Key factors for cardiac recovery in patients with left ventricular assist device for end stage heart failure
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants |
|Research Institution||National Cardiovascular Center Research Institute (2009-2010)|
Osaka University (2008)
FUJITA Tomoyuki 独立行政法人国立循環器病研究センター, 心臓血管外科, 医師 (10457012)
SAWA Yoshiki 大阪大学, 医学系研究科, 教授 (00243220)
ICHIKAWA Hajime 独立行政法人国立循環器病研究センター, 小児心臓外科, 医長 (60303939)
MATSUMIYA Goro 千葉大学, 大学院・医学研究院, 教授 (20314312)
KURATANI Toru 大阪大学, 医学系研究科, 准教授 (90448035)
UENO Takayoshi 大阪大学, 医学系研究科, 講師 (60437316)
SAKAGUCHI Taichi 大阪大学, 医学系研究科, 寄附講座准教授 (10467574)
SHIRAKAWA Yukitoshi 大阪大学, 医学系研究科, 助教 (20457013)
|Project Period (FY)
2008 – 2010
Completed (Fiscal Year 2010)
|Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|Keywords||心不全 / LVAD / 細胞治療 / 線維化 / リモデリング / LVAS / remodeling / ベッカー型筋ジストロフィー / 僧帽弁逆流 / 心機能 / 重症心不全 / 左室補助装置(LVAS) / recovery(回復) / reverse remodeling / 心電図同期MDCT / カラーカイネーシス / 左室unloading(負荷の軽減)|
Left ventricular assist device(LVAD) confers mechanical unloading to the patients in end stage heart failure to recover their own cardiac function. The mechanical unloading leads reverse remodeling which decreases LV diastolic and systolic diameter and increases LV ejection fraction. However, we found there are responders and non-responders. Among 34 patients who underwent LVAD-off test, 9 patients successfully recovered their own cardiac function and was weaned off from LVAD. The pathological examination revealed that less fibrosis and smaller cell size in these 9 patients. Therefore, we concluded that Cardiac fibrosis and myocyte size at the time of LVAD implantation were significant predictors of degree of improvement of cardiac function and the sustained recovery after the LVAD explantation.
Next, we examined cell transplantation to the patients who were unlikely recovered their own cardiac function because of their etiology of heart failure.
Simultaneous injection of autologous bone
marrow cells and skeletal myoblasts has been demonstrated to improve cardiac function in animal models. We evaluated the potential application of this combination cell therapy in patients with severe ischemic cardiomyopathy who required left ventricular assist device(LVAD) implantation.
Four patients(age range, 43-69 years) who required LVAD implantation due to severe ischemic cardiomyopathy were studied. Skeletal myoblasts were obtained from the thigh, while bone marrow mononuclear cells were collected and purified at the time of the operation. These cells were directly injected in a serial manner into the damaged myocardium.
No fatal arrhythmias or major complications were observed. The number of injected skeletal myoblasts ranged from 2.7×10(7) to 3.0×10(8), and their purity ranged from 25% to 96%. Two patients showed decreased brain natriuretic peptide levels and echocardiographic improvements in the transplanted areas, as well as increased perfusion revealed by H(2)(15) O positron emission tomography, of whom one was successfully weaned from LVAD. Histological findings at autopsy of the other patient showed a small amount of skeletal muscle in the injected area. Only marginal improvements were observed in the other two patients.
As a conclusion, the key is a viable myocytes to respond any kind of treatment such as mechanical unloading and cell transplantation. In addition, cell stability is another important factor for successful cell therapy. Less
Report (4 results)
Research Products (10 results)