Table 4

Experimental Studies Illustrating the Potential for Additive Cardioprotection With Multiple Cardioprotective Agents Or Interventions Targeting the Same Signaling Pathway but With Potentiating Effects

First Author, Year (Ref. #)Experimental AMI ModelCardioprotective Agents or InterventionsCardioprotective EffectSignaling Pathways
Xin et al., 2010 (62)In vivo ratLimb RIPerC (4 × 5/5-min cycles)
IPost (6 × 10/10-s cycles)
Additive effects on reducing MI size, reducing ROS at reperfusion and inhibiting apoptosisAdditive effects on Akt and Erk1/2 phosphorylation
Huang et al., 2011 (63)In vivo ratEsmolol infusion at reperfusion
Milrinone infusion at reperfusion
Additive effects on reducing MI size, and inhibiting apoptosisAdditive effects on PKA activity and Akt phosphorylation
Fan et al., 2012 (51)In vivo diabetic and nondiabetic ratsAtorvastatin at reperfusion
IPost (6 × 10/10 s)
Diabetic heart resistant to IPost and partially protected by atorvastatin. However, combination of IPost and atorvastatin reduces MI sizeAdditive effects on Akt and eNOS
Tratsiakovich et al., 2013 (46)In vivo rat and pigL-arginine at reperfusion
Tetrahydrobiopterin (BH4) at reperfusion
Additive effects on reducing MI size, and reducing ROS at reperfusionAdditive cardioprotection mediated by NOS
Wang et al., 2015 (64)In vivo ratLimb RIPerC (1 cycle of 10-min ischemia and 5-min reperfusion)
Vagal stimulation
Additive effects on reducing MI size and inflammationNot investigated

NOS = nitric oxide synthase; PKA = protein kinase A; other abbreviations as in Tables 1 and 3.

  • Other criteria are as per Table 1.