Hepatic ischemia-reperfusion syndrome and its effect on the cardiovascular system: The role of treprostinil, a synthetic prostacyclin analog

Abstract

Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities, such as major hepatic resections and liver transplantation. In addition to the organ’s post reperfusion injury, this syndrome appears to play a central role in the dysfunction of distant tissues and systems. Thus, continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates. Treprostinil is a synthetic analog of prostaglandin I2, and its experimental administration has shown encouraging results. It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation, where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min. Treprostinil improves renal and hepatic function, diminishes hepatic oxidative stress and lipid peroxidation, reduces hepatictoll-like receptor 9 and inflammation, inhibits hepatic apoptosis and restores hepatic adenosine triphosphate (ATP) levels and ATP synthases, which is necessary for functional maintenance of mitochondria. Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflammatory cytokines; therefore, it can potentially minimize ischemia-reperfusion injury. Additionally, it may have beneficial effects on cardiovascular parameters, and much current research interest is concentrated on this compound.

Keywords: Hepatic ischemia-reperfusion syndrome; Myocardial damage; Prostaglandins; Treprostinil; Liver transplantation; Hepatectomy

Core Tip: End-stage liver disease is one of the leading causes of morbidity and mortality worldwide. The role of liver transplantation and liver resection in malignant disease has changed over the last decades with the evolution of high-risk surgical techniques and the great improvement in long-term survival. However, hepatic ischemia-reperfusion syndrome remains a significant clinical problem, as it is the main reason for postoperative liver failure and multiple organ dysfunction. Treprostinil is a synthetic analog of prostaglandin I2 with potential protective effects against ischemia-reperfusion injury. We herein discuss the effect of hepatic ischemia-reperfusion syndrome on the cardiovascular system and the role of treprostinil as a new promising therapeutic option.