Huang C H, Kim S J, Ghaleh B, Kudej R K, Shen Y T, Bishop S P, Vatner S F
Cardiovascular and Pulmonary Research Institute, Allegheny University of the Health Sciences, Pittsburgh, Pennsylvania 15212, USA.
Am J Physiol. 1999 Feb;276(2):H368-75. doi: 10.1152/ajpheart.1999.276.2.H368.
The goal of this study was to determine whether the cardioprotective effects of an A1-receptor agonist and ischemic preconditioning (IPC) involve a shift in the pre-coronary artery occlusion (CAO) spatial distribution of myocardial blood flow, which might shed light on the mechanism of IPC and explain its heterogeneous effects. Accordingly, 60 min of CAO followed by 72 h of coronary artery reperfusion (CAR) was examined in three groups of conscious pigs 10-14 days after instrumentation with aortic and left atrial catheters and coronary artery occluders. Myocardial infarct size, expressed as a fraction of the area at risk (AAR), was reduced significantly (P < 0.05) by infusion of the A1 agonist (27.1 +/- 6.6%) and to a greater extent (P < 0.05) by IPC (11.6 +/- 5.1%) compared with infarct size in vehicle-treated animals (55.1 +/- 2.9%). Transmural myocardial blood flow (radioactive microspheres) in the AAR shifted toward lower levels after infusion of the A1 agonist (1.27 +/- 0.19 vs. 0.74 +/- 0.10 ml. min-1. g-1) or IPC (1.27 +/- 0.11 vs. 0.96 +/- 0.09 ml. min-1. g-1) but not after infusion of the vehicle (1.20 +/- 0.10 vs. 1.23 +/- 0.09 ml. min-1. g-1). This study demonstrated that both pretreatment with an adenosine A1 agonist and also IPC altered the spatial distribution of pre-CAO myocardial blood flow, which might reflect a downregulation of metabolic state and thus play a role in the cardioprotective effects of IPC.
本研究的目的是确定A1受体激动剂和缺血预处理（IPC）的心脏保护作用是否涉及冠状动脉闭塞（CAO）前心肌血流空间分布的改变，这可能有助于阐明IPC的机制并解释其异质性效应。因此，在三组清醒猪中进行了60分钟的CAO，随后进行72小时的冠状动脉再灌注（CAR），这些猪在植入主动脉和左心房导管以及冠状动脉闭塞器后10 - 14天。与给予赋形剂处理的动物相比，A1激动剂输注使心肌梗死面积（以危险区面积的分数表示）显著降低（P < 0.05）（27.1 ± 6.6%），IPC使其降低幅度更大（P < 0.05）（11.6 ± 5.1%）（赋形剂处理动物的梗死面积为55.1 ± 2.9%）。在输注A1激动剂（1.27 ± 0.19对0.74 ± 0.10 ml·min-1·g-1）或IPC（1.27 ± 0.11对0.96 ± 0.09 ml·min-1·g-1）后，危险区内跨壁心肌血流（放射性微球）向较低水平转移，但输注赋形剂后未出现这种情况（1.20 ± 0.10对1.23 ± 0.09 ml·min-1·g-1）。本研究表明，腺苷A1激动剂预处理和IPC均改变了CAO前心肌血流的空间分布，这可能反映了代谢状态的下调，从而在IPC的心脏保护作用中发挥作用。
