Yasushi Miyakita

FK506 therapy of experimental autoimmune myocarditis after onset of the disease

Preventive effects of FK506 on autoimmune myocarditis have been demonstrated, but the therapeutic efficacy of the agent in established myocarditis yet remains to be assessed. In this study, effects of FK506 on experimental autoimmune myocarditis were investigated by the use of the agent after the onset of the disease. Lewis rats were immunized with either cardiac myosin or bovine serum albumin (BSA) in complete Freunds adjuvant. The onset of the disease was ascertained by examining randomly chosen cardiac myosin-immunized rats. Animals were divided into four groups: the BSA-immunized saline-treated group (group A, n = 6); the BSA-immunized FK506-treated group (group B, n = 6); the myosin-immunized saline-treated group (group C, n = 6); and the myosin-immunized FK506-treated group (group D, n = 11). Saline or 1.0 mg/kg/day of FK506 were intramuscularly injected from day 16 to day 27. All the rats were put to death on day 28. Rats of group C became severely ill by the third week, while in contrast, rats of group D remained active, as did rats of groups A and B. The heart weight/body weight ratio was significantly lower in group D than in group C rats. Group mean values were 3.48 +/- 0.10 gm/kg for group A, 3.48 +/- 0.16 gm/kg for group B, 4.94 +/- 0.66 gm/kg for group C, and 3.88 +/- 0.43 gm/kg for group D. Rats of group C showed severe myocarditis with mononuclear cell infiltration, myocardial necrosis, and interstitial edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic linkage analyses of Romano-Ward syndrome (RWS) in 13 Japanese families

Romano-Ward syndrome (RWS) is an autosomal dominant disorder characterized by prolongation of the electrocardiographic QT interval, with clinical manifestations that include recurrent syncope and sudden death from ventricular arrhythmias. Presymptomatic diagnosis is difficult because of the variability in these signs among carriers, but it is important for clinical management to prevent sudden cardiac death. To find an LQT (long QT) locus in Japanese patients and to identify DNA markers useful for presymptomatic diagnosis, linkage analyses were undertaken in 13 Japanese families with RWS patients by means of two DNA markers located on 11p15.5. One of these marker loci, HRAS, was previously reported to be tightly linked to the LQT locus in another ethnic group. Our analyses of homogeneity suggest evidence for genetic heterogeneity of RWS within the Japanese population.

Efficacy of amlodipine besilate therapy for variant angina: evaluation by 24-hour Holter monitoring.

SummaryThe efficacy of amlodipine, a calcium antagonist, was investigated in 12 patients with variant angina. Amlodipine was administered at a dose of 5 mg once daily, and efficacy was assessed from the frequency of anginal attacks, the frequency of ST elevation or depression, and the extent of ST segment changes [ST segment elevation or depression (mm) × duration (seconds)] on the Holter ECG before and after treatment. The frequency of ST elevation during the observation period was 1.67 ± 0.33 times/day (symptomatic attacks: 1.17±0.21/day; asymptomatic attacks: 0.50±0.19/day), and this significantly decreased to zero per day (both symptomatic and asymptomatic attacks) after treatment (p<0.05). The extent of ST segment elevation during the observation period was 507.5±156.6 mm·sec/day (symptomatic: 382.5±102.9 mm·sec/day; asymptomatic: 125.0±62.0 mm·sec/day), and such changes were completely suppressed (both symptomatic and asymptomatic) by treatment (p<0.05). The frequency of ST depression was 2.08±0.42 times/day (symptomatic: 0.25±0.13/day; asymptomatic: 1.83±0.37/day) during the observation period, while it was 1.50±0.36 times/day (symptomatic: 0.25±0.13/day; asymptomatic: 1.25±0.30/day) after treatment. Although anginal attacks remained unchanged, asymptomatic attacks tended to decrease (p=0.07). The extent of ST depression during the observation period was 632.5±239.4 mm·sec/day (symptomatic: 105.0±64.4 mm·sec/day; asymptomatic: 527.5±189.5 mm·sec/day), and this significantly decreased to 333.8±111.4 mm·sec/day (symptomatic: 50.0±31.2 mm·sec/day; asymptomatic: 283.8±102.6 mm·sec/day) after treatment (p<0.05). The frequency of anginal attacks during the observation period was 1.27±0.18 times/day, and this significantly decreased to 0.40±0.12/day after 1 week of treatment and to 0.22±0.07/day after 2 weeks of treatment (p<0.05). These results suggest that amlodipine is effective for treating variant angina at a daily dose of 5 mg.

Clinical evaluation of serum amlodipine level in patients with angina pectoris

Serum amlodipine levels were determined in 18 patients with vasospastic angina. Patients were divided into two groups: Group A (n = 9) received amlodipine 5 mg by single daily administration, and Group B (n = 9) received 10 mg given by single daily administration for the first 3 days, then 5 mg from the 4th day on. The serum amlodipine concentration in Group A took 7 days to reach a steady state of around 8 ng/ml. The level in Group B was 8.9 ng/ml at 3 days. From these results, the optimal dosage of amlodipine in the treatment of angina pectoris is 10 mg for the initial 3 days followed by 5 mg thereafter.