Table 1

Experimental Studies Illustrating the Potential for Additive Cardioprotection With Multiple Cardioprotective Agents or Interventions Having Distinct Targets Within the Cardiomyocyte

First Author, Year (Ref. #)Experimental AMI ModelCardioprotective Agents or InterventionsCardioprotective EffectSignaling Pathways
Schwiebert et al., 2010 (58)In vivo ratXenon (20%) at reperfusion
Hypothermia (34°C) at reperfusion
Additive effects on reducing MI sizeNot investigated
Alburquerque-Béjar et al., 2015 (8)In vivo pigRIPerC
GIK or exenatide at reperfusion
Additive effects of RIPerC with either insulin or exenatideRIPerC—less oxidative stress and reduced eNOS uncoupling
GIK and exenatide—shift to glycolysis
Sun et al., 2016 (59)In vivo miceNaHS (H2S donor) at reperfusion
SNAP (NO donor) at reperfusion
Additive effects on reducing MI sizeNaHS—S-sulfhydration
SNAP—S-nitrosylation

Experimental studies illustrating the potential for additive cardioprotective effects with 2 or more agents or interventions given acutely in combination during ischemia or shortly after reperfusion. Only those agents given in the short term in combination during ischemia or shortly after reperfusion, and demonstrating a reduction in infarct size that is additive are shown.

AMI = acute myocardial infarction; eNOS = endothelial nitric oxide synthase; GIK = glucose/insulin/potassium; MI = myocardial infarction; NaHS = Sodium hydrosulfide; NO = nitric oxide; RIPerC = remote limb ischemic per-conditioning during cardiac ischemia; SNAP = S-nitroso-N-acetylpenicillamine.