1992 Fiscal Year Final Research Report Summary
REDUCTION OF REPERFUSION INJURY BY PRECONDITIONING OF MYOCARDIUM WITH PRECEDING TRANSIENT ISCHEMIA
| Project/Area Number |
03670465
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
TANI Masato Keio Univ., Sch. of Mad., ASSISTANT PROFESSOR, 医学部, 講師 (50163613)
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| Co-Investigator(Kenkyū-buntansha) |
SHINMURA Ken Keio Univ., Sch. of Med., ASSISTANT, 医学部, 助手 (70206332)
EBIHARA Yoshinori Keio Univ., Sch. of Med., ASSISTANT, 医学部, 助手 (30194020)
ASAKURA Yasushi Keio Univ., Sch. of Med., ASSISTANT, 医学部, 助手 (70184140)
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| Project Period (FY) |
1991 – 1992
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| Keywords | PRECONDITIONING / REPERFUSION INJURY / Ca OVERLOAD / MYOCARDIAL ISCHEMIA / SARCOPLASMIC RETICULUM |
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| Research Abstract |
Preconditioning (PC) reduces myocardial damage and improves recovery after reperfusion of the ischemic myocardium. However, the mechanism of this effect has not been clarified. In hearts perfused by the Langendorff procedure, we induced brief ischemia and performed intermittent perfusion 0 to 3 times (5 min. each. PC 0 - PC 3) before 25 min. of sustained global ischemia. The hearts were then reperfused for 30 min. with buffer containing ^<45>Ca^<2+>. We monitored left ventricular(LV) pressure and measured myocardial Ca^<2+> overload and energy metabolites (ATP, creatine phosphate and lactate) by ^<45>Ca^<2+> uptake and by enzymatic methods, respectively. In other hearts induced brief ischemia and performed intermittent perfusion 0 to 3 times hearts were taken before 25 min. of ischemia or after 30 min. of reperfusion without ^<45>Ca^<2+>. The left ventricle of each heart was homogenized with imidazole buffer (pH 7.0). Ca^<2+> uptake function of sarcoplasmic reticulum (SR) was assayed w
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ith no drug, ruthenium red or ryanodine in the presence of ATP, ^<45>Ca^<2+>, NaN_3. Elevation of LV end-diastolic pressure decreased according to the number of episodes of PC (PC 0 ; 14.3*3.3, PC 1 ; 8.2*3.3, PC 2 ; 4.5*2.0, PC 3 ; 1.3*1.3mmHg). Recovery of LV systolic pressure did not differ between the four groups. However, the percent recovery of LV developed pressure in PC 3 was greater than that in PC 0 (PC 0 ; 50.1*5.0, PC 3 ; 73.9*8.1%). The percent recovery of peak positive and peak negative dP/dt of LV in PC 3 was also significantly superior to that in PC 0 (PC 0;52.5*5.9, 51.4*5.4, PC 3 ; 73.9*8.1, 75.8*8.0%, respectively). The restoration of high energy phosphates did not differ between the groups. In contrast, an increase in PC episodes was associated with reduced myocardial Ca^<2+> uptake (PC 0 ; 3.2*0.3, PC 1 ; 3.4*0.9, PC 2 ; 2.9*0.6, PC 3 ; 1.3*0.2 mol/g dwt). Ca^<2+> uptake of SR before induction of 25 min. ischemia was not different between PC 0 and PC 3. After 30 min. of reperfusion, SR Ca^<2+> uptake function recovered to 80% of preischemic value in PC 3 while it overshot to 130 to 160% in PC 0. These results suggest that reductions in Ca^<2+> overload but not changes in energy metabolism or SR Ca^<2+> function may be responsible for improved post-ischemic LV function in the preconditioned myocardium. Less
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