Tsuneo Kaburagi

Clinical effects of intravenous nifedipine on renal function.

Summary Nifedipine, a calcium antagonist, was administered intravenously (13.3 μg/min) for 45 min, and the changes in blood pressure, glomerular filtration rate (GFR), renal blood flow (RBF), total renal resistance, urinary volume, urinary sodium and potassium excretion, plasma renin activity, and plasma aldosterone concentration were studied. GFR and RBF were measured by intravenous infusion of sodium thiosulfate and sodium para-aminohippurate, respectively. The subjects included 12 cases of essential hypertension, nine of chronic glomerular nephritis with hypertension, 14 of chronic glomerular nephritis without hypertension, and 12 normotensive controls. In patients with essential hypertension, GFR and RBF increased markedly (by 45.6% and 44.8%, respectively), but in normotensive and hypertensive patients with chronic glomerular nephritis, these indices did not change significantly. The urinary volume and urinary sodium excretion increased in all groups. The natriuresis induced by nifedipine is probably due to the increase of GFR and RBF. The results of this study suggest a difference in renal vascular pathophysiology between essential hypertension and chronic glomerular nephritis. The results also suggest a functional change of the renal vascular system in essential hypertension, i.e., the increased vascular tone and the particular sensitivity of renal arterioles to nifedipine.

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.

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.

Two forms of hypertrophic cardiomyopathy distinguished by inheritance of HLA haplotypes and left ventricular outflow tract obstruction

In this study we have performed human leukocyte antigen (HLA)-A and B typing on nine patients with hypertrophic cardiomyopathy (HCM) and their relatives. Four patients had relatives who also had the disease. HLA typing of the familial form of HCM revealed a very close association of a given HLA-A,B haplotype with the occurrence of the disease. All four patients who had affected relatives had obstruction of left ventricular outflow (LVOT), while four patients with unaffected relatives did not have obstruction. One additional patient with obstruction and without familial incidence was an only child and had few living relatives. Thus, HCM can be divided into two subtypes: a familial form linked to the HLA-A,B system, which may be related to obstructive type, and a sporadic form not linked to HLA antigens. These data confirm the existence of at least two separate forms of hypertrophic cardiomyopathy. The study also confirms their existence in the Japanese population, with a completely different gene pool than the population from the southeastern United States in whom the observation was initially described.

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.

Clinical application of Indium-111 antimyosin antibody and Thallium-201 dual nuclide single photon emission computed tomography in acute myocardial infarction

The significance of indium-111 antimyosin antibody and thallium-201 dual nuclide single photon emission computed tomography (SPECT) was evaluated in 7 patients with acute myocardial infarction (AMI) who underwent emergency coronary angiography with successful revascularization by intracoronary thrombolysis. Indium-111 antimyosin antibody and thallium-201 dual nuclide SPECT was performed 11 to 36 days after the onset of AMI Antimyosin SPECT images delineated areas of myocardial necrosis in all 7 patients (100%), but planar images detected necrotic areas in only 4 of 7 patients (57 %). Peak CPK-MBs of the 3 patients in which no necrotic area was detected by indium-111 planar image showed a tendency to be smaller. Indium-111 antimyosin antibody/thallium-201 overlap was observed in all patients. The area of overlap was at the center of necrosis in 4 patients (2 anterior infarction, 1 inferior infarction, 1 inferolateral infarction) and at the peripheral portion in 3 patients (all 3 had inferior infarction). Indium-111 antimyosin antibody and thallium-201 dual nuclide SPECT is useful in identifying the localization of myocardial infarction and the overlap of these tracers might reflect the presence of salvaged myocardium adjacent to the necrotic myocardium.

Value of thallium-201 early reinjection for assessment of myocardial viability.

To assess the efficacy of early reinjection forpredicting post intervention improvement in thallium-201 (Tl) uptake and regional wall motion, we reinjected a small dose of Tl following post-stress imaging and obtained reinjection early images (10 min after early reinjection) and reinjection delayed images (3 hr afterwards) in 40 patients who were referred to us for revascularization (group I). Twenty-nine patients in group I also underwent conventional stress-redistribution Tl scintigraphy (group II). Conventional stress-redistribution Tl scintigraphy was repeated after intervention. Contrast left ventriculography was performed before and after intervention and changes in regional wall motion were assessed in 22 of 40 patients. In group I, the predictive value for improvement and no improvement (the accuracy) of reinjection early images in perfusion was 83%, while that of reinjection delayed images was 91%. Furthermore, the accuracy of reinjection early images in regional wall motion was 80%, while it was 91% for reinjection delayed images. In group II, the accuracy in perfusion was 78% and the value in regional wall motion was 70%. Both accuracy in perfusion and in regional wall motion obtained from reinjection delayed images were significantly higher than the values in group II (p < 0.05). These data suggest that early reinjection is useful for predicting postintervention thallium uptake and regional wall motion.