Janelle G M, Urdaneta F, Blas M L, Shryock J, Tang Y S, Martin T D, Lobato E B
Department of Anesthesiology, University of Florida College of Medicine, Gainesville, 32610, USA.
Anesth Analg. 2001 Jun;92(6):1377-83. doi: 10.1097/00000539-200106000-00004.
Inotropes are often used to treat myocardial dysfunction shortly after cardiopulmonary bypass (CPB). beta-Adrenergic agonists improve contractility, in part by increasing cyclic adenosine monophosphate (cAMP) production, whereas phosphodiesterase type III inhibitors prevent its breakdown. CPB is associated with abnormalities at the beta-receptor level and diminished adenyl cyclase activity, both of which tend to decrease cAMP. These effects may be increased in the presence of preexisting myocardial dysfunction. We tested the hypothesis that inhibition of phosphodiesterase type III before global myocardial ischemia and pharmacologic arrest results in the preservation of intramyocardial cAMP concentration during CPB. Twenty adult patients undergoing coronary artery bypass grafting with CPB were studied. After CPB was instituted, a myocardial biopsy was obtained from the apex of the left ventricle. Patients were randomized to receive either placebo or milrinone (50 micro/kg) through the bypass pump 10 min before aortic cross-clamping. Another myocardial biopsy was performed adjacent to the left ventricular apex just before weaning from CPB. Myocardial cAMP concentration was determined by radioimmunoassay. Myocyte protein content was determined by the Bradford method by using a commercial kit. There were no significant demographic differences between the groups; however, patients in the Milrinone group had a lower left ventricular ejection fraction than placebo (41% +/- 13% vs 53% +/- 7%; P < 0.05). Patients who received milrinone had larger cAMP concentrations at the end of CPB compared with placebo (21 +/- 12.5 pmol/mg protein versus 12.8 +/- 2.2 pmol/mg protein; P < 0.05). The administration of milrinone before aortic cross-clamping is associated with increased intramyocardial cAMP concentration at the end of CPB.
The administration of a single dose of milrinone before aortic cross-clamping resulted in significantly larger intramyocardial cyclic adenosine monophosphate concentration in myocardial biopsy specimens compared with controls.
正性肌力药物常用于体外循环（CPB）后不久治疗心肌功能障碍。β-肾上腺素能激动剂部分通过增加环磷酸腺苷（cAMP）生成来改善心肌收缩力，而III型磷酸二酯酶抑制剂则阻止其分解。CPB与β受体水平异常及腺苷酸环化酶活性降低有关，这两者均倾向于降低cAMP。在存在预先存在的心肌功能障碍时，这些影响可能会增强。我们检验了这样一个假设，即在全心肌缺血和药物性心脏停搏前抑制III型磷酸二酯酶可在CPB期间保存心肌内cAMP浓度。对20例接受CPB冠状动脉搭桥术的成年患者进行了研究。CPB开始后，从左心室心尖获取心肌活检标本。患者在主动脉阻断前10分钟通过体外循环泵随机接受安慰剂或米力农（50微克/千克）。在脱离CPB前，在左心室心尖附近再次进行心肌活检。通过放射免疫测定法测定心肌cAMP浓度。使用商业试剂盒通过Bradford法测定心肌细胞蛋白含量。两组之间在人口统计学方面无显著差异；然而，米力农组患者的左心室射血分数低于安慰剂组（41%±13%对53%±7%；P<0.05）。与安慰剂相比，接受米力农的患者在CPB结束时的cAMP浓度更高（21±12.5皮摩尔/毫克蛋白对12.8±2.2皮摩尔/毫克蛋白；P<0.05）。在主动脉阻断前给予米力农与CPB结束时心肌内cAMP浓度增加有关。
与对照组相比，在主动脉阻断前给予单剂量米力农可使心肌活检标本中的心肌内环磷酸腺苷浓度显著更高。
