Advances in treatment strategies for ischemia reperfusion injury

ABSTRACT

Introduction: Ischemia-reperfusion injury (IRI) involves a complex sequence of events and limits the outcome of various surgical interventions. Clinical trials, based on the data of experimental models, aim to prove whether a pharmacological or technical approach could be suitable to provide a beneficial effect in humans. Due to the complexity of IRI, few pharmacological treatments have been investigated in clinical Phase III.

Areas covered: In this review we report clinical trials that test specific drugs in clinical trials of organ transplantation. These studies form part of Phase II trials and examine the administration of caspase inhibitors, P-selectin antagonist or an antioxidant component in order to attenuate cold IRI during transplantation. Moreover, we provide a brief description of drugs tested on trials of different clinical situations associated to IRI, such as the coronary artery bypass graft surgery and percutaneous coronary intervention.

Expert opinion: Future clinical trials could be centered on the application of techniques suitable for organs with increased vulnerability toward IRI. Furthermore, the standardization of reliable biomarkers and a careful estimation of the impact of high risk factors may be the key in order to achieve a more critical evaluation of the obtained results.

KEYWORDS:

• Clinical trial
• inflammation
• ischemia-reperfusion injury
• suboptimal grafts

Article highlights.

• Clinical trials for the prevention of ischemia-reperfusion injury (IRI) are limited, due to the multifactorial agents implicated in IRI pathophysiology.

• Drugs against cold IRI in clinical trials of organ transplantation have targeted to inhibit caspases, to block P-selectin and to decrease reactive oxygen species (ROS).

• Administration of the ROS scavenger NAC provided the most promising results in Phase II clinical trials of transplantation.

• Phase III clinical trials associated to IRI are mainly focused on heart (CABG surgery).

• To the best of our knowledge, no Phase III clinical trials have been established for the prevention of IRI in vulnerable organs such as pancreas and fatty liver.

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Declaration of interest

Supported by Fondo de Investigaciones Sanitarias (FIS PI12/00519). E Pantazi is the recipient of a fellowship from Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, 2012FI_B00382), Generalitat de Catalunya, Barcelona, Catalonia, Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.