Vargas Pelaez Alvaro F, Gao Zhaohui, Ahmad Tariq A, Leuenberger Urs A, Proctor David N, Maman Stephan R, Muller Matthew D
Penn State Heart and Vascular Institute, Penn State University College of Medicine, Hershey, Pennsylvania.
Division of General Internal Medicine, Penn State University College of Medicine, Hershey, Pennsylvania.
Physiol Rep. 2016 May;4(10). doi: 10.14814/phy2.12806.
Myocardial oxygen supply and demand mismatch is fundamental to the pathophysiology of ischemia and infarction. The sympathetic nervous system, through α-adrenergic receptors and β-adrenergic receptors, influences both myocardial oxygen supply and demand. In animal models, mechanistic studies have established that adrenergic receptors contribute to coronary vascular tone. The purpose of this laboratory study was to noninvasively quantify coronary responses to adrenergic receptor stimulation in humans. Fourteen healthy volunteers (11 men and 3 women) performed isometric handgrip exercise to fatigue followed by intravenous infusion of isoproterenol. A subset of individuals also received infusions of phenylephrine (n = 6), terbutaline (n = 10), and epinephrine (n = 4); all dosages were based on fat-free mass and were infused slowly to achieve steady-state. The left anterior descending coronary artery was visualized using Doppler echocardiography. Beat-by-beat heart rate (HR), blood pressure (BP), peak diastolic coronary velocity (CBVpeak), and coronary velocity time integral were calculated. Data are presented as M ± SD Isometric handgrip elicited significant increases in BP, HR, and CBVpeak (from 23.3 ± 5.3 to 34.5 ± 9.9 cm/sec). Isoproterenol raised HR and CBVpeak (from 22.6 ± 4.8 to 43.9 ± 12.4 cm/sec). Terbutaline and epinephrine evoked coronary hyperemia whereas phenylephrine did not significantly alter CBVpeak. Different indices of coronary hyperemia (changes in CBVpeak and velocity time integral) were significantly correlated (R = 0.803). The current data indicate that coronary hyperemia occurs in healthy humans in response to isometric handgrip exercise and low-dose, steady-state infusions of isoproterenol, terbutaline, and epinephrine. The contribution of β1 versus β2 receptors to coronary hyperemia remains to be determined. In this echocardiographic study, we demonstrate that coronary blood flow increases when β-adrenergic receptors are stimulated (i.e., during exercise and different intravenous infusions). Our infusion paradigms and beat-by-beat imaging methodologies can be used in future studies to evaluate age-, sex-, and disease- differences in adrenergic control of coronary blood flow.
心肌氧供与需求不匹配是缺血和梗死病理生理学的基础。交感神经系统通过α - 肾上腺素能受体和β - 肾上腺素能受体影响心肌的氧供和需求。在动物模型中，机制研究已证实肾上腺素能受体对冠状动脉血管张力有影响。本实验室研究的目的是无创量化人体冠状动脉对肾上腺素能受体刺激的反应。14名健康志愿者（11名男性和3名女性）进行等长握力运动直至疲劳，随后静脉输注异丙肾上腺素。部分个体还接受了去氧肾上腺素（n = 6）、特布他林（n = 10）和肾上腺素（n = 4）的输注；所有剂量均基于去脂体重，且缓慢输注以达到稳态。使用多普勒超声心动图观察左前降支冠状动脉。逐搏计算心率（HR）、血压（BP）、舒张期冠状动脉峰值流速（CBVpeak）和冠状动脉流速时间积分。数据以M ± SD表示。等长握力运动使BP、HR和CBVpeak显著增加（从23.3 ± 5.3增加至34.5 ± 9.9 cm/秒）。异丙肾上腺素使HR和CBVpeak升高（从22.6 ± 4.8增加至43.9 ± 12.4 cm/秒）。特布他林和肾上腺素诱发冠状动脉充血，而去氧肾上腺素未显著改变CBVpeak。不同的冠状动脉充血指标（CBVpeak和流速时间积分的变化）显著相关（R = 0.803）。当前数据表明，在健康人体中，等长握力运动以及低剂量、稳态输注异丙肾上腺素、特布他林和肾上腺素会引发冠状动脉充血。β1受体与β2受体对冠状动脉充血的贡献仍有待确定。在这项超声心动图研究中，我们证明当β - 肾上腺素能受体受到刺激时（即在运动期间和不同静脉输注期间）冠状动脉血流增加。我们的输注模式和逐搏成像方法可用于未来研究，以评估肾上腺素能对冠状动脉血流控制的年龄、性别和疾病差异。
