Santarpino G, Caroleo S, Onorati F, Dimastromatteo G, Abdalla K, Amantea B, Santangelo E, Gulletta E, Renzulli A
Cardiac Surgery Unit, Magna Graecia University of Catanzaro, Italy.
Int J Clin Pharmacol Ther. 2009 Feb;47(2):78-88. doi: 10.5414/cpp47078.
Recent reports have showed an antiinflammatory effect of phosphodiesterase III inhibitors (PDEi) in patients undergoing cardiopulmonary bypass (CPB). We sought to evaluate the immunological and hemodynamic response to enoximone and methylprednisolone in patients undergoing CABG.
Prospective, randomized, controlled study.
Cardiac surgery unit in a university hospital.
40 patients undergoing CPB-CABG.
Patients receive enoximone (20, Group A) or methylprednisolone (20, Group B).
Hemodynamic response was evaluated by Swan-Ganz catheter serial measurements and perioperative Lactate and Troponin I leakage, immunological response was analyzed by IL-2, IL-4, IL-6, TNF-alpah, IFN-gamma, IL-10 before anesthetic induction (T0), at aortic-declamping (T1), at the end of surgery (T2), ITU admission (T3), 24 hs (T4) postoperatively. Morbidity and mortality were comparable between the two groups. Group A demonstrated higher cardiac index at T2 (2.93 l/min m2 vs 2.06, p < 0.001), at T3 (3.01 vs 2.18, p < 0.001), lower indexed systemic vascular resistance at T2 (2,044 dyne s cm-5 m-2 vs 3,132, p < 0.001). Except for higher TNF-alpha in Group B at T2 (15.89 vs 22.68, p = 0.005) proinflammatory cytokines were comparable. IL-10 was higher in Group B at any postoperative time (IL-10: T1 80.74 vs 143.3, p < 0.001, T2 165.7 vs 377.4, p < 0.001, T3 203.4 vs 443.5, p < 0,001, T4 251.8 vs 437.1, p < 0.001), whereas IL-4 and IFN-gamma proved higher in Group A at all time-points (IL-4: T1 45.9 vs 31.2, p = 0.008, T2 67.2 vs 39.7, p < 0.001, T3 77.9 vs 39.2, p < 0.001, T4 102.9 vs 42.2, p < 0.001. IFN-gamma: T1 25.8 vs 15.8, p < 0.001, T2 52.2 vs 30.3, p < 0.001, T3 78.4 vs 40.8, p < 0.001, T4 159.9 vs 67.4, p < 0.001).
Despite comparable major clinical endpoints enoximone showed a different antiinflammatory pattern compared to methylprednisolone, however, the better hemodynamic response in enoximone compared to methylprednisolone suggests enoximone as a potential antiinflammatory tool to improve the outcome in cardiac surgery.
近期报告显示磷酸二酯酶III抑制剂（PDEi）对接受体外循环（CPB）的患者具有抗炎作用。我们旨在评估接受冠状动脉旁路移植术（CABG）的患者对依诺昔酮和甲泼尼龙的免疫和血流动力学反应。
前瞻性、随机、对照研究。
大学医院的心脏外科病房。
40例接受CPB-CABG的患者。
患者接受依诺昔酮（20例，A组）或甲泼尼龙（20例，B组）。
通过Swan-Ganz导管连续测量评估血流动力学反应以及围手术期乳酸和肌钙蛋白I泄漏情况，通过麻醉诱导前（T0）、主动脉阻断时（T1）、手术结束时（T2）、重症监护病房入院时（T3）、术后24小时（T4）的白细胞介素-2（IL-2）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、白细胞介素-10（IL-10）分析免疫反应。两组的发病率和死亡率相当。A组在T2时心脏指数较高（2.93升/分钟/平方米对2.06，p<0.001），在T3时（3.01对2.18，p<0.001），在T2时体循环血管阻力指数较低（2044达因·秒/厘米⁻⁵/平方米对3132，p<0.001）。除B组在T2时肿瘤坏死因子-α较高（15.89对22.68，p = 0.005）外，促炎细胞因子相当。术后任何时间B组的白细胞介素-10均较高（白细胞介素-10：T1 80.74对143.3，p<0.001，T2 165.7对377.4，p<0.001，T3 203.4对443.5，p<0.001，T4 251.8对437.1，p<0.001），而A组在所有时间点白细胞介素-4和干扰素-γ均较高（白细胞介素-4：T1 45.9对31.2，p = 0.008，T2 67.2对39.7，p<0.001，T3 77.9对39.2，p<0.001，T4 102.9对42.2，p<0.001。干扰素-γ：T1 25.8对15.8，p<0.001，T2 52.2对30.3，p<0.001，T3 78.4对40.8，p<0.001，T4 159.9对67.4，p<0.001）。
尽管主要临床终点相当，但与甲泼尼龙相比，依诺昔酮显示出不同的抗炎模式，然而，与甲泼尼龙相比，依诺昔酮更好的血流动力学反应表明依诺昔酮是改善心脏手术结局的潜在抗炎工具。
