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

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>。在其他心脏中，诱导短暂缺血并进行0至3次间歇灌注。在缺血25分钟前或再灌注30分钟后，在没有^<45>Ca^&lt;2+&gt;的情况下取出心脏。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

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