Haruhiko Date

Increased plasma adrenomedullin in acute myocardial infarction

Adrenomedullin has a potent vasodilating effect comparable to that of calcitonin gene-related peptide. To investigate the pathophysiologic role of endogenous adrenomedullin, we determined sequentially the plasma adrenomedullin level in 15 consecutive patients with acute myocardial infarction (AMI). Plasma adrenomedullin was higher immediately after the onset of AMI and decreased gradually; plasma levels during the 3-week period after the AMI were higher than plasma levels in 15 healthy control subjects (p < 0.001), with higher levels in patients with congestive heart failure than in patients without congestive heart failure throughout the period of the study (p < 0.05). Plasma adrenomedullin was positively correlated with pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and heart rate in the early stage of AMI. These findings suggest that the elevation of plasma adrenomedullin is related to the retention of body fluid volume, the enhancement of sympathetic activity, and/or the elevation of pressure in pulmonary vascular beds. Adrenomedullin may act against excessive vasoconstrictors increased in AMI.

Involvement of C-reactive protein obtained by directional coronary atherectomy in plaque instability and developing restenosis in patients with stable or unstable angina pectoris

We investigated whether positive immunohistochemical staining of C-reactive protein (CRP) in initial culprit lesions is related to coronary plaque instability and whether it could affect the outcome of directional coronary atherectomy (DCA). The plasma level of CRP is a reliable marker of the risk of coronary events and restenosis after percutaneous coronary intervention. However, the influence of tissue CRP in atheromatous plaque on plaque vulnerability and restenosis remains unknown. Samples of DCA obtained from 12 patients with stable angina pectoris and 15 patients with unstable angina pectoris were immunohistochemically stained with a monoclonal antibody against CRP. We performed follow-up coronary angiography on 22 of 27 patients to evaluate the presence of restenosis after DCA. Immunoreactivity to CRP was localized to macrophages, smooth muscle cells, and necrotic areas. The ratio of CRP positive cells to total cells was significantly higher in DCA samples from patients with unstable (17.9 +/- 2.0%) than with stable angina (11.0 +/- 2.5%) (p <0.05). Follow-up coronary angiography showed that 12 of 22 patients developed restenosis after DCA. The ratio was also significantly higher in DCA specimens from patients with restenosis (19.3 +/- 2.8%) compared with those without restenosis (11.0 +/- 2.0%) (p <0.05). In addition, the ratio significantly correlated with late luminal loss (r = 0.428, p <0.05) and loss index (r = 0.636, p = 0.0011) after DCA. Immunoreactivity to CRP in coronary atheromatous plaque increases in culprit lesions of unstable angina, and it affects restenosis after DCA. These findings suggest that CRP in atheromatous plaque plays an important role in the pathogenesis of unstable angina and restenosis after coronary intervention.

Increased adrenomedullin immunoreactivity and mRNA expression in coronary plaques obtained from patients with unstable angina

Objective: To examine the expression and localisation of adrenomedullin in human coronary atherosclerotic lesions from patients with unstable angina (UAP) and stable angina (SAP), and to study the relation between adrenomedullin expression and plaque instability. Design: A retrospective observational study. Patients: Directional coronary atherectomy samples were obtained from 15 patients with UAP and 12 with SAP. Methods: The localisation of adrenomedullin was examined by immunohistochemistry, and adreno-medullin mRNA expression was measured by quantitative polymerase chain reaction. Results: Adrenomedullin immunoreactivity was preferentially localised in macrophages, intimal smooth muscle cells, and proliferated microvessels. The mean number of adrenomedullin positive cells in five high power fields (× 400) per specimen was higher in patients with UAP than in those with SAP (mean (SEM), 110 (13) v 76 (7); p < 0.05); and the ratio of adrenomedullin positive to total cells was higher in patients with UAP (43.0 (2.2)% v 34.2 (2.0)%; p < 0.01). More adrenomedullin mRNA was expressed in the plaque of patients with UAP than in those with SAP (60.4 (16.9)% v 9.7 (3.3)%; p < 0.01). Conclusions: The findings suggest that adrenomedullin is involved in the development of atherosclerosis and plaque instability in human coronary arteries, in an autocrine or paracrine manner.

Outcome of target sites escaping high-grade (>70%) restenosis after percutaneous transluminal coronary angioplasty

This study examined the fate of target sites that escaped high-grade restenosis (> or = 70% diameter narrowing) after percutaneous transluminal coronary angioplasty. Although favorable long-term prognosis after successful percutaneous transluminal coronary angioplasty is well documented, little is known about the stability of target sites. Long-term follow-up (mean 6.5 years, range 1.0 to 12.0) was performed in 693 patients with 948 narrowings (stenosis <70% in diameter at follow-up coronary angiography). Among them, 249 patients (36%) with 303 target sites received late follow-up coronary angiography. The relation of target sites to the culprit lesions for coronary events or newly developed angina was angiographically reviewed and progression/regression was also examined, focusing on the target sites. Regression was observed in 16 of 255 target sites in subjects with <50% stenosis and in 21 of 48 sites in the group with midgrade stenosis of 50% to 69% luminal narrowing (16 of 255, 6.3% vs 21 of 48, 43.8%, p <0.001). Progression was observed in 33 and 4 sites (33 of 255, 12.9% vs 4 of 48, 8.3%; p = NS) in each group, respectively. The rest remained within the same range of stenosis. Culprit lesions for 2 acute myocardial infarctions, 7 unstable anginas, and 17 newly developed anginas were related to the original target sites. Three lesions developed in the midgrade stenosis group. Those 26 lesions were a component of 8.6% of 303 angiographically confirmed sites and 2.7% of total target sites. Target sites that escape high-grade restenosis frequently regress and become stable plaques and rarely trigger coronary events.

Osteoprotegerin is Secreted Into the Coronary Circulation: A Possible Association with the Renin-Angiotensin System and Cardiac Hypertrophy

The circulating osteoprotegerin (OPG) level reflects a series of cardiovascular diseases; however, the source(s) of circulating OPG remain(s) to be determined. This study explored whether OPG is released in the coronary circulation and whether it is associated with cardiac structure and function. Fifty-six patients (67±10 years old, male 57%, hypertension 73%, coronary artery disease 50%) were enrolled, and blood samples were collected simultaneously from the orifice of the left coronary artery (CA) and the coronary sinus (CS) after angiography. The concentration of OPG was higher in the CS than in the CA (7.7±4.1 vs. 6.7±3.6 pmol/l, p<0.001). The trans-cardiac OPG concentration was significantly (p=0.019) decreased in patients who have been prescribed either an angiotensin converting enzyme inhibitor or an angiotensin II type 1 receptor blocker (ACEI/ARB). In patients subgroup who did not take an ACEI/ARB (n=27), the trans-cardiac OPG level was positively correlated with age (r=0.396, p=0.041) and relative wall thickness of left ventricle (r=0.534, p=0.004). In multivariate linear regression analysis, relative wall thickness remained to be the independent variable for the trans-cardiac OPG level (p=0.004). Moreover, trans-cardiac OPG was significantly (p=0.021) increased in patients with relative wall thickness greater than 0.45 but it did not differ if the left ventricular mass index was increased (≥116 for males, or ≥ 104 for females, g/m(2)) or not (p=0.627). This study suggests that OPG is secreted into the coronary circulation and is associated with concentric remodeling/hypertrophy of LV, possibly in interactions with the renin-angiotensin system.

Reciprocal Production of Adiponectin and C-reactive Protein in Coronary Circulation of Patients with and without Coronary Artery Disease

Introduction & The adipocyte-specifi c plasma protein adi ponectin was originally isolated from human adipose tissues. Adiponectin has anti-atherosclerotic properties such as the suppression of adhesion molecule expression on endothelial cells, the proliferation of vascular smooth muscle cells, and the transformation of macrophages to foam cells. Systemic clinical hypoadiponectinemia is closely associated with obesity, type 2 diabetes, and coronary artery disease (CAD) [1] . These data suggest that adiponectin contributes to suppressing the initiation and progression of atherosclerosis. We already reported that adiponectin is locally produced in the coronary circulation and might participate in modulating the coronary circulation [2] . Iacobellis et al. recently showed that epicardial adipose tissue expresses adiponectin protein and that the level is signifi cantly lower in patients with, than in those without, CAD [3] . Locally produced adiponectin might exert local anti-atherosclerotic action on the adjacent coronary artery [3] . These fi ndings together indicate that the locally produced adiponectin in the coronary circulation might be at least partly attributable to its production and secretion from epicardial adipose tissue and affect coronary atherosclerosis. However, whether the plasma level of adiponectin in the coronary circulation varies with the presence of CAD remains unknown. We therefore investigated the relationship between the presence of CAD and the amount of adiponectin production in the coronary circulation and compared with the amount of C-reactive protein (CRP) in the coronary circulation of patients with and without CAD.

SIGNIFICANCE OF CARDIAC TROPONIN T LEVELS IN SUPRAVENTRICULAR TACHYCARDIA

Background: Cardiac troponin T is sensitive and specific markers of myocardial injury and is used routinely for the diagnosis of acute coronary syndrome. Recently, the magunitude of troponin T levels in heart failure patients has been reported to correlate with severity of the disease and with adverse outcomes. They may suggest ongoing myocardial damage. In supraventricular tachycardia, common atrial flutter (AFL) and atrial tachycardia (AT) often produce changes in cardiac function and structure, but atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) do not. To our knowledge, there are no reports about the relationship between the levels of troponin T and the types of supraventricular tachycardia. We examined the clinical usefulness of previously unmeasurable levels of troponin T (hs-TnT) by using highly sensitive assay for the differential diagnosis of supraventricular tachycardia.

[Ventricular fibrillation in a patient with Wolff-Parkinson-White syndrome].

症例は30歳,男性.動悸,気分不良が初めて出現し,近医を受診.待合室で意識消失し,心室細動を認めたため,電気的除細動を施行された.心電図でデルタ波を認め,電気生理学検査で副伝導路の順行性有効不応期は250msecと短かったためカテーテルアブレーションを施行した.無症候性WPW症候群は予後良好といわれているが,本症例は初発の頻拍発作が心室細動に至っており,注意を要すると思われた.