論文

Identification of patients with acute chest pain due to acute coronary syndrome is a common and difficult challenge for emergency physicians. A prospective study was conducted to assess the diagnostic value of a bedside test of cardiac troponin T in the emergency room setting. Forty-nine consecutive patients, who visited the emergency room within 6 hours of the onset of acute chest pain, were enrolled. Of the 26 patients who were ultimately diagnosed as having acute coronary syndrome, seven patients (27%) had positive cardiac troponin T assay results, whereas none of the patients without acute coronary syndrome had positive results (0%). For patients with acute coronary syndrome who presented later than 3 hours after the onset (n = 4), the test was positive in all cases (positive predictive value: 100%, negative predictive value: 100%, p < 0.01). However, the positive rate was only 14% for those who presented earlier than 3 hours after the onset (n = 22) (positive predictive value: 100%, negative predictive value: 47%, p = 0.84). In conclusion, bedside troponin T test results should be evaluated considering the time interval from the onset of chest symptoms.

Background: The specific changes in the gating kinetics of the sodium current (INa) responsible for its phenotype have remained to be elucidated. In the present study the effect of changes in the gating kinetics of INa on early repolarization (ER) and initiation of phase 2 reentry (P2R) were evaluated in a theoretical epicardial ventricular fiber model. Methods and Results: Miyoshi-ICaL was incorporated into the modified Luo-Rudy dynamic (LRd) model. Dispersion at Ito-density was set within a theoretical fiber composed of serially arranged epicardial cells with gap junctions. The following changes in INa kinetics were made: (1) a -10mV shift in steady-state inactivation, (2) a +10mV shift in steady-state activation curve, (3) a small inactivation time constant (DEC); P2R and ER were observed. A conduction disturbance within the fiber was simulated and only when the INa-density was decreased did DEC, especially, show a marked increase in the likelihood of causing ER and P2R. Conduction disturbance significantly increased the likelihood causing ER or P2R. Conclusions: In this one-dimension model with Ito-density dispersion, DEC-INa precipitates INa-blocker inducible ER. This suggests that the characteristic ST-segment elevation in the Brugada syndrome with SCN5A mutation can be interpreted in part by DEC-INa. Concomitant conduction disturbance may be required to cause P2R at physiological Ito density.

Objectives: We evaluated serial changes of electrical and mechanical parameters of atrial remodeling in dogs subjected to rapid atrial pacing. Background: Prolonged rapid atrial excitation causes electrical and mechanical remodeling, which contributes to persistence of atrial fibrillation and clot formation. However, the temporal relationship between these two types of atrial remodeling remains unknown. Methods: In 8 dogs, rapid pacing at 400 ppm was continued for 14 days. The electrophysiologic and transesophageal echocardiographic studies were performed on the day before and after 2, 7, and 14 days of rapid pacing, then 1 and 7 days after the cessation of pacing. These were compared with sham-operated dogs (instrumented but not paced, n=6). Results: With rapid pacing, there was an immediate shortening of the effective refractory period (ERP) and decreases in the transmitral atrial wave velocity (MAV) and the left atrial appendage emptying velocity (LAAV). In contrast, conduction velocity (CV) decreased and the left atrial appendage area (LAAA) increased progressively over 14 days. During the recovery, ERP, MAV, and LAAV returned to the baseline in 1 day, whereas CV and LAAA did in 7 days. ERP was highly positively correlated with LAAV (r=0.78, p<0.001) and MAV (r=0.73, p<0.001), while CV was negatively correlated only with LAAA (r=-0.58, p<0.001). Conclusions: Pacing-induced electrical and mechanical remodeling of the atrium exhibits divergent patterns of progression and regression such that changes of ERP and contractile function take place more rapidly than those of CV and atrial size. © 2004 Elsevier Ireland Ltd. All rights reserved.

Calcium overload plays a key role in the development of atrial electrical remodeling. The effect of an L-type Ca channel blocker in preventing this remodeling has been reported to be short lasting, partly due to down-regulation of this channel and persisting Ca entry through the T-type Ca channel. To prove if efonidipine, a dual L- and T-type Ca channel blocker exerts a greater effect than an L-type Ca channel blocker verapamil, 21 dogs underwent rapid atrial pacing at 400 bpm for 14 days, pretreatment with efonidipine in 7 (E), verapamil in 7 (V), and none in 7 (C). We measured the atrial effective refractory period (ERP) serially during 14 days of rapid pacing. In response to rapid pacing, ERP decreased progressively in C. In contrast, in E and V, ERP remained greater than ERP in C (P < 0.01) on days 2 through 7. However, on the 14th day, ERP in V decreased to the level seen in C, whereas ERP in E remained significantly longer than ERPs in C or V (P < 0.01). The blockade L-type Ca channel alone is not sufficient, but the addition of a T-type Ca channel blockade shows a more sustained effect to prevent atrial electrical remodeling.

Background: Calcium overload plays a major role in the development of electrical and mechanical remodeling during atrial fibrillation, but the potential of verapamil, a Ca blocker, for preventing atrial electrical remodeling remains controversial. Methods and Results: Pacing and recording electrodes were sutured to the right atrium in 16 dogs. After a 5-day recovery period, rapid atrial pacing at 400 ppm was initiated in 8 dogs (control group). In the remaining 8 dogs, oral administration of verapamil (8 mg/kg per day) was started 1 week before the initiation of rapid pacing (verapamil group). On the day before and at 2, 7, 14 days after rapid pacing, electrophysiological (EP) and transesophageal echocardiographic (TEE) studies were performed under autonomic blockade. In response to rapid pacing, EP and TEE parameters changed progressively in the control group (p<0.05 vs day 0), whereas in the verapamil group, no significant changes in the various parameters were observed for the first 7 days. However, verapamil failed to prevent progression of both types of remodeling after 14 days of pacing. Conclusion: Verapamil can attenuate the progression of electrical and mechanical remodeling of the atrium for at least 7 days.

This study was designed to evaluate the electrophysiologic effects of E4031 (a pure IKr blocker) and azimilide (AZ: a combined 1kr + IKs blocker) at various stages of atrial electrical remodeling. Twelve dogs underwent continuous rapid atrial pacing (400/min) for 14 days. The electrophysiologic study was performed on the day before as well as after 2, 7, and 14 days of rapid atrial pacing both before and after the administration of either E4031 (n = 6) or AZ (n = 6). In response to rapid atrial pacing, the atrial effective refractory period (ERP), conduction velocity, and wavelength decreased significantly at pacing cycle lengths (PCLs) of 200 and 400 ms (P < 0.05). E4031 prolonged ERP in a reverse use-dependent manner throughout the study period. AZ also prolonged ERP during the 14 days of rapid pacing. ERP prolongation at a PCL of 200 ms was significantly greater with AZ than with E4031 (P < 0.05). The effects of blocking IKr by E4031 and IKr + IKs by AZ were well preserved at various stages of atrial electrical remodeling. However, the effect of prolonging ERP at a shorter PCL was more prominent by AZ than by E4031. Thus, IKs blockade may add a favorable anti-fibrillatory effect to IKr blockade even in the remodeled atrium.

Prolonged rapid atrial excitation gives rise to atrial electrical remodeling, which perpetuates atrial fibrillation (AF). However, there has been controversy regarding the nature of temporal changes in conduction characteristics during the development and recovery of electrical remodeling. This study was designed to clarify the nature of the development and recovery of electrical remodeling in relation to AF inducibility in dogs subjected to rapid atrial pacing. Eleven dogs underwent rapid atrial pacing (400/min) for 28 days. The electrophysiological study was performed on the day just prior to the commencement of pacing, on days 2, 7, 14, and 28 of rapid pacing, as well as 1 and 7 days after the cessation of pacing. In response to rapid atrial pacing, atrial effective refractory period (ERP), conduction velocity and wavelength decreased significantly (p<0.05). ERP had shortened significantly and rapidly within 2 days of pacing, while conduction velocity decreased more gradually. During the recovery, ERP returned to almost baseline levels within a day, whereas conduction velocity returned to baseline by day 7. Sustained AF became inducible in 37% of the dogs from 7 days of pacing until 1 day after the cessation, when wavelength fell below 8.7 cm. In conclusion, rapid atrial excitation causes a progressive but discordant temporal pattern of a decrease in ERP and conduction velocity. The resultant shortening of the wavelength determines the inducibility and maintenance of AF. The electrophysiological changes produced by one month of rapid atrial pacing can be fully reversed within a week, although in a discordant temporal pattern. Copyright © 2002 by the Japanese Heart Journal.

Background: Intravenous verapamil has been reported to prevent electrical remodeling induced by rapid atrial excitation of several minutes to several hours. However, the clinical efficacy of verapamil when taken orally and daily remains controversial. Purpose: We attempted to demonstrate our hypothesis that if verapamil prevents calcium (Ca) overload, its efficacy would be greater when taken before, rather than after, the onset of rapid atrial excitation. Methods: In 24 dogs, pacing and recording electrodes were sutured onto the right atrium. After a 5-day recovery period, rapid atrial pacing at 400 ppm was started, followed 2 days later by oral verapamil (8 mg/kg per day) in eight dogs (After group; A). In another eight dogs, oral verapamil administration was begun 1 week before the initiation of rapid pacing (Before group; B). In the remaining eight dogs, only rapid atrial pacing was started, without oral verapamil (Control group; C). We measured the effective refractory period (ERP) and conduction velocity (CV), and calculated wavelength (WL) at cycle lengths 200 and 300 ms on the day before (P0), and after 2 (P2), 7 (P7), 14(P14) days of rapid pacing. Results: In response to rapid atrial pacing, ERP, CV, WL decreased and progressively and comparably in A and C (P<0.05 vs. P0). In contrast, in B, these parameters did not change significantly and remained greater than those in A and C (P<0.05). Moreover, the adaptation of ERP to rate was preserved only in B. The duration of atrial fibrillation (AF) was shorter in B than in A and C (P<0.05). The inducibility of AF tended to be lower, and the fibrillation cycle length was longer in B than in A and C. Conclusions: Oral verapamil started before but not after rapid atrial excitation prevents electrical remodeling. Verapamil may exert beneficial effects when it is taken during sinus rhythm, but not after more than 2 days of atrial tachyarrhythmia. © 2002 Elsevier Science B.V. All rights reserved.