| Project/Area Number |
03670453
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Shimane Medical University |
|---|
Principal Investigator |
MORIOKA Shigefumi Shimane Medical University, Dept. of Internal Medicine, Associate Prof., 医学部, 助教授 (00157877)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISHINAGA Yuji Shimane Medical University, Dept. of Internal Medicine, Instructor, 医学部, 助手 (70243433)
HONDA Masaaki Shimane Medical University, Dept. of Internal Medicine, Associate Prof., 医学部, 講師 (90127530)
|
|---|
| Project Period (FY) |
1991 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
|
|---|
| Keywords | Heart failure / Cardiac hypertrophy / Calcium transients / Single myocytes / Ultrastructures / Adenosine metabolism / Calcium transients / Adenosine metabolism / Monocrotaline / Isoproterenol / PDE inhibitor / Eー1020 |
|---|
| Research Abstract |
(Purpose, Materials & Methods) We examined calcium transients (Ca-T), adenosine metabolism, and membranous ultrastructure in the heart during development of cardiac hypertrophy and heart failure. Right ventricular hypertrophy (RVH) model was induced by single subcutaneous injection of monocrotaline (60 mg/kg) into male SD rats (6 weeks old), which showed progressive RVH with resultant heartfailure (HF). Ca-T was examined using Fura-2/AM after separation of myocytes by Langendorff apparatus. Concentration of adenosines in the whole heart was examined enzymatically. Membranous ultrastruture was examined by scanning electron microscopy after preparation of specimens using O-D-O method. (Results) I.Changes in Ca-T : Characteristic changes in Ca-T were observed during the changes from adaptation to maladaptation. Briefly, mobilization and sequestration of calcium ions were enhanced at the early stage of RVH, but they were depressed at the late stage with HF.Stimulatory frequency affected Ca-T, especially at the late stage of RVH with HF, remarkable changes in Ca-T were observed. Moreover, beta adrenergic responsiveness of Ca-T altered during the changes from adaptation to maladaptation. II.Ultrastructures : Ultrastructures of sarcoplasmic reticulm (SR), surface caveolae (SC), mitochondria (MT) were examined. These structures also alterd during the changes from adaptation to maladaptation. Morphological changes in SR correlated with the changes in peak ratio of Ca-T.III.Adenosine metabolism : At the early stage of RVH, ATP tended to increase with significant decrease in AMP, but energy change potential increased significantly. However, at the stage of HF, all these parameters decreased significantly. Contractile properties of muscle strips depressed at the early stage of RVH and depressed progressively during the development of HF.(Conclusion) Our results revealed pathophysiological changes in the heart during the changes from adaptation to maladaptation and also provide
|
