Van Iterson Erik H, Karpen Stephen R, Baker Sarah E, Wheatley Courtney M, Morgan Wayne J, Snyder Eric M
School of Kinesiology, University of Minnesota, Cooke Hall, 1900 University Ave SE., Minneapolis, MN, 55455, USA.
Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Respir Res. 2015 Sep 5;16(1):103. doi: 10.1186/s12931-015-0270-y.
Pulmonary system dysfunction is a hallmark of cystic fibrosis (CF) disease. In addition to impaired cystic fibrosis transmembrane conductance regulator protein, dysfunctional β2-adrenergic receptors (β2AR) contribute to low airway function in CF. Recent observations suggest CF may also be associated with impaired cardiac function that is demonstrated by attenuated cardiac output (Q), stroke volume (SV), and cardiac power (CP) at both rest and during exercise. However, β2AR regulation of cardiac and peripheral vascular tissue, in-vivo, is unknown in CF. We have previously demonstrated that the administration of an inhaled β-agonist increases SV and Q while also decreasing SVR in healthy individuals. Therefore, we aimed to assess cardiac and peripheral hemodynamic responses to the selective β2AR agonist albuterol in individuals with CF.
18 CF and 30 control (CTL) subjects participated (ages 22 ± 2 versus 27 ± 2 and BSA = 1.7 ± 0.1 versus 1.8 ± 0.0 m(2), both p < 0.05). We assessed the following at baseline and at 30- and 60-minutes following nebulized albuterol (2.5mg diluted in 3.0mL of normal saline) inhalation: 12-lead ECG for HR, manual sphygmomanometry for systolic and diastolic blood pressure (SBP and DBP, respectively), acetylene rebreathe for Q and SV. We calculated MAP = DBP + 1/3(SBP-DBP); systemic vascular resistance (SVR) = (MAP/Q)•80; CP = Q•MAP; stroke work (SW) = SV•MAP; reserve (%change baseline to 30- or 60-minutes). Hemodynamics were indexed to BSA (QI, SVI, SWI, CPI, SVRI).
At baseline, CF demonstrated lower SV, SVI, SW, and SWI but higher HR than CTL (p < 0.05); other measures did not differ. At 30-minutes, CF demonstrated higher HR and SVRI, but lower Q, SV, SVI, CP, CPI, SW, and SWI versus CTL (p < 0.05). At 60-minutes, CF demonstrated higher HR, SVR, and SVRI, whereas all cardiac hemodynamics were lower than CTL (p < 0.05). Reserves of CP, SW, and SVR were lower in CF versus CTL at both 30 and 60-minutes (p < 0.05).
Cardiac and peripheral hemodynamic responsiveness to acute β2AR stimulation via albuterol is attenuated in individuals with CF, suggesting β2AR located in cardiac and peripheral vascular tissue may be dysfunctional in this population.
肺系统功能障碍是囊性纤维化（CF）疾病的一个标志。除了囊性纤维化跨膜传导调节蛋白受损外，功能失调的β2肾上腺素能受体（β2AR）也导致CF患者气道功能低下。最近的观察结果表明，CF可能还与心功能受损有关，这在静息和运动时的心输出量（Q）、每搏输出量（SV）和心脏功率（CP）降低中得到体现。然而，CF患者体内β2AR对心脏和外周血管组织的调节尚不清楚。我们之前已经证明，吸入β激动剂可增加健康个体的SV和Q，同时降低体循环血管阻力（SVR）。因此，我们旨在评估CF患者对选择性β2AR激动剂沙丁胺醇的心脏和外周血流动力学反应。
18名CF患者和30名对照（CTL）受试者参与研究（年龄分别为22±2岁和27±2岁，体表面积分别为1.7±0.1和1.8±0.0 m²，均p<0.05）。我们在基线以及雾化吸入沙丁胺醇（2.5mg稀释于3.0mL生理盐水中）后30分钟和60分钟评估以下指标：通过12导联心电图测量心率（HR），用手动血压计测量收缩压和舒张压（分别为SBP和DBP），通过乙炔再呼吸法测量Q和SV。我们计算平均动脉压（MAP）=DBP + 1/3（SBP - DBP）；体循环血管阻力（SVR）=（MAP/Q）•80；心脏功率（CP）=Q•MAP；每搏功（SW）=SV•MAP；储备（从基线到30或60分钟的变化百分比）。血流动力学指标以体表面积进行校正（QI、SVI、SWI、CPI、SVRI）。
在基线时，CF患者的SV、SVI、SW和SWI低于CTL，但HR高于CTL（p<0.05）；其他指标无差异。在30分钟时，与CTL相比，CF患者的HR和SVRI较高，但Q、SV、SVI、CP、CPI、SW和SWI较低（p<0.05）。在60分钟时，CF患者的HR、SVR和SVRI较高，而所有心脏血流动力学指标均低于CTL（p<0.05）。在30分钟和60分钟时，CF患者的CP、SW和SVR储备均低于CTL（p<0.05）。
CF患者对通过沙丁胺醇进行的急性β2AR刺激的心脏和外周血流动力学反应减弱，提示该人群中心脏和外周血管组织中的β2AR可能功能失调。
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