REDUCTION OF REPERFUSION INJURY BY PRECONDITIONING OF MYOCARDIUM WITH PRECEDING TRANSIENT ISCHEMIA

通过对先前发生短暂性缺血的心肌进行预处理来减少再灌注损伤

• 批准号: 03670465
• 负责人: TANI Masato
• 金额: $ 1.22万
• 依托单位: KEIO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670465/
• 关键词: PRECONDITIONING; REPERFUSION INJURY; Ca OVERLOAD; MYOCARDIAL ISCHEMIA; SARCOPLASMIC RETICULUM; Reperfusion Injury; Sarwplasmic Peticulum; 再潅流傷害(repefision injory); 心筋虚血前条件付け(precoditioing); Ca^<2+>過負荷; Na^+; Ca^<2+>交換; H^+交換; 心筋虚血; 摘出心

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 … More 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

预处理（PC）可减轻心肌损伤，促进缺血心肌再灌注后的恢复。然而，这种影响的机制尚未阐明。在Langendorff程序灌注的心脏中，我们诱导短暂缺血并进行0至3次（每次5分钟）间歇灌注。PC 0 - PC 3）。然后用含^ Ca^&lt;2+&gt;的缓冲液再灌注心脏30分钟<45>。我们监测了左心室（LV）压力，并分别通过^ Ca^&lt;2 +&gt;摄取和酶法测量了心肌Ca^&lt;2 +&gt;超负荷和能量代谢产物（ATP、磷酸肌酸和乳酸）<45>。在另一些心脏中，诱导短暂缺血并进行0 ~ 3次间歇灌注，在缺血前25分钟或再灌注30分钟后取出心脏，无^<45>Ca^&lt;2+&gt;。用咪唑缓冲液（pH 7.0）匀浆每个心脏的左心室。采用透射电镜观察肌浆网（SR）钙摄取功能， ...更多信息 在ATP、~<45>（2+）Ca ~（2+）、NaN_3存在下，不加药物、钌红或兰尼定。左室舒张末期压升高随PC发作次数的增加而降低（PC 0 ; 14.3*3.3，PC 1 ; 8.2*3.3，PC 2 ; 4.5*2.0，PC 3 ; 1.3*1.3mmHg）。左室收缩压的恢复在四组之间没有差异。然而，PC 3的LV发展压力的恢复百分比大于PC 0（PC 0 ; 50.1*5.0，PC 3 ; 73.9*8.1%）。PC 3中LV的峰阳性和峰阴性dP/dt的回收率百分比也显著上级优于PC 0（PC 0;分别为52.5*5.9、51.4*5.4，PC 3 ; 73.9*8.1、75.8* 8.0%）。高能量磷酸盐的恢复在各组之间没有差异。相反，PC发作次数增加与心肌Ca^2+摄取减少相关（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）。在诱导25分钟缺血前，PC 0和PC 3的SR的Ca^&lt;2+&gt;摄取没有差异。再灌注30分钟后，PC 3的SR Ca^&lt;2+&gt;摄取功能恢复到缺血前的80%，而PC 0的SR Ca^&lt;2 +&gt;摄取功能超过缺血前的130 ~ 160%。这些结果表明，预处理心肌缺血后左室功能改善可能与钙超载的减少有关，而与能量代谢或SR钙功能的改变无关。少

项目成果

谷 正人: "心筋収縮過程に及ぼす虚血の影響(目でみる循環器病シリーズ2.心不全ショック)" メジカルビュー, (1993)

Masato Tani：“缺血对心肌收缩过程的影响（视觉心血管疾病系列2.心力衰竭休克）”医学观点，（1993）

YASUSHI ASAKURA, MASATO TANI, KEN SHINMURA, YOSHINORI EBIHARA, SHUNN- NOSUKE HANDA, YOSHIRO NAKAMURA: "POSSIBLE MECHANISM OF EFFECT OF PRE- CONDITIONING ON ISCHEMIC MYOCARDIUM IN ISOLATED RAT HEARTS" J MOL CELL CARDIOL 23 (SUPPLE-II). S.39. (1991)

Yasushi Asakura、Masato Tani、KEN SHINMURA、YOSHINORI EBIHARA、SHUNNNOSUKE HANDA、YOSHIRO NAKAMURA：“预处理对离体大鼠心脏缺血性心肌影响的可能机制”J MOL CELL CARDIOL 23（补充-II）。

谷 正人,朝倉 靖,新村 健,海老原 良典,中村 芳郎,半田 俊之介: "第4章・生体医学関係:心筋虚血後の再潅流傷害(reperfusion injary):先行する短時間虚血による心筋preconditionringの影響.同財団研究成果報告集7" 持田記念医学薬学振興財団, 300 (1991)

Masato Tani、Yasushi Asakura、Ken Niimura、Yoshinori Ebihara、Yoshiro Nakamura、Shuunosuke Handa：“第 4 章生物医学：心肌缺血后的再灌注损伤：短期缺血引起的心肌预处理”持田医学和制药科学振兴纪念基金会， 300 (1991)

MASATO TANI: "EFFECTS OF ISCHEMIA ON MYOCARDIAL CONTRACTION" MEDICAL VIEW PRESS. (1993)

Masato Tani：“缺血对心肌收缩的影响”医学观点出版社。

Y.Asakura: "Possible mechanism of effect of preconditioning on ischemic myocardium in isolated rat hearts" J.Mol.Cell.Cardiol. 23. S39- (1991)

Y.Asakura：“预处理对离体大鼠心脏缺血心肌影响的可能机制”J.Mol.Cell.Cardiol。