricular sites and 1 left ventricular site, and isoproterenol was infused when VT was not induced. To determine the 'effective' antiarrhythmic drug, all sustained ventricular arrhythmias had to be prevented during the whole induction protocol, but repetitive ve...
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