Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia , Kelowna, British Columbia , Canada.
Cardiff School of Sport, Cardiff Metropolitan University , Cardiff , United Kingdom.
Am J Physiol Heart Circ Physiol. 2018 Jul 1;315(1):H132-H140. doi: 10.1152/ajpheart.00689.2017. Epub 2018 Mar 30.
It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po and Pco or if coronary vascular responses are the result of concomitant increases in myocardial O consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po and Pco would be attenuated in healthy men when [Formula: see text] was attenuated with β-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LAD; Doppler echocardiography), heart rate, and arterial blood pressure. LAD values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (ME) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, ME, and LAD, but only RPP and ME were attenuated (4-18%) after β-adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and ME responses, β-adrenergic receptor blockade did not attenuate the mean LAD vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β-adrenergic receptor blockade. These results indicate a direct influence of arterial Po on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po and Pco during hypercapnic hypoxia.
目前尚不清楚人体冠状动脉血管系统是否对动脉 Po 和 Pco 的变化固有敏感，或者冠状动脉血管反应是否是心肌 O 消耗/需求增加的结果([公式：见正文])。我们假设，当β-肾上腺素能受体阻断时，健康男性的 Po 和 Pco 对冠状动脉的反应会减弱。在一项双盲、随机交叉研究中，健康男性(年龄：25 ± 1 岁，n = 11)接受静脉注射艾司洛尔(β-肾上腺素能受体拮抗剂)或容量匹配的生理盐水，并暴露于变温低氧、等碳酸低氧和高碳酸低氧中。在每种气体处理的稳定状态 5 分钟后测量的指标包括左前降支冠状动脉血流速度(LAD；多普勒超声心动图)、心率和动脉血压。在每个低氧条件结束时，比较艾司洛尔和安慰剂组的 LAD 值。在β-肾上腺素能受体阻断后(RPP 和 ME 降低 4-18%，P < 0.05)，所有气体操作均增加了 RPP、ME 和 LAD，但只有 RPP 和 ME 降低。尽管 RPP 和 ME 反应减弱，但与安慰剂相比，β-肾上腺素能受体阻断并不能减弱变温低氧(29.4 ± 2.2 比 27.3 ± 1.6 cm/s)和等碳酸低氧(29.5 ± 1.5 比 30.3 ± 2.2 cm/s)期间的平均 LAD 血管扩张反应。高碳酸低氧引起的反馈性冠状动脉扩张被β-肾上腺素能受体阻断所阻断。这些结果表明，动脉 Po 对冠状动脉血管调节有直接影响，与[公式：见正文]无关。新发现和值得注意的地方在人类中，动脉低氧血症导致心外膜冠状动脉血流速度增加。尽管心肌 O 需求减少，但β-肾上腺素能受体阻断并不能减弱低氧血症对冠状动脉的反应。这些数据表明，低氧血症可以独立于心肌 O 消耗调节冠状动脉血流。左前降支冠状动脉血流速度-压力乘积关系的平均平台表明，β-肾上腺素能受体介导的、反馈性的心外膜冠状动脉扩张。此外，我们在高碳酸低氧中观察到 Po 和 Pco 的协同作用。
