论文部分内容阅读
目的研究强心苷类正性肌力代表药去乙酰毛花苷与非强心苷类正性肌力代表药米力农的心血管动力学作用特点,分析其长期使用死亡率差别的可能机制。方法 1大鼠在体压力-容积环分析:经左侧颈外静脉缓慢推注去乙酰毛花苷0.17 mg·kg~(-1)或米力农0.78 mg·kg~(-1),Miller导管记录大鼠压力-容积环变化及动脉压。2大鼠离体心脏左心室收缩压测定:实验按正常灌流液→0.01→0.1→1μmol·L~(-1)浓度梯度灌流去乙酰毛花苷,或正常灌流液→0.1→1→10μmol·L~(-1)灌流米力农。3大鼠心肌细胞钙释放测定:测定去乙酰毛花苷或米力农各10μmol·L~(-1)加药前后钙释放。结果 1在体实验表明:去乙酰毛花苷显著增加大鼠动脉压与心室收缩末期压、心输出量、搏出功、心室收缩末期压最大上升速率和心室收缩弹性;降低舒张弹性及心室收缩末期容积;延长动脉收缩压回复50%的时间;缩短主动脉瓣关闭时间(P<0.05)。米力农显著降低大鼠动脉压与室收缩末期压、降低心室收缩及舒张末期容积、搏出功;增加每搏输出量、射血分数、输出量、心率、心室收缩末期压与舒张弹性;缩短心室内压及动脉收缩压回复50%的时间(P<0.05)。2两者均能浓度依赖性地增加离体大鼠心脏收缩的发展力及收缩压最大上升速率,但去乙酰毛花苷减慢心率,而米力农增加心率(P<0.05)。3两者均能增加大鼠心肌细胞钙释放幅值,米力农还能缩短钙回吸收时间(P<0.05)。结论去乙酰毛花苷具有正性肌力作用,而对外周阻力无明显影响。米力农发挥正性肌力作用,但有明显的扩张血管作用,且明显增加心率;这些作用可能是米力农长期使用导致死亡率增加的原因。
Objective To study the cardiovascular pharmacokinetic characteristics of cardiac glycosides, the representative agent of acetoacetylvinoside and non-cardiac glycosides, and the possible mechanism of the difference in long-term use of mortality . Method 1 Rat in-body pressure-volume ring analysis: A slow bolus of levosipin 0.17 mg · kg -1 or milrinone 0.78 mg · kg -1 was bolted into the left external jugular vein. Miller Catheter recording rat pressure - volume ring changes and arterial pressure. Left ventricular systolic pressure measurement in isolated rat heart: The rats were perfused with diacetylthiogalacturonate (normal perfusate → 0.01 → 0.1 → 1μmol·L -1) or normal perfusate → 0.1 → 1 → 10μmol · L ~ (-1) perfusion Milrinone. 3 Determination of calcium release from rat cardiomyocytes: Calcium release was measured before and after administration of 10 μmol·L -1 deacetylmastoside or milrinone. Results 1 In vivo experiments showed that stilbene significantly increased arterial pressure and ventricular end-systolic pressure, cardiac output, stroke power, maximum rate of ventricular end systolic pressure rise and ventricular contraction elasticity; decreased diastolic elasticity and ventricular contraction End-volume; prolongation of arterial systolic pressure recovery 50% of the time; shorten the aortic valve closure time (P <0.05). Milrinone significantly reduced arterial pressure and ventricular end-systolic pressure in rats, decreased ventricular systolic and end-diastolic volume and stroke volume; increased stroke volume, ejection fraction, output, heart rate, end-systolic pressure and diastolic elasticity; Shorten the ventricular pressure and arterial systolic blood pressure recovery 50% of the time (P <0.05). 2 both increased heart development and systolic pressure rise in isolated rat hearts in a concentration-dependent manner, but stilbene slowed heart rate, whereas milrinone increased heart rate (P <0.05). 3 both can increase the amplitude of calcium release from myocardial cells in rats, and Milrinone can shorten the recovery time of calcium (P <0.05). Conclusion Stilbene has positive inotropic effect, but no significant effect on peripheral resistance. Milrinone plays a positive inotropic effect, but with significant dilation of blood vessels and a significant increase in heart rate; these effects may be responsible for the increased mortality caused by long-term use of milrinone.