Biomedical subjects

Takahisa Kondo

Publications and source records attributed to Takahisa Kondo.

At least 19 recordsLinked to original sources

PubMed2006

Therapeutic angiogenesis using novel vascular endothelial growth factor-E/human placental growth factor chimera genes.

BACKGROUND: Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis but causes adverse side effects such as edema or tissue inflammation. VEGF-E, found in the genome of the Orf virus, specifically binds to VEGF receptor-2 and shows mitotic activity on endothelial cells. Recently, we created two forms of VEGF-E and human placental growth factor (PlGF) chimera genes (VEGF-E chimera #9 and VEGF-E chimera #33), which are humanized genes with VEGF-E function but showing less antigenicity. METHODS AND RESULTS: We examined potential proangiogenic activities of these chimera genes. Four types of expression plasmids (pCDNA3.1-LacZ, phVEGF-A, pVEGF-Echimera#9, and pVEGF-Echimera#33) were administered in a rat model of hindlimb ischemia. Either pVEGF-Echimera#9, pVEGF-Echimera#33, or phVEGF-A significantly increased the ratio of ischemic/normal hindlimb blood-flow compared with the control pCDNA3.1-LacZ treated group (by 1.5-fold, 1.5-fold, and 1.4-fold, respectively, P<0.05). Histochemical staining by alkaline phosphatase also revealed that either pVEGF-Echimera#9, pVEGF-Echimera#33, or phVEGF-A increased the capillary density compared with the pCDNA3.1-LacZ treated group (1.4-fold, 1.5-fold, and 1.5-fold, respectively, P<0.05). Furthermore, immunostaining for anti-ED1 revealed that fewer macrophages had infiltrated in both pVEGF-Echimera#9 and pVEGF-Echimera#33 groups compared with the phVEGF-A group (P<0.05). CONCLUSIONS: Novel VEGF-E/human PlGF chimera genes, pVEGF-Echimera#9, and pVEGF-Echimera#33 significantly stimulated angiogenesis in response to tissue ischemia to an almost identical extent to that induced by phVEGF-A with fewer tissue inflammation responses.

Animals↗

PubMed2006

l-Caldesmon regulates proliferation and migration of vascular smooth muscle cells and inhibits neointimal formation after angioplasty.

OBJECTIVE: Light-type caldesmon (l-CaD) is a potent cytostatic and antiangiogenic protein that regulates cell growth and survival via modulation of the cell shape and cytoskeleton. The aim of this study is to explore the potential value of l-CaD for use as a cytostatic agent to inhibit neointimal formation after angioplasty by suppressing vascular smooth muscle cell (VSMC) growth and migration. METHODS AND RESULTS: We tested the cytostatic function of l-CaD in cultured VSMCs using assays for apoptosis, cell proliferation, and migration, and evaluated the expression pattern of relevant signaling proteins (focal adhesion kinase [FAK] and mitogen-activated protein kinases) in VSMCs. Transfection of adenoviral vector encoding l-CaD (Ad-l-CaD) resulted in progressive loss of actin stress fibers and cell retraction. Enzyme-linked immunosorbent assay demonstrated that Ad-l-CaD transfection increased the apoptosis rate by 75% and reduced BrdU uptake by 49%. Furthermore, transfection of Ad-l-CaD inhibited migration of VSMCs induced by platelet-derived growth factor-BB (PDGF) by 36% (P<0.05). Immunoblotting analysis revealed that l-CaD overexpression reduced PDGF-induced phosphorylation of both FAK and extracellular signal regulated-kinase (ERK). In balloon-injured rat carotid arteries, Ad-l-CaD transfection inhibited neointimal formation by 37% (P<0.05) without delaying re-endothelialization at 14 days. CONCLUSIONS: Overexpression of l-CaD suppressed cell growth and survival in VSMCs and inhibited neointimal formation after experimental angioplasty, partly by regulating the cytoskeletal tension-FAK-ERK axis.

Angioplasty↗

PubMed2006

The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) are known to be involved in vasculogenesis and mobilized after acute myocardial infarction (AMI). To test the hypothesis that the angiogenic function of EPCs affects post-myocardial infarction (MI) myocardial salvage, we evaluated the number and potential differentiation of EPCs and compared these data with clinical parameters 6 months after MI. METHODS AND RESULTS: Consecutive 51 patients (age, 61+/-8 years, mean+/-SD) with primary AMI who were successfully treated with stenting were enrolled. EPC identified as CD45low, CD34+, CD133+, and VEGFR2+ was quantified by a flow cytometry. The potential of EPCs to differentiate into endothelial cells (EPC differentiation) was also confirmed by the upregulation of CD31 and VEGFR2 after 7 days of culture. According to the proportion of EPC fraction, patients were divided into 2 groups (cut-off value=median). Although no difference was seen in myocardial damage shown by mean peak CK leakage and mean area at risk between the differentiated group (n=26) and nondifferentiated group (n=25), the number of attached cell was greater in differentiated group than in the nondifferentiated group (P=0.023). Left ventricular function and ischemic damaged area were assessed by scintigraphic images of (123)I-BMIPP in the acute phase and (99m)Tc-tetrofosmin in the chronic phase. We found that a greater increase in myocardial salvage (P=0.0091), decrease in end-systolic volume (P=0.012), and recovery of ejection fraction (P=0.011) occurred in the group with differentiated EPCs than in the nondifferentiated group. CONCLUSIONS: In patients with primary AMI, the capability of EPCs to differentiate influences the functional improvement and infarct size reduction, indicating that manipulation of EPCs could be a novel therapeutic target to salvage ischemic damage.

Aged↗

PubMed2006

Combination of in vivo angiopoietin-1 gene transfer and autologous bone marrow cell implantation for functional therapeutic angiogenesis.

OBJECTIVE: Autologous bone marrow mononuclear cell (BM-MNC) implantation into ischemic tissues promotes angiogenesis, but a large amount of marrow aspiration is required, which is a major clinical limitation. Angiopoietin-1 (Ang-1) is requisite for vascular maturation during angiogenesis. We examined the impacts of combinatorial Ang-1 gene transfer and low-dose autologous BM-MNC implantation on therapeutic angiogenesis in a rabbit model of hind limb ischemia. METHODS AND RESULTS: Rabbits were divided into 4 groups: phosphate-buffered saline (control), 500 microg Ang-1 plasmid (Ang-1), 1 x 10(6) autologous BM-MNCs (BMC), and Ang-1 plasmid plus BM-MNCs (combination). The Ang-1 group had a greater angiographic score and capillary density compared with the control (P<0.05), but the Ang-1 gene therapy alone did not improve transcutaneous oxygen pressure (TcO2) and skin ulcer score. However, the combination group showed a significant improvement in not only angiographic score and capillary density (P<0.05) but also TcO2 (P<0.05) and skin ulcer score. These efficacies were greater in the combination group compared with the BMC group. CONCLUSIONS: This Ang-1 gene and BM-MNC combination therapy enhances not only quantitative but also qualitative angiogenesis in ischemic tissues. Moreover, the combination therapy will enable a reduction in the amount of BM aspiration required for significant therapeutic angiogenesis.

Angiography↗

PubMed2006

Plasma atrial natriuretic Peptide and brain natriuretic Peptide levels after radiofrequency catheter ablation of atrial fibrillation.

It has been reported that plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels are elevated in patients with atrial fibrillation (AF). The aim of this study was to investigate the change in these patients after pulmonary vein isolation (PVI). In 66 patients with paroxysmal AF (PAF) and without any structural heart disease, plasma ANP and BNP levels were measured before and 3 months after successful PVI. At baseline, in 14 patients, ANP and BNP levels were elevated, and in 52 patients, only BNP levels were elevated. There were no significant relations between the attack frequency or the duration of PAF episodes and ANP or BNP levels. Neither ANP nor BNP level at baseline was a valid predictor of AF recurrence. Even in 31 patients (47%) with recurrent PAF, attacks of PAF were significantly reduced. In 66 patients with elevated ANP and/or BNP levels at baseline, levels were significantly reduced after PVI independent of PAF recurrence (ANP: 69.0+/-23.0 vs 25.0+/-7.7 pg/ml, p<0.0001; BNP: 58.4+/-50.7 vs 22.5+/-27.1 pg/ml, p<0.0001). In 42 patients without AF recurrences, ANP and BNP levels were reduced to within the normal range. In conclusion, in patients with PAF without any structural heart disease, ANP and/or BNP levels were elevated. In those patients, relief of the AF burden by successful PVI significantly reduced elevated plasma ANP and BNP levels.

Atrial Fibrillation↗

PubMed2006

Usefulness of esophageal leads for determining the strategy of pulmonary vein ablation to avoid complications associated with the esophagus.

To avoid fatal complications after extensive pulmonary vein (PV) ablation, it has been proved important to comprehend the anatomic relation between the PVs and the esophagus. In 42 consecutive patients with atrial fibrillation, PV ostial isolation was performed using a basket catheter. The shortest distance and anatomic relation between the esophageal lead and PV ostium, determined by successful PV ostial isolation, was analyzed in biplane fluoroscopic views. In 18 left superior PVs (LSPVs) (43%), 13 left inferior PVs (32%) (LIPVs), and all the right PVs (group A), the shortest distance was > 10 mm in > or = 1 of the biplane fluoroscopic views. In 4 LSPVs (10%) and 2 LIPVs (5%) (group B), the shortest distance was < or = 5 mm in the fluoroscopic views. In the remaining PVs (group C), the esophagus was situated directly behind 10 LSPVs (24%) and 12 LIPVs (29%) (group C1), posteromedial to 1 LSPV (2%) and 9 LIPVs (22%) (group C2), and medial to 9 LSPVs (21%) and 5 LIPVs (12%) (group C3). The risk of esophagus-associated complications with ablation around the left PV ostia was suggested to be high in group B, very low in group A, and relatively low in group C. In group C3, extensive PV ablation might increase the risk of that complication. In conclusion, esophageal leads are useful for determining strategies for PV ablation to avoid esophagus-associated complications, because they enable comprehension of the anatomic relation between the PVs and the esophagus.

Atrial Fibrillation↗

PubMed2006

Incidence, location, and cause of recovery of electrical connections between the pulmonary veins and the left atrium after pulmonary vein isolation.

AIMS: The aim of this study was to reveal the incidence, location, and cause of recovery of the electrical connections (ECs) between the left atrium and the pulmonary veins (PVs) after the segmental ostial PV isolation (PVI). METHODS AND RESULTS: Pulmonary vein mapping and successful PVI were performed using a computerized three-dimensional mapping system (QMS2trade mark) with a basket catheter in 167 PVs in 53 consecutive patients with atrial fibrillation (AF). In 14 patients with recurrent AF after PVI, the same PV mapping and isolation as in the first procedure were performed, and the PV potential maps constructed by QMS2 in two different procedures were compared. Forty-nine recovered ECs were observed in 27 PVs, and all were eliminated by a few local radiofrequency (RF) applications. Thirty-four (69%) of those ECs recovered at the edge of original ECs, and another 15 (31%) recovered at the mid-portion of the continuous broad original ECs. CONCLUSION: Electrical connection recovery occurred most commonly at the edges of original ECs and occasionally at the mid-portion of continuous broad original ECs after PVI probably due to tissue oedema neighbouring the segmental RF lesions. Further RF lesions at the edge of original ECs and linear ablation to the continuous broad ECs may help reduce AF recurrence.

Atrial Fibrillation↗

PubMed2006

Comparison of circulating adiponectin and proinflammatory markers regarding their association with metabolic syndrome in Japanese men.

BACKGROUND: Anti-inflammatory and proinflammatory molecules purportedly play an important role in developing metabolic syndrome (MetS). However, little is known as to the relative importance of these molecules in the association with MetS. METHODS AND RESULTS: We studied 624 middle-aged Japanese men without medical history of cardiovascular disease or cancer and investigated the associations of circulating tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein (CRP), and adiponectin with MetS. We used the respective definitions proposed by the National Cholesterol Education Program Adult Treatment Panel III (ATP-III), the International Diabetes Federation, and the Japanese Society of Internal Medicine. Decreased serum adiponectin was observed in those with any of the ATP-III-MetS components, whereas this was not the case with increased TNF-alpha, IL-6, or CRP. Adiponectin and CRP levels linearly deteriorated with an increasing number of ATP-III-MetS components (trend P<0.001, respectively). Significantly higher CRP and lower adiponectin levels were observed in those who met any MetS criteria, whereas increased TNF-alpha was observed in only those with ATP-III-MetS. Finally, odds ratios (ORs) for MetS prevalence of a 1-SD increase/decrease in log-transformed 4 markers were calculated with multivariate logistic regression analyses. Consequently, decreased adiponectin was associated most strongly with ATP-III-MetS (adiponectin: OR, 1.90 [95% CI, 1.44 to 2.51]; P<0.001; CRP: OR, 1.33 [95% CI, 1.01 to 1.74]; P=0.03; TNF-alpha: OR, 1.25 [95% CI, 0.94 to 1.67]; P=0.12; and IL-6: OR, 0.87 [95% CI, 0.63 to 1.19]; P=0.37). This result was not altered by using the other 2 criteria. CONCLUSIONS: The present results raise the possibility that decreased serum adiponectin might be fundamentally involved in the development of MetS.

Adiponectin↗

PubMed2006

Electrophysiological pulmonary vein antrum isolation with a multielectrode basket catheter is feasible and effective for curing paroxysmal atrial fibrillation: efficacy of minimally extensive pulmonary vein isolation.

BACKGROUND: How extensive should an appropriate pulmonary vein (PV) ablation be is a matter of controversy. OBJECTIVE: The study's aim was to investigate the efficacy of minimally extensive PV ablation for isolating the PV antrum (PVA) with the guidance of electrophysiological parameters. METHODS: Fifty-five consecutive symptomatic paroxysmal atrial fibrillation (PAF) patients underwent PV mapping with a multielectrode basket catheter (MBC). A 31-mm MBC was deployed in 3-4 PVs as proximally as possible without dislodgement, and the longitudinal PV mapping enabled us to recognize single sharp potentials formed by the total fusion of the PV and left atrial potentials around the PV ostium or the transverse activation patterns that were observed. Those potentials were defined as PVA potentials. Radiofrequency ablation was performed circumferentially targeting PVA potentials with the end point being their elimination. RESULTS: After circumferential PVA ablation, electrical disconnection was achieved in 77% and residual PVA conduction gaps were observed in 23% of all targeted PVs. Those residual conduction gaps were mainly located at the border between ipsilateral PVs (42%) and between the left PVs and left atrial appendage (33%) and were eliminated by a mean of 3 +/- 2 minutes of local radiofrequency deliveries. During the follow-up period (11 +/- 5 months), 46 (84%) patients were free of symptomatic PAF without any anti-arrhythmic drugs. No PV stenosis or spontaneous left atrial flutter occurred. CONCLUSIONS: Electrophysiological PVA ablation with an MBC is feasible and effective for curing PAF because this minimally extensive PVA isolation technique targets the optimal sites, achieving both high efficacy and safety.

Aged↗

PubMed2006

Effect of green tea consumption on endothelial function and circulating endothelial progenitor cells in chronic smokers.

BACKGROUND: The present study was designed to investigate the effect and relationship of endothelial function and endothelial progenitor cells (EPCs) by green tea consumption in chronic smokers. The numbers of circulating EPCs have an inverse correlation with chronic smoking and endothelial dysfunction. Green tea catechin improved endothelial dysfunction in chronic smokers. METHOD AND RESULTS: In 20 young healthy smokers, endothelial functions, defined by flow-mediated endothelium dependent vasodilation (FMD) of the brachial artery via ultrasound as well as the number of EPCs isolated from peripheral blood, were determined at baseline and at 2 weeks after green tea consumption (8 g/day). Circulating EPCs were quantified by flow cytometry as CD45lowCD34+KDR2+ cells and by acyl-low-density lipoprotein and fluorescein isotiocyanate-lectin double positive cells after culture for 7 days. Clinical characteristics and laboratory findings were not significantly different between the baseline and at 2 weeks after green tea intake. EPC levels were inversely correlated with the number of cigarettes smoked. Circulating EPCs by flow cytometry (78.6+/-72.6 vs 156.1+/-135.8 /ml, p<0.001) and cultured EPCs (118.2+/-35.7 vs 169.31+/-58.3/10 field, p<0.001) increased rapidly at 2 weeks after green tea consumption. FMD was significantly improved after 2 weeks (7.2+/-2.8 vs 9.3+/-2.4, p<0.001). The FMD correlated with EPC counts (r=0.67, p=0.003) before treatment and after 2 weeks (r=0.60, p=0.013). CONCLUSIONS: A short-term administration of green tea consumption induces a rapid improvement of EPC levels and FMD. Green tea consumption may be effective to prevent future cardiovascular events in chronic smokers.

Adult↗

PubMed2006

Clinical protocol for angiogenesis by intramyocardial injection of autologous bone marrow mononuclear cells in patients with severe coronary artery disease: TACT-NAGOYA-HEART.

BACKGROUND: Despite recent improvements in the treatments of coronary artery disease (CAD), there are a considerable number of patients who can not receive complete revascularization because of severe or total arterial occlusion. Intramyocardial injection of autologous bone marrow mononuclear cells (ABMMCs) has been shown to induce neovascularization of ischemic myocardium. METHODS AND RESULTS: The study will investigate the safety and feasibility of intramyocardial injections of ABMMCs and test the hypothesis that this treatment would promote neovascularization and improve left ventricular (LV) global and/or regional function in patients with severe CAD who have no other option. ABMMCs (approximately 10(6) cells) will be injected into the area of ischemic myocardium where the coronary artery is not graftable, in combination with bypass surgery to the other coronary branches. Myocardial perfusion and LV global and regional function will be evaluated, based on the micromanometer-tipped catheter method, single-photon emission tomography, and myocardial enhanced and color tissue Doppler echocardiography at baseline and during 12 month follow-up. CONCLUSIONS: This project will demonstrate that intramyocardial injection of ABMMCs with or without coronary artery bypass surgery could be a safe and effective method for therapeutic neovascularization, resulting in an improvement of cardiac function in patients with severe CAD.

Bone Marrow Cells↗

PubMed2006

Increase in electrocardiographic R-waves after revascularization in patients with acute myocardial infarction.

BACKGROUND: The physiological mechanism of the increase in the electrocardiographic (ECG) R-wave voltage after revascularization in patients with acute myocardial infarction (MI) needs to be elucidated. METHODS AND RESULTS: One hundred and thirty-eight MI patients (83: anterior MI, 45: inferior MI, 10: lateral MI) underwent ECG and echocardiography in both the acute and subacute phases after emergency revascularization, as well as a resting thallium-201/iodine-123 15-p-iodophenyl-3-(R,S)-methyl pentadecanoic acid myocardial scintigraphy in the acute phase. The total sum of the R-wave voltage (SigmaR) was calculated over multiple leads on ECG for each infarcted lesion. Scintigraphic defect on each tracer was expressed as the percentage (%) defect of the total left ventricular (LV) myocardium. The % defect-discordance on both images in the acute phase and the % increase in SigmaR and the absolute increase in LV ejection fraction from the acute to the subacute phase (DeltaEF) were also calculated. The SigmaR in the subacute phase was significantly greater than that in the acute phase (p<0.0001). The % increase in SigmaR significantly correlated with the DeltaEF (r=0.57, p<0.0001). The % increase in SigmaR also correlated with the % defect-discordance (r=0.68, p<0.0001). CONCLUSIONS: The increase in the ECG R-wave voltage reflects not only the improvement in myocardial perfusion but also the presence of salvaged myocardium after revascularization in acute MI patients.

Aged↗

PubMed2006

Can segmental pulmonary vein ablation reduce the recurrence of atrial fibrillation when using a higher RF power, larger tip electrode catheter, and additional RF deliveries?: the limitations of point-by-point RF ablation.

The aim of this study was to investigate whether segmental ostial catheter ablation (SOCA) designed to prevent the electrical connections (ECs) between the left atrium and pulmonary veins (PVs) might help increase the efficacy of SOCA in paroxysmal atrial fibrillation (PAF). PV mapping and successful SOCA were performed with a basket catheter in 108 consecutive patients with PAF. Radiofrequency energy was delivered using a maximum output of 30 W with a 4 mm tip catheter (group I; 47) or 40 W with an 8 mm tip catheter (group II; 61). Only in the group II patients were additional radiofrequency deliveries to the specific sites where the ECs tended to recover performed after successful SOCA. After the first procedure, PAF recurred in 47% of the group I patients and 32% of the group II patients. In all 27 patients who underwent repeat procedures, EC recoveries were observed more frequently in group I than in group II (69% versus 49%; P < 0.05). After multiple procedures, there was more freedom from PAF in group II (84%) than in group I (66%) (P < 0.05). SOCA with a higher RF power, larger tip catheter, and additional RF deliveries could achieve a more effective SOCA.

Aged↗

PubMed2005

Inverse association between adiponectin and C-reactive protein in substantially healthy Japanese men.

OBJECTIVE: An inverse association between adiponectin and C-reactive protein (CRP) has been shown in certain pathological states including obesity, diabetes, and coronary artery disease, which themselves might have confounded this association. This study investigated the association between adiponectin and CRP among substantially healthy subjects. METHODS AND RESULTS: A population of 2347 middle-aged Japanese men with no medical history of cardiovascular disease, cancer, diabetes, hypertension, or hyperlipidemia was evaluated. Those with some metabolic syndrome components from serological and anthropometric tests were excluded, leaving 714 men for analysis. Serum adiponectin and CRP were significantly correlated (r = -0.21, P < 0.001). After categorization into quartiles from the lowest to the highest adiponectin concentration (Q1 to Q4), the CRP level was found to be significantly higher in Q1 than in Q2, Q3 and Q4 (0.41 mg/L versus 0.30, 0.25 and 0.24 mg/L, P = 0.043, P < 0.001 and P < 0.001, respectively). These associations remained significant even after adjustment for covariates. Moreover, multiple linear regression analysis revealed that adiponectin contributed more strongly to CRP than other factors, including the index of insulin resistance. CONCLUSIONS: An inverse and strong association between adiponectin and CRP in substantially healthy subjects implies that decreased serum adiponectin might be fundamentally associated with the early stage of low-grade inflammation.

Adiponectin↗

PubMed2005

Therapeutic angiogenesis with intramuscular injection of low-dose recombinant granulocyte-colony stimulating factor.

OBJECTIVE: In vivo administration of granulocyte colony-stimulating factor (G-CSF) has been shown to facilitate regeneration of cardiovascular tissues. However, G-CSF causes marked leukocytosis that potentially induces adverse cardiovascular events. Earlier studies showed that G-CSF had direct stimulatory actions on mature endothelial cells, resulting in promotion of angiogenesis. We thus examined whether low doses of recombinant human G-CSF (rhG-CSF) locally injected into ischemic tissues would stimulate angiogenesis without inducing severe leukocytosis. METHODS AND RESULTS: Reverse-transcription polymerase chain reaction (PCR) revealed expression of G-CSF receptor in human umbilical vein endothelial cells (HUVECs). rhG-CSF (100 ng/mL) enhanced migration and tube formation but not proliferation of HUVECs in vitro. We then examined the effects of rhG-CSF on angiogenesis in a rat model of hindlimb ischemia. Nude rats received in their ischemic skeletal muscles either rhG-CSF (2, 10, 20 microg/kg per day) or saline (control) for 6 days. Laser Doppler blood flowmetry (LDBF) revealed an augmented ischemic/normal limb LDBF ratio and an increased capillary density in the rhG-CSF-treated groups compared with the control at days 14, 21, and 28 (P<0.05). These doses of rhG-CSF induced only mild leukocytosis ( approximately 1.4-fold increases versus baseline). CONCLUSIONS: rhG-CSF promoted endothelial migration and tube formation in vitro. Local injection of low doses rhG-CSF effectively augmented ischemia-induced angiogenesis in vivo. This treatment regimen of low-dose rhG-CSF may become a new and safe modality for therapeutic angiogenesis.

Animals↗

PubMed2005

Computerized three-dimensional potential mapping with a multielectrode basket catheter can be useful for pulmonary vein electrical disconnection.

INTRODUCTION: Pulmonary vein (PV) isolation (PVI) has been recently proposed as an effective technique to cure atrial fibrillation (AF). AIMS OF THE STUDY: The aim of this study was to investigate the efficacy of a novel technique utilizing a computerized three-dimensional mapping system (QMS2) with a multielectrode basket catheter (MBC) for PVI and to reveal the relation between the style of breakthrough and the network of the PV musculature. METHODS: Sixty-five consecutive patients with frequent AF attacks underwent PV mapping with a 31-mm MBC, and a three-dimensional color animation of the potential map was constructed by the QMS2. The animation color schema was arranged to minimize the low-amplitude left atrial (LA) potentials and emphasize the high-amplitude PV potentials (PVPs). The longitudinal PVP map enabled us to recognize the true breakthroughs and reveal the network of the PV musculature. RESULTS: A total of 205 PVs (65 left superior PVs, 65 right superior PVs, 57 left inferior PVs and 18 right inferior PVs) were mapped and successful PVI was achieved in all PVs, except one that had no PVPs, with a mean radiofrequency duration of 7 +/- 5 minutes per PV. In about 90% of the PVs, a final radiofrequency application eliminated all the distal PVPs simultaneously because the PVI was performed at the appropriate LA-PV junction. A single segmental breakthrough was detected in 17 PVs, single broad breakthrough in 83 PVs, multiple separate breakthroughs with a distal connection between the PV musculatures extending from each separate breakthrough in 88 PVs and multiple separate breakthroughs without that connection in 16 PVs. During the follow-up period, fifty-one (78%) patients were free of symptomatic AF without any antiarrhythmic drugs after multiple procedures (thirty-three (51%) of those patients after the first procedure) and no PV stenosis was found. CONCLUSIONS: Computerized three-dimensional potential mapping can be useful for PVI because it can not only identify the true breakthrough, but can also confirm the elimination of the breakthroughs by the change in the activation sequence through the network of the PV musculature.

Analysis of Variance↗

PubMed2004

Molecular evaluation of endothelial progenitor cells in patients with ischemic limbs: therapeutic effect by stem cell transplantation.

OBJECTIVE: Although some patients with limb ischemia have recently undergone therapeutic angiogenesis by cell transplantation, their angiogenic potential has not been well characterized. It is also important to evaluate endothelial progenitor cell (EPC) contents in different stem cell sources to choose the best material for therapeutic angiogenesis. METHODS AND RESULTS: We quantitated the mRNA expression of EPC-specific molecules (eg, Flk-1, Flt-1, CD133, VE-cadherin, etc) in bone marrow-derived or peripheral blood-derived mononuclear cells obtained from patients with ischemic limbs, using real-time reverse-transcription polymerase chain reaction technique. The mRNA expression level of EPC markers was significantly lower in the patients than in healthy controls, which was consistent with results of flow cytometric analysis. However, the implantation of autologous bone marrow mononuclear cells increased the circulating EPCs in the peripheral blood of patients. We furthermore revealed the different expression pattern of EPC markers in possible sources for stem cell transplantation, including normal bone marrow, peripheral blood obtained from recombinant granulocyte colony-stimulating factor-treated donor, and umbilical cord blood. CONCLUSIONS: Patients with peripheral obstructive arterial diseases may have lower angiogenic potential because of decreased expression of EPC specific molecules in their marrow and blood. Therapeutic angiogenesis by transplantation of autologous marrow mononuclear cells increased circulating EPCs in the patients and improved ischemic symptoms.

AC133 Antigen↗

PubMed2004

Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers.

OBJECTIVE: Circulating endothelial progenitor cells (EPCs) contribute to postnatal angiogenesis. The number of circulating EPCs has an inverse correlation with coronary risk scores. However, the effect of smoking on the number of circulating EPCs is not well-known. METHODS AND RESULTS: We examined the effects of chronic smoking and of smoking cessation on EPC levels. Circulating EPCs were quantified by flow cytometry as CD45lowCD34+CD133+ (progenitor cells [PCs]) or CD45lowCD34+CD133+VEGFR2+ (EPCs) in 14 nonsmokers and in 15 smokers. All smokers quit smoking. Eight quit smoking with nicotine patch and 7 without nicotine patch. PC/EPC levels were inversely correlated with the number of cigarettes smoked. Circulating PCs/EPCs increased rapidly after cessation (P<0.0001) and decreased again after resumption of smoking to the level similar to that before cessation (P=0.0031). The magnitude of increase in EPCs was greater in light smokers than in heavy smokers. CONCLUSIONS: The number of circulating PCs/EPCs was reduced in chronic smokers. Smoking cessation led to a rapid restoration of PC/EPC levels. The recovery of EPC levels was greater in light smokers than in heavy smokers. The decreased number of circulating EPCs would make smokers susceptible to cardiovascular disease, and even short-time cessation of smoking may be an effective means to reduce cardiovascular risk.

AC133 Antigen↗