About this Research Topic
Surgery is the mainstay for treating several liver pathological conditions. The need to reduce intraoperative hemorrhage mandates thorough liver blood flow control during surgery leading inevitably to one of the most frequent complications of liver surgery - ischemia–reperfusion injury (IRI). During ischemia, mitochondria become temporarily dysfunctional and unable to effectively cope with the burst of new oxygen brought by the reestablishment of blood flow. This causes a significant increase in oxidative stress exacerbating the cellular damage already sustained during ischemia, triggering general microvascular and parenchymal injury, accompanied by an intense acute inflammatory reaction that compromises liver function, namely its metabolic, synthetic and detoxification systemic role. The severe inflammation induced by IRI leads to necrosis and to the release of damage associated molecular patterns (DAMPs) that eventually contribute to distant organ damage and systemic dysfunction, making liver IRI one of the main contributors to morbidity and mortality following liver surgery.
Despite intensive efforts dedicated to the implementation of new therapeutical strategies to minimize the deleterious effects of liver IRI, none has shown substantial benefits. The complexity of the molecular mechanisms linked to liver IRI that include microcirculation dysfunction, hypoxia, oxidative stress and cell death remain poorly understood which also limits the development of interventions addressing the etiological mechanisms involved in liver IRI. Recently, pre–operative exercise has emerged as a promising strategy to increase patients fitness and preparedness for surgery with mounting evidence showing benefits in terms or lower rates of complications, faster recovery and improved quality of life. Importantly, in addition to the pleiotropic benefits of exercise, exercise seems to be able to address also some of the etiological mechanisms involved in liver IRI. This research topic aims to explore the mechanisms involved in liver IRI and its associated systemic complications as well as the mechanistic benefits of exercise pre-conditioning in mitigating this condition.
The objectives of this research topic are to explore the mechanisms underlying metabolic, synthetic and detoxification processes and their interaction networks, as well as networks underlying distant organ damage and systemic dysfunction involved in the pathogenesis of hepatic IRI, with an emphasis on injury occurring during liver surgery involving the Pringle maneuver. Of special interest are systemic effects of liver IRI, namely those associated with the effects of inflammation and the release of DAMPs on lung, cardiac and renal microcirculation, and metabolism networks. In addition, the research topic focuses on exploring the potential role of exercise pre-conditioning as a strategy for preventing liver surgery associated hepatic IRI, with an emphasis on mechanistic insights. The scope of this research topic encompasses investigations within the Network Physiology framework, including experimental studies on animals or human volunteers, case reports, network-based modeling approaches, narrative reviews, systematic reviews with meta-analysis and perspective articles.
Despite intensive efforts dedicated to the implementation of new therapeutical strategies to minimize the deleterious effects of liver IRI, none has shown substantial benefits. The complexity of the molecular mechanisms linked to liver IRI that include microcirculation dysfunction, hypoxia, oxidative stress and cell death remain poorly understood which also limits the development of interventions addressing the etiological mechanisms involved in liver IRI. Recently, pre–operative exercise has emerged as a promising strategy to increase patients fitness and preparedness for surgery with mounting evidence showing benefits in terms or lower rates of complications, faster recovery and improved quality of life. Importantly, in addition to the pleiotropic benefits of exercise, exercise seems to be able to address also some of the etiological mechanisms involved in liver IRI. This research topic aims to explore the mechanisms involved in liver IRI and its associated systemic complications as well as the mechanistic benefits of exercise pre-conditioning in mitigating this condition.
The objectives of this research topic are to explore the mechanisms underlying metabolic, synthetic and detoxification processes and their interaction networks, as well as networks underlying distant organ damage and systemic dysfunction involved in the pathogenesis of hepatic IRI, with an emphasis on injury occurring during liver surgery involving the Pringle maneuver. Of special interest are systemic effects of liver IRI, namely those associated with the effects of inflammation and the release of DAMPs on lung, cardiac and renal microcirculation, and metabolism networks. In addition, the research topic focuses on exploring the potential role of exercise pre-conditioning as a strategy for preventing liver surgery associated hepatic IRI, with an emphasis on mechanistic insights. The scope of this research topic encompasses investigations within the Network Physiology framework, including experimental studies on animals or human volunteers, case reports, network-based modeling approaches, narrative reviews, systematic reviews with meta-analysis and perspective articles.
Keywords: Ischemia-Reperfusion Injury, necrosis, apoptosis, myocardial infarction, stroke, liver transplant, damage-associated molecular pattern, network physiology, integrative physiology, liver surgery
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