Intrahepatic Tissue pO₂ during Continuous or Intermittent Vascular Inflow Occlusion in a Pig Liver Resection Model

Abstract

Background: Temporary vascular inflow occlusion of the liver (clamping of the hepatic pedicle) can prevent massive blood loss during liver resections. In this study, intrahepatic tissue pO₂ was assessed as parameter of microcirculatory disturbances induced by ischemia and reperfusion (I/R) in the liver following continuous (Cnt) or intermittent (Int) clamping in a hemihepatectomy model in the pig. Methods: Pigs (20–34 kg) were divided into 2 groups: I/R without hemihepatectomy (–HH; n = 10) and I/R with hemihepatectomy (+HH; n = 8). Ischemia during 90 min was Cnt or Int (6 sequential periods of 12 min of ischemia and 3 min of reperfusion), followed by 120 min of reperfusion. Intrahepatic pO₂ histograms (polarographic pO₂ needle electrode) were constructed before ischemia, at the end of 90 min of ischemia and after 120 min of reperfusion, along with assessment of plasma AST, ALT and LDH. Bile production was monitored continuously. Results: Cumulative frequency distribution curves (CFDC) after 120 min of reperfusion in the Cnt–HH group were not different from preischemic CFDC (means ± SEM), whereas in the Int–HH group a left shift occurred indicating more hypo(non)perfused liver areas (pO₂ < 10 mm Hg: 2.6 ± 1.2 and 41.0 ± 17.5% in Cnt–HH and Int–HH; p < 0.01). In the Cnt+HH group, a left shift in the CFDC occurred. In the Int+HH group, a left and a right shift occurred simultaneously, indicating both hypo(non)- and hyperperfused (shunting) liver areas (pO₂ < 10 mm Hg: 4.0 ± 2.7 and 9.6 ± 8.5%, n.s., and pO₂ > 60 mm Hg: 2.0 ± 2.0 and 17.3 ± 6.4%, p = 0.015, in Cnt+HH and Int+HH). Plasma AST, ALT and LDH levels were not increased after 120 min of reperfusion, except for AST in Cnt+HH and Int+HH (from 54.6 ± 14.0 to 270.4 ± 42.8 U/l, p < 0.01, and from 47.8 ± 9.4 to 176.5 ± 55.9 U/l, n.s.). Bile production (percentage of mean preischemic value) during 120 min of reperfusion was significantly reduced in the Int–HH group, as compared to the Cnt–HH group (57.0 and 117.0% after 120 min of reperfusion, p = 0.002). In Cnt+HH and Int+HH, bile production was significantly reduced (33.3 ± 20.0%, p = 0.05, and 38.5 ± 7.9%, p = 0.007); however it was not different between the two groups. Conclusions: (1) Intrahepatic tissue pO₂ as indicator of microvascular perfusion is a parameter of early I/R injury; (2) continuous vascular inflow occlusion resulted in less microcirculatory disturbances, when compared to intermittent occlusion.

Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution

“…Microvascular perfusion was assessed by performing intrahepatic tissue pO 2 measurements using a polarographic pO 2 needle electrode (SIGMA pO 2 -Histograph KIMOC, Eppendorf, Hamburg, Germany), as described previously [24,25]. A pO 2 histogram was constructed from 100 consecutive pO 2 values obtained by stepwise withdrawal of the needle over a 2-cm tract (pilgrim step method) in the right median liver lobe.…”

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.…”

“…Este é o ciclo mais freqüentemente utilizado na prática clínica, em humanos. Alguns autores preferiram utilizar ciclos com períodos de isquemia e/ou reperfusão maiores (12 ou 15 minutos de isquemia, 10 ou 15 minutos de reperfusão) em seus trabalhos experimentais 7,12,13,15 .…”

“…A falta de energia secundária à hipóxia prejudica o funcionamento da bomba de sódio-potássio-ATPase, permitindo o influxo celular de grande quantidade de sódio e água levando à ruptura celular. A utilização das transaminases e da LDH como parâmetro de lesão do hepatócito vem sendo bem demonstrada em diversos estudos, como o de Isozaki 8 , Kimura 9 , Luo 16 , Nishimura 17 , Urakami 15 e van Wagensveld 12,13 .…”

“…Apesar de existirem muitas opções entre as diversas substâncias utilizadas para qualificar e quantificar a lesão da célula hepáti-ca optamos pela dosagem de TGO, TGP e LDH por quatro motivos principais: 1) muitos dos estudos que utilizam outras substâncias também fazem dosagem de uma ou mais destas enzimas 9,12,13,15,17 ; 2) são as substâncias mais freqüentemente encontradas na literatura na avaliação do dano celular; 3) são de fácil acesso, podendo ser dosadas em qualquer laboratório; 4) são, efetivamente, o que utilizamos na prática clínica no acompanhamento de nossos doentes.…”