Merkus Daphne, Houweling Birgit, van Vliet Marion, Duncker Dirk J
Experimental Cardiology, Thoraxcenter, Cardiovascular Research School COEUR, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1306-13. doi: 10.1152/ajpheart.00631.2004. Epub 2004 Nov 11.
Previous studies demonstrated a decreased flow reserve in the hypertrophied myocardium early after myocardial infarction (MI). Previously, we reported that exacerbation of hemodynamic abnormalities and neurohumoral activation during exercise caused slight impairment of myocardial O(2) supply in swine with a recent MI. We hypothesized that increased metabolic coronary vasodilation [via ATP-sensitive K(+) (K(ATP)(+)) channels and adenosine] may have partially compensated for the increased extravascular compressive forces and increased vasoconstrictor neurohormones, thereby preventing a more severe impairment of myocardial O(2) balance. Chronically instrumented swine were exercised on a treadmill up to 85% of maximum heart rate. Under resting conditions, adenosine receptor blockade [8-phenyltheophylline (8-PT), 5 mg/kg i.v.] and K(ATP)(+) channel blockade (glibenclamide, 3 mg/kg i.v.) produced similar decreases in myocardial O(2) supply in normal and MI swine. However, while glibenclamide's effect waned in normal swine during exercise (P < 0.05), it was maintained in MI swine. 8-PT's effect was maintained during exercise and was not different between normal and MI swine. Finally, in normal swine combined treatment with 8-PT and glibenclamide produced a vasoconstrictor response that equaled the sum of the responses to blockade of the individual pathways. In contrast, in MI swine the vasoconstrictor response to 8-PT and glibenclamide was similar to that produced by glibenclamide alone. In conclusion, despite significant hemodynamic abnormalities in swine with a recent MI, myocardial O(2) supply and O(2) consumption in remodeled myocardium are still closely matched during exercise. This close matching is supported by increased K(ATP)(+) channel-mediated coronary vasodilation. Although the net vasodilator influence of adenosine was unchanged in remodeled myocardium, it became exclusively dependent on K(ATP)(+) channel opening.
以往研究表明，心肌梗死（MI）后早期肥厚心肌的血流储备降低。此前，我们报道过，近期发生MI的猪在运动期间血流动力学异常和神经体液激活加剧，导致心肌氧供轻度受损。我们推测，代谢性冠状动脉扩张增强[通过ATP敏感性钾（KATP+）通道和腺苷]可能部分抵消了血管外压迫力增加和血管收缩性神经激素增加的影响，从而防止心肌氧平衡受到更严重的损害。对长期植入仪器的猪在跑步机上进行运动，使其心率达到最大心率的85%。在静息状态下，腺苷受体阻断剂[8-苯基茶碱（8-PT），静脉注射5mg/kg]和KATP+通道阻断剂（格列本脲，静脉注射3mg/kg）使正常猪和MI猪的心肌氧供产生相似程度的降低。然而，虽然格列本脲在正常猪运动期间的作用减弱（P<0.05），但在MI猪中其作用得以维持。8-PT的作用在运动期间得以维持，正常猪和MI猪之间无差异。最后，在正常猪中，8-PT和格列本脲联合治疗产生的血管收缩反应相当于对各个途径阻断反应之和。相比之下，在MI猪中，对8-PT和格列本脲的血管收缩反应与单独使用格列本脲时相似。总之，尽管近期发生MI的猪存在明显的血流动力学异常，但在运动期间，重塑心肌的心肌氧供和氧消耗仍紧密匹配。这种紧密匹配得到KATP+通道介导的冠状动脉扩张增强的支持。虽然在重塑心肌中腺苷的净血管舒张影响未改变，但它完全依赖于KATP+通道开放。
