Yohko Uchikoba

Hemodynamic factors of thrombus formation in coronary aneurysms associated with Kawasaki disease

Abstract Background: We studied the mechanism of thrombus formation in coronary aneurysms based on rheological findings.

Cardiomyocyte regeneration from circulating bone marrow cells in mice.

We investigated the role of circulating bone marrow cells (BMC) in cardiomyocyte regeneration. BMC, isolated from transgenic mice expressing enhanced green fluorescent protein (GFP), were transplanted into lethally irradiated C57BL6 mice. Five weeks after bone marrow transplantation (BMT), flow cytometric analysis for GFP-positive cells confirmed reconstitution of transplanted bone marrow. Bone marrow transplant mice subsequently underwent left coronary artery ligation (myocardial infarction) or sham-operation, and were killed at 1 mo or 3 mo after operation. Infarct size was similar in bone marrow transplant mice at 1 mo (47.1 ± 5.9%) and at 3 mo (45.3 ± 7.8%), and echocardiography at 2 and 8 wk revealed decreasing left ventricular function. In infarcted heart, GFP-positive cells that expressed desmin and troponin T-C were identified by confocal microscopy. GFP and troponin T-C double-positive cells were predominantly in the peri-infarcted region (1 mo, 365 ± 45 cells/50 sections; 3 mo: 458 ± 100 cells/50 sections; p < 0.05 versus noninfarct, infarct, and sham-operated regions). Furthermore, BMC mobilization and differentiation into cardiomyocytes was found to be complete within 1 mo after myocardial infarction. These results demonstrate that circulating BMC undergo mobilization and differentiation in cardiac cells after myocardial infarction. Future studies are required to determine the molecular signaling mechanisms responsible for this phenomenon.

Possible Synergic Effect of Angiotensin-I Converting Enzyme Gene Insertion/Deletion Polymorphism and Angiotensin-II Type-1 Receptor 1166A/C Gene Polymorphism on Ischemic Heart Disease in Patients with Kawasaki Disease

ACE I/D and AT1R 1166A/C polymorphisms are considered to comprise individual risk factors for the development of coronary disease. We sought to demonstrate that the ACE I/D and AT1R 1166A/C polymorphisms affect coronary artery stenosis in patients with Kawasaki disease (KD). We examined 147 healthy controls and 281 Japanese children with KD. The patients were further divided into group N (n = 246, no ischemia) and group I (n = 35, severe coronary artery stenosis with myocardial ischemia), and we studied the genotype of ACE I/D and AT1R 1166A/C polymorphisms. We also examined ACE activity in patients with acute KD. We did not detect any prevalent genotypes of the ACE and AT1R polymorphisms between controls and KD patients. However, the prevalence of the D allele in the ACE polymorphism and of the C allele in the AT1R polymorphism tended to be higher in group I than in group N (odds ratios, 2.00 and 2.32, respectively). In addition, the presence of the D and/or C alleles significantly increased the relative risk of developing myocardial ischemia (odds ratio, 2.71; p = 0.038). During the convalescent phase of KD, ACE activity was increased despite significant attenuation during the acute phase. These results suggested that the renin-angiotensin system is associated with the formation of severe coronary artery stenosis and myocardial ischemia.

Longitudinal evaluation of anthracycline cardiotoxicity by signal‐averaged electrocardiography in children with cancer

Abstract Background : The aim of the present study was to investigate the detection of anthracycline cardiotoxicity by signal‐averaged electrocardiography (SAE) in children with cancer.

Criteria of Myocardial Fractional Flow Reserve and Coronary Flow Ratio for Detection of Myocardial Ischemia in Patients with Kawasaki Disease

Purpose of this study is to estimate the criteria of myocardial fractional flow reserve (FFRmyo) and coronary flow ratio (CFR) for detection of silent myocardial ischemia. 112 patients (1y-15y) were divided into three groups; normal coronary or coronary dilation without stenosis (N) group (n=61), coronary stenosis without ischemia (n-IS) group (n=30), myocardial ischemia (IS) group (n=21) by 2-D echo, and rest and exercised myocardial scintigraphy. FFRmyo is defined as the ratio of maximal achievable flow in myocardium subtended by a stenosed coronary artery to the maximal achievable myocardial flow induced by papaverine. CFR was calculated as a ratio of averaged peak velocity before and after papaverine. FFRmyo and CFR were calculated and compared among three groups. Sensitivity and specificity for detection of myocardial ischemia were calculated by abnormal values of FFRmyo and CFR. Moreover, FFRmyo and CFR tests estimated effectiveness of PTCA and CABG. Results: Criteria for detection of myocardial ischemia were defined the mean±2sds for values of FFRmyo and CFR in N group; <0.75 in FFRmyo and <2.0 in CFR. FFRmyo and CFR in IS group (0.64±0.3#, 1.2±0.4#) were significantly decrease (# p<0.05). Sensitivity and specificity for detection of myocardial ischemia were very high by FFRmyo and CFR. Moreover, FFRmyo and CFR were very useful index for analysis of coronary blood flow velocity and pressure dynamics before and after PTCA and CABG. Conclusions: The values of <0.75 in FFRmyo and <2.0 in CFR can be useful to estimate myocardial ischemia and to evaluate the effectiveness of PTCA and CABG.

ACE I/D and AT1 1166A/C Polymorphism as a Risk Factor for Coronary Artery Stenosis in Kawasaki Disease

Gene polymorphism is considered to become the individual risk factors for the disease developments. We studied the gene polymorphism of Angiotensin Converting Enzyme(ACE) I/D, and Angiotensin II Receptor1 (AT1) 1166A/C polymorphism in Kawasaki disease patients and examined whether these polymorphism associate with coronary artery stenosis. (Subjects and Methods) 195 Kawasaki disease patients were enrolled in this study. Written informed consents were acquired from all patients. We divided the patients into three groups. Group N (n=122); no coronary artery changes, Group C (n=40); coronary artery dilation and/or stenosis without myocardial ischemia, Group S (n=33); coronary artery stenosis with myocardial ischemia. Genomic DNA specific primers were designed and Polymerase Chain Reaction (PCR) were performed. PCR products were separated on the agarose gel directly (ACE I/D polymorphism), or after the sequence specific restriction enzymes digestion (AT1 1166A/C polymorphism). (Results) We could not detect any significant differences in specific genotypes between the groups. However, when we evaluated the patients whether they possess D allele of ACE I/D polymorphism and/or C allele of AT1 1166A/C polymorphism, the patients who own both ACE polymorphism D allele and AT1 polymorphism C allele were significantly higher in Group S (χ2 test; p<0.05). We concluded the Kawasaki disease patients who have both D allele in ACE I/D polymorphism and C allele in AT1 1166A/C polymorphism are exposed to the higher risk for coronary artery stenosis.