Ditchey R V, LeWinter M M, Higgins C B
Int J Cardiol. 1984 Sep;6(3):341-53. doi: 10.1016/0167-5273(84)90194-3.
Although chronic doxorubicin (adriamycin) cardiotoxicity often is attributed to repeated episodes of acute myocardial injury, the acute effects of doxorubicin on in vivo left ventricular performance have not been studied in a carefully controlled setting. Accordingly, we recorded high-fidelity left ventricular pressures and segmental dimensions before and after either intravenous or intracoronary doxorubicin in twelve open-chest dogs. Propranolol was administered to prevent reflex sympathetic stimulation, and heart rate was held constant by atrial pacing. Intravenous doxorubicin (1.5 mg/kg) (n = 6) caused significant decreases in all measured indices of myocardial contractility, in association with a large decrease in left ventricular systolic pressure (125 +/- 28 and 81 +/- 23 mm Hg before and 5 min after doxorubicin, respectively, P less than 0.01). Intracoronary doxorubicin (0.075 to 0.3 mg/kg) (n = 6) caused similar decreases in percent segment shortening (from 19 +/- 7 to 16 +/- 8, P less than 0.05), mean normalized shortening rate (from 0.87 +/- 0.34 to 0.71 +/- 0.37 segment lengths/sec, P less than 0.05), and peak positive left ventricular dP/dt (by 10 +/- 11%, P less than 0.07), although left ventricular systolic pressure was only modestly decreased (126 +/- 20 and 113 +/- 17 mm Hg before and after doxorubicin, respectively, P less than 0.01). Intracoronary doxorubicin also slowed the rate of left ventricular relaxation, as evidenced by an increase in the time constant for isovolumic pressure fall from 32.0 +/- 9.0 to 36.9 +/- 7.5 msec, and significantly altered the relationship between left ventricular pressure and dimension at end-diastole.
尽管慢性阿霉素（阿霉素）心脏毒性常被归因于急性心肌损伤的反复发作，但阿霉素对体内左心室功能的急性影响尚未在严格控制的条件下进行研究。因此，我们记录了12只开胸犬静脉或冠状动脉注射阿霉素前后的高保真左心室压力和节段尺寸。给予普萘洛尔以防止反射性交感神经刺激，并通过心房起搏使心率保持恒定。静脉注射阿霉素（1.5mg/kg）（n = 6）导致所有测量的心肌收缩力指标显著降低，同时左心室收缩压大幅下降（阿霉素注射前和注射后5分钟分别为125±28和81±23mmHg，P<0.01）。冠状动脉内注射阿霉素（0.075至0.3mg/kg）（n = 6）导致节段缩短百分比类似程度的降低（从19±7降至16±8，P<0.05），平均标准化缩短率（从0.87±0.34降至0.71±0.37节段长度/秒，P<0.05），以及左心室dP/dt峰值正向变化（降低10±11%，P<0.07），尽管左心室收缩压仅适度降低（阿霉素注射前后分别为126±20和113±17mmHg，P<0.01）。冠状动脉内注射阿霉素还减慢了左心室舒张速率，等容压力下降时间常数从32.0±9.0增加到36.9±7.5毫秒即证明了这一点，并且显著改变了舒张末期左心室压力与尺寸之间的关系。
