Tsuneo Hoshino

Impaired fibrinolysis early after percutaneous transluminal coronary angioplasty is associated with restenosis

This study examined the role of fibrinolytic components in the process of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Seventy-two patients with single-vessel disease who underwent successful PTCA were prospectively selected. Tissue plasminogen activator (TPA), free plasminogen activator inhibitor-1 (free PAI-1), TPA/PAI-1 complex, and total PAI-1 antigen levels were measured before, at 1 week after, and at 3 months after PTCA. Six months after PTCA, the study patients were divided into two groups: 41 patients without restenosis and 31 patients with restenosis. There were no significant differences with regard to sex, age, coronary risk factors, or morphologic changes in the target lesions between the two groups. There were no significant differences in plasma TPA, TPA/PAI-1 complex, or total PAI-1 levels at each sampling period, or in the time courses between the two groups, except for total PAI-1 levels at 1 week after PTCA. Although no significant differences in free PAI-1 levels before PTCA were observed, free PAI-1 levels after PTCA in the patients with restenosis were significantly higher than those in the patients without restenosis. In addition, each group had a significant change in the time course of free PAI-1 levels. The results suggest that impaired fibrinolysis early after PTCA might affect the repair process of vascular injury, which leads to restenosis, and also that serial determination of free PAI-1 levels could help predict restenosis.

Circadian fluctuations of tissue plasminogen activator antigen and plasminogen activator inhibitor-1 antigens in vasospastic angina

To elucidate the circadian variation of fibrinolytic components in vasospastic angina, plasma levels of tissue plasminogen activator antigen (t-PA), free plasminogen activator inhibitor antigen (free PAI-1), t-PA/PAI-1 complex, and total PAI-1 were measured in venous plasma samples. Samples were taken every 6 hours (6:00 AM, noon, 6:00 PM, and midnight) for 24 hours in 14 patients with vasospastic angina, in 9 patients with exertional angina, and in 19 normal subjects. Twenty-four-hour Holter monitoring (Holter monitor, Del Mar Avionics, Irvine, Calif.) was also carried out in all subjects. All of the fibrinolytic components showed circadian variation, with a peak level at 6:00 AM in every study group except for the t-PA/PAI-1 complex in the group of patients with exertional angina. The values for all or the fibrinolytic components at each sampling time were higher in patients with coronary artery disease than in normal subjects. In particular, the mean value of free PAI-1 at 6:00 AM in patients with vasospastic angina was significantly higher than that in normal subjects and that in patients with exertional angina. This value of free PAI-1 in patients with vasospastic angina was closely associated with the duration of ischemic attacks. These results suggested that the circadian fluctuation of fibrinolytic components may be an important factor that leads to coronary thrombosis at the time of coronary spasm, especially in the early morning.

Sympathetic nerve activity in the spasm-induced coronary artery region is associated with disease activity of vasospastic angina

OBJECTIVES We assessed the relation between sympathetic nerve activity and disease activity of vasospastic angina. BACKGROUND The autonomic nervous system has been proposed to play a key role in attacks of vasospastic angina. A unique feature of vasospastic angina attacks is periodic fluctuation, which complicates the assessment of disease activity. METHODS Twenty-five patients with left anterior descending coronary artery (LAD) spasm were studied: 12 with recent onset of chest pain (group 1) and 13 free of angina for more than 3 months after discontinuing medication (group 2). Group 1 underwent iodine-123 metaiodobenzylguanidine (MIBG) imaging (in the active phase) and atropine-stress MIBG imaging early after diagnostic angiography, and repeat MIBG imaging when they were free of angina for more than 3 months with medication (in the stable phase). Group 2 also underwent MIBG imaging (in remission). On a bulls-eye map, quantitative analysis of percent uptake and washout rate of MIBG was performed regionally. RESULTS In group 1 in the active phase, the washout rate of the LAD territory was significantly lower than the rates in the stable phase, in remission and during atropine-stress MIBG imaging. The regional washout rate of the territories of the right coronary artery and the circumflex artery in the active phase was also significantly lower than that during atropine-stress MIBG imaging. The washout rate of the LAD territory in the active phase was significantly lower than the rates of the other two regions. In contrast, there were no significant differences in the distribution of regional percent uptake in every image. A similar distribution of washout rate was observed among group 1 patients in the stable phase, in group 1 patients during atropine-stress MIBG imaging and in group 2 patients. CONCLUSIONS The MIBG washout rate of the spasm-induced coronary artery territory changed according to the degree of disease activity. Thus, sympathetic nerve activity could reflect disease activity of vasospastic angina.

A sustained increase in β-adrenoceptors during long-term therapy with metoprolol and bisoprolol in patients with heart failure from idiopathic dilated cardiomyopathy

Abstract Effects of long-term therapy with β 1 -selective antagonists (metoprolol, bisoprolol) on β-adrenoceptors in lymphocytes of patients with idiopathic dilated cardiomyopathy (DCM) were examined. There was a significant reduction in the number of lymphocyte β-adrenoceptors in patients with DCM compared to that in healthy volunteers, as demonstrated by a selective decrease in maximum number of binding sites (Bmax) for (−)-[ 125 I]iodocyanopindolol (CYP). A therapy with metoprolol and bisoprolol in these patients caused a marked increase in lymphocyte β-adrenoceptor density. The significant increase was observed from 2 or 3 months after the start of therapy with these drugs, and it was maintained during the therapy for 24 months. The left ventricular ejection fraction in patients with DCM was improved by the long-term therapy with metoprolol and bisoprolol, and this effect seems to be correlated with an observed enhancement of lymphocyte β-adrenoceptors in the time course. Also, the increase in lymphocyte β-adrenoceptors appears to be correlated with a gradual amelioration in circulating catecholamine levels by the long-term therapy with β-adrenoceptor antagonists in patients with DCM. Thus, the present study suggests that β-adrenoceptors in lymphocytes of patients with DCM are up-regulated by a long-term therapy with metoprolol and bisoprolol.

Significance of intimal tears in the mechanism of luminal enlargement in percutaneous transluminal coronary angioplasty: correlation of histologic and angiographic findings in postmortem human hearts.

Transluminal coronary angioplasty was performed in 17 coronary arteries with stenotic lesions of 15 postmortem human hearts. Morphologic changes of dilated vessels were examined angiographically and histologically. Angiographic evidence of coronary dissection was present in 8 (47%) of the 17 vessels. Histologic examination showed that intimal, medial, and adventitial tears were present in 17 (100%), 11 (65%), and one (6%) of the 17 vessels, respectively. In vessels with angiographic evidence of coronary dissection, the tear extended to more than one fourth of the circumference of the vessel. The tear was histologically demonstrated also in vessels which had no angiographic evidence of coronary dissection. Circumferential extension of the tear was greater in women than in men. There were no significant relationships between severity of the tear and histologic or angiographic characteristics of the target lesions. These results suggest that intimal or medial tears may frequently occur also in clinical cases treated with percutaneous transluminal coronary angioplasty and may be necessary for the success of the procedure.

Assessment of regional sympathetic nerve activity in vasospastic angina: Analysis of iodine 123–labeled metaiodobenzylguanidine scintigraphy ☆ ☆☆ ★

With the use of iodine 123-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy, this study evaluated regional sympathetic nerve activity in vasospastic angina. Twenty male patients with left anterior descending coronary artery spasm and 18 male patients with normal coronary arteries as a control group were studied. All patients underwent quantitative 123I-MIBG scintigraphy and atropine stress 123I-MIBG scintigraphy. Both groups showed a similar heterogeneous 123I-MIBG uptake in the left ventricle. However, the regional washout rate in patients with coronary artery spasm was significantly reduced in all three territories compared with that in the control group. In vasospastic angina, the regional washout rate in the left anterior descending coronary artery territory was significantly reduced as compared with the other two regions. After intravenous injection of 1 mg atropine, the regional washout rate in the three regions significantly increased in both groups, but the regional differences between the two groups disappeared. The current study demonstrated that cardiac sympathetic nerve activity in vasospastic angina was suppressed, especially in the territory of the spasm-induced coronary artery, probably because of the enhanced parasympathetic nerve activity.

DOWN-REGULATION OF ANGIOTENSIN II RECEPTORS IN HYPERTROPHIED HUMAN MYOCARDIUM

1. Specific [125I]‐angiotensin II (AngII) binding in normal and hypertrophied human myocardial membranes was saturable and of high affinity. Low concentrations of unlabelled AngII and saralasin competed with [125I]‐AngII for the binding sites in these tissues. Thus, saturable [125I]‐AngII binding in human myocardium exhibited pharmacological specificity that characterized high affinity receptors for AngII.

A clinical feature of myocardial stunning associated with acute myocardial infarction.

We report a case of myocardial stunning after acute myocardial infarction. In the hyperacute phase of myocardial infarction, the patient’s coronary arteries showed normal features on coronary angiography during extensive ST-segment elevation observed on a standard 12-lead electrocardiogram and extensive akinesis observed on a left ventriculogram. Thallium-201 emission computed tomography revealed extensive perfusion abnormality. In the chronic phase, the perfusion abnormality was markedly improved. However, the electrocardiogram demonstrated poor R wave progression, and the left ventriculography revealed slight hypokinesis in the anterolateral wall. The acetylcholine provocation test disclosed coronary vasospasm of the left anterior descending coronary artery. About six months thereafter, left ventricular wall motion became completely normal and no poor R wave progression was observed on the electrocardiogram. The findings in this case indicate that myocardial stunning resulted from brief but severe ischemia due to vasospasm which led to cardiogenic shock, and that the recovery of findings for thallium-201 perfusion might be followed by those of electrocardiography and left ventriculography in the stunned myocardium.

Physiologic capacity of well-developed collaterals in patients with isolated left anterior descending artery disease.

To assess the physiologic significance of well-developed collaterals, 34 patients, with isolated left anterior descending artery disease (LAD) and without overt prior myocardial infarction, underwent cardiac catheterization and exercise thallium-201 emission computed tomography. The patients were divided into 3 groups; 11 patients with 90% stenosis of the proximal LAD and without collaterals (group 1), 11 with 99% stenosis of the proximal LAD, and without collaterals (group 2) and 12 with a total occlusion of the proximal LAD which was completely filled by well-developed collaterals (group 3). On left ventriculography, shortening fractions of the anterior wall were significantly reduced in group 2 as compared to group 1 and 3 (group 1 vs group 2: p< 0.01, group 2 vs group 3: p< 0.05), which reflected the lower ejection fraction of group 2 (p< 0.01 and p< 0.05, respectively). The perfusion defects of the anterior wall on both the initial and the delayed images were severer in groups 2 and 3 than in group 1 (group 1 vs group 2 and group 1 vs group 3 on the initial image: p< 0.01, for both, group 1 vs group 2 and group 1 vs group 3 on the delayed image: p< 0.05, for both). However, recovery of the perfusion defects from the initial image to the delayed image was better in group 3 than in groups 1 and 2 (group 1 vs group 2 and group 1 vs group 3: p< 0.05, for both). Therefore, coronary blood flow through well-developed collaterals was considered to be comparable to the flow through a diseased vessel with 90% stenosis at rest. During maximal exercise, blood flow through well-developed collaterals was considered to be comparable to the flow through a diseased vessel with 99% stenosis, although the blood flow through well-developed collaterals was considered to be better than that through 99% stenosis during the recovery period. These findings suggest that patients with well-developed collaterals must be treated like those with severe stenosis.

Effects of beraprost sodium, a new prostaglandin I2 analog, on parameters of hemostasis, fibrinolysis, and myocardial ischemia in patients with exertional angina

SummaryThe purpose of this study was to investigate the effects of beraprost sodium, a stable prostacyclin analog, on the parameters of hemostasis, fibrinolysis, and myocardial ischemia in patients with exertional angina. Thirty-one patients with exertional angina who had significant organic coronary artery stenosis in at least one of the three major coronary arteries were selected. All patients underwent quantitative exercise thallium-201 emission computed tomography before and 1 month after 120 µg per day of beraprost sodium administration. Before exercise, blood samples were collected from 8:30 a.m. to 9:30 a.m. after the patients had been lying in bed undisturbed for at least 10 minutes. Plasma platelet factor 4 (PF4), fibrinopeptide A (FPA), tissue plasminogen activator antigen (t-PA), and plasminogen activator inhibitor-1 activity (PAI-1) were measured. There were no significant differences in exercise parameters on both exercise tests. However, both the extent and severity scores of ischemia were significantly aggravated (p<0.05 for both) during beraprost sodium administration. Plasma FPA levels decreased significantly during beraprost sodium administration (p<0.01). Likewise, plasma PF4 levels decreased significantly during beraprost sodium administration (p<0.05). As for plasma t-PA antigen levels, there was no significant difference before versus during beraprost sodium administration. Plasma PAI-1 activity levels decreased significantly during beraprost sodium administration (p<0.05). The results indicate that beraprost sodium has strong antithrombogenic properties. However, its aggravation of myocardial ischemia may limit clinical usage.