Cave A C, Collis C S, Downey J M, Hearse D J
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Cardiovasc Res. 1993 Apr;27(4):663-8. doi: 10.1093/cvr/27.4.663.
A brief period of ischaemia (5 min) and reperfusion (5 min), prior to a longer period of ischaemia and reperfusion, has been shown to reduce the extent of injury (necrosis, arrhythmias, or postischaemic contractile malfunction) caused by a subsequent longer period of ischaemia and reperfusion. Adenosine has been identified as a factor in the protection afforded against regional tissue necrosis by such preconditioning. The aim of this study was to assess the role of adenosine in preconditioning induced protection of postischaemic function in the globally ischaemic isolated rat heart.
The ability of global ischaemia to precondition against postischaemic contractile malfunction was first confirmed in the isolated ejecting rat heart preparation. Hearts (n = 6 per group) were perfused aerobically (37 degrees C, paced at 350 beats.min-1) for 20 min, at the end of which contractile function was measured. This was followed by 10 min of Langendorff perfusion (control group) or 5 min of global ischaemia plus 5 min of Langendorff reperfusion (preconditioned group). The hearts were then subjected to 20 min of global ischaemia (37 degrees C) and 35 min of reperfusion (15 min Langendorff and 20 min ejecting); function was then reassessed.
Postischaemic recovery of aortic flow was 26(SEM 8)% in the control group v 57(4)% in the preconditioned group (p < 0.05). To assess whether exogenous adenosine could mimic this protection, the experiments were repeated with the 5 min period of ischaemic preconditioning replaced by 5 min of aerobic Langendorff perfusion with adenosine-containing buffer (100, 50, or 10 mumol.litre-1). No protection of postischaemic function was observed in any of the adenosine treated groups. In further experiments, we assessed whether ischaemic preconditioning persisted in the presence of the A1/A2 adenosine antagonist, 8 (p-sulphophenyl) theophylline (8-SPT). Since pacing was not used in these studies, the ability of ischaemia to precondition the myocardium was again confirmed; the protocol was then repeated with 8-SPT (10 mumol.litre-1) present in the perfusate throughout. Although 8-SPT depressed recovery in both control and preconditioned hearts it failed to abolish the protective effects of ischaemic preconditioning.
There is no evidence from these results to support the involvement of adenosine to any major extent in preconditioning induced protection of postischaemic contractile function in the isolated rat heart.
在较长时间的缺血和再灌注之前，进行短时间的缺血（5分钟）和再灌注（5分钟），已被证明可减少随后较长时间的缺血和再灌注所导致的损伤程度（坏死、心律失常或缺血后收缩功能障碍）。腺苷已被确定为这种预处理对局部组织坏死提供保护作用的一个因素。本研究的目的是评估腺苷在预处理诱导的对整体缺血离体大鼠心脏缺血后功能保护中的作用。
首先在离体射血大鼠心脏标本中证实整体缺血对缺血后收缩功能障碍的预处理能力。心脏（每组n = 6）在有氧条件下（37℃，起搏频率为350次/分钟）灌注20分钟，结束时测量收缩功能。随后进行10分钟的Langendorff灌注（对照组）或5分钟的整体缺血加5分钟的Langendorff再灌注（预处理组）。然后心脏再经历20分钟的整体缺血（37℃）和35分钟的再灌注（15分钟Langendorff灌注和20分钟射血）；之后重新评估功能。
对照组缺血后主动脉血流恢复率为26（标准误8）%，而预处理组为57（4）%（p < 0.05）。为了评估外源性腺苷是否能模拟这种保护作用，重复实验，将5分钟的缺血预处理替换为用含腺苷缓冲液（100、50或10 μmol/L）进行5分钟的有氧Langendorff灌注。在任何腺苷处理组中均未观察到对缺血后功能的保护作用。在进一步的实验中，我们评估了在存在A1/A2腺苷拮抗剂8 - （对磺基苯基）茶碱（8 - SPT）的情况下缺血预处理是否仍然存在。由于这些研究中未使用起搏，再次证实了缺血对心肌的预处理能力；然后在整个灌注液中加入8 - SPT（10 μmol/L）重复该方案。尽管8 - SPT降低了对照组和预处理组心脏的恢复，但未能消除缺血预处理的保护作用。
这些结果没有证据支持腺苷在很大程度上参与预处理诱导的对离体大鼠心脏缺血后收缩功能的保护作用。
