Table 5

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

First Author, Year (Ref. #)Experimental AMI ModelCardioprotective Agents or InterventionsCardioprotective EffectSignaling Pathways
Rastaldo et al., 2012 (48)Isolated rat heartHybrid molecule containing NO donor and antioxidantAdditive effects on reducing MI sizeMitochondrial KATP channel
Lougiakis et al., 2016 (47)In vivo rabbitHybrid molecule containing H2S-donor and adenosine analogue at reperfusionAdditive effects on reducing MI sizecGMP/PKG/phospholamban pathway
García-Ruiz et al., 2016 (17) and Garcia-Prieto et al., 2017 (27)In vivo pig
In vivo mouse
Intravenous metoprolol targeting simultaneously cardiomyocytes (reducing energy demand), and neutrophils (inhibiting migration and neutrophil–platelet coaggregates)Reduces infarct size when given at different times of ischemia duration, but effect is stronger when given earlierCardiomyocyte oxygen consumption reduction and neutrophil conformational re-arrangements

cGMP = cyclic guanosine monophosphate; PKG = protein kinase G; other abbreviations as in Table 1.

  • Other criteria are as per Table 1.