Innami R
Nihon Kyobu Geka Gakkai Zasshi. 1989 Dec;37(12):2520-31.
Protective effect of aprotinin pretreatment was assessed by functional, biochemical and morphological preservation in four hour global ischemia followed by one hour reperfusion in dogs. Cardioplegia was induced by intermittent infusion of cold Mg-lidocaine solution. Aprotinin 10,000 KIU/kg was given in low dose group (8 dogs), and 20,000 KIU/kg in high dose group (6 dogs); one half was given before ischemia and another half during ischemia. Betamethasone, coenzyme Q and nifedipine were also given equally in both groups before ischemia. Results were as follows: 1. Four (50%) of low dose group and all of high dose group were successfully taken off CPB and survived for one hour reperfusion. 2. High dose group showed significantly higher blood pressure and LVSWI than low dose group after one hour reperfusion (p less than 0.05). 3. Serum N-acetyl-beta-D-glucosaminidase and mitochondrial aspartate aminotransferase showed the significantly lower activity in high dose group than in low dose group after one hour reperfusion (p less than 0.05). There was no significant difference in the activities of serum beta-glucuronidase and MB-creatine kinase. 4. Myocardial tissues, excised after one hour reperfusion, contained significantly higher creatine phosphate in high dose group than in low dose group (p less than 0.05). There was no significant difference in the contents of adenosine triphosphate, calcium and water. 5. Severely injured mitochondrion were significantly lesser in high dose group than in low dose group. All lysosomes showed mild swelling or enlargement, but those membranous structures were well-preserved in both groups. In conclusion, aprotinin pretreatment might be effective in myocardial protection against prolonged global ischemia, by inhibiting the "leak out" of lysosomal enzymes.
通过对犬进行4小时全心缺血后再灌注1小时期间的功能、生化及形态学保存情况,评估抑肽酶预处理的保护作用。通过间歇性输注冷的镁-利多卡因溶液诱导心脏停搏。低剂量组(8只犬)给予抑肽酶10,000 KIU/kg,高剂量组(6只犬)给予20,000 KIU/kg;一半剂量在缺血前给予,另一半在缺血期间给予。两组在缺血前还均给予了倍他米松、辅酶Q和硝苯地平。结果如下:1. 低剂量组4只(50%)和高剂量组全部成功脱离体外循环并存活至再灌注1小时。2. 再灌注1小时后,高剂量组的血压和左室每搏功指数显著高于低剂量组(p<0.05)。3. 再灌注1小时后,高剂量组血清N-乙酰-β-D-氨基葡萄糖苷酶和线粒体天冬氨酸氨基转移酶的活性显著低于低剂量组(p<0.05)。血清β-葡萄糖醛酸酶和MB-肌酸激酶的活性无显著差异。4. 再灌注1小时后切除的心肌组织中,高剂量组的磷酸肌酸含量显著高于低剂量组(p<0.05)。三磷酸腺苷、钙和水的含量无显著差异。5. 高剂量组严重受损的线粒体明显少于低剂量组。所有溶酶体均有轻度肿胀或增大,但两组的溶酶体膜结构均保存良好。总之,抑肽酶预处理可能通过抑制溶酶体酶的“渗漏”对心肌抵抗长时间全心缺血具有保护作用。