Terumitsu Tanaka

Elevated basic fibroblast growth factor in pericardial fluid of patients with unstable angina

BACKGROUND Collateral growth is induced by chemical signals from the ischemic myocardium. We hypothesized that angiogenic growth factors are produced by cardiac tissue; they are diffusible, more concentrated in pericardial fluids, and are increased by myocardial ischemia. METHODS AND RESULTS With the use of an enzyme-linked immunosorbent assay, we measured the concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in pericardial fluids of 12 patients with unstable angina (group 1) and of 8 patients with nonischemic heart diseases (group 2). The levels of protein in pericardial fluids were quite comparable between the two groups (34 +/- 2 versus 32 +/- 4 mg/mL). The concentration of bFGF in pericardial fluids in group 1 was 2036 +/- 357 pg/mL, significantly (P < .001) higher than the 289 +/- 72 pg/mL in group 2. The amount of bFGF per milligram of protein was also significantly (P < .05) higher in group 1 than in group 2 (67 +/- 15 versus 12 +/- 4 pg/mg). The concentration of VEGF in pericandial fluids tended to be higher in group 1, but the difference was statistically insignificant (39 +/- 7 versus 22 +/- 6 pg/mL). The amount of VEGF per milligram of protein was 1.2 +/- 0.3 pg/mg in group 1, similar to the 0.8 +/- 0.4 pg/mg in group 2. CONCLUSIONS This finding provides new evidence that bFGF plays an important role in mediating collateral growth in humans.

Improvement of exercise capacity by sarpogrelate as a result of augmented collateral circulation in patients with effort angina.

OBJECTIVES The purpose of this study was to evaluate whether a serotonin blocker, sarpogrelate, improves exercise capacity as a result of vasodilation of coronary collateral channels in patients with effort angina. BACKGROUND Serotonin has been reported to decrease coronary collateral blood flow by collateral vasoconstriction in a canine model, suggesting that platelet activation in feeding coronary arteries of the collateral network has the potential to cause collateral vasoconstriction. METHODS The subjects consisted of 22 patients with effort angina and reproducible ischemic threshold (group A, 11 patients with thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow of the ischemia-related coronary artery and Rentrops collateral index 0 or 1; group B, 11 patients with TIMI grade 0 or 1 flow and Rentrops collateral index 2 or 3). We repeated the symptom-limited treadmill exercise test using the Balke-Ware protocol and exercise tetrofosmin myocardial perfusion scintigraphy with and without pretreatment with 200 mg orally administered sarpogrelate. Each exercise test was performed at 9:00 a.m. on different days. The order of tests with and without sarpogrelate was randomized. RESULTS In group A, sarpogrelate increased neither exercise time at 0.1 mV ST depression nor double product at 0.1 mV ST depression. In contrast, in group B sarpogrelate increased the exercise duration at 0.1 mV ST depression from 181+/-112 (SD) to 248+/-131 s (p < 0.05) and also increased the double product at 0.1 mV ST depression by 21% (p < 0.01). The severity score using myocardial perfusion scintigraphy at the same workload was significantly (p < 0.01) decreased by 37% in group B, but not in group A (11%), due to the sarpogrelate treatment. CONCLUSIONS Sarpogrelate augments flow reserve of the collateral circulation and improves exercise capacity in anginal patients with well-developed collaterals. These findings indicate that a serotonin blocker, sarpogrelate, is useful not only as an antiplatelet drugs, but as an antianginal drug.

Marked Elevation of Brain Natriuretic Peptide Levels in Pericardial Fluid Is Closely Associated With Left Ventricular Dysfunction

OBJECTIVES The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in pericardial fluid. BACKGROUND ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides. METHODS With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and pericardial fluid simultaneously in 28 patients during coronary artery bypass graft surgery. RESULTS The pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or pericardial fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or pericardial fluid. Both plasma and pericardial fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP pericardial fluid levels had closer relations with LVEDVI (r = 0.679, p < 0.0001) and LVESVI (r = 0.686, p < 0.0001) than did BNP plasma levels (LVEDVI: r = 0.567, p = 0.0017; LVESVI: r = 0.607, p = 0.0010). BNP levels in pericardial fluid but not in plasma correlated with left ventricular end-diastolic pressure (r = 0.495, p = 0.0074). CONCLUSIONS BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.

Clinical Application of Transluminal Endovascular Graft Placement for Aortic Aneurysms

BACKGROUND In recent years, transluminal endovascular graft placement techniques have been developed for the treatment of aortic aneurysms. We report our initial clinical experience with endovascular graft placement using a graft developed in our laboratory. METHODS The procedure was performed in 20 patients with a diagnosed aortic aneurysm. The graft is constructed from a Dacron cylinder, and the surface of the graft is supported with multiple rings of extraflexible wire. After the compactly folded graft is delivered through the sheath to the predetermined target point, the graft is deployed and then pressed against the vessel by balloon inflation. Straight graft insertion was attempted in 10 patients, bifurcated graft insertion in 8, and branched graft insertion in 2. RESULTS Graft placement was successful in 19 of the patients and unsuccessful in 1. There were no cases of graft migration, aneurysm rupture, or graft destruction during a mean follow-up period of 9 months. CONCLUSIONS Initial clinical results demonstrated the efficacy and safety of endovascular graft placement using this graft.

Relation between preexistent coronary collateral circulation and the incidence of restenosis after successful primary coronary angioplasty for acute myocardial infarction.

OBJECTIVES The purpose of this study was to test the hypothesis that the incidence of restenosis after primary percutaneous transluminal coronary angioplasty for acute myocardial infarction is largely influenced by the preexistent coronary collateral circulation to the infarct-related coronary artery. BACKGROUND The occurrence of restenosis after coronary angioplasty is the most serious limitation of this procedure. However, prediction of restenosis is difficult. Severe preexistent stenosis of the infarct-related coronary artery causing the development of collateral circulation may result in a high frequency of restenosis. METHODS The study group consisted of 152 consecutive patients undergoing primary coronary angioplasty within 12 h after the onset of a first acute myocardial infarction. Of this group, 124 patients were angiographically followed up during the convalescent period of infarction and were classified into two groups according to the extent of preexistent collateral circulation to the infarct-related coronary artery. RESULTS Restenosis occurred in 26 (38%) of 69 patients with poor or no collateral circulation (group A) in contrast to 35 (64%) of 55 patients with good angiographic collateral circulation (group B, p < 0.005). The frequency of preinfarction angina was significantly lower (p < 0.05) in group A (26% [18 of 69]) than in group B (44% [24 of 55]). CONCLUSIONS These findings indicate that the presence of well developed collateral circulation to the infarct-related coronary artery predicts a higher frequency of restenosis after primary coronary angioplasty. The difference in restenosis rates observed between the patients with and without good collateral circulation probably reflects the impact of underlying severity of stenosis on the long-term outcome after coronary angioplasty.

Marked elevation of vascular endothelial growth factor and basic fibroblast growth factor in pericardial fluid of patients with angina pectoris.

Although we reported that basic fibroblast growth factor (bFGF) levels in pericardial fluid of patients with unstable angina are apparently increased, it was unclear whether vascular endothelial growth factor (VEGF) is also increased in patients with myocardial ischemia. Using an enzyme-linked immunosorbent assay, we measured the concentrations of VEGF and bFGF in pericardial fluid of 51 patients with open heart surgery. Patients were divided into group A (n=10) with class III unstable angina (Braunwalds classification), group B (n=24) with class I or II unstable angina or stable angina and group C (n=17) with non-ischemic heart disease. The VEGF level in pericardial fluid in group A was 83±7 pg/ml, being significantly (p<0.001) higher than the 27±3 pg/ml in group B and the 28±5 pg/ml in group C. The concentrations of bFGF in pericardial fluid in groups A and B were 1461±579 and 1224±161 pg/ml, respectively, significantly (p<0.05) higher than the 292±97 pg/ml in group C. The level of VEGF in pericardial fluid was increased only in patients with severe rest angina within 2 days before emergency coronary artery bypass graft surgery (CABG), while bFGF was increased in all patients undergoing CABG for coronary artery disease. Thus VEGF and bFGF may play important roles in mediating collateral growth in humans.

Fate of Collateral Vessels After Successful Coronary Angioplasty in Patients With Effort Angina

OBJECTIVES The purpose of the present study was to evaluate whether severe restenosis after percutaneous transluminal coronary angioplasty (PTCA) promotes collateral development and whether successful dilation regresses collateral vessels. BACKGROUND It is well known that in the presence of severe coronary stenosis, native collateral arterioles mature to small coronary arteries with several layers of smooth muscle cells. However, it remains unclear whether well developed collateral vessels regress after removal of coronary stenosis. METHODS The study group comprised 41 patients who underwent elective PTCA for effort angina due to single-vessel disease, followed by repeat PTCA to treat restenosis. We classified the patients into three groups depending on the change in baseline Thrombolysis in Myocardial Infarction (TIMI) flow grade of the ischemia-related artery at initial and repeat PTCA, and we compared the extent of ST segment elevation at 1 min of the first balloon inflation between the two procedures. The average interval from initial to repeat PTCA was 125 days. RESULTS The three patient groups comprised group A, 12 patients with decreased flow grade because of severe coronary restenosis; group B, 12 patients with increased flow grade who had severe initial stenosis and relatively mild restenosis; and group C, 17 patients with unchanged flow grade. In the presence of comparable rate-pressure products at initial and repeat PTCA, patients in group A had significantly greater ST segment elevation (p < 0.01) at initial than at repeat PTCA (mean +/- SD 0.42 +/- 0.31 vs. 0.13 +/- 0.22 mV). In group B, ST segment elevation was significantly less at initial than at repeat PTCA (0.13 +/- 0.25 vs. 0.19 +/- 0.17 mV, p < 0.05), and in group C, it was comparable at the two procedures (0.37 +/- 0.32 vs. 0.35 +/- 0.33 mV, p = 0.50). CONCLUSIONS These findings indicate that severe restenosis after PTCA promotes collateral development and that successful dilaton regresses collateral vessels during a relatively short period of time.

Assessment of long-term left internal thoracic artery graft patency by exercise Doppler echocardiography

R E F E R E N C E S 1. Hirsh J, Dalen JE, Deykin D, Poller L, Bussey H. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1995;108:(suppl):231S-46S. 2. Butchart EG, Lewis PA, Grunkemeier GL, Kulatilake N, Breckenridge IM. Low risk of thrombosis and serious embolic events despite low-intensity anticoagulation: experience with 1,004 Medtronic Hall valves. Circulation 1988;78(Suppl):I6677. 3. Meschengieser SS, Fondevilla CG, Frontroth J, Santarelli MT, Lazzari MA. Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical prosthetic heart valves. J Thorac Cardiovasc Surg 1997;113:910-6.

Responses of internal mammary artery to local administration off acetylcholine

Abstract In conclusion, the well-preserved endothelial function of the IMA compared with that of the coronary artery might contribute to the higher patency rate among arterial grafts.

Diagnostic dilemma of mitral annulus calcification imitating intracardiac tumor

Transthoracic echocardiography in a 76-year-old woman showed a round mass located in the posterior periannular region of the mitral valve and the valve itself, with high echo density and no clear internal echolucent area, resembling an intracardiac tumor (Figure 1). Transesophageal echocardiography indicated severe mitral valve regurgitation and moderate stenosis. Coronary angiography showed no coronary artery disease and no staining of the mass by the contrast medium. Computed tomography of the heart demonstrated a heavily calcified mass in the region of Asian Cardiovascular & Thoracic Annals 20(1) 89–90 The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492311421564 aan.sagepub.com