| Project/Area Number |
07457285
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | HOKKAIDO UNIVERSITY |
|---|
Principal Investigator |
MURASHITA Toshifumi Hokkaido Uni., Fac.of Med., Lecturer, 医学部, 講師 (20261290)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YASUDA Keishu Hokkaido Uni., Medical Hospital. , Professor, 医学部付属病院, 教授 (60125359)
|
|---|
| Project Period (FY) |
1995 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥3,300,000 (Direct Cost: ¥3,300,000)
|
|---|
| Keywords | immature heart / cardioplegia / heart preservation / ischemia-Reperfusion injury / Na-H exchange / multidose cardioplegia / adhesion molecle / 接着分子 / 白血球 / 血液灌流モデル / Langendorff model / St. Thomas液 / Bretschneider液 / HEPES / histidine / Na / H exchange / 緩衝剤 |
|---|
| Research Abstract |
In isolated working hearts model (n=8/group from rabbit aged 7-10 days), all hearts received a preischemic infusion of cardioplegic infusion at pH 7.8 followed by subsequent infusions at pH 6.6,7.0,7.4,7.8 or 8.2. Functional recovery was enhanced and cumulative creatine kinase leakage during cardioplegic infusions reduced when pH was 7.8 or lower. The detrimental effects of pH 8.2 solution was also reflected by the changes in coronary vascular resistance. The inclusion of a selective Na/H exchange blocker in the subsequent infusion of pH 8.2 solution improved postischemic recovery of cardiac function. In addition, the inclusion of a HEPES buffer which is not permeable to cell membrane reduced post ischemic recovery of cardiac function. These suggest that postischemic recovery could improve when intra-and extra-cellular pH and buffering capacity are adjusted preferably.
The two clinically used cardioplegic solutions, St.Thomas' (bicarbonate buffered extracelluar solution) and Bretschneider's solution (histidine buffered intracellular solution), were examined to compare the protective properties of single-dose and multidose cardioplegia. Although Bretchneider's solution possessed higher buffering capacity, postischemic recovery of cardiac function is better in St.Thomas'solution than Bretschneider's solution.
In order to apply in clinical use, blood perfused heart model was mandatory to test the efficacy of substrate as an additive to solution, particularly buffering capacity is involved. We initially developed blood perfused rat heart model, which can apply to neonatal rabbit heart in the future. Using this model, the effect of monoclonal antibody to leukocyte adhesion molecule on ischemia-reperfusion injury was investigated. The results clearly confirmed that the monoclonal antibody improved postischemic cardiac function and endothelial function suggesting an important roll of leukocyte in ischemia-reperfusion injury.
|
