Relationship between serum lipoprotein(a) concentrations and coronary vasomotion in coronary spastic angina.

BACKGROUND: Elevated lipoprotein(a) (Lp(a)) concentrations are reported to impair endothelium-dependent vasodilatation of the epicardial coronary artery. However, the effects on vasomotor abnormalities in coronary spastic angina (CSA) have not been thoroughly investigated. METHODS AND RESULTS: In the present study 80 sites of spasm (spastic sites) without significant organic stenosis (% diameter stenosis <50%) were assessed in 80 patients with CSA diagnosed by intracoronary ergonovine (EM) test. Spastic sites were divided into 2 groups: Group 1 included 30 sites provoked by the full dose (=50 microg) of EM, and Group 2 included 50 sites provoked with less than 50 microg (34.7+/-8.2 microg). Control subjects (n=22) did not show coronary spasm with the EM test. Serum Lp(a) concentrations were measured in all patients. Group 2 had a significantly greater basal coronary artery tone in the spastic sites than Group 1 (p<0.001). Lp(a) level in Group 2 was significantly higher compared with both the control group and Group 1 (p<0.05 by analysis of variance). Multivariate analysis confirmed that only serum Lp(a) concentration was associated with low-dose EM spasm provocation. CONCLUSIONS: Serum Lp(a) concentration could be a marker for high disease activity in CSA.

Expression of coxsackievirus and adenovirus receptor in neointima of the rat carotid artery.

Our previous study revealed that the coxsackievirus and adenovirus receptor (CAR) is a homophilic cell adhesion molecule and may function as a sensor of cell-cell interactions in the brain and damaged heart. In this study, we investigated if CAR expression is involved in the formation of neointimal hyperplasia using a balloon injury model of rat carotid artery. Cultured vascular smooth muscle cells (SMCs) from rat aorta were also studied. CAR antigen was constitutively detected in the endothelial cells (ECs) but not in SMCs before injury. On Day 5 after balloon injury, CAR was expressed strongly in the first layer of medial SMCs. Neointimal hyperplasia was observed on Day 7, and strong expressions of CAR concomitantly with proliferating cell nuclear antigen (PCNA) were obvious in the neointimal SMCs, while CAR in medial SMCs disappeared. The expression of CAR mRNA reached a peak on Day 7 and declined gradually to the basal levels. When the ECs regenerated on Day 14, CAR antigen was observed in the ECs but disappeared in the neointima. CAR together with PCNA was expressed abundantly in the proliferating SMCs in vitro and diminished in cells grown to a confluent state. The abundant expression of CAR in the neointima may facilitate an adenoviral gene therapy.

Plasma concentrations of monocyte chemoattractant protein 1 (MCP-1) and neopterin in the coronary circulation of patients with coronary artery disease.

BACKGROUND: The dynamics of MCP-1 and neopterin and the relation between their concentrations in coronary circulation and the severity of coronary atherosclerosis were evaluated in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Blood samples were obtained from the aortic root (Ao) and coronary sinus (CS) of 78 patients who underwent coronary angiography. Plasma MCP-1 and neopterin concentrations were measured using an enzyme-linked immunosorbent assay method and the CS-Ao differences were calculated. The severity of coronary heart disease (CHD) was evaluated in 52 patients who had no history of coronary angioplasty, using 3 coronary scoring systems: the clinical 1- to 3-vessel disease score, the American Heart Association extension score (1-15 segments), and the Gensini score. The plasma MCP-1 and neopterin concentrations increased significantly with age. The CS-Ao differences for neopterin showed weak, but significant, positive correlation with the Gensini score (r=0.347, p=0.013). There were no correlations among the MCP-1 concentrations in the Ao or CS, or in the CS-Ao difference, with the severity of CHD. CONCLUSIONS: The results indicate that neopterin is a useful marker of the severity of coronary atherosclerosis in patients with stable CAD, acting as an index of the activity of monocytes/macrophages.

Plasma levels of soluble thrombomodulin, C-reactive protein, and serum amyloid A protein in the atherosclerotic coronary circulation.

Plasma levels of C-reactive protein (CRP) and serum amyloid A protein (SAA), inflammatory markers, and soluble thrombomodulin (s-TM), a marker of endothelial damage. are thought to be related to coronary artery disease. However, the relationship between these inflammatory markers and endothelial injury in atherosclerotic coronary arteries is still unclear. Fifty-five patients who underwent coronary angiography were classified into 3 groups according to the severity of left coronary arterial atherosclerosis evaluated by the Gensini score (GS; normal: score = 0, n = 15; mild: 0 < score < 15, n = 29; severe: score > or = 15, n = 11). Blood samples were obtained from the aortic root (Ao) and coronary sinus (CS) and plasma CRP and SAA levels were measured by latex turbidimetric immunoassays, and s-TM levels were determined by an enzyme-linked immunosorbent assay. The difference between marker concentrations in the Ao and CS of the coronary circulation was expressed as the coronary sino-arterial (CS-Ao) difference. The CS-Ao differences of s-TM and SAA were significantly higher in patients with severe atherosclerosis than in normal patients (P < 0.01), and showed weak but significant positive correlations with the GS (r = 0.34, P < 0.01 and r = 0.33, P < 0.05, respectively). The CS-Ao differences in CRP did not differ among the three groups, and did not correlate with the GS. The results of our study reveal a possible relationship between endothelial cell injury and inflammation in atherosclerotic coronary arteries.

Analysis of postextrasystolic relaxation response in the human heart.

Postextrasystolic potentiation is the phenomenon in which ventricular contractile force is strengthened by a preceding premature beat. However, the response of diastolic function after an extrasystole is unknown. We studied 58 patients with chronic heart failure (CHF) and two control subjects to evaluate the response of relaxation following extrasystole. At cardiac catheterization, from the derivative of the left ventricular (LV) pressure, the ratio of LV peak negative dP/dt (-dP/dt) of a postextrasystole to a basal beat was calculated and defined as the postextrasystolic relaxation response (PRR). PRR was compared with parameters of left ventriculography: LV end-diastolic volume index (EDVI), LV end-systolic volume index (ESVI), and LV ejection fraction (EF). The PRRs of the two control subjects were 0.80 and 0.84. The mean PRR of the CHF patients was 0.99 +/- 0.15. In all subjects, including patients and controls, correlation analysis between (EDVI, ESVI, and EF) and PRR yielded the following: (a) EDVI vs. PRR: R = 0.273, p = 0.036; (b) ESVI vs. PRR: R = 0.446, p < 0.001; and (c) EF vs. PRR: R = -0.520, p < 0.001. Thus, normal or non-failing human hearts showed a decline of -dP/dt in postextrasystole compared with the basal beats, but failing hearts had potentiated relaxation following an extrasystole.

Association between coronary endothelial dysfunction and local inflammation of atherosclerotic coronary arteries.

We have examined a possibility whether or not severity and extent of coronary atherosclerosis may associate with degree of local inflammation in relation to endothelial dysfunction as is indicated by reduced NO formation. Blood samples were obtained from aortic root (Ao) and coronary sinus (CS) of 39 patients who underwent coronary angiography. Plasma NOx levels (nitrite + nitrate, stable NO end-products) were evaluated by HPLC-Griess system, and markers of inflammation, C-reactive protein (CRP) and serum amyloid A protein (SAA), were measured by Latex Turbidimetric Immunoassay. To evaluate the changes of these substances through coronary circulation, the percentage changes of respective markers [(CS - Ao) x 100/Ao] were calculated. The extent and severity of atherosclerosis of left coronary arteries were evaluated with Gensini Score (GS). The GS correlated with the percentage changes of NOx (r = -0.35, p < 0.05) and that of SAA (r = 0.43, p < 0.05) across coronary circulation, but not with changes in CRP. Moreover, the percentage changes of NOx correlated with that of SAA (r = -0.36, p < 0.05). These results indicated that severity and extent of coronary atherosclerosis related to degree of local inflammation which has a possible association with coronary endothelial dysfunction.

Significance of asymmetric dimethylarginine (ADMA) concentrations during coronary circulation in patients with vasospastic angina.

The basal activity of nitric oxide (NO) is reduced in spastic arteries of patients with vasospastic angina (VSA). Elevated concentrations of ADMA are associated with reduced NO production and impaired endothelium-dependent vasodilatation. The aim of this study was to elucidate the role of ADMA and its relationship to NO end-products (NOx; nitrate + nitrite) during coronary circulation in patients with VSA. The plasma ADMA and NOx concentrations during coronary circulation were evaluated in 16 VSA and 16 control patients. Blood samples were obtained from the coronary sinus (V) and the ostium of the left coronary artery (A), and the (V-A) differences of ADMA and NOx were determined. The coronary sinus plasma ADMA concentration in patients with VSA was higher than that in the control. The coronary sinus - arterial (V-A) difference of NOx was negative in the VSA group and approximately zero in the control group (VSA group =-1.4 micromol/L, control group =-0.1 micromol/L, p=0.0005). Furthermore, in the VSA patients, there was a negative correlation between the (V-A) difference of NOx and the basal coronary artery tone at the site of spasm (r=-0.60, p=0.015). A significant negative correlation between the (V-A) differences of NOx and ADMA was observed in patients with VSA (r=-0.52, p<0.05), but not in those of the control. Higher ADMA concentrations might cause the reduced formation of NO that underlies the pathophysiology of coronary vasospasm.

Acute pulmonary thromboembolism induced by prophylactic heparin use and a heparin-coated catheter: a case of heparin-induced thrombocytopenia and thrombosis syndrome.

Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is a potentially life-threatening side effect of heparin therapy, triggered by an immune response, and has been reported to be related not only to the therapeutic use of heparin but also to heparin-coated catheters. A 45-year-old woman with intrapelvic malignancy developed an acute pulmonary thromboembolism (PE) after hysterectomy despite prophylactic heparin use. Subsequent large doses of heparin for treatment of the PE exacerbated the thrombocytopenia and, moreover, a large thrombus formed around the heparin-coated central venous catheter. Anti-heparin-platelet factor 4 complex antibody and heparin-induced platelet aggregation assay were positive, so the diagnosis was HITTS, and heparin was replaced by argatroban after carrying out thrombectomy. This therapy was successful, and the patient made favorable progress.

Levels of soluble E-selectin and ICAM-1 in the coronary circulation of patients with stable coronary artery disease: association with the severity of coronary atherosclerosis.

The recruitment of circulating leukocytes to atherosclerotic sites is mediated by a family of adhesion molecules. The objective of the present study was to evaluate the relationship between circulating adhesion molecule levels in the coronary circulation and the severity of coronary atherosclerosis in patients with stable coronary artery disease. The subjects were 79 patients undergoing coronary angiography. According to the severity of coronary atherosclerosis as assessed by the Gensini Score (GS) of the left coronary artery, they were classified into three groups: group C (no organic stenosis, score 0, n = 14), group M (mild organic stenosis, score 1-13, n = 39) and group S (severe organic stenosis, score > or = 14, n = 26). Blood samples were taken from the aorta (Ao) and coronary sinus (CS), and plasma levels of soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured by enzyme-linked immunosorbent assay. These levels were then compared between groups. There were no significant differences in plasma sICAM-1 levels in the Ao or CS between the three groups. The difference in sICAM-1 levels between the CS and Ao (CS-Ao) also showed no significant difference. Plasma sE-selectin levels in both the Ao and CS were significantly higher in group S than in groups C and M (p < 0.05), but there were no significant differences in CS-Ao. There was a weak but significant correlation between the plasma levels of these adhesion molecules and the number of coronary risk factors present. Multivariate analysis showed that the number of coronary risk factors was the only positive predictor (p = 0.0048) of the GS; there was no association between the plasma level of either adhesion molecule and the GS. In patients with stable coronary artery disease, sICAM-1 plasma levels do not indicate the severity of coronary atherosclerosis, while sE-selectin plasma levels appear to reflect the severity of systemic rather than coronary atherosclerosis.