Endogenous adenosine increases O-2 utilisation efficiency in isoprenaline-stimulated canine myocardium
Endogenous adenosine increases O-2 utilisation efficiency in isoprenaline-stimulated canine myocardium
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DOI：
10.1016/s0008-6363(95)00166-2
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发表时间：
1996-01-01
影响因子：
10.8
通讯作者：
Downey, HF
中科院分区：
文献类型：
--
作者：
Mallet, RT;Lee, SC;Downey, HF
目的：我们以前已经证明，心肌是能够下调其O-2的需求，从而避免缺血时，O-2供应是有限的。本研究验证了这一假设，即内源性腺苷产生这种保护性反应时，O-2供应减少中度冠状动脉低灌注或中度冠状动脉低氧血症。研究方法：在麻醉犬中，通过左胸廓切开术暴露心脏，并安装仪器以测量心室内压和局部心肌节段长度。分离左前降支冠状动脉，插管，体外灌注。通过将冠状动脉灌注压从100 mmHg降至60 mmHg或将冠状动脉O-2含量降低50%，可适度降低冠状动脉O-2供应。在用异丙肾上腺素刺激β-肾上腺素能期间，用冠状动脉内输注腺苷、腺苷脱氨酶以降解内源性腺苷或用邻位-9-（2-羟基-3-壬基）-腺嘌呤盐酸盐（EHNA）以抑制内源性腺苷脱氨酶对腺苷的降解来处理心脏。左前降支灌注区的心功率指标为心率、左室收缩压峰值和收缩段缩短百分比的乘积。O-2利用效率取为功率指数/心肌O-2消耗的比值。结果：在O-2供应减少之前，异丙肾上腺素没有改变O-2利用效率。冠状动脉内腺苷使异丙肾上腺素刺激时的O-2利用率增加23%（P <0.05）。在异丙肾上腺素刺激过程中，EHNA略微增加O-2利用率（10%; P <0.05）;腺苷脱氨酶没有影响。当冠状动脉灌注压降低时，腺苷脱氨酶在异丙肾上腺素刺激期间急剧降低心脏功率和O-2利用效率，而EHNA增强异丙肾上腺素增强功率并增加效率。在低氧血症期间，腺苷脱氨酶降低局部功率，但不影响异丙肾上腺素输注效率; EHNA不影响功率，但降低O-2消耗，提高效率。在异丙肾上腺素刺激过程中，心肌乳酸提取和收缩功能并没有因O-2供应减少而减弱，表明在这些条件下不会发生心肌缺血。结论：内源性腺苷在β-肾上腺素能刺激期间增加心肌O-2利用效率，从而有助于避免心肌O-2供应减少时的缺血。
Objective: We have previously demonstrated that myocardium is capable of down-regulating its O-2 requirements and thus avoiding ischaemia when O-2 supply is limited. The present study tested the hypothesis that endogenous adenosine produced this protective response when O-2 supply was decreased by moderate coronary hypoperfusion or moderate coronary hypoxaemia. Methods: In anaesthetised dogs, hearts were exposed by left thoracotomy and instrumented for measuring intraventricular pressure and regional myocardial segment length. The left anterior descending coronary artery was isolated, cannulated, and extracorporeally perfused. Coronary O-2 supply was moderately reduced by lowering coronary perfusion pressure from 100 to 60 mmHg or by lowering coronary arterial O-2 content by 50%. Hearts were treated with intracoronary infusions of adenosine, adenosine deaminase to degrade endogenous adenosine or with erythro-9-(2-hydroxy-3-nonyl)-adenine HCl (EHNA) to inhibit adenosine degradation by endogenous adenosine deaminase, during beta-adrenergic stimulation with isoprenaline. Cardiac power in the left anterior descending perfusion territory was indexed by the product of heart rate left ventricular peak systolic pressure percent systolic segment shortening. O-2 utilisation efficiency was taken as the ratio of power index/myocardial O-2 consumption. Results: Prior to a reduction in O-2 supply, isoprenaline did not alter O-2 utilisation efficiency. Intracoronary adenosine increased O-2 utilisation efficiency during isoprenaline stimulation by 23% (P < 0.05). EHNA slightly increased O-2 utilisation efficiency during isoprenaline stimulation (10%; P < 0.05); adenosine deaminase was without effect. When coronary perfusion pressure was decreased, adenosine deaminase sharply lowered cardiac power and O-2 utilisation efficiency during isoprenaline stimulation, whereas EHNA augmented isoprenaline-enhanced power and increased efficiency. During hypoxaemia, adenosine deaminase lowered regional power bur not efficiency during isoprenaline infusion; EHNA did not affect power but lowered O-2 consumption and increased efficiency. Myocardial lactate extraction and contractile function during isoprenaline stimulation were not attenuated by reduced O-2 supply, indicating that myocardial ischaemia did not occur under these conditions. Conclusion: Endogenous adenosine increases myocardial O-2 utilisation efficiency during beta-adrenergic stimulation, and thus helps avert ischaemia when myocardial O-2 supply is reduced.