Experimental Study of Liver Injury after Partial Hepatectomy with Intermittent or Continuous Hepatic Vascular Occlusion

Abstract

The degree of residual liver injury in normal and cirrhotic rats undergoing 70% hepatectomy with hepatic inflow occlusion was examined. The total duration of clamping was 60 min and animals were divided into 3 groups according to the ischemic modality: a 15-min intermittent clamping group (group I); a 30-min intermittent clamping group (group II), and a 60-min continuous clamping group (group III). In normal liver rats, the survival rates after operation in groups I, II and III were 90, 90 and 30%, respectively, compared to 70, 50 and 38%, respectively, in cirrhotic rats. The serum aspartate aminotransferase (AST) level increased markedly with prolongation of each period of clamping in rats with normal liver, showing higher AST levels than those with cirrhotic liver. The liver tissue adenosine-5’-triphosphate (ATP) levels and energy charge (EC) values decreased with prolongation of each period of clamping. Cirrhotic livers showed lower ATP levels and EC values than normal livers. Although there was no significant difference in the mitochondrial function between normal and cirrhotic livers in the group of the same form of ischemia, phosphorylative efficiency of mitochondria was maintained satisfactorily in normal groups I and II and in the cirrhotic group I. Even though cirrhotic livers showed a smaller necrotic response to ischemia than normal livers, they were more vulnerable to ischemia because of an inability to maintain energy metabolism. Therefore, when performing resection of a cirrhotic liver, a 15-min intermittent clamping method should be adopted.

Intermittent ischemia reduces warm hypoxia-reoxygenation–induced JNK1/SAPK1 activation and apoptosis in rat hepatocytes

“…Liver resections are frequently performed under complete or partial vascular occlusion to reduce blood loss, and it has been shown that intermittent rather than continuous pedicle occlusion leads to lower postoperative morbidity and mortality rates. 2,4,[20][21][22][23] Significant improvement of postoperative liver function has been observed in rats 22 and humans after intermittent ischemia. 23 Recently, Sakamoto et al 24 showed that the upper limit of cumulative intermittent hepatic ischemia could be extended to 322 minutes without any postsurgical complications.…”

Isquemia hepática normotérmica em ratos: estudo da lesão celular através do uso de clampeamento pedicular contínuo e intermitente

“…Com o objetivo de minimizar as lesões provocadas pela isquemia e pela reperfusão alguns estudos foram elaborados utilizando a manobra de Pringle por curtos perío-dos, seguidos de reperfusão em vários ciclos [7][8][9][10][11][12][13][14] . Teoricamente, nos pequenos intervalos em que o órgão era perfundido haveria retorno da atividade aeróbia, o que diminuiria a produção de ácido láctico e radicais livres, já sabidamente envolvidos na etiologia da lesão celular.…”

“…Entretanto, vários trabalhos que compararam os dois tipos de clampeamento, mesmo que com a utilização de intervalos de isquemia e reperfusão diferentes ou de animais doentes ou sadios na metodologia, utilizando-se uma avaliação enzimática precoce ou tardia 8,9,11,13,20 , chegaram às mesmas conclusões: há benefício da utilização do clampeamento intermitente, especialmente em situações de necessidade de isquemia prolongada.…”

Review: Research Toward Safer Resectionof the Cirrhotic Liver

“…Techniques of occluding hepatic inflow (Pringle maneuver) and outflow are being investigated as means of reducing blood loss in healthy livers [16]. However, the ability of cirrhotic liver to tolerate blood flow occlusion has not yet been fully elucidated and may limit its use in this situation [35]. In a pilot study involving 15 patients with cirrhosis who had hepatic inflow occlusion (Pringle maneuver) for 9-32 minutes during hepatic resection, a significant decrease in blood loss was achieved compared to a similar group of 15 patients operated on without the use of blood flow occlusion.…”