Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
Elife. 2017 Nov 9;6:e29280. doi: 10.7554/eLife.29280.
After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic 'no-reflow' has been attributed to capillary constriction by contractile pericytes. We now show that occlusion of a rat coronary artery, followed by reperfusion, blocks 40% of cardiac capillaries and halves perfused blood volume within the affected region. Capillary blockages colocalised strongly with pericytes, where capillary diameter was reduced by 37%. The pericyte relaxant adenosine increased capillary diameter by 21% at pericyte somata, decreased capillary block by 25% and increased perfusion volume by 57%. Thus, cardiac pericytes constrict coronary capillaries and reduce microvascular blood flow after ischaemia, despite re-opening of the culprit artery. Cardiac pericytes are therefore a novel therapeutic target in ischaemic heart disease.
心肌缺血后，即使上游动脉血流恢复，冠状动脉微血管灌注仍常持续减少。这种“无复流”现象会使患者预后恶化。在脑卒中等情况下，类似的缺血后“无复流”现象归因于收缩性周细胞引起的毛细血管收缩。我们现在发现，大鼠冠状动脉阻塞后继发再灌注会导致 40%的心脏毛细血管闭塞，并使受影响区域的灌流血液量减少一半。毛细血管闭塞与周细胞强烈共定位，其中毛细血管直径缩小了 37%。周细胞松弛剂腺苷使周细胞体的毛细血管直径增加 21%，使毛细血管闭塞减少 25%，灌流体积增加 57%。因此，尽管罪犯动脉再通，但心肌周细胞在缺血后会收缩冠状动脉毛细血管并减少微血管血流。因此，心肌周细胞是缺血性心脏病的一个新的治疗靶点。
