Neckár Jan, Papousek Frantisek, Nováková Olga, Ost'ádal Bohuslav, Kolár Frantisek
Institute of Physiology, Academy of Sciences of the Czech Republic, Centre for Experimental Cardiovascular Research, Prague.
Basic Res Cardiol. 2002 Mar;97(2):161-7. doi: 10.1007/s003950200007.
The objective of the work was to examine whether adaptation to intermittent high altitude hypoxia and ischaemic preconditioning provide additive protection of the heart against subsequent acute ischaemic injury. Adult male rats were exposed to hypoxia (7000 m, 8 h/day, 24-30 exposures) in a hypobaric chamber. Susceptibility of their hearts to ischaemia-induced ventricular arrhythmias and infarction was evaluated in open-chest animals subjected to 30-min coronary artery occlusion and 4-h reperfusion. Preconditioning was induced by either two (PC1) or five (PC2) occlusions of the same artery for 5 min, each followed by 5-min reperfusion. Adaptation to hypoxia decreased the arrhythmia score from 2.75 +/- 0.13 in normoxic controls to 2.17 +/- 0.18. Both PC1 and PC2 reduced the arrhythmia score in the controls (0.15 +/- 0.10 and 0.71 +/- 0.24, respectively), as well as in the hypoxic groups (0.40 +/- 0.15 and 0.27 +/- 0.15, respectively). The infarct size was reduced from 66.6 +/- 2.3% of the area at risk in the controls to 50.2 +/- 1.9% in the adapted rats. PC1 conferred further protection in adapted animals (38.4 +/- 2.8%) but this combined effect was of the same magnitude as that of preconditioning in the controls (37.5 +/- 1.6%). Similar results were obtained using PC2. It is concluded that adaptation to hypoxia decreases the efficiency of ischaemic preconditioning; cardioprotective effects of these two phenomena are not additive. The results are consistent with the view that the mechanisms of protection conferred by chronic hypoxia and preconditioning may share the same signalling pathway.
这项工作的目的是研究间歇性高海拔低氧适应和缺血预处理是否能为心脏提供额外保护，使其免受随后的急性缺血性损伤。成年雄性大鼠在低压舱中暴露于低氧环境（7000米，每天8小时，共24 - 30次暴露）。在开胸动物中，通过30分钟冠状动脉闭塞和4小时再灌注，评估其心脏对缺血诱导的室性心律失常和梗死的易感性。预处理通过同一条动脉的两次（PC1）或五次（PC2）闭塞5分钟诱导，每次闭塞后再灌注5分钟。低氧适应使心律失常评分从常氧对照组的2.75±0.13降至2.17±0.18。PC1和PC2均降低了对照组（分别为0.15±0.10和0.71±0.24）以及低氧组（分别为0.40±0.15和0.27±0.15）的心律失常评分。梗死面积从对照组危险区域的66.6±2.3%降至适应大鼠的50.2±1.9%。PC1在适应动物中提供了进一步的保护（38.4±2.8%），但这种联合效应与对照组预处理的效应大小相同（37.5±1.6%）。使用PC2也得到了类似结果。结论是，低氧适应降低了缺血预处理的效率；这两种现象的心脏保护作用并非相加。这些结果与慢性低氧和预处理所赋予的保护机制可能共享相同信号通路的观点一致。
