Frishman W, Smithen C, Befler B, Kligfield P, Killip T
Am J Cardiol. 1975 May;35(5):635-44. doi: 10.1016/0002-9149(75)90049-1.
Nineteen patients with severe but stable angina pectoris entered a double blind controlled study to evaluate the effect of orally administered propranolol on exercise tolerance measured with a bicycle ergometer, and left ventricular function measured by echocardiography and systolic time intervals. In the group treated with propranolol the dose was increased from 80 to 320 mg/day. Studies including determination of propranolol blood levels were obtained before treatment and for each dose of propranolol. With propranolol, 80 mg/day, total work performance increased by 128 percent from 765 plus or minus 125 before treatment to 1,792 plus or minus 285 kilopond-meters (mean plus or minus standard error) (P less than 0.01). With 160 mg of propranolol daily, total work performance decreased, but remained higher than at control levels. In the group given propranolol, left ventricular function decreased progressively with increasing doses of the drug. As measured from the echocardiogram, maximal endocardial posterior wall velocity decreased 42 percent, from 72 plus or minus 7 to to 41 plus or minus 4 mm/sec (P less than 0.02); ejection fraction decreased 13 percent, from 0.68 plus or minus 0.01 to 0.59 plus or minus 0.01; and end-diastolic bolume increased 28 percent, from 79 plus or minus 11 to 102 plus or minus 9 ml/m2 (P less than 0.05). The preejection period and the ratio between preejection period and left ventricular ejection time significantly increased with progessive dose increments. There was no correlation between blood level of propranolol and improved work performance. Exercise tolerance was maximally improved with doses of 80 to 160 mg/day. At higher dose levels left ventricular function deteriorated and exercise work decreased. Noninvasive assessment of left ventricular function proved more valuable than determination of drug blood levels in managing patients with angina pectoris and provided a guide to optimal adjustment of dosage.
19名患有严重但稳定型心绞痛的患者进入一项双盲对照研究，以评估口服普萘洛尔对用自行车测力计测量的运动耐量以及用超声心动图和收缩期时间间期测量的左心室功能的影响。在普萘洛尔治疗组中，剂量从80毫克/天增加到320毫克/天。在治疗前以及每增加一次普萘洛尔剂量时，都进行了包括测定普萘洛尔血药浓度在内的研究。服用80毫克/天的普萘洛尔时，总工作能力从治疗前的765±125千磅-米增加到1792±285千磅-米，增幅为128%（平均值±标准误）（P<0.01）。每日服用160毫克普萘洛尔时，总工作能力下降，但仍高于对照水平。在服用普萘洛尔的组中，左心室功能随着药物剂量的增加而逐渐下降。从超声心动图测量来看，最大心内膜后壁速度从72±7毫米/秒降至41±4毫米/秒，下降了42%（P<0.02）；射血分数从0.68±0.01降至0.59±0.01，下降了13%；舒张末期容积从79±11毫升/平方米增加到102±9毫升/平方米，增加了28%（P<0.05）。射血前期以及射血前期与左心室射血时间的比值随着剂量的逐渐增加而显著增加。普萘洛尔血药浓度与工作能力改善之间没有相关性。80至160毫克/天的剂量能最大程度地提高运动耐量。在更高剂量水平时，左心室功能恶化，运动工作量减少。在管理心绞痛患者时，左心室功能的无创评估比药物血药浓度测定更有价值，并为最佳剂量调整提供了指导。
