Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle

The concept of the plasticity or transdifferentiation of adult stem cells has been challenged by the phenomenon of cell fusion. In this work, we examined whether neonatal cardiomyocytes fuse with various somatic cells including endothelial cells, cardiac fibroblasts, bone marrow cells, and endothelial progenitor cells spontaneously in vitro. When cardiomyocytes were cocultured with endothelial cells or cardiac fibroblasts, they fused and showed phenotypes of cardiomyocytes. Furthermore, cardiomyocytes reentered the G2-M phase in the cell cycle after fusing with proliferative noncardiomyocytes. Transplanted endothelial cells or skeletal muscle–derived cells fused with adult cardiomyocytes in vivo. In the cryoinjured heart, there were Ki67-positive cells that expressed both cardiac and endothelial lineage marker proteins. These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes

Long-term prognosis of diabetic patients with acute myocardial infarction in the era of acute revascularization

Abstract Background The long-term prognosis of diabetic patients with acute myocardial infarction (AMI) treated by acute revascularization is uncertain, and the optimal pharmacotherapy for such cases has not been fully evaluated. Methods To elucidate the long-term prognosis and prognostic factors in diabetic patients with AMI, a prospective, cohort study involving 3021 consecutive AMI patients was conducted. All patients discharged alive from hospital were followed to monitor their prognosis every year. The primary endpoint of the study was all-cause mortality, and the secondary endpoint was the occurrence of major cardiovascular events. To elucidate the effect of various factors on the long-term prognosis of AMI patients with diabetes, the patients were divided into two groups matched by propensity scores and analyzed retrospectively. Results Diabetes was diagnosed in 1102 patients (36.5%). During the index hospitalization, coronary angioplasty and coronary thrombolysis were performed in 58.1% and 16.3% of patients, respectively. In-hospital mortality of diabetic patients with AMI was comparable to that of non-diabetic AMI patients (9.2% and 9.3%, respectively). In total, 2736 patients (90.6%) were discharged alive and followed for a median of 4.2 years (follow-up rate, 96.0%). The long-term survival rate was worse in the diabetic group than in the non-diabetic group, but not significantly different (hazard ratio, 1.20 [0.97-1.49], p = 0.09). On the other hand, AMI patients with diabetes showed a significantly higher incidence of cardiovascular events than the non-diabetic group (1.40 [1.20-1.64], p Conclusions Although diabetic patients with AMI have more frequent adverse events than non-diabetic patients with AMI, the present results suggest that acute revascularization and standard therapy with aspirin and RAS inhibitors may improve their prognosis.</p

経皮的旧バルーン動脈形成術後の再狭窄に関する5HT_2A受容体拮抗薬(塩酸サルポグレラート)の有用性

〔背景〕セロトニン受容体,特に5HT_2受容体は血管収縮および血小板凝集に大いに関与し,また,経皮的冠動脈形成術(PTCA)後の血管内皮機能障害の進行にも影響を及ぼしている. 〔目的〕5HT_2A受容体拮抗薬(塩酸サルポグレラート)が経皮的旧バルーン動脈形成術(POBA)後の再狭窄率の減少に有用であるか否かアスピリンと対比し検討する.〔方法〕1996年3月より1997年6月までに急性冠症候群の診断で入院となりPOBAを施行した56例(男性45例,女性11例;平均年齢63歳)について検討した. 56例中無作為に抽出した26例に対し5HT_2A受容体拮抗薬150mg(分3)を投与し,残りの30例に対してはアスピリン81mg(分1)を投与した.また,QCA法により計測し6ヵ月後(follow up時)の冠動脈造影上で標的血管に50%以上の狭窄を認めた場合を再狭窄と定義した.〔結果〕56例すべてにおいてfollow upを行った. POBA前後での両群間における対照血管最小血管経(MLD)に有意差は認めなかった(5HT_2A群vsアスピリン群:2.67±0.53mm vs 2.79±0.56mm; p=0.42). POBA後6ヵ月後(follow up時)のMLDは5HT_2A群の方がアスピリン群より有意に大きい結果であった(5HT_2A群vsアスピリン群: 1.64±0.69mm vs 1.06±0.91mm; p=0.03).再狭窄率は5HT_2A群7/26(27%),アスピリン群13/30(43%)であった.また, 5HT_2A群において,診断造影上右冠動脈に有意狭窄を認めた症例でPOBA後の再狭窄が少ない傾向を認めた.全経過中に明らかな合併症は認めなかった.〔結語〕5HT_2A受容体拮抗薬(塩酸サルポグレラート)はPOBA後の再狭窄率の減少に有用かつ明らかな合併症を認めない安全な薬剤であり,診断造影上右冠動脈に有意狭窄を認めた症例においては特に有用な薬剤であると思われる.Background: Serotonin receptors, especially 5HT_2 receptors, are important in vasoconstriction and platelet aggregation and are involved in the chronic progression of endothelial dysfunction after percutaneous transluminal coronary angioplasty (PTCA). Objective: To determine whether the 5HT_2A receptor antagonist, sarpogrelate hydrochloride, was more effective than aspirin in reducing the rate of restenosis after percutaneous old balloon angioplasty (POBA). Methods: Between March 1996 and June 1997, 45 men and 11 women (average age of 63 years) underwent POBA for acute coronary syndromes. Of these, 26 received the 5HT_2A receptor antagonist 50 mg three times a day and 30 received aspirin 81 mg daily in a randomized, open trial. Restenosis was defined as a narrowing of the target vessel of at least 50% at follow-up, as measured by quantitative coronary angiography (QCA). Results: The angiographic follow-up rate was 100%. The reference minimal lumen diameter (MLD) before and after POBA did not differ significantly between the two groups (post MLD: 2.67 (0.53) in the 5HT_2A group and 2.79 (0.56) in the aspirin group; p=0.42). The mean (SD) MLD at 6 months was significantly larger in the 5HT_2A group than in the aspirin group (1.64 (0.69) mm vs 1.06 (0.91) mm; p =0.03). Angiographically identified restenosis occurred in 7/26 (27%) of the patients in the 5HT_2A group and in 13/30 (43%) of those in the aspirin group. In the 5HT_2A group, restenosis rate was likely to be less frequent in patients with right coronary artery (RCA) stenosis on the initial diagnostic angiogram (p=0.040). No complications were observed during the follow-up period. Conclusions: The 5HT_2A receptor antagonist, sarpogrelate hydrochloride, reduced the rate of restenosis after POBA, especially in patients with RCA stenosis on the initial diagnostic angiogram. No adverse events were reported in this series

冠動脈内圧測定により得られる病変重症度の新しい生理学的指標Epicardial Resistance Indexの基礎理論

冠動脈狭窄性病変の機能的重症度を評価するため,我利よ独自に,病変に特異的な新たな指標であるepicardial resistance index(ERI)を考案した.本論文ではERIの概念および理論的基礎を論説する.ERIは,薬物による最大充血状態(hyperemia)下において,心外膜に存在する冠動脈の狭窄性病変の血管抵抗と狭窄以下の末梢心筋部の抵抗の比で表される指標である.ERIは先端に圧センサーチップを有する圧測定ワイヤーを用いて,狭窄病変前後の冠動脈内圧を測定することで得られる病変部の圧較差を,末梢部血管内圧-中心静脈圧(末梢部心筋での圧較差)で除することにより計算される.測定を最大充血状態で行うのは,冠動脈内圧の自己調整機構の影響を排除するためである.冠動脈内圧の測定による狭窄病変の評価としては,従来fractional flow reserve(FFR)が指標として用いられていたが,同一冠動脈内に複数の病変を有する場合,個々の病変の重症度を個別に評価することは不可能であった.今回我々が考案した新たな指標であるERIは,個々の病変の抵抗を表す指標であるため,病変特異的に重症度評価を行うことが可能となった.単一病変において,虚血が生じえる病変の重症度の閾値は,FFRではcut-off値0.33であることを証明した.さらにFFRと異なり,同一血管に複数の病変がある場合もこのERI値が個々に計算可能で,重症度評価の指標となることを明らかにした.実臨床90病変において,PCI前後で病変のERI測定および定量的冠動脈造影を比較した結果,ERIと血管造影上の狭窄度はr=0.67と良好な正相関を示した.我々の考案したERIは,実際の臨床上問題となる複数の病変を有する複雑病変の治療に際し,どの病変を治療すれば虚血を解除することが可能か事前に判別することができ,不要な治療を避け,必要な病変のみ選択治療を施行できるという点で,特にカテーテルによる冠動脈治療上大きな意義があると考えられる.To assess functional severity of the coronary stenotic lesion, we introduce a novel lesion-specific parameter, the epicardial resistance index (ERI), and describe its concept and theoretical basis. The ERI is defined as the ratio of the resistance of an epicardial coronary stenosis to that of downstream myocardium under hyperemic condition. The ERI is calculated as the trans-lesional pressure gradient divided by (Pd-Pv) at maximum hyperemia, where Pd represents the mean distal coronary pressure in the absence of any stenosis and Pv represents the central venous pressure. Based on theoretical conversion of fractional flow reserve (FFR) to ERI, the reported FFR cut-off value of 0.75 for inducible ischemia corresponds to an ERI of 0.33. This new parameter allows the resistance of the each coronary stenosis to be assessed separately even in the presence of multiple lesions in a coronary artery tree. Using the 170 measurements performed in the 90 lesions, the correlation of ERI with the anatomical parameters obtained from QCA was analyzed. By polynomial regression analysis, the ERI showed a significant positive correlation with the QCA-derived %DS (r=0.67, p<0.001). ERI may have wide application in routine clinical practice especially in the setting of complex catheter-based coronary intervention

冠動脈内圧測定により得られる病変重症度の新しい生理学的指標Epicardial Resistance Indexの基礎理論

冠動脈狭窄性病変の機能的重症度を評価するため,我利よ独自に,病変に特異的な新たな指標であるepicardial resistance index(ERI)を考案した.本論文ではERIの概念および理論的基礎を論説する.ERIは,薬物による最大充血状態(hyperemia)下において,心外膜に存在する冠動脈の狭窄性病変の血管抵抗と狭窄以下の末梢心筋部の抵抗の比で表される指標である.ERIは先端に圧センサーチップを有する圧測定ワイヤーを用いて,狭窄病変前後の冠動脈内圧を測定することで得られる病変部の圧較差を,末梢部血管内圧-中心静脈圧(末梢部心筋での圧較差)で除することにより計算される.測定を最大充血状態で行うのは,冠動脈内圧の自己調整機構の影響を排除するためである.冠動脈内圧の測定による狭窄病変の評価としては,従来fractional flow reserve(FFR)が指標として用いられていたが,同一冠動脈内に複数の病変を有する場合,個々の病変の重症度を個別に評価することは不可能であった.今回我々が考案した新たな指標であるERIは,個々の病変の抵抗を表す指標であるため,病変特異的に重症度評価を行うことが可能となった.単一病変において,虚血が生じえる病変の重症度の閾値は,FFRではcut-off値<0.75と報告されている.我々は,数学的変換によりこの虚血閾値がERIでは,ERI値>0.33であることを証明した.さらにFFRと異なり,同一血管に複数の病変がある場合もこのERI値が個々に計算可能で,重症度評価の指標となることを明らかにした.実臨床90病変において,PCI前後で病変のERI測定および定量的冠動脈造影を比較した結果,ERIと血管造影上の狭窄度はr=0.67と良好な正相関を示した.我々の考案したERIは,実際の臨床上問題となる複数の病変を有する複雑病変の治療に際し,どの病変を治療すれば虚血を解除することが可能か事前に判別することができ,不要な治療を避け,必要な病変のみ選択治療を施行できるという点で,特にカテーテルによる冠動脈治療上大きな意義があると考えられる.To assess functional severity of the coronary stenotic lesion, we introduce a novel lesion-specific parameter, the epicardial resistance index (ERI), and describe its concept and theoretical basis. The ERI is defined as the ratio of the resistance of an epicardial coronary stenosis to that of downstream myocardium under hyperemic condition. The ERI is calculated as the trans-lesional pressure gradient divided by (Pd-Pv) at maximum hyperemia, where Pd represents the mean distal coronary pressure in the absence of any stenosis and Pv represents the central venous pressure. Based on theoretical conversion of fractional flow reserve (FFR) to ERI, the reported FFR cut-off value of 0.75 for inducible ischemia corresponds to an ERI of 0.33. This new parameter allows the resistance of the each coronary stenosis to be assessed separately even in the presence of multiple lesions in a coronary artery tree. Using the 170 measurements performed in the 90 lesions, the correlation of ERI with the anatomical parameters obtained from QCA was analyzed. By polynomial regression analysis, the ERI showed a significant positive correlation with the QCA-derived %DS (r=0.67, p<0.001). ERI may have wide application in routine clinical practice especially in the setting of complex catheter-based coronary intervention

QT prolongation and torsades de pointes during emergency treatment with nifekalant for refractory ventricular tachyarrhythmias: Post-hoc analysis from a large-scale multicenter post-marketing survey in Japan

Background: Nifekalant, a first-line drug for the treatment of ventricular tachycardia/ventricular fibrillation (VT/VF) in Japan, has been known to prolong the QT interval; however, the incidence of excess QT/QTc prolongation and subsequent torsades de pointes (TdP) has not yet been reported. Methods: The QT/QTc interval and occurrence of TdP during nifekalant therapy were evaluated in 1402 emergency patients with VT/VF. Results: Thirty-five cases (2.5%) of QT/QTc prolongation and 54 cases (3.9%) of TdP were reported. High nifekalant doses and long QTc intervals were associated with frequent TdP. The incidence of TdP was 1.4% for QTc intervals <0.43, 3.9% for those 0.44–0.49, 5.3% for those 0.50–0.55, 7.3% for those 0.56–0.61, 11.1% for those 0.62–0.67, and 12.5% for those ≥0.68. The odds ratio for TdP was elevated in women (2.48); in patients with any heart disease (4.68), New York Heart Association (NYHA) III or IV (1.81), Forrester subset 2 or worse (2.13), depressed cardiac function (1.86), or liver dysfunction (2.06); and in patients who were receiving concomitant drugs (2.67). In 42 patients (77.8%), TdP required treatment with direct current shock or a second drug. Conclusion: Nifekalant was effective for refractory VT/VF, although careful observation of the QT/QTc interval and possible occurrence of TdP is required, especially in high-risk patients