Hidefumi Ohsawa

Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis

In preheparin serum, there exists lipoprotein lipase (LPL) mass with little activity. The clinical significance of this preheparin serum LPL mass (preheparin LPL mass) is unclear. We studied the levels of preheparin LPL mass in patients with coronary atherosclerosis, comparing the results with those in healthy men. We also evaluated the correlation between preheparin LPL mass and the severity of coronary atherosclerosis by comparing with other risk factors such as age, smoking, family history, hypertension, hyperuricemia, diabetes mellitus, total cholesterol, triglyceride, high density lipoprotein-cholesterol and body mass index. The subjects, 70 men presenting with symptoms of coronary artery disease, underwent coronary angiographic examination. Significant narrowness was defined as > or = 75%. Control group comprised 77 men who had annual health checks and showed no abnormal findings. Preheparin LPL mass in the stenosis group was lower than normal coronary group and also than the control group. Multivariate analysis showed that preheparin LPL mass had the highest t-value (-2.53) for the number of lesions among the risk factors listed above. These results suggest that low preheparin LPL mass may be deeply involved in the progression of coronary atherosclerosis.

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty

BACKGROUND We recently confirmed that pemirolast potassium, an antiallergic agent, markedly inhibits migration and proliferation of vascular smooth muscle cells. It has also been reported that pemirolast inhibits intimal hyperplasia in animal experiments. METHODS AND RESULTS To elucidate the preventive effects of pemirolast on restenosis after percutaneous transluminal coronary angioplasty (PTCA), 227 patients were enrolled in this prospective, randomized trial. A total of 205 patients who were compatible with the protocol were analyzed (pemirolast group, 104 patients with 140 lesions; control group, 101 patients with 133 lesions). Patients in the pemirolast group received 20 mg/d of pemirolast from 1 week before PTCA until the time of follow-up angiography (4 months after PTCA). Angiographic restenosis was defined as diameter stenosis >/=50% at follow-up. Restenosis rates were significantly lower in the pemirolast group than in the control group (24.0% vs 46.5% of patients, 18.6% vs 35.3% of lesions, P <.01, respectively). During 8 months of follow-up, there were no coronary events (death, myocardial infarction, coronary artery bypass surgery, or repeated PTCA) in 81.7% of the pemirolast group and in 63.4% of the control group (P =.013). CONCLUSIONS This study suggested that pemirolast would be useful in the clinical setting to prevent restenosis after PTCA.

Study of the efficacy of nicorandil in patients with ischaemic heart disease using Exercise-Tl-201 myocardial tomography

SummaryThe effect of nicorandil on myocardial perfusion in ischaemic heart disease has been studied using exercise-load Tl-201 myocardial SPECT (Ex-SPECT). Ex-SPECT was carried out in 12 patients with previous myocardial infarction (OMI) and 9 with angina pectoris (AP) before and after administration of nicorandil 15 mg/day, for three or more weeks; % Tl uptake and the washout rate in infarcted or ischaemic areas were calculated from short axial images using the Bulls eye method.In the OMI group, % Tl uptake and washout rates in the infarction areas improved significantly from 52.4% and 0.25 before nicorandil to 60.4% and 0.38 after it. In the AP group, too, % Tl uptake and washout rates showed a significant improvement from 56.9% and 0.10 before to 69.1% and 0.33 after administration. Six subjects who had not received the drug, and who showed negative washout rates, had high improvement rates when nicorandil was administered, suggesting that the drug could increase myocardial perfusion during exercise loading as well as suppressing coronary spasm.Ex-SPECT was done in 4 subjects before and after nicorandil and after subsequent surgical treatment (PTCA or CABG) and the effects of the two therapies were compared. The washout rate was improved from 0.01 to 0.34 by administration of nicorandil, and a notable increase in coronary artery blood flow was achieved compared to the level after surgical treatment, i.e. 0.50.It was concluded that, normal dosages of nicorandil have a powerful direct effect of dilating the coronary arteries without any influence on preload or afterload.

Angioscopic Evaluation of Stabilizing Effects of Bezafibrate on Coronary Plaques in Patients With Coronary Artery Disease

Background Since long-term administrations of anti-hyperlipidemic agents result in reduction in % stenosis or increase in minimum lumen diameter (MLD) of stenotic coronary segments, it is generally believed that anti-hyperlipidemic agents stabilize vulnerable coronary plaques. However, recent pathologic and angioscopic studies revealed that vulnerability of coronary plaques is not related to severity of stenosis and the rims rather than top of the plaques disrupt, and therefore, angiography is not adequate for evaluation of vulnerability. Angioscopy enables macroscopic pathological evaluation of the coronary plaques. Therefore, we carried out a prospective angioscopic open trial for evaluation of the stabilizing effects of bezafibrate on coronary plaques. Methods From April, 1997 to December, 1998, 24 patients underwent coronary angioscopy of the plaques in the non-targeted vessels during coronary interventions and 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrat (14 patients, 21 plaques) groups. Oral administration of bezafibrate (Bezatol SR, 400mg/day) was started immediately after the interventions and was continued for 6 months. The vulnerability score was determined based on angioscopic characteristics of plaques and it was compared before and 6 months later. Results Six months later, vulnerability score was reduced (from 1.6 to 0.8;p < 0.05) in bezafibrate group and unchanged (from 1.4 to 1.3; NS) in control group. In bezafibrate group, the changes in vulnerability score was not correlated with those in % stenosis or MLD. Conclusion The results indicate that bezafibrate can stabilize coronary plaques.

Percutaneous dye image cardioscopy for detection of endocardial lesions.

Endocardial lesions are caused not only by inflammatory processes but also by myocardial ischemia, resulting in endocardial thrombosis and cerebral embolism. We deviced a method for direct visualization of endocardial damages by a novel dye image cardioscopy with Evans blue and examined its feasibility in patients with heart disease. The dye was injected into the left ventricle before and after endomyocardial biopsy. Endocardial surface was stained in dark blue in 63% of patients with angina pectoris before biopsy. After biopsy, the biopsied portions were stained in blue in all. The results indicate that endocardium is damaged even in apparently intact LV in patients with ischemic heart disease and that endomyocardial biopsy causes severe endocardial damages.

Importance of Efficient Coordination of Long-Term, Large-Scale Clinical Trials and Problems Arising-Role of Hospital Pharmacists in this Activity-

We felt that pharmacists should participate more actively in the evaluation of efficacy and safety in clinical trials. To improve the capability of pharmacists in this respect, we evaluated the support we gave to the investigators of the Japan EPA Lipid Intervention Study (JELIS), a long-term, large-scale clinical trial conducted at the Department of Pharmacy of our hospital. To identify the problems in our support, we investigated the number of days required to complete the Case Report Form (CRF) and the reliability of the data collected, by considering the adequacy of the items observed and the clinical inspection terms. Our findings indicated that it was feasible for pharmacists to handle the coordination of JELIS in addition to their everyday workload and we also noted an improvement in the clinical inspection rate, from 76.6% to 100% for JELIS I and from 97.5% to 100% for JELIS II. Moreover, we found the number of days required to complete the CRF was reduced from 109.8 days to 20.3 days for JELIS I and from 79.5 days to 21.0 days for JELIS II. These results show that the pharmacists in our hospital helped to maintain the reliability of clinical data.