Abstract：
UNASSIGNED: Exercise preconditioning has been shown to protect against doxorubicin (DOX)-induced cardiac dysfunction when hearts are maintained under resting conditions. However, it is unclear whether this exercise-induced protective effect is maintained when the heart is challenged with the β 1 -adrenergic receptor agonist dobutamine (DOB), which mimics acute exercise stress. Fischer 344 rats were randomly assigned to sedentary (SED) or voluntary wheel running (WR) groups for 10 weeks. At week 11, rats were treated with either 15 mg/kg DOX or saline. Five days later, ex vivo cardiac function was assessed using an isolated working heart model at baseline, during the infusion of 7.5 μg·kg -1 ·min -1 DOB, and during recovery. DOB infusion significantly increased left ventricular developed pressure (LVDP), maximal (dP/dt max ) and minimal (dP/dt min ) rate of left ventricular pressure development, and heart rate in all groups ( P < 0.05). SED + DOX also showed a lower baseline and recovery LVDP than WR + DOX (83 ± 12 vs. 109 ± 6 mm Hg baseline, 76 ± 11 vs. 100 ± 10 mm Hg recovery, P < 0.05). WR + DOX showed higher dP/dt max and lower dP/dt min when compared with SED + DOX during DOB infusion (7311 ± 1481 vs. 5167 ± 1436 mm Hg/s and -4059 ± 1114 vs.-3158 ± 1176 mm Hg/s, respectively). SED + DOX dP/dt max was significantly lower during baseline and during recovery when compared with all other groups ( P < 0.05). These data suggest that exercise preconditioning preserved cardiac function after DOX exposure even when the heart is challenged with DOB, and it appeared to preserve the heart\'s ability to recover from this functional challenge.
摘要：
当心脏保持在静息状态时，运动预处理已被证明可以防止DOX引起的心脏功能障碍。然而,尚不清楚当心脏受到β1-肾上腺素能受体激动剂多巴酚丁胺（DOB）的攻击时，这种运动引起的保护作用是否得以维持，模仿急性运动压力。Fischer344只大鼠被随机分配到久坐（SED）或自愿车轮运行（WR）组，持续10周。在第11周,用15mg/kgDOX或盐水(SAL)处理大鼠。五天后,在基线时使用隔离的工作心脏模型评估离体心脏功能，在输注7.5μg/kg/minDOB期间，在恢复期间。DOB输注显着增加左心室发育压（LVDP），左心室压力发展的最大（dP/dtmax）和最小（dP/dtmin）速率，所有组的心率和心率（p<0.05）。SED+DOX也显示较低的基线和恢复LVDP比WR+DOX（83±12vs.109±6mmHg基线，76±11vs.100±10mmHg恢复，p<0.05)。与DOB输注期间的SEDDOX相比，WRDOX显示出较高的dP/dtmax和较低的dP/dtmin（7311±1481vs.5167±1436mmHg/s和-4059±1114vs.-3158±1176mmHg/s,分别)。当与所有其他组相比时,SED+DOXdP/dtmax在基线期间和恢复期间显著更低(p<0.05)。这些数据表明，即使心脏受到DOB的挑战，运动预处理也能在DOX暴露后保留心脏功能。它似乎保留了心脏从这种功能挑战中恢复的能力。
