Yoritaka Otsuka

Exercise training without ventricular remodeling in patients with moderate to severe left ventricular dysfunction early after acute myocardial infarction

BACKGROUNDnThe purpose of this study was to determine whether or not patients with moderate to severe left ventricular (LV) dysfunction benefit from exercise training starting early after acute myocardial infarction (AMI) without deteriorating LV remodeling.nnnMETHODSnWe investigated changes in exercise capacity and LV end-diastolic dimension (LVDd by two-dimensional echocardiography) before and after exercise training in 126 patients after AMI. Patients were divided into three groups according to LV ejection fraction (EF) at the beginning of exercise training: 74 patients with LVEF>/=45% (Group H), 35 patients with 35%</=LVEF<45% (Group M), and 17 patients with LVEF<35% (Group L). Exercise training was prescribed at a moderate intensity (50-60% of heart rate reserve or Karvonens equation). Exercise capacity was assessed by peak work rate (WR) and peak oxygen uptake (VO(2)) by upright cardiopulmonary exercise test before and after 3 months of exercise training. LVDd was measured before and at 27+/-10 months of follow-up period.nnnRESULTSnAt the baseline, Group L had a significantly lower LVEF (H 55+/-7 vs. M 40+/-3 vs. L 30+/-3%, P<0.05), significantly greater LVDd (49+/-6 vs. 52+/-7 vs. 56+/-6 mm, P<0.05), and a higher incidence of anterior infarction (P<0.01) compared with Groups H and M, whereas there were no difference in age, sex, coronary risk factors, the incidence of multivessel disease, prior myocardial infarction, peak WR or peak VO(2) among the three groups. After 3 months of exercise training, exercise capacity increased significantly (all P<0.01) in all groups. The magnitudes of the increases in peak VO(2) (%Deltapeak VO(2): 18+/-20 vs. 15+/-19 vs. 18+/-17%, NS) and peak WR (%Deltapeak WR: 17+/-17 vs. 16+/-14 vs. 15+/-13%, NS) were similar among the three groups. In addition, there was no significant correlation between %Deltapeak VO(2) and baseline LVEF. No increase in LVDd was observed in any group at follow-up (H 48+/-5 to 49+/-4 mm vs. M 53+/-8 to 52+/-8 mm vs. L 57+/-5 to 57+/-7 mm, NS in each group).nnnCONCLUSIONnPatients with moderate to severe LV dysfunction benefit from exercise training starting early after AMI without deteriorating LV remodeling, with a similar magnitude of improvement in exercise capacity to that in patients with mild LV dysfunction.

Inhibition of Platelet Adherence to Mononuclear Cells by α-Tocopherol Role of P-Selectin

Background—Platelet-leukocyte interaction is an early important event for thrombogenesis, and this process is mainly mediated by P-selectin on platelets. Although &agr;-tocopherol has been shown to inhibit thrombotic disorders, the effect of &agr;-tocopherol on platelet P-selectin expression and platelet-leukocyte interaction is little known. Methods and Results—We examined whether &agr;-tocopherol inhibited human platelet P-selectin expression and platelet-leukocyte interaction. &agr;-Tocopherol (50 to 500 μg/mL) inhibited thrombin-induced or phorbol 12-myristate 13-acetate (PMA)-induced P-selectin expression on platelets. &agr;-Tocopherol suppressed platelet–mononuclear cell (MNC) interaction, platelet aggregation, and platelet protein kinase C (PKC) activity stimulated with either PMA (100 nmol/L) or thrombin. Inhibitory actions of &agr;-tocopherol against the platelet functions were mimicked by staurosporine, a selective PKC inhibitor. After oral supplementation of &agr;-tocopherol (300 mg/d for 3 weeks) in healthy subjects, thrombin-mediated or PMA-mediated P-selectin expression, platelet-MNC interaction, and platelet aggregation ex vivo were suppressed. Conclusions—&agr;-Tocopherol inhibited P-selectin expression on human platelets and thereby attenuated platelet-MNC interactions, which were mediated at least in part by the inhibition of intraplatelet PKC activity. These actions of &agr;-tocopherol on platelet functions provide new insights into the antithromboatherogenic properties of &agr;-tocopherol.

Comparison of pharmacokinetics of the limus‐eluting stents in Japanese patients

: The aim of this study was to compare the pharmacokinetics of the four limus‐eluting stents used in Japanese patients.

Comparison of pharmacokinetics of the sirolimus-eluting stent in Japanese patients with those in American patients.

The aim of this study was to evaluate the pharmacokinetics of the sirolimus-eluting stent (SES) implanted in 20 Japanese patients with angina pectoris and compare it with that in US study. Bx VELOCITY stent loaded with a total sirolimus dose of 150 μg was used in this study. Ten patients were treated by single-SES (group 1) and 10 patients were treated by double-SES (group 2). Sirolimus levels in whole blood were serially measured in the 2 groups after the SES implantation and compared with the pharmacokinetics in US study. We also evaluated the side effect of sirolimus, major adverse clinical events, and binary angiographic restenosis at 8 months after the SES implantation. Peak concentrations were observed approximately 4 hours after the SES implantation, and sirolimus half-lives were approximately 120 hours in each group. Mean peak sirolimus levels were 0.86 and 2.00 ng/mL for the group 1 and group 2, respectively. The peak concentrations of sirolimus in this study were twice higher in Japanese than in Americans, but they were much lower than effective concentration of sirolimus when orally administrated as an immunosuppressive agent. There were no side effects of sirolimus and no binary angiographic restenosis in any patients. One patient had target vessel revascularization at 8 months after the SES implantation. Although blood concentrations of sirolimus in Japanese patients after SES implantation are somewhat higher than those in American patients, its level is extremely low compared with the systemic administration, indicating the same clinical benefits by the SES could be safely expected in Japanese patients.

Favorable pharmacokinetics of biolimus A9 after deployment of Nobori stent for coronary artery disease: insights from Nobori PK study in Japanese subjects

The Nobori stent is a new drug-eluting stent (DES) with biodegradable polymer coating limited to the abluminal side of stents. Biolimus A9 is a novel sirolimus derivative specifically developed for DES, and polymer load 15.6xa0μg of biolimus A9 per 1xa0mm of stent. A non-randomized multicenter trial was conducted in Japan. Twenty-two de novo lesions were treated by Nobori stents and biolimus A9 concentration in whole blood was serially measured at 14 predetermined time points using a validated chromatography-tandem mass spectrometry (LC–MS/MS) assay. The Cmax was 85.3xa0±xa037.9xa0pg/mL (min–max 46.7–169xa0pg/mL) in the 18xa0mm cohort and 198xa0±xa081xa0pg/mL (min–max 82.5–365xa0pg/mL) in the ≥28xa0mm cohort and no early or late bursts of biolimus A9 release were documented. After 4xa0weeks, no measurable concentration of biolimus A9 was observed in any patient. Estimated AUC0–t was 1.12xa0±xa01.16xa0ng/mLxa0h in the 18xa0mm group, and 5.93xa0±xa04.41xa0ng/mLxa0h for the ≥28xa0mm group. A significant association between loaded biolimus A9 dose adjusted by patient weight and pharmacokinetic parameters was observed. The systemic exposure of biolimus A9 eluting from the Nobori stent was low and proportional to the loaded amount of biolimus A9, and clearance from the blood was rapid. These findings suggest that the Nobori stent is feasible and safe. Systemic lower exposure of biolimus A9 after Nobori stent implantation may have beneficial effects on stent endothelialization.

Favorable clinical outcome in patients with cardiogenic shock due to fulminant myocarditis supported by extracorporeal membrane oxygenation: Comparison with those with acute (nonfulminant) myocarditis

Yasuhide Asaumi, Satoshi Yasuda, lsao Morii, Hiroyuki Kakuchi, Yoritaka Otsuka, Atsushi Kawamura, Hiroshi Nonogi, Yoshikado Sasako, Shunichi Miyazaki, National Cardiovascular Center, Suita, Japan Background: The application of extracorporeal membrane oxygenation (ECMO) wtth percutaneous cardiopulmonary bypass has been recently extended to temporaiy circula- tory support in patients with fulminant myocarditis. However, the survival and prognosis of patients who are particularly ill remain poorly understood. Methods: Patients with myocarditis were divided into the following two groups. Fourteen patients who required ECMO for cardiogenic shock were defined as having fulminant myocarditis (F group), whereas 13 patients who had acute onset of symptoms but did not have compromised hemodynamics were defined as having acute (nonfulminant) myocarditis (non-F group). Results: In F group, 10 patients were successfully weaned from ECMO. Therefore, the overall survival rate at the time of discharge was 71%. Between patients who died (D) and those survived (S) in F group. there were significant differences (PcO.05) in left ven- tricular end-diastolic dimension (D:36& vs S:50*2 [mean&EM] mm), end-systolic dimension (D:34+6 vs S:45+2mm), wall thickness (D:15+1 vs S:l lilmm). maxCPK-MB levels (D:353*145 vs S:120+35U/L) and serum creatinine levels (D:2.1*0.5 vs S:l.O+O.lmg/dl). Compared with the non-F group, the fractional shortening in the F group was more severely depressed in the acute phase (F:lOil vs non-F:23*3%, P<O.O5), but recovered in the chronic phase (F:30*2 vs non-F:33*3%, P=NS). Rates for adverse clin- ical events were also similar between the F and non-F groups during the follow-up period of 36 months on average. Conclusions: In patients with fulminant myocarditis, a hemo- dynamic support using ECMO results in excellent swival. Once a patient recovers from inflammatory myocardial damage, the subsequent clinical outcome is favorable, similar to that observed in patients with acute (nonfulminant) myocardltis. 1208-66

Coronary Hematoma Visualized by Intravascular Ultrasound and Magnetic Resonance Imaging

Transluminal interventions such as balloon dilation, directional atherectomy, and stenting for coronary artery disease sometimes induce vessel wall dissection associated with the formation of an intramural hematoma. In a patient who underwent stent deployment in the mid-right coronary artery (Figure 1A), intravascular ultrasound demonstrated a semilunar-shaped area just proximal to the edge of the stent (Figure 1B). The echo intensity and characteristic shape of the image indicated an intramural hematoma. The coronary site proximal to this portion …