Cargnoni A, Ceconi C, Curello S, Benigno M, de Jong J W, Ferrari R
Fondazione Clinica del Lavoro, Centro di Fisiopatologia Cardiovascolare Salvatore Maugeri, Brescia, Italy.
Mol Cell Biochem. 1996 Jul-Aug;160-161:187-94. doi: 10.1007/BF00240049.
We studied the effect of 12-36 min of global ischemia followed by 36 min of reperfusion in Langendorff perfused rabbit hearts (n = 26). Metabolism was determined in terms of peak and total release of purines (adenosine, inosine, hypoxanthine), lactate and noradrenaline during reperfusion; and myocardial content of nucleotides (ATP, ADP, AMP), glycogen and noradrenaline at the end of reperfusion. An inverse relationship (r = -0.79) existed between duration of ischemia and developed pressure post-ischemia. Early during reperfusion, after 12 min of ischemia, the purine concentration (peak release) increased 100x (p < 0.01), that of lactate and noradrenaline 10x (p < 0.05). Total purine release rose with progression of the ischemic period (30x after 36 min of ischemia; p < 0.01), concomitant with a reduction in nucleotide content. Lactate release was independent from the duration of ischemia, although glycogen had declined by 30% (p < 0.01) after 36 min of ischemia. The acid insoluble glycogen fraction, which presumably contains proglycogen, increased substantially during short-term ischemia. Peak noradrenaline increased 100x, and 200x, (p < 0.05) after 24 and 36 min of ischemia, respectively. Total noradrenaline release due to various periods of ischemia mirrored its peak release. Function recovery was inversely related to total purine and noradrenaline efflux (both r = -0.81); it correlated with tissue nucleotide content (r = 0.84). In conclusion, larger amounts of noradrenaline are released only after a substantial drop in myocardial ATP. During severe ischemia ATP consumption more than limited ATP production by anaerobic glycolysis, is a key factor affecting recovery on subsequent reperfusion. In contrast to lactate efflux, purine and noradrenaline release are useful markers of ischemic and reperfusion damage.
我们研究了在Langendorff灌注兔心脏（n = 26）中，12 - 36分钟全心缺血后再灌注36分钟的影响。根据再灌注期间嘌呤（腺苷、肌苷、次黄嘌呤）、乳酸和去甲肾上腺素的峰值释放量和总释放量来测定代谢情况；并在再灌注结束时测定心肌中核苷酸（ATP、ADP、AMP）、糖原和去甲肾上腺素的含量。缺血持续时间与缺血后发展压力之间存在负相关关系（r = -0.79）。在再灌注早期，缺血12分钟后，嘌呤浓度（峰值释放）增加了100倍（p < 0.01），乳酸和去甲肾上腺素浓度增加了10倍（p < 0.05）。随着缺血时间的延长，嘌呤总释放量增加（缺血36分钟后增加30倍；p < 0.01），同时核苷酸含量降低。乳酸释放与缺血持续时间无关，尽管缺血36分钟后糖原含量下降了30%（p < 0.01）。可能含有前糖原的酸不溶性糖原部分在短期缺血期间大幅增加。缺血24分钟和36分钟后，去甲肾上腺素峰值分别增加了100倍和200倍（p < 0.05）。不同缺血时间导致的去甲肾上腺素总释放量反映了其峰值释放量。功能恢复与嘌呤和去甲肾上腺素总流出量呈负相关（两者r = -0.81）；与组织核苷酸含量相关（r = 0.84）。总之，只有在心肌ATP大幅下降后才会释放大量去甲肾上腺素。在严重缺血期间，ATP消耗超过无氧糖酵解产生的有限ATP，是影响后续再灌注恢复的关键因素。与乳酸流出不同，嘌呤和去甲肾上腺素释放是缺血和再灌注损伤的有用标志物。
