Ischemic preconditioning and methylprednisolone both equally reduce hepatic ischemia/reperfusion injury

Glanemann, Matthias; Strenziok, Romy; Kuntze, Robert; Münchow, S; Dikopoulos, Nektarios; Lippek, Frank; Langrehr, Jan M.; Dietel, Manfred; Neuhaus, P.; Nüssler, Andreas K.

doi:10.1016/j.surg.2003.08.011

Cited by 50 publications

(47 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Why IPC resulted in increased biochemical RP injury in both studies-an IPC paradox-is not clear, but could be related to our modification of the traditional IPC protocol with longer periods of RP prior to circulatory arrest. However, data in cardiac IPC which show that the early phase of IPC protection lasts up to 2 h (8), and data from liver IPC in experimental animals, which show that RP periods of 30-45 min provide better protection than RP periods of 10-15 min supported the use of our modified protocol (23). Also, it is noteworthy that the examples of this IPC paradox are evident in the literature-including literature in DDLT-substantiating our belief that the modified IPC protocol implemented in our trials is an unlikely cause of this phenomenon.…”

Section: Koneru Et Almentioning

confidence: 72%

The Ischemic Preconditioning Paradox in Deceased Donor Liver Transplantation—Evidence from a Prospective Randomized Single Blind Clinical Trial

Koneru¹,

Shareef²,

Dikdan³

et al. 2007

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

Section: Koneru Et Almentioning

confidence: 72%

The Ischemic Preconditioning Paradox in Deceased Donor Liver Transplantation—Evidence from a Prospective Randomized Single Blind Clinical Trial

Koneru¹,

Shareef²,

Dikdan³

et al. 2007

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…Even though the exact molecular-biologic mechanisms of steroids action on hepatic I/R injury remain partially unknown, it is thought that steroid therapy suppresses liver injury by a variety of mechanisms, including increased tissue blood flow and suppression of oxygen free radicals, inhibition of lysosomal proteases, suppression of calpain activation, inhibition of apoptotic activity and reduced cytokine production. [26][27][28][29][30] In this study, preoperative methylprednisolone administration attenuated significantly I/R associated tissue injury and lowered postoperative indicators of hepatocyte damage and recovery. Although some series recommended preoperative steroids administration, 31,32 concerns exist on the clinical use of steroids in liver surgery, because of the possible negative effects on liver regeneration after resection.…”

Section: Discussionmentioning

confidence: 94%

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

et al. 2006

View full text Add to dashboard Cite

Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response. The human body reacts to surgical stimuli through various systemic responses including the endocrine, metabolic, coagulation, and immune systems. However, extended damage may result in an exaggerated systemic response with an overwhelming activation of immune cells and the release of various mediators of stress. [1][2][3] The systemic reaction to the operation is considered to be equivalent to the systemic inflammation response syndrome, mainly caused by cytokine networks. 4,5 Raised levels of inflammatory cytokines have been related to higher postoperative mortality and morbidity rates. 2,3,6 Therefore, increased attention has evolved toward modulating potentially deleterious inflammatory response to the operation.The anti-inflammatory and immune modulating effects of steroids have been known for decades and have found extensive therapeutic use in a wide range of diseases in which inflammatory responses play major role. 7,8 Several trials have investigated the benefits of administering corticosteroids as a modulator of cytokine response in patients undergoing elective cardiothoracic or gastrointestinal surgery, as well as in cases of septic shock, suggesting that several aspects of the surgical stress responses, organ dysfunction, and postAbbreviations: POD, postoperative day; ALT, alanine aminotr...

show abstract

“…Inhibition of muscle proteolysis, in particular the calpain system, by corticosteroids has been suggested in several in vitro [7,19,28,29] and in vivo [14,30,31] studies. In addition, treatment with methylprednisolone has been shown to reduce caspase-3 mRNA and protein expression in several animal models [11-13]. …”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of caspase-3 by corticosteroids was previously shown in different animal models [11-13]. Indeed, administration of methylprednisolone (30 or 60 mg/kg) to piglets (corresponding ~6.5 or 13 mg/kg in humans [19]) with cardio-pulmonary bypass resulted in a reduction of myocardial caspase-3 activity [12].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

et al. 2010

View full text Add to dashboard Cite

BackgroundHigh dose of corticosteroids has been previously shown to protect against controlled mechanical ventilation (CMV)-induced diaphragmatic dysfunction while inhibiting calpain activation. Because literature suggests that the calpain inhibiting effect of corticosteroid depends on the dose administered, we determined whether lower doses of corticosteroids would also provide protection of the diaphragm during CMV. This may be important for patients undergoing mechanical ventilation and receiving corticosteroids.MethodsRats were assigned to controls or to 24 hours of CMV while being treated at the start of mechanical ventilation with a single intramuscular administration of either saline, or 5 mg/kg (low MP) or 30 mg/kg (high MP) of methylprednisolone.ResultsDiaphragmatic force was decreased after CMV and this was exacerbated in the low MP group while high MP rescued this diaphragmatic dysfunction. Atrophy was more severe in the low MP group than after CMV while no atrophy was observed in the high MP group. A significant and similar increase in calpain activity was observed in both the low MP and CMV groups whereas the high dose prevented calpain activation. Expression of calpastatin, the endogenous inhibitor of calpain, was decreased in the CMV and low MP groups but its level was preserved to controls in the high MP group. Caspase-3 activity increased in all CMV groups but to a lesser extent in the low and high MP groups. The 20S proteasome activity was increased in CMV only.ConclusionsAdministration of 30 mg/kg methylprednisolone during CMV protected against CMV-induced diaphragm dysfunction while 5 mg/kg was more deleterious. The protective effect is due mainly to an inhibition of the calpain system through preservation of calpastatin levels and to a lesser extent to a caspase-3 inhibition.

show abstract

Ischemic preconditioning and methylprednisolone both equally reduce hepatic ischemia/reperfusion injury

Cited by 50 publications

References 34 publications

The Ischemic Preconditioning Paradox in Deceased Donor Liver Transplantation—Evidence from a Prospective Randomized Single Blind Clinical Trial

The Ischemic Preconditioning Paradox in Deceased Donor Liver Transplantation—Evidence from a Prospective Randomized Single Blind Clinical Trial

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

Contact Info

Product

Resources

About