藤田 英雄

[Background] In the clinical settings, quantity as well as quality of daily duties is increasingly demanded, where human resources are hardly satisfied in Japan. [Objective] To solve this imbalance problem, we specifically sought a practical solution in the catheter operation room using Android mobile tablets. [Methods] It was simply needed to install VNC software in PC terminals of our specially designed reporting system for adding to the new function of remote operation. [Results] Our experimental operations show that this enhancement achieved by Android and VNC remarkably decreased the amount of physical movement of co-medical members, resulting in increased attention to assisting operation. [Conclusion] Thus we propose that our solution is easy and cost-effective to improve efficiency in the medical facilities.

Objectives: A strong degree of co-existence between coronary artery disease (CAD) and abdominal aortic aneurysm (AAA) is widely acknowledged, however, it remains to be elucidated whether the existence of CAD is associated with an accelerated expansion rate of AAA. Also, the relationship between preoperative CAD and postoperative major adverse cardiovascular events (MACE) has not been examined in Japanese patients. The aim of this study was to investigate the deleterious effects of CAD on the progression of AAA and the onset of postoperative MACE after elective AAA repair. Methods and results: A retrospective cohort study of 665 consecutive Japanese patients who underwent elective surgical repair for infrarenal AAA at 2 high-volume Tokyo hospitals from 2003 through 2010 was performed. Preoperative CAD was shown to be a significant determinant of postoperative MACE (HR 2.29; 95% CI, 1.12-4.66; p = 0.02). In the analysis of 510 patients for whom there were at least 2 follow-up CT scans of the size of their AAA before repair, the existence of CAD was shown to be inversely associated with the accelerated expansion rate of AAA. Conclusion: This study on the patients undergone elective repair for infrarenal AAA identified an inverse association between the existence of CAD and progression of AAA as well as the significant impact of preoperative CAD on the occurrence of postoperative MACE after elective AAA repair. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Background: The ratio of early diastolic transmitral flow velocity (E) to tissue Doppler (TD) mitral annular early diastolic velocity (E/E'VEL-TD) has been widely used for the noninvasive assessment of LV diastolic filling pressures. However, it has been reported that E/E'VEL-TD is not accurate particularly when being applied to patients with advanced heart failure. Methods: Fifty-six ICU patients with decompensated heart failure underwent simultaneous echocardiography and PCWP measurements. Patients with elevated PCWP (n = 41) were compared with patients normal PCWP (n = 15) as well as age-matched healthy controls (n = 32). In the apical 4-chamber view, the ratio of E to speckle tracking (ST) mitral annular velocity (E/E'VEL-ST) and early diastolic global LV longitudinal strain rate (E/E'SR-ST) were evaluated as new surrogate markers of elevated PCWP. Results: Correlations with PCWP were observed for speckle tracking derived E/E'VEL-ST (r = 0.40,P = 0.002) and E/E'SR-ST (r = 0.56, P < 0.001), although the traditional E/E'VEL-TD did not show a significant correlation (r = 0.23, P = 0.082). Compared with controls, patients with elevated PCWP had significant increases in all variables. The best cutoff values and diagnostic accuracies for identifying elevated PCWP were E/E'VEL-TD>12 (Sensitivity/Specificity/area under the ROC curve: 0.58/0.90/0.78), E/E'VEL-ST > 14 (0.60/0.85/0.80), and E/E'SR-ST > 93 (0.80/0.88/0.89). Conclusion: Speckle tracking derived E/E'SR-ST may be a robust surrogate marker of elevated LV filling pressure. In ICU patients, E/E'SR-ST showed better correlation with PCWP and higher diagnostic accuracy than the tissue Doppler approach. (Echocardiography 2012;29:404-410)

Background: Macrocytosis, as a qualitative abnormality of erythrocytes, has not drawn attention as a prognostic indicator after PCI, while anemia, as a quantitative abnormality of erythrocytes, has been recognized as a predictor of adverse outcomes. The aim of this study was to perform prognostic risk stratification of patients after PCI based on the presence or absence of macrocytosis. Methods: The clinical records of 941 consecutive patients who underwent PCI at a single institution were retrospectively reviewed. The prognostic implication of macrocytosis was evaluated by univariate and multivariate Cox's proportional hazard regression analysis. Results: There were 130 (13.8%) patients with macrocytosis. A significantly higher all-cause and cardiac mortality, as well as incidence of composite adverse events were observed in the Macrocytic group. Kaplan-Meier analysis also showed a significantly poorer overall survival in patients with macrocytosis. Even after exclusion of anemic patients, this tendency was still observed. Furthermore, macrocytosis was significantly and independently associated with adverse outcomes after PCI (aHR of cardiac death: 3.45, 95%CI: 1.22-9.80, P = 0.019). Interestingly, fewer patients with macrocytosis were prescribed statins compared with those without it (33.8% vs. 47.1%, P = 0.005). Conclusions: The results of the study indicate that measuring mean corpuscular volume (MCV) as a qualitative index of erythrocytes might be helpful for a prognostic risk stratification of patients subjected to PCI. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

This paper proposes a novel telemedicine system for type 2 diabetes patients. The proposed system supports the patient self-management via a set of telemedicine devices, consisting of health sensors and a smart phone. The proposed system covers not only the sensor data but also the diet (food) and exercise data. To capture the food information, we also developed the voice recognition module focusing on the food names. The basic feasibility of the system is practically demonstrated in the preliminary experiment. Copyright © 2012, Association for the Advancement of Artificial Intelligence. All rights reserved.

The 'evidence' in evidence-based medicine (EBM) is often limited to knowledge obtained from randomized controlled clinical trials (RCT). Most RCTs, however, have strict enrollment criteria which make patient background characteristics and clinical histories significantly different from those encountered in actual practice. Thus it is important to accumulate and analyze data obtained in daily practice to gain insight into a larger clinical picture. Recent developments in information technology and its lowered cost have enabled us to record clinical activity in much greater detail at a lower cost. These factors prompted us to design and develop a coronary angiography and intervention reporting system (CAIRS) to collect data and analyze outcomes of coronary intervention. The resulting advanced CAIRS can record detailed data on coronary angiographic and interventional procedures. To date, data on 10,025 cases of coronary angiography, of which 3,574 were interventional, have been collected over a 5.5 year period. There were 4,343 unique patients, 3,115 (71.7%) of which were male. The overall mean age was 67.0 +/- 11.5. The mean age of males was 66.3 +/- 11.4 and that of females was 69.0 +/- 11.4. About one-third of the patients never underwent a PCI procedure at our institution. For patients that underwent at least one PCI procedure at our institution, the prescription rate of stain increased from 50.8% in 2005 to 80.3% in 2011, while those of nitrate and ticlopidine decreased from 36.7% and 90.8% in 2005 to 21.3% and 0.8% in 2011, respectively. We have also implemented the same system at another institution and compared the data on stem usage between the two institutions, which revealed vastly different stent usage profiles. In conclusion, we have successfully developed and implemented an advanced coronary angiography and intervention reporting system which we call CAIRS. Implementing the same system at multiple institutions and analyzing data collected from several institutions will provide detailed and timely insight into the 'real world' of coronary angiography and interventional procedures and their outcome. (Int Heart J 2012; 53: 35-42)

症例は39歳女性。他院で乏突起膠星細胞腫瘍に対し開頭摘出術を施行後15日目に急性前壁心筋梗塞を発症し当院へ救急搬送された。緊急冠動脈造影にて左前下行枝(LAD)中間部に99%狭窄を認め、引き続き同病変へ経皮的冠動脈形成術を施行した。血管内エコーにて病変は冠動脈解離を伴っていることが明らかとなり、解離腔のエントリー閉鎖を目的にステントを留置した。しかし、ステント近位部に解離が拡大しLADの完全閉塞に陥ったため、さらなるインターベンションによる解離の拡大を懸念し手技を終了した。1週間後の冠動脈CTでは依然完全閉塞であったが、3ヵ月後には解離腔は狭小化し内腔は開存していた。特発性冠動脈解離は極めてまれな疾患であるが、若年女性の急性冠症候群の原因として念頭に置くべきである。(著者抄録)

Procedure-related coronary dissection is associated with an increased risk of major adverse cardiovascular events after percutaneous coronary intervention (PCI). In most patients with such an iatrogenic complication, further PCI or bypass surgery aimed at complete revascularization is performed. Moreover, conventional coronary angiography has been used as a standard modality in the follow-up of such patients. The present report describes a 70 year old female patient who was complicated by catheter-related extensive coronary dissection in the right coronary artery (RCA) when treated for an acute myocardial infarction. Although RCA flow was insufficient, we decided against revascularization and followed her medically without additional revascularization procedures. Her clinical course had been uneventful for 4 years. However, symptoms of effort angina developed and re-examinations were performed at approximately 5 years after the myocardial infarction. Although conventional coronary angiography failed to show the culprit lesion responsible for the angina symptoms, the superior spatial resolution of the coronary CT angiography clearly identified significant progression of the stenotic lesion in the true lumen of the dissected RCA. Thus, coronary CT angiography might be considered as a possible first-line follow-up modality in patients with procedure-related coronary dissection. (Int Heart J 2011; 52: 240-242)

Background: In patients with diabetic retinopathy (DR), vitreous hemorrhage (VH) is a common complication that threatens visual acuity and hence, quality of life. A considerable number of DR patients at risk of VH require coronary revascularization, but little is known about the prevalence of VH after coronary revascularization. Methods and Results: This study investigated 151 patients with DR who were followed up by ophthalmologists between April 2004 and September 2008, and underwent coronary revascularization (coronary artery bypass surgery n=36 or drug-eluting stent implantation n=115). At the time of coronary revascularization 56 had non-proliferative DR (NPDR) and 95 had proliferative DR (PDR). During an average follow-up of 531 days after revascularization, VH occurred in 24 (15.9%) patients, 18 (11.9%) of whom experienced VH within 6 months of the procedure. In VH patients, PDR rather than NPDR predominated as the background to VH (21 vs. 3, respectively). The 1-year prevalence of VH was higher in patients with PDR than in those with NPDR (22.0% vs. 1.9%, P=0.0055). Conclusions: VH is not a rare complication following coronary revascularization among patients with DR, especially in those with PDR. Thus, in terms of maintaining quality of life, VH after coronary revascularization needs further attention in these patients. (Circ J 2011; 75: 329-335)

Background: This study examines whether the serum concentration of cystatin C (Cys C) correlates with the severity of coronary artery disease (CAD) and whether it provides additional information on the risk for CAD in patients without chronic kidney disease (CKD) estimated by the creatinine-based glomerular filtration rate (GFR). Methods and Results: The relationship between serum Cys C and the severity of CAD in 526 patients was investigated. Based on GFR, patients were divided into those with and without CKD. The relationship of serum Cys C with the severity of CAD was examined. Serum Cys C was closely correlated with GFR in all cases and in CKD patients, but not in non-CKD patients. The average number of stenotic coronary arteries was significantly higher in the quartiles of higher concentration of Cys C as well as in those of GFR. In 348 patients (66%) the GFR was >= 60ml.min(-1).1.73 m(-2). Those patients with increased Cys C (>0.90 mg/L, 143 patients) had a significantly larger number of stenotic coronary arteries than those patients with normal Cys C. Conclusions: Among patients considered to be at low risk based on the estimated GFR using serum creatinine, those with high concentrations of Cys C could have severe CAD. Besides CKD, Cys C might serve as a marker of CAD severity. (Circ J 2010; 74: 2441-2447)

症例は79歳男性。72歳時3枝病変を認めるも保存的加療となった。2009年労作時胸痛が出現、冠動脈病変の進行と心機能低下を認め、前下行枝に対しバイパス術施行。術直後から持続性/非持続性心室頻拍(VT)が頻発、回旋枝へPCI施行後、Overdrive pacingとニフェカラント/ランジオロールの持続投与にても消失せず。薬物抵抗性のVTと判断、LVマッピング下に電気的焼灼術を2回施行。しかし敗血症を機にVT stormに至り、挿管管理下に再度pacingとニフェカラント/ランジオロール持続点滴を併用し、ICD植込み術を施行。アミオダロン+カルベジロール内服開始したが、点滴薬漸減するとVT出現するためソタロールを追加。以後VT消失したため前医に転院となった。虚血性心筋症の血行再建に伴う難治性VTに対し、アブレーションに加えアミオダロン/ソタロールの併用が奏効した症例を経験したので報告する。(著者抄録)

Background Clinical evidence suggests that intracoronary thrombus formation is associated with a high incidence of late restenosis after successful coronary intervention in patients with myocardial infarction (MI). However, little is known about the mechanism by which intracoronary thrombi play pathological roles. Methods and Results We analysed the cellular constituents of 108 thrombi aspirated from coronary lesions with a thrombectomy device in 62 patients who underwent emergent coronary intervention for the treatment of acute (<24 h) or recent (24-72 h) ST-segment elevation MI (44 men, 18 women, aged 68.0619.3 years). Immunohistological analysis of aspirated thrombotic materials revealed that the content of platelets, as determined by immunostaining for CD42a, had a negative correlation with the time after the onset of chest pain (correlation coefficient -0.683, p<0.01). Immunofluorescent staining for CD34 and breast cancer-resistant protein-1 (bcrp-1) detected primitive cells in intracoronary thrombi. Furthermore, the ratio of CD34-positive cells in intracoronary thrombi had a significant positive correlation with restenosis at follow-up coronary angiography (correlation coefficient 0.76, p=0.01). Conclusions The findings of this study indicate that the early accumulation of primitive cells in platelet aggregates may play a role in neointimal growth after successful coronary intervention in patients with acute coronary syndrome.

Background: The relationship between renal dysfunction and the severity of coronary artery disease (CAD) was examined. Methods and Results: The severity of CAD in 572 patients was graded according to the number of stenotic coronary arteries, and the estimated glomerular filtration rate (eGFR) was monitored for 3 years. Patients were stratified into 3 eGFR groups: normal (>75 ml.min(-1).1.73 m(-2)), mild reduction (60-75) and chronic kidney disease (CKD: <60). There were 161 patients in the CKD group. The average number of stenotic coronary arteries was larger in the CKD group than in the other groups (normal vs mild reduction vs CKD =1.35 +/- 0.07 (SE) vs 1.22 +/- 0.08 vs 1.69 +/- 0.08 vessel disease (VD), P<0.001). During the 3-year follow-up, the renal function of 13.8% of the patients worsened. Those who showed more deterioration of eGFR had more severe CAD than those who did not (1.20 +/- 0.06 vs 1.61 +/- 0.06 VD, P<0.001). Multivariate analysis revealed that the severity of CAD was independently and significantly associated with the deterioration of eGFR. Conclusions: Patients with CKD had more severe CAD, which may explain the high rate of cardiovascular events in these patients. Moreover, the prognosis of renal function was poor in patients with severe CAD, and CAD was found to be an independent risk factor for worsening of renal dysfunction. (Circ J 2010; 74: 786-791)

Background: The optimal revascularization strategy for unprotected left main coronary artery (ULMCA) disease in the era of drug-eluting stents (DES) has become more controversial between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). Methods and Results: Since April 2004, 89 patients underwent CABG, including 82 (92.1%) off-pump procedures and 63 patients underwent PCI with DES for ULMCA disease. Major adverse cardiac and cerebrovascular events (MACCE: death, acute myocardial infarction, stroke and repeat revascularization) and hospitalization costs were compared. Patients in the CABG group were likely to have multivessel disease and higher euroSCORE. The mean follow-up was 2.2±1.1 years in the CABG group and 1.6±0.8 years in the DES group (P&lt 0.001). The overall survival rate did not differ (P=0.288) between the groups (CABG: 93.4% and DES: 91.9% at 2 years). The MACCE-free survival rate was better (P=0.033) in the CABG group (CABG: 82.2% and DES: 62.6% at 2 years). Total hospitalization costs were lower (P=0.013) in the CABG group (median: 3,225 thousand yen) than in the DES group (median: 4,192 thousand yen). Conclusions: CABG might be associated with cost-effectiveness and could be still the first revascularization strategy for ULMCA disease.

今回われわれは, 両側腎動脈狭窄症 (RAS) による再発性の心不全と急性腎不全, あるいは治療抵抗性高血圧をきたした2症例を経験した.<BR>症例1: 72歳, 女性. 僧帽弁置換術後の低左心機能症例で心不全入院を繰り返していた. 今回心不全加療中に急性腎前性腎不全を発症して血液透析導入となり, その後両側RASの存在が判明した. 両腎とも8.5cm大と軽度萎縮していたが, 透析から離脱困難だったこともあり腎機能と血行動態の改善を目指してステント留置による経皮的腎動脈形成術 (PTRA) を施行した. 術直後より著明な腎機能の改善が得られ, 透析から離脱できるとともに慢性期の心不全の管理も容易となった.<BR>症例2: 63歳, 女性. 冠動脈3枝病変に対するバイパス術直前に, 両側RASによる難治性高血圧が顕在化した. 腎動脈エコー上, 腎硬化症の指標である腎抵抗係数は両側とも1.0と著明高値であったが, 薬物治療抵抗性の高血圧であったため両側RASに対してPTRA (ステント留置によるPTRA) を施行した. 術後血圧は著明に改善して降圧薬の減量が可能となり, その後冠動脈バイパス術が無事に施行された. 以上の2症例はいずれも症候性RASに対してPTRAが有効であった. 特異的な臨床徴候に乏しく見逃されることの多いRASとその病態, および適応をめぐっていまだ議論の多いPTRAを考えるうえで示唆に富む2症例であり, ここに報告する.

Objectives: We hypothesized that a large number of patients with diabetic retinopathy who could benefit greatly from early coronary artery bypass grafting would not be identified. Methods: Patients with diabetic retinopathy receiving ophthalmologic care as outpatients in our hospital in whom coronary artery disease was not previously suspected were referred randomly to the diabetic retinocoronary clinic and were asked to participate in diagnostic tests, including an exercise treadmill test and exercise thallium scintigraphy or coronary computed tomography. Patients who had type 1 diabetes mellitus, required hemodialysis, or both were excluded from this study. A definitive diagnosis of coronary artery disease was confirmed by means of coronary angiography. Results: Of 214 patients with diabetic retinopathy, 55 (25.7%) were confirmed as having significant stenotic coronary artery disease. Patients with angiographically confirmed coronary disease were older than those with negative results on diagnostic tests (62.2 +/- 9.8 vs 57.9 +/- 10.3 years, P = .01). Fifteen had 1-vessel disease, 17 had 2-vessel disease, 14 had 3-vessel disease, 1 had left main trunk plus 1-vessel disease, 2 had left main trunk plus 2-vessel disease, and 5 had left main trunk plus 3-vessel disease. Eight patients had left main trunk disease, and 18 patients with non-left main trunk disease had proximal left anterior descending coronary artery (LAD) disease. Forty-two patients showed indications of coronary revascularization (coronary artery bypass grafting in 17 and percutaneous coronary intervention in 25). During the entire follow-up (287.6 +/- 183.2 days) of 39 patients undergoing coronary revascularization, all were alive without myocardial infarction, but 8 experienced vitreous hemorrhage. Conclusions: Approximately 25% of patients with diabetic retinopathy receiving ophthalmologic care as outpatients have a significant stenotic coronary artery disease. Of the total diabetic population, a large number of patients with diabetic retinopathy who show strong indications for early coronary artery bypass grafting might well go unrecognized. (J Thorac Cardiovasc Surg 2010; 139: 92-7)

Background: Patients with diabetic retinopathy (DR) have an increased risk of death from coronary heart disease and myocardial infarction. The purpose of this study was to compare the outcomes of revascularization strategies (sirolimus-eluting stent [SES] and coronary artery bypass surgery [CABG]) in patients with DR according to the stage of retinopathy: non-proliferative retinopathy (NPDR) and proliferative retinopathy (PDR). Methods: From April 2004 until February 2007, 627 patients including 51 NPDR and 62 PDR patients underwent SES implantation. For each retinopathy group, a historical comparison group at the same stages of retinopathy undergoing CABG was selected. Cardiac events were defined as a composite of cardiac death, myocardial infarction, and repeat revascularization. Results: The average follow-up from the time of the initial revascularization was 27.7 +/- 8.5 months for NPDR-SES patients, 69.6 +/- 36.6 months for NPDR-CABG patients, 26.4 +/- 9.7 months for PDR-SES patients, and 68.3 +/- 44.2 months for PDR-CABG patients; and Kaplan-Meier estimates of the percentages of events at 24 months were 47.0%, 22.8%, 28.5%, and 26.0%. Kaplan-Meier curves for cardiac events differed significantly between the SES group and the CABG group in NPDR patients (p = 0.04), whereas the curves did not differ significantly between the two groups of PDR patients. The adjusted hazard ratio of SES implantation for cardiac events in the entire group of DR patients was 1.75 (95% confidence interval [CI] 1.02-3.00, p = 0.04). Conclusions: SES implantation is not a suitable method of revascularization in DR patients, especially in NPDR patients. CABG may become the first-choice revascularization technique for these patients. (c) 2008 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.

Background. We compared the 1-year outcome of coronary revascularization with sirolimus-eluting stents (SESs) or coronary artery bypass grafting (CABG) for coronary artery disease involving the left anterior descending artery (LAD) in diabetic patients according to their retinal status: no diabetic retinopathy (NDR) and diabetic retinopathy (DR). Methods. Between April 2004 and October 2005, 220 consecutive patients with coronary artery disease involving the LAD underwent implantation of SESs; of these, 25 patients had NDR and 54 had DR. For each group, we included a comparison group of diabetic patients who had undergone CABG and had the same retinal status. Results. During 1 year after revascularization, five cardiac events (cardiac death, myocardial infarction, and repeat revascularization) were noted in NDR-SES patients, four in NDR-CABG, 24 in DR-SES, and eight in DR-CABG patients. Most cardiac events were repeat revascularizations. Kaplan-Meier estimates of the incidence of cardiac events at 1 year were 21.1%, 11.4%, 44.0%, and 14.0%, respectively. Kaplan-Meier curves for cardiac events in SES patients were different from those of CABG patients for the DR group (p = 0.003), but not NDR groups. After adjustments for the potential confounders, the hazard ratio of cardiac events in DR-SES patients was 2.8 (95% confidence interval, 1.1 to 6.9; p = 0.02). Conclusions. Compared with SES implantation, CABG is more suitable for revascularization in patients with coronary artery disease involving the LAD and DR.

OBJECTIVE - The expansion of adipose tissue mass seen in obesity involves both hyperplasia and hypertrophy of adipocytes. However, little is known about how adipocytes, adipocyte precursors, blood vessels, and stromal cells interact with one another to achieve adipogenesis. RESEARCH DESIGN AND METHODS - We have developed a confocal microscopy-based method of three-dimensional visualization of intact living adipose tissue that enabled us to simultaneously evaluate angiogenesis and adipogenesis in db/db mice. RESULTS - We found that adipocyte differentiation takes place within cell clusters (which we designated adipogenic/angiogenic cell clusters) that contain multiple cell types, including endothelial cells and stromal cells that express CD34 and CD68 and bind lectin. There were close spatial and temporal interrelationships between blood vessel formation and adipogenesis, and the sprouting of new blood vessels from preexisting vasculature was coupled to adipocyte differentiation. CD34 + CD68+ lectin-binding cells could clearly be distinguished from CD34- CD68+ macrophages, which were scattered in the stroma and did not bind lectin. Adipogenic/angiogenic cell clusters can morphologically and immunohistochemically be distinguished from crownlike structures frequently seen in the late stages of adipose tissue obesity. Administration of anti-vascular endothelial growth factor (VEGF) antibodies inhibited not only angiogenesis but also the formation of adipogenic/angiogenic cell clusters, indicating that the coupling of adipogenesis and angiogenesis is essential for differentiation of adipocytes in obesity and that VEGF is a key mediator of that process. CONCLUSIONS - Living tissue imaging techniques provide novel evidence of the dynamic interactions between differentiating adipocytes, stromal cells, and angiogenesis in living obese adipose tissue. © 2007 by the American Diabetes Association.

Introduction: The prognostic value of identifying the retinal status of diabetic patients undergoing coronary implantation of drug-eluting stents is unknown. Methods: We evaluated the outcomes of 318 consecutive patients undergoing implantation of sirolimus-eluting stents for coronary artery disease. Patients were divided into 5 groups according to the diabetic and retinal status: diabetic patients without retinopathy (43 patients) diabetic patients with nonproliferative retinopathy (34) diabetic patients with proliferative retinopathy (37) diabetic patients with unknown retinal status (30) and nondiabetic patients (174). Results: During a mean follow-up of 385 days, 64 patients had target-vessel failure (defined as a composite of death from cardiac causes, myocardial infarction, and target-vessel revascularization). At 1 year, Kaplan-Meier estimates of the rate of target-vessel failure were 15.3% for diabetic patients without retinopathy, 56.6% for those with nonproliferative retinopathy, 17.3% for those with proliferative retinopathy, 19.0% for those with unknown retinal status, and 16.0% for nondiabetic patients. After adjustment for the potential confounders and differences between groups, the relation of nonproliferative retinopathy to target-vessel failure remained significant. In an analysis in which diabetic patients without retinopathy were used as the reference group, the hazard ratios for target-vessel failure were 3.9 for those with nonproliferative retinopathy, 1.3 for those with proliferative retinopathy, 1.1 for those with unknown retinal status, and 1.4 for nondiabetic patients (P for trend = 0.015). Conclusions: As compared with diabetic patients without retinopathy, those with nonproliferative retinopathy have an increased risk for target-vessel failure after coronary implantation of sirolimus-eluting stents. © 2007, the Authors.

Objective: To elucidate the interdependence between the mechanical state of the myocardium and its electrical activity, previous studies have been performed at the cellular level. However, the information to date has been limited by the technical difficulties associated with stretching single myocytes. Methods: We solved this problem by combining two techniques, namely a carbon fiber technique for stretching rat myocytes with wide ranges of amplitude and speed, and ratiometric measurement of a fluorescent indicator (di8-ANEPPS) for evaluating the membrane potential in the non-contact mode. Results: During systole, stretching caused depolarization that prolonged the action potential duration without affecting the peak amplitude, but the effect was only significant in the late phase. Application of a stretch to quiescent myocytes depolarized the membrane potential in amplitude- and speed-dependent manners, but the response was suppressed by cytochalasin D treatment, suggesting participation of the cytoskeleton in the mechanotransduction mechanism. Finally, ion replacement experiments revealed that although Na+ was the dominant charge carrier for large amplitude stretches, Ca2 + permeation was involved in small amplitude stretches, suggesting amplitude-dependent ion selectivity. Conclusions: Application of axial stretching to rat ventricular myocytes changed the membrane potential in phase-, amplitude- and speed-dependent manners. Amplitude may also modulate the ion selectivity of stretch-activated channels. © 2006 European Society of Cardiology.

Nowadays, evidence-based medicine has entered the mainstream of clinical judgement and the human genome has been completely decoded. Even the concept of individually designed medicine, that is, tailor-made medicine, is now being discussed. Due to their complexity, however, management methods for clinical information have yet to be established. We have conducted a study on a universal technique which enables one to select or produce by employing information processing technology clinical findings from various clinical information generated in vast quantity in day-to-day clinical practice, and to share such information and/or the results of analysis between two or more institutions. In this study, clinically useful findings have been successfully obtained by systematizing actual clinical information and genomic information obtained by an appropriate collecting and management method of information with due consideration to ethical issues. We report here these medical achievements as well as technological ones which will play a role in propagating such medical achievements. Copyright © 2004 by the Japanese Heart Journal.

Objective: To investigate the functional role of myosin light chain (MLC) isoforms in cardiac muscles, we examined the motor function of two different myosins the structure of which differed only in the MLC. Methods: We purified myosin from atria (A-myosin) and ventricles (V-myosin) of young rats, which contained atrial-type and ventricular-type MLCs, respectively, but having identical α-heavy chain isoform. Actin filament velocity (Vel) was determined in the in vitro motility assay. Average force of myosin molecules (F) was estimated and single events of actin-myosin interaction were recorded with the laser trap technique. Results: Vel was slightly higher in A-myosin than in V-myosin, while actin-activated ATPase activity was not different. F, determined from force versus actin filament length relation, was ∼60% higher in V-myosin (3.3 vs. 2.1 pN/μm). The mean duration of isometric force events was longer in V-myosin than in A-myosin (323±13 vs. 294±30 ms, p&lt 0.05), while the amplitudes of unitary displacement and force of a single myosin molecule did not differ between them. Conclusion: The MLC isoform can be a determinant of force-generating ability of cardiac myosin by modulating crossbridge kinetics without affecting the catalytic activity. © 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

To facilitate cardiac muscle research, we developed a novel method by which the force and length of a single ventricular myocyte can be recorded with a pair of carbon graphite fibers attached firmly to both ends. One fiber was stiff, whereas the other fiber was compliant to allow the recording of force and shortening during twitch contractions. The image of the compliant carbon fiber was projected onto a pair of photodiodes, and their output was fed to a piezoelectric transducer after variable amplifications to alter the effective compliance of the carbon fiber. Thus contraction of the myocyte was induced under virtually isometric conditions as well as under auxotonic conditions. We obtained a bell-shaped relation between the compliance under an auxotonic load and the work output of the myocyte, which was directly related to myocyte performance in the heart. Because it is easy to attach myocytes to the experimental apparatus, the present method would allow us to study cardiac muscle mechanics at the cellular and molecular levels.

Background: Conventional vasodilators increase ventilation-perfusion mismatch and do not improve gas exchange even though they reduce pulmonary hypertension. However, the effects of nitric oxide inhalation on ventilatory and gas exchange values in patients with congestive heart failure are not known. Objective: To investigate the effect of nitric oxide inhalation on gas exchange in patients with congestive heart failure, Design: Randomized, controlled trial. Setting: University hospital. Patients: 16 patients with congestive heart failure (New York Heart Association class II or III). Interventions: Patients inhaled nitric oxide gas at graded concentrations (n = 8) or were given intravenous isosorbide dinitrate, 2.5 mg (n = 8). Measurements: Hemodynamic and ventilatory variables and blood gases were measured 5 minutes after inhalation of different doses of nitric oxide and 10 minutes after administration of isosorbide dinitrate. Results: Nitric oxide inhalation reduced the mean pulmonary arterial pressure in a dose-dependent manner without altering the mean arterial pressure or cardiac output. At a dose of 40 parts per million, nitric oxide inhalation increased PaO2 (change from baseline, 12.0 mm Hg [95% Cl, 2.3 to 21.7 mm Hg] P = 0.014) and decreased the alveolar-arterial difference in partial pressure of oxygen (change, -8.6 mm Hg [Cl, -16.8 to -0.4 mm Hg] P = 0.038) and the ventilatory equivalent for carbon dioxide output (change, -6.7 [Cl, -10.3 to -3.1] P &lt 0.001). Although isosorbide dinitrate similarly decreased pulmonary arterial pressure, it did not alter gas exchange or ventilatory variables. Conclusions: Because nitric oxide inhalation improved gas exchange, it may be used as a supportive therapy when other conventional vasodilators worsen gas exchange.

To provide information on the mechanism of cardiac adaptation at the molecular level, we compared the unitary displacements and forces between the 2 rat cardiac myosin isoforms, V1 and V3. A fluorescently labeled actin filament, with a polystyrene bead attached, was caught by an optical trap and brought close to a glass surface sparsely coated with either of the 2 isoforms, so that the actin-myosin interaction took place in the presence of a low concentration of ATP (0.5 μmol/L). Discrete displacement events were recorded with a low trap stiffness (0.03 to 0.06 pN/nm). Frequency distribution of the amplitude of the displacements consisted of 2 gaussian curves with peaks at 9 to 10 and 18 to 20 nm for both V1 and V3, suggesting that 9 to 10 nm is the unitary displacement for both isoforms. The duration of the displacement events was longer for V3 than for V1. On the other hand, discrete force transients were recorded with a high trap stiffness (2.1 pN/nm), and their amplitude showed a broad distribution with mean values between 1 and 2 pN for V1 and V3. The durations of the force transients were also longer for V3 than for V1. These results indicate that both the unitary displacements and forces are similar in amplitude but different in duration between the 2 cardiac myosin isoforms, being consistent with the reports that the tension cost is higher in muscles consisting mainly of V1 than those consisting mainly of V3.

To clarify the physiological significance of myosin isoform redistribution in cardiac adaptation process, we compared the kinetic property of the two cardiac myosin isoforms using in vitro motility assay techniques. Cardiac myosin isoforms V1 and V3 were obtained from ventricular muscle of young rats and hypothyroid rats respectively. On each of these myosin isoforms fixed on a glass coverslip, fluorescently labeled actin filaments were made to slide in the presence of ATP. To measure the force generated by actomyosin interaction, a small latex bead was attached to the barbed end of an actin filament and the bead was captured by the laser optical trap installed in a microscope. The force was determined from the distance between the bead and the trap positions under either auxotonic or isometric conditions. The time-averaged force generated by multiple cross- bridges did not differ significantly between the two isoforms. On the other hand, the unitary force measurement revealed the same level of amplitude but a longer duration for V3 isoform. The same level of time-averaged force is in agreement with not only our previous finding but the results of maximum force measurement in muscle preparations. The difference in kinetic characteristics of the two isoforms could account for the difference in economy of force development and the basis for cardiac adaptation mechanism.

Familial hypertrophic cardiomyopathy (FHC) is caused by missence mutations in β-myosin heavy chain or other various sarcomeric proteins. To elucidate the functional impact of FHC mutations in myosin heavy chain, we generated Dictyostelium discoideum myosin II mutants equivalent to human FHC mutations by site-directed mutagenesis, and characterized their molecular- basis motor function. The current mutants, i.e. R397Q, F506C, G575R, A699R, K703Q and K703W are equivalent to R403Q, F513C, G584R, G716R, R719Q and R719W FHC mutants respectively. We measured the molecular-basis force and the sliding velocity generated by these myosin mutants. The measurement revealed that the A699R, K703Q and K703W myosins exhibited the lowest level of force with their preserved actin-activated MgATPase activity. F506C mutant showed the least impairment of the motile and enzymatic activities. The motor function of R397Q and G575R myosins were classified as intermediate. These results suggest that ELC binding domain might be important for force production.

Recent studies have revealed that familial hypertrophic cardiomyopathy (FHC) is caused by missence mutations in myosin heavy chain or other sarcomeric proteins. To investigate the functional impact of FHC mutations in myosin heavy chain, mutants of Dictyostelium discoideum myosin II equivalent to human FHC mutations were generated by site-directed mutagenesis, and their motor function was characterized at the molecular level. These mutants, i.e., R397Q, F506C, G575R, A699R, K703Q, and K703W are respectively equivalent to R403Q, F513C, G584R, G716R, R719Q, and R719W FHC mutants. We measured the force generated by these myosin mutants as well as the sliding velocity and the actin-activated ATPase activity. These measurements showed that the A699R, K703Q, and K703W myosins exhibited unexpectedly weak affinity with actin and the lowest level of force, though their ATPase activity remained rather high. F506C mutant which has been reported to have benign prognosis exhibited the least impairment of the motile and enzymatic activities. The motor functions of R397Q and G575R myosins were classified as intermediate. These results suggest that the force level of mutant myosin molecule may be one of the key factors for pathogenesis which affect the prognosis of human FHC.

Distinct crossbridge kinetics among cardiac myosin isoforms have been proposed as the basis of differences in energetic characteristics. However, direct evidence for this hypothesis is lacking because of experimental difficulty. As a preliminary approach to this problem, we applied an in-vitro force measurement technique to directly observe force impulse generated by a single cardiac myosin molecule. The force measurement system was constructed with an inverted microscope coupled with a laser optical trap. With the feedback of the position signal to the driving circuit for a galvanomirror that steers the laser beam, trap stiffness was increased thus, isometric force measurement was made possible. We measured the force generated by the cardiac myosin V3 isoform purified from hypothyroid rat ventricular muscle. With very low myosin density and low adenosine triphosphate (ATP) concentration of the assay buffer, we successfully observed a single force impulse similar in shape to that of skeletal muscle myosin. With this approach, we will be able to gain a clear view of the molecular basis of cardiac mechanoenergetics.

MCI-154 (6-[4-(4′-pyridylamino)phenyl]-4,5-dihydro-3(2H)pyridazinone hydrochloride trihydrate) is a potent novel cardiotonic agent whose positive inotropism is shown to be mainly based on an increase in Ca2+ sensitivity of the contractile apparatus. To elucidate the exact mechanism through which this drug acts, we investigated the movement of the reconstituted thin filament on a myosin layer in vitro. Cardiac thin filaments were reconstituted from actin and tropomyosin-troponin complex purified from rat cardiac acetone powder separately. Double staining of the filament showed that tropomyosin-troponin complex was integrated along actin filament homogeneously. Thin filaments thus prepared were fluorescently labeled and made to slide on rat cardiac myosin fixed on a glass coverslip while varying the [Ca2+] of the medium (control, pH 7.2 at 25°C). When [Ca2+] was low, the filaments showed only brownian motion. However, above a certain level of [Ca2+] (the threshold [Ca2+]), the filaments started to slide, and the velocity increased, reaching the maximum velocity within a very narrow range of [Ca2+]. The regulation was completely abolished by using simple actin filaments without tropomyosin-troponin complex, demonstrating that the regulatory proteins are responsible for this Ca2+ regulation of the movement of the reconstituted thin filament. Under the control condition, addition of MCI-154 shifted the threshold [Ca2+] to a lower level (sensitization) in a concentration-related manner. And 10-4 mol/L of MCI-154 reversed the desensitization effect induced by either acidosis (pH 6.8), low temperature (15°C), or the addition of inorganic phosphate (10 mmol/L). However, the maximum sliding velocity was not affected by the drug under any condition. In conclusion, MCI-154 directly sensitized the contractile apparatus under not only physiological but also pathophysiological conditions. This in vitro motility assay technique using reconstituted thin filaments is a useful tool for studying the mechanism of action of Ca2+ sensitizers.