Stable Effort Angina Research Articles

Prognostic value of serum hepatocyte growth factor in patients with acute coronary syndromes.

The present study examined whether or not hepatocyte growth factor (HGF), an endothelium-specific growth factor that stimulates regeneration of the endothelium, is increased or has a prognostic significance in patients with acute coronary syndromes. HGF was measured in 106 patients with coronary artery disease (20 stable effort angina, 12 unstable angina without adverse events, 24 unstable angina with adverse events and 50 acute myocardial infarction) on admission and 21 normal volunteers. The measurements in all patients were recorded before administration of heparin, and in acute myocardial infarction patients they were recorded from days 2 to 6 after heparin discontinuation on day 1. HGF levels (ng/ml) were 0.30+/-0.06 for the controls, 0.31+/-0.08 for stable effort angina patients, 0.31+/-0.08 for unstable angina patients without adverse events, 0.40+/-0.20 for unstable angina patients with adverse events and in acute myocardial infarction patients they were 0.45+/-0.18 on day 0, 0.57+/-0.45 on day 2, 0.50+/-0.35 on day 3, 0.48+/-0.32 on day 4, 0.44+/-0.20 on day 5, and 0.38+/-0.14 on day 6. HGF plays a crucial role in the restoration of injured endothelial cells and is a predictor of adverse events in patients with acute coronary syndromes.

Role of cytokines and adhesion molecules in ischemia and reperfusion in patients with acute myocardial infarction.

Although acute myocardial infarction (AMI) may involve both plaque rupture and ischemia-reperfusion injury, the pathogenesis of these phenomena is unclear. To elucidate the pathogenesis of AMI, serial measurements of platelet activating factor (PAF), interleukin-6 and cell adhesion molecules were made in patients with AMI. The PAF levels were measured upon hospital admission and at 24 and 72h in 8 patients with AMI. Serum levels of interleukin-6, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule- 1 (sVCAM- 1) were measured upon admission and at 24 h and 4 weeks in 30 patients with AMI and 15 patients with stable effort angina. PAF levels were higher in patients with AMI than in normal volunteers; the increased levels lasting at least 72h. In contrast, interleukin-6 increased at 24h. sE-selectin was elevated at admission and sVCAM-1 increased later. sE-selectin levels upon admission in patients with additional ST-segment elevation after reperfusion were significantly higher than those in patients without ST-elevation. In patients with AMI, the time-course of changes in blood levels of cytokines varied according to the individual substances. Although it is unclear what is the precise role of each of the cytokines in the pathophysiology of AMI, sE-selectin may be possibly related to the reperfusion injury in the infarcted myocardium.

Consumption of vitamin E in coronary circulation in patients with variant angina.

The plasma status of vitamin E has been suggested to be linked to the activity of coronary artery spasm. This study was designed to determine whether vitamin E is actually consumed in the coronary circulation in patients with active variant angina having repetitive spasm-induced transient myocardial ischemia and reperfusion. Blood samples were obtained simultaneously from the aortic root, coronary sinus and right atrium in 12 patients with variant angina due to spasm of the left coronary artery, nine patients with stable effort angina and nine control subjects. Plasma vitamin E (alpha- and gamma-tocopherol) concentrations were determined by use of high-performance liquid chromatography and plasma lipid peroxides were measured as thiobarbituric acid-reactive substances (TBARS). At baseline, both plasma alpha- (p < 0.01) and gamma- (p < 0.05) tocopherol levels were significantly lower in the coronary sinus (5.50 +/- 0.50 and 0.55 +/- 0.07 mg/l, mean +/- SEM) than in the aortic root (6.63 +/- 0.57 and 0.63 +/- 0.08 mg/l) and also in the right atrium (6.44 +/- 0.61 and 0.63 +/- 0.09 mg/l) in the variant angina group. The TBARS level was significantly (p < 0.05) higher in the coronary sinus than in the aortic in this group. In contrast, these levels were not significantly different between the samples from the coronary sinus and the aortic root or the right atrium in the control group and also in the stable effort angina group. The coronary sinus-aortic difference in plasma vitamin E levels in the variant angina group was not significantly altered after left coronary artery spasm induced by intracoronary injection of acetylcholine. Also, the plasma vitamin E levels in the aortic root, coronary sinus and right atrium all remained unchanged in the stable effort angina group after pacing-induced angina and in the control group after intracoronary administration of acetylcholine. Transcardiac reduction in plasma vitamin E concentrations concomitant with lipid peroxide formation was demonstrated in patients with active variant angina, suggesting actual consumption of this major endogenous antioxidant. Oxidative stress and vitamin E exhaustion may be involved in the pathogenesis of coronary artery spasm.

Effects of infusion of L-arginine on exercise-induced myocardial ischemic ST-segment changes and capacity to exercise of patients with stable angina pectoris

Results of recent studies show that intracoronary administration of L-arginine, the precursor of nitric oxide, restores endothelial function in subjects with coronary risk factors and minimal coronary artery lesions. However, few investigators have examined the clinical feasibility of using L-arginine for treatment of myocardial ischemia due to coronary artery disease. To examine the effect of supplementary L-arginine on exercise-induced myocardial ischemia and capacity to exercise of patients with stable effort angina pectoris. Twelve patients confirmed to have a single epicardial coronary artery stenosis underwent two treadmill exercise tests after infusion of 10% L-arginine solution or placebo (5% dextrose) according to a randomized single-blind crossover design on two days separated by an interval of less than 1 week. Respiratory gas exchange kinetics were measured and myocardial ischemia was estimated by electrocardiography before and during exercise. Infusion of L-arginine did not alter exercise-induced changes in heart rate and blood pressure, and objective parameters of capacity to exercise. Exercise-induced maximum ST-segment depression (by 2.1 +/- 0.9 mm; with L-arginine; by 1.9 +/- 0.9 mm with placebo, NS) and onset of 1 mm ST-segment depression after exercise (after 261 +/- 131 s with L-arginine; after 247 +/- 136 s with placebo, NS) also remained unchanged. However, ST-segment depression was restored to baseline after exercise significantly more quickly after infusion of L-arginine than it did with placebo (after 331 +/- 167 s with L-arginine; after 400 +/- 165 s with placebo: P < 0.01). Intravenous administration of L-arginine did not alter capacity to exercise or the threshold for exercise-induced myocardial ischemia. However, it did reduce the time taken for recovery after ST-segment depression, suggesting that an earlier resolution of exercise-induced myocardial ischemia occurred.

Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes

Objectives. This study was sought to investigate whether peripheral blood levels of matrix metalloproteases (MMPs) are affected in patients with acute coronary syndromes (ACS).Background. Synthesis of MMPs has been reported in coronary atherosclerotic lesions in patients with unstable angina (UA), suggesting a pathogenic role of MMPs in the development of ACS.Methods. Using sandwich enzyme immunoassay, serum MMP-2 and plasma MMP-9 were measured in 33 patients with ACS (22 with acute myocardial infarction [AMI], 11 with UA), 17 with stable effort angina (EA) and 17 normal control subjects.Results. Serum MMP-2 in patients with UA and AMI on day 0 was two times greater than that in control subjects, and patients with EA showed higher MMP-2 levels than those in control subjects. Plasma MMP-9 in patients with UA and AMI on day 0 was elevated by threefold and twofold versus that in control subjects, respectively. In patients with UA and AMI who underwent medical treatment (n = 11 and 13, respectively), MMP-2 elevation was sustained until day 7. In patients with UA, MMP-9 elevation on day 0 was followed by a gradual decrease toward the control range up to day 7. Some patients with AMI showed a transient MMP-9 elevation with a peak on day 3, whereas in others, MMP-9 levels were significantly elevated on day 0 and remained higher than those in control subjects up to day 3.Conclusions. Serial changes in serum MMP-2 and plasma MMP-9 were documented in patients with ACS. These findings provide an insight into the molecular mechanism of plaque destabilization.

Resting 123I-BMIPP scintigraphy in diagnosis of effort angina pectoris with reference to subsets of the disease.

This study was undertaken to assess the diagnostic value of resting 123I-BMIPP scintigraphy in patients with effort angina pectoris. One hundred and four patients underwent scintigraphic and angiographic examinations. The subsets of the patients were stable effort angina pectoris (stable type) in 27 cases, new onset of effort angina pectoris (new onset type) in 21 cases, and worsening effort angina pectoris (worsening type) in 35 cases. The remaining 21 cases were subjects without evidences of coronary artery disease (non-CAD). 123I-BMIPP was injected under resting and pain free condition, then data for single photon emission tomography (SPECT) were acquired. The positive regional 123I-BMIPP defects in three coronary territories were visually judged on the tomographic images. The overall sensitivity to diagnose the patients was 62.6% (52/83) and the overall specificity to exclude non-CAD subjects was 95.2% (20/21). The detection rate in each subset of the disease was 48.1% (13/27) in stable type, 47.6% (10/21) in new onset type and 77.1% (27/35) in worsening type (p < 0.05 versus two other types). For detection of stenosed vessels, the overall sensitivity was 41.4% (56/148) and the overall specificity was 93.8% (152/164). The rate of detection of stenosed vessels was 31.7% (13/41) in stable type, 31.4% (11/35) in new onset type, and 55.6% (40/72) in worsening type (p < 0.05 versus two other types). Vessels with 75% stenosis were more sensitively detected in the worsening type (33.3%; 4/12) compared to the remaining two types (8.3%; 1/12) even though the difference was not significant. The resting 123I-BMIPP scintigraphy was therefore valuable in diagnosing patients with effort angina pectoris and involved coronary arteries especially in the subset of patients with worsening type.

High-density lipoprotein particles are large in patients with variant angina.

Dyslipidemia in patients with coronary vasospasm may be characterized by low level of high-density lipoprotein (HDL)-cholesterol as well as apolipoprotein (apo) A-I but not high level of low-density lipoprotein-cholesterol. This study sought to examine the HDL particle size in patients with variant angina. The HDL particle size was examined by analyzing serum lipid levels in 38 patients with variant angina to compare with those of 40 control subjects and 30 normocholesterolemic patients with stable effort angina. Also, actual HDL size distribution was assessed by electrophoresis. The HDL-cholesterol, apoA-I and apoA-II levels were all lower (P < 0.01 for each) in patients with variant angina and patients with stable effort angina as compared with control subjects. The apoA-II level was lower (P < 0.01) in patients with variant angina than in patients with stable effort angina. The apoA-I/apoA-II ratio was lower (P < 0.01) in patients with stable effort angina, but not in patients with variant angina as compared with control subjects. In contrast, the HDL-cholesterol/apoA-I ratio was higher in patients with variant angina than in control subjects (P < 0.01) and also patients with stable effort angina (P < 0.01). The slope of the regression line, comparing HDL-cholesterol and apoA-I levels, was greater in patients with variant angina than in control subjects (P < 0.05) and patients with stable effort angina (P < 0.05), suggesting an increase in larger HDL particles. Native polyacrylamide gel electrophoresis revealed that HDL particles in patients with variant angina were skewed towards larger sizes compared with control subjects (P < 0.01) and patients with stable effort angina (P < 0.01). The abnormal serum lipid values were normalized in the patients with variant angina after the medical treatment and inactivation of the coronary spasm. High HDL-cholesterol/apoA-I levels associated with low serum HDL-cholesterol and apoA-I levels were characteristic in patients with variant angina, in whom HDL particles were large, cholesterol-rich and possibly malfunctioning.

Different Mechanism of Acute Luminal Gain by Coronary Intervention; Comparison Between Acute Myocardial Infarction and Stable Effort Angina Pectoris

Different Mechanism of Acute Luminal Gain by Coronary Intervention; Comparison Between Acute Myocardial Infarction and Stable Effort Angina Pectoris

Different mechanism of acute luminal gain by coronary intervention: comparison between acute myocardial infarction and stable effort angina pectoria

Different mechanism of acute luminal gain by coronary intervention: comparison between acute myocardial infarction and stable effort angina pectoria

Do nitrates affect the anti-coagulation effect of heparin in Japanese?

We evaluated whether a drug interaction between intravenous nitrates and heparin exists. Study 1: Twelve patients with acute coronary syndrome (acute myocardial infarction 6, unstable angina 6) were enrolled. Intravenous infusion of heparin was started with intravenous nitroglycerin for five hours, followed by intravenous isosorbide dinitrate for the next five hours, and switched back to intravenous nitroglycerin for the final five hours. Study 2: Nine patients with stable effort angina or chest pain syndrome were enrolled. Intravenous infusion of heparin was started alone for twelve hours at least, then intravenous infusion of nitrate was added onto the prior drip infusion of heparin on the second day, and switched back to intravenous infusion of heparin alone on the third day. Activated clotting time (ACT), activated partial thromboplastin time (APTT), and antithrombin III (AT-III) measurements were taken every five hours (Study 1), or at every drug exchange point (Study 2). Nitrates did not induce attenuation in the anticoagulation effect of heparin. Thus there was no interaction between nitroglycerin or isosorbide dinitrate and heparin in the Japanese.

Soluble E-selectin, ICAM-1 and VCAM-1 levels in systemic and coronary circulation in patients with variant angina.

The purpose of this study was to assess whether the plasma levels of soluble adhesion molecules including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are elevated in patients with variant angina and whether they are released in the coronary circulation. Antecubital venous plasma samples were collected from 33 patients with variant angina, 22 patients with stable effort angina and 20 control subjects. Samples were also collected from the aortic root (AO) and the coronary sinus (CS) in 18 patients with variant angina before and after left coronary spasm induced by intracoronary injection of acetylcholine. The soluble adhesion molecules were assayed by enzyme immunoassay. Antecubital venous plasma soluble E-selectin (P < .05), ICAM-1 (P < .01) and VCAM-1 (NS) levels were higher in the variant angina group than in the control group, respectively. The plasma soluble ICAM-1 level was also higher (P < .01) in the variant angina group than in the stable effort angina group. In the variant angina group, both soluble ICAM-1 (P < .05) and VCAM-1 (P < .01) levels were significantly lower in CS than AO at baseline. In contrast, after the spasm the plasma soluble ICAM-1 level was (P < .05) higher in CS than AO and the CS-AO differences of soluble ICAM-1 (P < .05) and VCAM-1 (P < .05) increased as compared with the baseline, respectively. These values were remained unchanged in the stable effort angina group after rapid atrial pacing and in the control group after administration of acetylcholine. Circulating plasma levels of both soluble E-selectin and ICAM-1 were elevated in patients with variant angina, indicating an association of an inflammatory reaction with coronary spasm. Both soluble ICAM-1 and VCAM-1 appeared to be trapped in the coronary circulation at baseline and released into the coronary circulation following coronary spasm and reperfusion in the patients.

Hepatocyte growth factor(HGF): a new biochemical marker for acute myocardial infarction.

The purpose of this study was to investigate the use of hepatocyte growth factor as a biochemical marker for acute myocardial infarction. Several biochemical markers are used for noninvasive detection of acute myocardial infarction. However, hepatocyte growth factor has not been used previously for this purpose. We measured hepatocyte growth factor, creatine phosphokinase, and MB isoenzyme (CK-MB) levels in 6 patients with stable effort angina after diagnostic catheterization (controls) and in 12 patients with acute myocardial infarction (AMI). The measurements in the AMI patients were recorded twice a day for the first 3 days after onset of chest pain and once a day for the next 4 days. Furthermore, in each patient we evaluated the time to reach the maximum level and the time for the level to decline to less than half the maximum. Hepatocyte growth factor levels (ng/ml) were 0.3+/-0.1 for angina pectoris patients, and 15.7+/-9.1 within 6h and 12.5+/-4.6 within 12h after the onset for AMI patients, respectively. The correlation coefficients between hepatocyte growth factor and creatine phosphokinase and between hepatocyte growth factor and CK-MB were 0.68 and 0.74, respectively. The time to reach the maximum (h) and the time to decline to less than half of the maximum level (days) were 6.6+/-2.6 and 1.2 +/-0.2 for hepatocyte growth factor, 19.4+/-8.7 and 2.5+/-1.4 for creatine phosphokinase, and 16.6+/-7.7 and 1.5+/-0.4 for CK-MB, respectively. Hepatocyte growth factor is useful as a prognostic indicator and reflects the clinical course in patients with acute myocardial infarction.

Enhanced red cell sodium-hydrogen exchange in microvascular angina.

Enhanced calcium content in arterial smooth muscle cells and altered reactivity of coronary vessels to alkalinization have been reported in angina pectoris due to impaired motility of coronary arteries. An altered function of sodium-hydrogen exchange, a ubiquitous membrane transport system that links proton efflux to calcium drifts, may mediate these phenomena. Twenty patients with microvascular angina (stable effort angina, reversible perfusion defects during effort thallium 201 heart scintigraphy, and angiographically normal coronary arteries) were compared to 20 patients with stable effort angina due to coronary atherosclerosis and 20 healthy subjects. The sodium-hydrogen exchange was defined as the initial fraction of the amiloride-sensitive proton efflux from red cells with inhibited anion exchanger (pHi 6.00-6.05) into an Na(+)-containing medium (pHo 8.00-8.05). 12-0-tetradecanoylphorbol-13-acetate (TPA, 600 nmol.l-1) and staurosporine (100 nmol.l-1) were used as phosphorylation modulators in vitro. The mean red blood cell Na+/H+ exchange was increased in patients with microvascular angina (451 +/- 37 vs 142 +/- 17 and 124 +/- 21 umol H+.1 cells-1.min-1, P < 0.01). TPA and staurosporine abolished differences between the groups. Microvascular angina is associated with enhanced Na+/H+ exchange in erythrocytes, probably due to more extensive phosphorylation of the membrane antiporter sites.

Modulation of Myocardial Oxygen Consumption Through ACE Inhibitors

In this issue of Circulation ,1 Zhang and coworkers provide convincing evidence that ACE inhibitors reduce myocardial oxygen consumption by preventing the degradation of bradykinin, which subsequently stimulates the release of nitric oxide (NO). They propose that NO inhibits mitochondrial respiration, thus reducing myocyte oxygen use. This is an exciting observation because it provides a new mechanism whereby ACE inhibitors might benefit ischemia beyond simply inhibiting the formation of angiotensin II, thus reducing the vasoconstrictor effect of this octapeptide. These results are further evidence for a role of bradykinin in the response of tissues to ACE inhibitors. The mechanism enabling these interactions to occur is coming to light on the basis of studies such as the current one from Zhang et al. Interest in bradykinin and related kinins as cardiovascular mediators has grown tremendously in the past several years, largely because it has been recognized that they potently stimulate release of NO and prostacyclin from endothelial cells. Bradykinin and Lys-bradykinin, respectively, are formed when one of a family of enzymes, known as kallikreins, act on either heavy- or low-molecular-weight kininogens.2 This action involves cleavage of amino acids from both the C- and N-terminal ends of the kininogen peptides and takes place both in plasma (for heavy-molecular-weight kininogen) and tissues (for low-molecular-weight kininogen). The kininogens were previously thought to be expressed primarily by hepatocytes; however, it is now clear that many tissues, including vascular cells3 4 and the heart,5 also express kininogens. The kallikreins as well are made by many cell types and are produced by vascular cells in a continuous fashion.6 Thus, many tissues, including the heart and vascular cells, have an intact kallikrein/kininogen system capable of producing bradykinin. The mechanisms whereby bradykinin production is regulated remain unclear; however, there is some evidence that flow …

Efficacy of Amlodipine in the Treatment of Stable Effort Angina

The purpose of this double-blind placebo-controlled crossover study was to assess the antianginal efficacy of oral amlodipine (10mg once daily) in 16 patients with stable effort angina.

Aminophylline Reduces Cardiac Ischemic Pain During Percutaneous Transluminal Coronary Angioplasty

ObjectivesWe investigated the effect of aminophylline, an antagonist of the adenosine P1 receptor, on cardiac pain experienced during percutaneous transluminal coronary angioplasty (PTCA). BackgroundAdenosine may mediate cardiac pain because the administration of adenosine provokes cardiac pain like angina. However, it is not known whether endogenous adenosine released during myocardial ischemia is responsible for cardiac pain. MethodsThis was a single-blind, placebo-controlled randomized study. Of 21 men with stable effort angina with one-vessel coronary artery disease who underwent balloon inflation four times during PTCA, 11 received intravenously administered aminophylline before the fourth balloon inflation and the other 10 were given saline solution. The severity of cardiac pain based on the pain score and ST segment elevation on standard surface and intracoronary electrocardiograms were assessed. ResultsAll patients experienced cardiac pain during balloon inflation. Aminophylline significantly prolonged the duration of both the symptom-free interval (from 42±13 to 64±27 s, mean±SD, p<0.05) and inflation time (from 79±23 to 103±20 s, p<0.05), and it significantly reduced the pain score from 7.6±1.4 to 4.6±2.3 (p<0.01). However, aminophylline did not affect ST segment elevation. Saline solution did not affect any of these variables. Balloon diameter and pressure were not different between the third and the fourth inflation in either group. ConclusionsAminophylline significantly reduced the severity of cardiac pain during PTCA without affecting ST segment elevation. These findings suggest that the activation of P1 receptors by endogenous adenosine may be partially responsible for cardiac pain during ischemia.

Vitamin E deficiency in variant angina.

Oxidative modification of LDL has been suggested to increase coronary vasoreactivity to agonists. A deficiency of vitamin E, a major antioxidant, may be related to the occurrence of coronary artery spasm. Vitamin E levels were determined with the use of high-performance liquid chromatography in normolipidemic subjects, including 29 patients with active variant angina (group 1), 13 patients with inactive stage of variant angina without anginal attacks during the past 6 months (group 2), 32 patients with a significant (>75%) organic coronary stenosis and stable effort angina (group 3), and 30 patients without coronary artery disease (group 4). Total lipid levels in blood were calculated as total cholesterol plus triglyceride levels. The plasma alpha-tocopherol levels as well as alpha-tocopherol/lipids were significantly lower in group 1 than in groups 2 through 4. Also, the plasma gamma-tocopherol levels were significantly lower in group 1 than in groups 2 through 4. The vitamin E levels were not significantly different between group 1 patients with and those without a significant organic stenosis. In group 1, both alpha- and gamma-tocopherol levels were significantly elevated after a > or = 6-month angina-free period. The alpha-tocopherol levels in the LDL fraction were significantly lower in group 1 than in group 4. Plasma alpha-tocopherol levels were significantly correlated with those in the LDL fractions. In 6 patients of group 1 still having anginal attacks while receiving calcium channel blockers, the addition of vitamin E acetate (300 mg/d) significantly elevated plasma alpha-tocopherol levels and inhibited the occurrence of angina. Plasma vitamin E levels were significantly lower in patients with active variant angina than in subjects without coronary spasm, suggesting an association between vitamin E deficiency and coronary artery spasm.

Effects of angiotensin-converting enzyme inhibitor alacepril in patients with stable effort angina during chronic isosorbide dinitrate treatment

Nitrate tolerance has been reported to be reversed by certain types of angiotensin-converting enzyme (ACE) inhibitors. We examined whether alacepril, a new long-acting oral ACE inhibitor, has beneficial effects against exercise-induced angina in patients with stable effort angina after sustained isosorbide dinitrate (ISDN) treatment. Thirteen men with stable effort angina were treated with oral ISDN (80 mg/d) for >3 weeks. After this period, the efficacy of single oral administration of either alacepril (50 mg) or its placebo on exercise-induced angina and electrocardiographic changes was examined by treadmill exercise test in a double-blind crossover design. Alacepril significantly improved the exercise duration by 9.1 % (p = 0.03), the time to 1 mm ST-segment depression by 19% (p < 0.01), and the maximal ST-segment depression by 33% (p = 0.015) compared with placebo. Alacepril did not significantly alter the rate-pressure product, a marker of myocardial oxygen demand, during exercise test compared with placebo. Plasma renin activity was significantly increased (p < 0.05) after administration of alacepril, indicating that alacepril significantly blocked ACE activity in our patients. In conclusion, a single oral administration of the ACE inhibitor alacepril (50 mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chronic nitrate treatment. These effects may be mediated by increased coronary blood flow.

Celiprolol. An evaluation of its pharmacological properties and clinical efficacy in the management of hypertension and angina pectoris.

Celiprolol is a beta 1-selective adrenoceptor antagonist (beta-blocker) which acts as a weak agonist at beta 2-adrenoceptors. The drug demonstrates vasodilator properties and does not depress heart rate to the same extent as propranolol, atenolol or metoprolol. Celiprolol has shown equivalent antihypertensive efficacy to other beta-blockers, notably propranolol, atenolol, metoprolol and pindolol, in patients aged 18 to 75 years with mild to moderate essential hypertension. The drug has also shown similar antihypertensive efficacy to the angiotensin converting enzyme inhibitor enalapril and to combination diuretic therapy with hydrochlorothiazide and amiloride. Celiprolol was equally effective in adult patients of all ages, although no data are available for patients aged over 75 years. Data from a small number of clinical trials indicate celiprolol to be as effective as both propranolol and atenolol in improving work capacity and reducing the frequency of anginal attacks in patients with stable effort angina. However, the drug has not yet been evaluated in postmyocardial infarction patients. Celiprolol offers advantages over other beta-blockers, including reduction of peripheral vascular resistance and maintenance of resting heart rate, cardiac output and renal perfusion. The drug is also associated with improvements in plasma lipid profiles and does not appear to adversely affect carbohydrate metabolism or lung function, although its use in patients with reversible obstructive pulmonary disease is not recommended. Celiprolol is therefore a highly cardioselective beta-blocker with ancillary characteristics which are potentially useful in patients with hypertension and angina complicated by other conditions commonly associated with advanced age. These include impaired glucose tolerance or diabetes mellitus, peripheral vascular disease and hyperlipidaemia. The drug may also be preferred to other beta-blockers in patients in whom a reduction in heart rate would be particularly undesirable. Further long term (> 12 months) clinical trials and pharmacoeconomic data are now required to confirm the clinical relevance of the pharmacodynamic advantages of celiprolol therapy.

Increased Soluble Form of P-Selectin in Patients With Unstable Angina

P-selectin in platelets and endothelial cells mediates adhesive interaction with leukocytes to form thrombi. The purpose of the present study was to investigate the plasma levels of P-selectin in patients with unstable angina and in those with stable effort angina of different pathophysiologies. Plasma P-selectin levels were determined by a monoclonal antibody-based enzyme immunoassay on plasma samples taken from 12 patients with unstable angina, 11 patients with stable effort angina, and 15 healthy volunteers. Patients with unstable angina had angina at rest associated with ECG changes. In patients with unstable angina, plasma P-selectin levels within 1 hour (361 +/- 90 ng/mL) and at 3 hours (282 +/- 56 ng/mL) after angina were significantly (P < .05) higher than those in volunteers (177 +/- 31 ng/mL). Plasma P-selectin levels at 5 hours after attack (242 +/- 46 ng/mL) did not differ from those in volunteers. Although patients with stable effort angina developed angina with ST-segment depressions by treadmill exercise, their plasma P-selectin levels did not change (before, 178 +/- 45; immediately after, 186 +/- 36; and 1 hour after the exercise, 179 +/- 34 ng/mL). Plasma P-selectin levels after angina increased significantly in patients with unstable angina but did not in patients with stable effort angina. These findings may contribute to understanding of the pathophysiology of the acute coronary syndrome of unstable angina.