Pharmacological postconditioning: a molecular aspect in ischemic injury

J Pharm Pharmacol. 2020 Nov;72(11):1513-1527. doi: 10.1111/jphp.13336. Epub 2020 Jul 28.

Abstract

Objective: Ischaemia/reperfusion (I/R) injury is defined as the damage to the tissue which is caused when blood supply returns to tissue after ischaemia. To protect the ischaemic tissue from irreversible injury, various protective agents have been studied but the benefits have not been clinically applicable due to monotargeting, low potency, late delivery or poor tolerability.

Key findings: Strategies involving preconditioning or postconditioning can address the issues related to the failure of protective therapies. In principle, postconditioning (PoCo) is clinically more applicable in the conditions in which there is unannounced ischaemic event. Moreover, PoCo is an attractive beneficial strategy as it can be induced rapidly at the onset of reperfusion via series of brief I/R cycles following a major ischaemic event or it can be induced in a delayed manner. Various pharmacological postconditioning (pPoCo) mechanisms have been investigated systematically. Using different animal models, most of the studies on pPoCo have been carried out preclinically.

Summary: However, there is a need for the optimization of the clinical protocols to quicken pPoCo clinical translation for future studies. This review summarizes the involvement of various receptors and signalling pathways in the protective mechanisms of pPoCo.

Keywords: ischemia/reperfusion injury; pharmacological agents; pharmacological postconditioning; postconditioning; signalling pathways.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Animals
  • Humans
  • Ischemic Postconditioning / methods*
  • Ischemic Preconditioning / methods
  • Protective Agents / administration & dosage*
  • Protective Agents / adverse effects
  • Protective Agents / pharmacology
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / physiopathology
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Protective Agents