Table 2

Experimental Studies Illustrating the Potential for Additive Cardioprotection With Multiple Cardioprotective Agents or Interventions Combining Cardiomyocyte Targets With Noncardiomyocyte Targets

First Author, Year (Ref. #)Experimental AMI ModelCardioprotective Agents or InterventionsCardioprotective EffectCardiomyocyte and Noncardiomyocyte Targets
Koshinuma et al., 2014 (42)Isolated guinea pig heartZ-VAD during ischemia and first 30 min of reperfusion
Necrostatin-1 during ischemia and first 30 min of reperfusion
Additive effects on reducing MI sizeZ-VAD—apoptosis inhibition
Necrostatin-1—necroptosis inhibition
Yang et al., 2015 (60)In vivo ratCangrelor at reperfusion
Endonuclease III at reperfusion
Additive effects of cangrelor and endonuclease III on reducing MI sizeCangrelor, P2Y12 inhibitor—platelets
Endonuclease III, targets mitochondrial DNA—cardiomyocyte
Alexopoulos et al., 2017 (61)In vivo rabbitExenatide at reperfusion
Cyclosporine-A at reperfusion parstatin 1-26 at reperfusion
Additive effects with exenatide combined with either cyclosporine-A or parstatin 1-26 on reducing MI sizeExenatide-GLP-1 signaling—cardiomyocytes
Cyclosporine-A—MPTP cardiomyocytes
Parstatin 1-26—inflammation
Audia et al., 2018 (41)In vivo ratVX-765 and ticagrelor or cangrelor at reperfusionAdditive reduction in MI size after 2-h and 3-day reperfusion.P2Y12 inhibitor—platelets
VX-765, caspase 1 inhibitor—inhibition of cardiomyocyte pyroptosis

MPTP = mitochondrial permeability transition pore; VAD = val-ala-asp; Z-VAD = Z-val-ala-asp. Other abbreviations as in Table 1.

  • Other criteria are as per Table 1.