Akira Hirosaka

Increased plasminogen activator inhibitor-1 and apolipoprotein (a) in coronary atherectomy specimens in acute coronary syndromes.

BACKGROUND Although increased tissue factor expression is known in vulnerable plaques, there is no reported study to compare plaque fibrinolysis in stable and unstable plaques. This study investigates the extent of plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein (a) [apo(a)] in the plaques of different types of coronary artery disease as well as the correlation between these molecules and infiltration of macrophages to plaques. METHODS Using immunohistochemical staining, we examined PAI-1 expression and apo(a) deposition in coronary atherosclerotic specimens obtained by directional coronary atherectomy from 19 patients with acute myocardial infarction (AMI), 12 with unstable angina pectoris (UAP), and 13 with stable angina pectoris (SAP). The percentages of the total areas of specimens stained with PAI-1 or apo(a) were estimated by an NIH image program. The proportion of macrophages as a percentage of all cells in plaques was calculated as the macrophage density. RESULTS We found significantly higher percentages of total areas of specimens stained with PAI-1 in AMI (25.5 +/- 8.6%, P < 0.001) and UAP (22.2 +/- 10.4%, P < 0.005) than in SAP (9.5 +/- 5.0%), as well as with apo(a) (AMI; 11.7 +/- 7.1%, P < 0.005, UAP; 11.1 +/- 5.5%, P < 0.01 versus SAP; 3.9 +/- 1.5%). Linear regression analysis of all the samples showed a correlation between PAI-1 or apo(a) and macrophage density (PAI-1: r = 0.75, P < 0.001 and apo(a): r = 0.56, P < 0.001). CONCLUSIONS Our results suggest a possible contribution of increased PAI-1 and apo(a) in plaques to the pathogenesis of acute coronary syndromes including impaired fibrinolysis.

Recurrent Multiple Thrombosis in a Patient with Abnormal Plasminogenemia and Behçet's Disease

MINI REPORT Recurrent Multiple Thrombosis in a Patient with Abnormal Plasminogenemia and Behcet’s Disease Masayuki Miyata1, Yoichi Sakata2, Seiji Madoiwa2, Kaoru Sato1, Osamu Munakata1, Ryoji Yoshioka1, Akira Hirosaka3, Keiji Iwatsuki4, Yukio Sato1 and Reiji Kasukawa1 1Department of Internal Medicine II, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295; 2Division of Hemostasis and Thrombosis Research, Institute of Hematology, Jichi Medical School, Minamikawachi-Machi, Kawachi-Gun, Tochigi 329-0498, Japan; 3Department of Internal Medicine I and 4Department of Dermatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.

Comparison of Intracoronary Injection of Acetylcholine and Ergonovine in All Vessel Segments in Patients with and without Vasospastic Angina Pectoris

To compare the effects of provocative agents on coronary vascular tone, we performed intracoronary injections of acetylcholine (ACh) and ergonovine (EM) in 12 patients with vasospastic angina pectoris (VSA) and in 11 patients without coronary artery disease (control group). Incremental doses of ACh (20–100μg) were injected, followed by EM (20–50 μg) after the disappearance of ACh action. The reduction ratio of coronary artery diameter (RR-CAD), (1-after ACh or EM CAD/after isosorbide dinitrate (ISDN CAD) × 100(%), was calculated in every AHA segment. In patients with VSA, coronary spasms (RR-CAD > 99%) were induced by ACh in 10/12 patients, by EM in 10/12, and by both agents in 8/12 in the same segment, whereas in the control group, spasms were induced only by ACh, in 1 of 11 patients, and chest pain was not experienced. Responses to ACh and EM in each AHA segment in the VSA group, except in spasm-induced sites, tended to be greater than in the control group, i.e., RR-CAD values (mean ± SEM) including all American Heart Association (AHA) segments following ACh and EM administration were 47.0 ± 7.1% and 50.8 ± 6.8% respectively, in the VSA group and 35.8 ± 7.8% and 40.7 ± 5.0% respectively, in the control group. We conclude that the sensitivity to ACh and EM challenge was the same, but that both agents were needed to achieve more accurate diagnosis.

Paradoxical Response of Epicardial Coronary Arteries and Small Resistance Vessels to Intracoronary Acetylcholine in Vasospastic Angina

This study was carried out to examine the response of epicardial arteries (A-epi) and small resistance vessels (A-res) to intracoronary (IC) acetylcholine (Ach) in patients with and without vasospastic angina. Injection of Ach (20, 50 μg) into the left coronary artery (LCA) was performed in ten patients whose LCAs were angiographically normal. Ach-induced spasm of the left anterior descending artery (LAD) occurred in five patients (group A), and did not occur in the other five (group B). We injected nitroglycerin (NTG; 0.2 mg) into the LCA to remove A-epi tone, followed by the same amount of Ach to evaluate the response of A-res. Thereafter, papaverine (10 mg) was injected into the LCA to evaluate the maximum vasodilation capacity. Flow in the great cardiac vein, measured by Webster’s method, and coronary angiography were performed following the IC injection of each drug. We calculated the coronary vascular resistance ratio (R) to maximum dilator response and measured LAD diameter after each procedure. Percent changes in LAD diameter after IC Ach following IC NTG did not differ in the two groups. The R(NTG)-R(Ach) value was larger in group A than in group B (0.35 ± 0.1 vs 0.12 ± 0.1; P < 0.01). These findings suggest that IC injection of Ach produces significant vasodilation in A-res in vasospastic angina, in contrast to the constriction produced in A-epi by this treatment.