Hitzeschock-Protein 70: ein neuer Biomarker für das Ischämie-Reperfusionstrauma nach dem Pringle-Manöver

Abstract

Zusammenfassung. Grundlagen: Das Pringle-Manöver ist eine bewährte Methode, um große Blutverluste bei Leberteilresektionen zu vermeiden. Diese Methode führt jedoch zu einem Ischämie-Reperfusionsschaden der Leber. Der Ischämie-Reperfusionsschaden ist mit der Expression von Hitzeschock-Proteinen assoziiert.Methodik: Sechzehn Patienten nahmen an der Studie teil. Es wurden drei Leberproben von jedem Patienten entnommen, die erste vor dem Pringle-Manöver, die zweite etwa 30 Minuten nach Beginn des Manövers und die dritte Probe während Reperfusion. Die Proben wurden quantitativ mittels Echtzeit-Polymerase-Kettenreaktion auf die Expressionsdaten von HSP70-mRNA untersucht. GAP-DH wurde als Referenzgen verwendet.Ergebnisse: Die Expression von HSP70-mRNA war signifikant (P = 0.001) höher in Probe drei verglichen mit Probe eins mit Ausnahme zweier Patienten. Die Erhöhung der HSP70-mRNA-Werte korrelierte mit der Entnahmezeit der Reperfusionsprobe und den postoperativen Serum-Transaminase-Werten (P = 0.039). Bezugnehmend auf jene zwei Patienten ohne Erhöhung waren deren klinische Daten vergleichbar mit denen der anderen Patienten, jedoch zeigte einer der beiden präexistent höhere HSP70-mRNA-Werte.Schlussfolgerungen: HSP70 kann als Biomarker für den Ischämie-Reperfusionsschaden bei Leberteilresektionen dienen. Dieser Marker kann zur Entwicklung neuer Strategien in der Leberchirurgie beitragen.Schlüsselwörter: Hitzeschock-Protein 70, Leber, Ischämie-Reperfusionsschaden, Leberteilresektion, Präkonditionierung, Pringle-Manöver. Summary. Background:The Pringle maneuver is a common method to avoid blood loss during liver resection. This method, however, leads to an ischemic-reperfusion injury of the liver. The ischemic-reperfusion injury is associated with expression of heat shock proteins.Methods: Sixteen patients entered this study. Three liver tissue samples were taken from each patient, the first sample prior to Pringle maneuver, the second approximately 30 minutes after the beginning of the maneuver, and the third sample during reperfusion. The samples were quantitatively analyzed by real-time polymerase chain reaction for mRNA levels of HSP70. GAP-DH was used as a reference gene.Results: HSP70 mRNA levels were significantly (P = 0.001) higher in sample three compared to sample one, except in two patients. The elevation of HSP70 mRNA levels correlated with the time point of achieving the sample in reperfusion and with serum transaminase levels found after surgery (P = 0.039). Referring to those two patients without elevation, their clinical data were comparable to the others; however, one of them had a preexisting higher mRNA level of HSP70.Conclusions: HSP70 can be used as a biomarker for ischemic-reperfusion injury following liver resection. This marker can help to design new strategies in liver surgery.

Hepatobiliary transporter expression and post‐operative jaundice in patients undergoing partial hepatectomy

“…In contrast to the investigated transporters, the control protein HSP70 levels showed highly significant changes due to the Pringle manoeuvre resulting in a median 3.7 and 6.4-fold increase which is in accordance to previous results and validates the chosen time point as adequate to assess potential changes due to IR (12). Interestingly, the baseline mRNA expression (compared to 28s) of HSP70 showed higher mRNA levels in the low bilirubin group compared to the high bilirubin group indicating a possible protective effect of high HSP70 levels against IR injury.…”

“…The Pringle manoeuvre had no statistical significant influence on the mRNA expression of hepatobiliary transporters showing only a marginal decrease, while HSP70, a marker of IR injury , showed a median 4.5‐fold increase after Pringle manoeuvre (mean 7.9 ± 8.2; P < 0.001) (Fig. ).…”

“…Histological normal liver tissue was obtained from patients undergoing liver resection for single colorectal liver metastasis using continuous Pringle manoeuvre. Two liver tissue samples were taken from each patient according to a previously established protocol . Samples were taken in the operating theatre with biopsy needles (Temno ® ; Cardinal Health, Toronto, Canada) or resected by scalpel from non‐tumourous affected tissue.…”

“…Thus, the aims of the study were firstly, to determine the potential impact of IR injury due to Pringle manoeuvre during liver resection on transporter expression; secondly, to test whether disturbances in hepatobiliary transporter expression may contribute to post‐operative jaundice; and thirdly, to determine if pre‐operative baseline expression patterns of hepatobiliary transporter systems can predict the development of post‐operative jaundice, therefore providing the basis for potential preventive pharmaceutical strategies. Furthermore, heat shock protein 70 (HSP70) was determined as a positive control since it has previously been shown to serve as a marker of IR injury . To the best of our knowledge, this is the first report investigating the influence of hepatobiliary transporter systems on development of post‐operative jaundice in humans undergoing liver resection under Pringle manoeuvre as a stressing factor.…”

Surgery for liver metastases originating from sarcoma—case series

“…The Pringle manoeuvre had no influence on the number of applied blood transfusions and the operation time. It is known that Pringle's manoeuvre produces an ischemiareperfusion injury in the short term [30]. However, since the introduction of new blood-saving dissection devices, the manoeuvre has become less important.…”