De Jong J W, Van der Meer P, Owen P, Opie L H
Cardiochemical Laboratory, Erasmus University Rotterdam, The Netherlands.
Bratisl Lek Listy. 1991 Mar-Apr;92(3-4):165-73.
Using Langendorff rat hearts, we tested whether 1. adenosine as a cardioplegic agent, and 2. inosine administered during reperfusion could prevent and treat ischemic injury, respectively. For cardioplegic arrest (37 degrees C), buffer supplemented with 20 mM K+ (K), K + 1 mM adenosine (KA), or none (Control, C), was infused for 3 min at 3 ml/min. Arrest time was 260 +/- 16 s (C), 22 +/- 4 s (K) and 10 +/- 2 s (KA, p less than 0.02 vs K). During 20 min total ischemia, resting tension increased only in C, and remained elevated after 20 min reperfusion. In treated hearts resting tension rose somewhat and returned to baseline. Developed tension: heart rate (g/min) after reperfusion was superior with KA:C (3,180 +/- 830), K (4,380 +/- 390), and KA (6,250 +/- 740, p less than 0.05 vs. K.). Our electrophysiological studies suggest that adenosine increases K(+)-permeability and thereby arrests the sinus node. It did not affect high-energy phosphates. We also tested whether inosine could regenerate nucleotides. We perfused hearts with buffer containing glucose +/- pyruvate. After 15 min no-flow, hearts were reperfused for 45 min with 20 microM inosine and 0.5 mM ribose. Adenine nucleotide levels tended to recover better in the purine-treated groups. Inosine decrease the ATP/ADT ratio by 15% (p less than 0.05) and increased the IMP level 2 times (p less than 0.01) whom pyruvate was absent. It increased the effluent adenosine concentration 6 times (p less than 0.005). Inosine administration +/- pyruvate did not affect function recovery, heart rate or coronary flow. Thus adenosine as adjunct to K(+)-cardioplegia shortened arrest time, and was also beneficial for post-ischemic recovery. Inosine given during reperfusion failed to improve heart function. Both treatments hardly affected cardiac adenine nucleotide levels.
我们使用Langendorff大鼠心脏，测试了：1. 腺苷作为心脏停搏剂，以及2. 再灌注期间给予肌苷是否能分别预防和治疗缺血性损伤。对于心脏停搏（37℃），以3ml/min的速度灌注补充有20mM K+（K组）、K + 1mM腺苷（KA组）或无补充剂（对照组，C组）的缓冲液3分钟。停搏时间分别为260±16秒（C组）、22±4秒（K组）和10±2秒（KA组，与K组相比p<0.02）。在20分钟的总缺血期间，仅C组的静息张力增加，且在再灌注20分钟后仍保持升高。在处理过的心脏中，静息张力略有上升并恢复到基线。再灌注后的心脏作功张力：心率（g/min），KA组：C组为（3,180±830），K组为（4,380±390），KA组为（6,250±740，与K组相比p<0.05）。我们的电生理研究表明，腺苷增加K+通透性，从而使窦房结停搏。它不影响高能磷酸盐。我们还测试了肌苷是否能再生核苷酸。我们用含有葡萄糖±丙酮酸的缓冲液灌注心脏。在15分钟无血流后，心脏用20μM肌苷和0.5mM核糖再灌注45分钟。在嘌呤处理组中，腺嘌呤核苷酸水平的恢复趋势更好。在无丙酮酸的情况下，肌苷使ATP/ADT比值降低15%（p<0.05），使IMP水平增加2倍（p<0.01）。它使流出的腺苷浓度增加6倍（p<0.005）。给予肌苷±丙酮酸不影响功能恢复、心率或冠状动脉血流。因此，腺苷作为K+心脏停搏的辅助剂缩短了停搏时间，对缺血后恢复也有益。再灌注期间给予肌苷未能改善心脏功能。两种处理对心脏腺嘌呤核苷酸水平几乎没有影响。
