Mehrabi Arianeb, Golling Markus, Kashfi Arash, Boucsein Tamara, Schemmer Peter, Gutt Carsten N, Schmidt Jan, Büchler Markus W, Kraus Thomas W
Division of Liver Transplantation, Department of General, Visceral, and Transplant Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
Liver Transpl. 2005 Feb;11(2):174-87. doi: 10.1002/lt.20299.
Catecholamines are often administered during and after liver transplantation (LTx) to support systemic perfusion and to increase organ oxygen supply. Some vasoactive agents can compromise visceral organ perfusion. We followed the hypothesis that the vasculature of transplanted livers presents with a higher sensitivity, which leads to an increased vulnerability for flow derangement after application of epinephrine (Epi) or norepinephrine (NorEpi). Hepatic macroperfusion and microperfusion during systemic Epi or NorEpi infusion were measured by Doppler flow and thermodiffusion probes in porcine native, denervated, and transplanted livers (n = 16 in each group). Epi or NorEpi were infused (n = 8 in each subgroup) in predefined dosages (low dose = 5 microg/kg/minute and high dose = 10 microg/kg/minute) over 240 minutes. Systemic cardiocirculatory parameters were monitored continuously. Hepatic perfusion data were compared between all groups at comparable time points and dosages. In all native, denervated, and transplanted liver groups, Epi and NorEpi induced an inconsistent rise of mean arterial pressure and heart rate shortly after onset of infusion in both dosages compared with baseline. No significant differences of cardiovascular parameters at comparable time points were observed. In native livers, Epi and NorEpi induced only temporary alterations of hepatic macrocirculation and microcirculation, which returned to baseline 2 hours after onset of infusion. No significant alterations of hepatic blood flow were detected after isolated surgical denervation of the liver. By contrast, transplanted livers showed a progressive decline of hepatic macrocirculation (33-75% reduction) and microcirculation (39-58% reduction) during catecholamine infusions in a dose-dependent fashion. Characteristics of liver blood flow impairment were comparable for both vasoactive agents. In conclusion, pronounced disturbances of hepatic macrocirculation and microcirculation were observed during systemic Epi and NorEpi infusion after LTx compared with native and denervated livers. Microcirculation disturbances after LTx might be explained by impairment of hepatic blood flow regulation caused by an increased sensitivity of hepatic vasculature after ischemia-reperfusion and by lengthening of vasopressor effects caused by reduced hepatocyte metabolism. Clinicians should be aware of this potentially hazardous effect. Therefore, application of catecholamines after clinical LTx should be indicated carefully.
在肝移植(LTx)期间及术后常使用儿茶酚胺来维持全身灌注并增加器官氧供。一些血管活性药物可能会损害内脏器官灌注。我们遵循这样的假设,即移植肝脏的血管系统具有更高的敏感性,这导致在应用肾上腺素(Epi)或去甲肾上腺素(NorEpi)后血流紊乱的易感性增加。通过多普勒血流仪和热扩散探头测量猪的正常肝脏、去神经肝脏和移植肝脏(每组n = 16)在全身输注Epi或NorEpi期间的肝脏宏观灌注和微观灌注。以预定剂量(低剂量 = 5微克/千克/分钟,高剂量 = 10微克/千克/分钟)在240分钟内输注Epi或NorEpi(每个亚组n = 8)。持续监测全身心脏循环参数。在可比的时间点和剂量下比较所有组的肝脏灌注数据。在所有正常肝脏、去神经肝脏和移植肝脏组中,与基线相比,两种剂量的Epi和NorEpi在输注开始后不久均导致平均动脉压和心率不一致地升高。在可比时间点未观察到心血管参数的显著差异。在正常肝脏中,Epi和NorEpi仅引起肝脏宏观循环和微观循环的暂时改变,在输注开始后2小时恢复到基线。肝脏单独手术去神经后未检测到肝血流的显著改变。相比之下,在儿茶酚胺输注期间,移植肝脏的肝脏宏观循环(减少33 - 75%)和微观循环(减少39 - 58%)呈剂量依赖性逐渐下降。两种血管活性药物的肝血流损害特征相似。总之,与正常肝脏和去神经肝脏相比,肝移植后全身输注Epi和NorEpi期间观察到明显的肝脏宏观循环和微观循环紊乱。肝移植后的微循环紊乱可能是由于缺血再灌注后肝脏血管系统敏感性增加导致肝血流调节受损,以及肝细胞代谢降低导致血管升压作用延长所致。临床医生应意识到这种潜在的有害影响。因此,临床肝移植后儿茶酚胺的应用应谨慎指征。