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

预适应(PC)可减轻缺血心肌的损伤，促进缺血心肌再灌注后的恢复。然而，这一效应的作用机制尚不清楚。在用朗宁多夫程序灌流的心脏上，我们诱导短暂的缺血，并进行间歇灌流0-3次(5分钟。每个人。PC 0-PC 3)在25分钟之前。持续的全球缺血。心脏再灌流30分钟。具有包含^&lt；45&gt；Ca^&lt；2+&gt；的缓冲区。分别采用心肌摄取和酶法测定心肌钙超载和能量代谢产物(ATP、肌酸和乳酸)，监测左室压。其他心脏诱导短暂缺血，在25min前间断灌流0~3次。缺血期或30min后。无再灌注组：45&gt；每只心脏均用咪唑缓冲液(pH 7.0)匀浆。用…法测定肌浆网(SR)钙摄取功能有ATP、45-gt；2+-gt；2+-gt；NaN_3存在时，LV舒张末压力升高随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±1.3 mm Hg)。四组患者的左心室收缩压恢复无差异。但PC3组LV发展压恢复率高于PC0组(PC0：50.1×5.0，PC3：73.9×8.1%)。PC3组LV正峰和负峰dp/dt恢复率也明显优于PC0组(分别为52.5×5.9、51.4×5.4、73.9±8.1、75.8×8.0%)。高能磷酸盐的修复在两组之间没有差异。相反，PC发作次数的增加与心肌钙摄取减少相关(PC 0；3.2*0.3，PC 1；3.4*0.9，PC 2；2.9*0.6，PC 3；1.3*0.2mol/g Dwt)。在诱导25min前摄取SR。缺血30min后，PC0与PC3无明显差异。再灌流时，PC 3的SR钙摄取功能恢复到缺血前的80%，而PC 0的摄取功能恢复到缺血前的130~160%。这些结果提示，预适应心肌缺血后左心功能的改善可能与钙超载的减少而不是能量代谢或肌浆网钙离子功能的改变有关。较少

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