Ischemia/Reperfusion Injury: Pathophysiology, Current Clinical Management, and Potential Preventive Approaches

Table 1

Main perspectives for the treatment of MIRS.

Clinical trial or animal model	Treatment	Proposed mechanisms of action	Findings	Reference
CT	αCD11/CD18	Reduction of neutrophil recruitment	No difference in baseline, angiographic of angioplasty characteristics	[68]
CT	αCD18	Reduction of neutrophil recruitment	No differences in coronary blood flow, infarct size, or ECG ST-segment elevation resolution	[69]
AM	Chemerin-15	Enhanced AAMs and IL-10; reduced ROS, neutrophils, IL-6, and TNF-α	Amelioration of MI	[85]
AM	Netrin-1	Reduction of neutrophil and macrophage recruitment, induction of AAMs	Decreased cardiomyocyte apoptosis	[86]
CT	αIL-1β	Reduction of M/M inflammatory activation	Enhanced hemodynamics and left ventricular remodeling	[87]
CT	αIL-1β	Reduction of CRP	No differences with the placebo-treated group	[88]
AM	αIL-1β	n.a.	Reduces infarct size and improves left ventricle remodeling	[90]
AM	Azithromycin	Induction of AAMs, inhibition of the PI3K/Akt pathway	Neuroprotection on an animal model of stroke	[97]
AM	Rosuvastatin	Treg expansion, reduction of inflammatory infiltrates	Reduced cardiac troponin I, infarct size	[106]
CT	αC5	n.a.	No reduction of infarct size but improved survival	[108]
CT	αC5	n.a.	Enhanced survival	[109]
CT	αC5	n.a.	Reduction of troponin T and creatine kinase-MB	[110]
CT	C1-esterase inhibitor	C1, C3c, and C4 reduction	No difference in postoperative complications, hospital stay, or in-hospital mortality	[111]
CT	C1-esterase inhibitor	C3a and C4a reduction	Enhanced mean arterial pressure, cardiac index, and stroke volume. Lower levels of cardiac troponin	[112]
AM	Low dose of methylprednisolone	n.a.	Reduced infarction size and scar	[118]
CT	Alpha-1 antitrypsin (AAT)	Reduction of CRP	Lower creatine kinase myocardial levels	[116]
AM	Galectin-1	Reduction of macrophages, NK cells, and T lymphocytes. Increase in Tregs	Enhanced heart’s contractility	[100]
AM	Intranasal troponin	Increased IL-10 and reduced IFN-γ	Reduction of infarct size	[104]
AM	Super-antagonistic αCD28 antibody	Treg and AAM induction	Increased collagen de novo expression, decreased rates of left ventricular ruptures	[49]

Abbreviations: CT: clinical trial; AM: animal model; αCD11/18: anticluster of differentiation 11/18; αC5: anti-C5 complement protein; AAM: alternatively activated macrophages; ROS: reactive oxygen species; M/M: monocyte/macrophage; CRP: C-reactive protein; Treg: T-regulatory cell, IL-1β: interleukin-1β; IL-10: interleukin-10, ECG: electrocardiogram; n.a.: not available; MI: myocardial infarction.