Development of hyperpoliazed cardioplegic solution for the senescent myocardium

2000 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671322
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kobe University
• Principal Investigator: TAKURO Tsukube Kobe University Hospital, Department of Surgery II, Assistant Professor, 医学部・附属病院, 助手 (50304100)
• Project Period (FY): 1999 – 2000
• Keywords: myocardial protection / ischemia-reperfusion injury / myocyte / apoptosis / aging / hyperpolarization

Research Abstract

Effect of Hyperpolarized cardioplegic solution on the ischemia-reperfusion injury of the senescent myocardium.
Matured rabbit heart was excised and perfused under Langendorff apparatus with modified Krebs-Henseleit buffer solution and adenosine cardioplegia (with 10mM magnesium sulfate) was infused prior to the ischemia. Functional recovery (% recovery of the left ventricular developed pressure) after 30 minutes ischemia demonstrated 14±3% greater recovery than control. In aged rabbit heart, global ischemia without treatment showed 60±5% recovery of LV developed pressure and improved in 22±3% with adenosine cardioplegia. After 45 minutes of ischemia followed by 240 minutes of reperfusion under cardiopulmonary bypass, adenosine cardioplegia improved LV pressure (25±5%) as compared to global ischemia without treatment. TUNEL stainin positive myocyte was significantly decreased in adenosine cardioplegia (23±5%) as compared to control ischemia (32±7%). These findings proved hyperpolarized cardioplegia ameliorated ischemia-reperfusion injury on both mature and aged myocardium.
Effect of calcineurin inhibitors on myocardial apoptosis
To prevent myocardial apoptosis, calciueurin inhibitor (FK-506) was applied and functional recovery and TUNEL staining were evaluated in both mature and aged rabbit hearts. In the mature hearts, % recovery of LV developed pressure was greater in FK-506 pretreated group (20±4%) than in ischemia without treatment. TUNEL staining positive myocytes were significantly decreased in FK-506 group. In the aged hearts, FK-506 significantly improved functional recovery (17±3%) and decreased TUNEL staining positive myocytes (32±7%) as compared to those in ischemia without treatment. These studies proved that myocardial apoptosis was key disease process of ischemia-reperfusion injury and hyperpolarized cardioplegia ameliorated these insults on aged myocardium.