Cardiovascular Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Eur J Cardiothorac Surg. 2010 Apr;37(4):942-9. doi: 10.1016/j.ejcts.2009.10.030. Epub 2009 Dec 6.
In contrast to the clinical evidence, experimental studies showed that chronic hypoxia (CH) confers a certain degree of protection against ischaemia-reperfusion damage. We studied the effects of daily reoxygenation during CH (CHReox) on hearts exposed to ischaemia-reperfusion. We also separated the intrinsic effects on the myocardium of CH and CHReox from those related to circulatory and nervous factors.
Fifty-one Sprague-Dawley rats were maintained for 15 days under CH (10% O(2)) or CHReox (10% O(2)+1 h day(-1) exposure to air). Normoxic (N, 21% O(2)) rats were the control. The animals were randomly assigned to one of the three following protocols: (1) protocol A: hearts (n=7 per group) were subjected to 30-min occlusion of the left anterior descending (LAD) coronary artery followed by 3-h reperfusion, with measurement of the injury by tetrazolium staining; (2) protocol B: the end-diastolic pressure (EDP) and left ventricular developed pressure x heart rate (LVDP x HR) were measured in Langendorff-perfused isolated hearts (n=5 per group) during 30-min global ischaemia and 45-min reperfusion; and (3) protocol C: hearts (n=5 per group) were frozen for the determination of levels of endothelial nitric oxide synthase (eNOS) by Western blotting.
CHReox hearts displayed greater phosphorylation of the eNOS and enhanced plasma level of nitrates and nitrites in comparison to CH hearts (P<0.0001, Bonferroni's post-test). The infarct size was greater in CH than in N hearts (P<0.0001, Bonferroni's post-test) while it was reduced in CHReox in comparison to CH and N hearts (P<0.0001). At the end of reperfusion, EDP was higher in CH than CHReox and N hearts (P=0.01, Bonferroni's post-test) while LVDP x HR was higher in CHReox and N than in CH hearts (P=0.03, Bonferroni's post-test).
Exposure to CH results in impairment of myocardial tolerance to ischaemia-reperfusion, greater injury and reduced recovery of performance, in agreement with clinical evidence. Infarct size, diastolic contracture and myocardial performance have been reduced, respectively, by 63%, 64% and 151% with daily reoxygenation compared with chronic hypoxia by accelerating intrinsic adaptive changes.
与临床证据相反，实验研究表明，慢性缺氧（CH）对缺血再灌注损伤有一定程度的保护作用。我们研究了 CH 期间每日复氧（CHReox）对缺血再灌注暴露的心脏的影响。我们还将 CH 和 CHReox 对心肌的固有影响与循环和神经因素相关的影响分开。
51 只 Sprague-Dawley 大鼠在 CH（10% O2）或 CHReox（10% O2+1 h 每日暴露于空气）下维持 15 天。常氧（N，21% O2）大鼠作为对照。动物随机分为以下三个方案之一：（1）方案 A：心脏（每组 7 只）经历 30 分钟左前降支（LAD）冠状动脉闭塞，随后 3 小时再灌注，通过四唑染色测量损伤；（2）方案 B：在 Langendorff 灌注分离心脏（每组 5 只）期间测量 30 分钟全缺血和 45 分钟再灌注期间的舒张末期压力（EDP）和左心室发展压 x 心率（LVDP x HR）；和（3）方案 C：心脏（每组 5 只）用于通过 Western 印迹法测定内皮型一氧化氮合酶（eNOS）的水平。
与 CH 心脏相比，CHReox 心脏的 eNOS 磷酸化程度更高，血浆硝酸盐和亚硝酸盐水平也更高（P<0.0001，Bonferroni 检验后）。CH 心脏的梗死面积大于 N 心脏（P<0.0001，Bonferroni 检验后），而 CHReox 心脏的梗死面积小于 CH 和 N 心脏（P<0.0001）。再灌注结束时，CH 心脏的 EDP 高于 CHReox 和 N 心脏（P=0.01，Bonferroni 检验后），而 CHReox 和 N 心脏的 LVDP x HR 高于 CH 心脏（P=0.03，Bonferroni 检验后）。
暴露于 CH 会导致心肌对缺血再灌注的耐受性受损，损伤更大，性能恢复减少，这与临床证据一致。与慢性缺氧相比，每日复氧分别减少了 63%、64%和 151%的梗死面积、舒张性收缩和心肌性能，通过加速内在适应性变化。
