Fleg J L, Schulman S, O'Connor F, Becker L C, Gerstenblith G, Clulow J F, Renlund D G, Lakatta E G
Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Md.
Circulation. 1994 Nov;90(5):2333-41. doi: 10.1161/01.cir.90.5.2333.
The cardiovascular response to beta-adrenergic stimulation is markedly blunted with advancing age, and this blunting may underlie some of the prominent age-associated changes in the hemodynamic profile during dynamic exercise. To examine this hypothesis, we administered the nonselective beta-adrenergic receptor blocker propranolol (0.15 mg/kg IV) to 25 healthy normotensive men ages 28 to 72 years from the Baltimore Longitudinal Study of Aging (BLSA) immediately before maximal upright cycle ergometry with 99mTc gated cardiac blood pool scintigraphy. Their hemodynamic responses to exercise were compared with those of 70 age-matched healthy unmedicated male BLSA control subjects. The maximal cycle work rate achieved was similar in propranolol-treated men (158 +/- 32 W) and control subjects (148 +/- 32 W) and declined similarly with age in both groups. Hemodynamics at seated rest were not age-related in either group; however, propranolol-treated men had lower heart rates (HR), systolic blood pressure (SBP), ejection fraction, and cardiac index than control subjects but higher end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) by covariance analysis. At maximal effort, several striking age-drug interactions were evident: Propranolol caused a greater reduction in HR and greater increases in EDVI and stroke volume index (SVI) in younger than in older men. Hence, at maximal work rate, HR declined less with age in the propranolol group (0.46 versus 1.09 beats per minute per year, P < .05 by covariance analysis); EDVI and SVI decreased with age (0.27 and 0.48 mL/m2 per year, respectively) after propranolol compared with increases of 0.47 and 0.16 mL/m2 per year in control subjects, respectively, each P < or = .05 by covariance analysis. The left ventricular contractility index, SBP/ESVI, at exhaustion was reduced by propranolol to a greater extent in younger than older men. Thus, acute beta-adrenergic blockade reverses the age-associated ventricular dilation at end diastole and end systole observed during upright cycle exercise and blunts the decline in maximal HR and myocardial contractility. These data suggest that the age-associated declines in maximal HR and left ventricular contractility during vigorous exercise are manifestations of reduced beta-adrenergic responsivity with advancing age which is partially offset by exercise-induced ventricular dilation.
随着年龄的增长，心血管系统对β-肾上腺素能刺激的反应明显减弱，这种减弱可能是动态运动期间血流动力学特征中一些与年龄相关的显著变化的基础。为了验证这一假设，我们在巴尔的摩纵向衰老研究（BLSA）中，对25名年龄在28至72岁的健康血压正常男性，在进行最大强度直立自行车测力计运动前，立即静脉注射非选择性β-肾上腺素能受体阻滞剂普萘洛尔（0.15mg/kg），同时进行99mTc门控心血池闪烁扫描。将他们对运动的血流动力学反应与70名年龄匹配的健康未用药男性BLSA对照受试者的反应进行比较。普萘洛尔治疗组男性（158±32W）和对照组受试者（148±32W）达到的最大自行车工作率相似，且两组均随年龄下降情况相似。两组在静息坐位时的血流动力学与年龄无关；然而，通过协方差分析，普萘洛尔治疗组男性的心率（HR）、收缩压（SBP）、射血分数和心脏指数低于对照组，但舒张末期容积指数（EDVI）和收缩末期容积指数（ESVI）更高。在最大努力时，明显出现了一些显著的年龄-药物相互作用：普萘洛尔导致年轻男性的心率降低幅度大于老年男性，EDVI和每搏量指数（SVI）增加幅度也更大。因此，在最大工作率时，普萘洛尔组心率随年龄下降的幅度较小（每年0.46次/分钟对1.09次/分钟，协方差分析P<0.05）；与对照组受试者每年分别增加0.47和0.16mL/m2相比，普萘洛尔治疗后EDVI和SVI随年龄下降（分别为每年0.27和0.48mL/m2），协方差分析各P≤0.05。运动至疲劳时，左心室收缩性指数SBP/ESVI，普萘洛尔使年轻男性降低的程度大于老年男性。因此，急性β-肾上腺素能阻滞可逆转直立自行车运动期间观察到的与年龄相关的舒张末期和收缩末期心室扩张，并减弱最大心率和心肌收缩性的下降。这些数据表明，剧烈运动期间与年龄相关的最大心率和左心室收缩性下降是随着年龄增长β-肾上腺素能反应性降低的表现，而运动诱导的心室扩张可部分抵消这种降低。
