Cardioplegia is used to partially alleviate the effects of surgically induced global ischemia injury; however, the molecular mechanisms involved in this cardioprotection remain to be elucidated. To improve understanding of the molecular processes modulating the effects of global ischemia and the cardioprotection afforded by cardioplegia we have constructed rabbit heart cDNA libraries and have isolated, sequenced and identified a compendium of non-redundant cDNAs for use in transcriptomic and proteomic analysis. New Zealand White rabbits were used comparison of the effects of global ischemia and cardioplegia as compared to control (non-ischemic) hearts. The effects of RNA and protein synthesis on the cardioprotection afforded by cardioplegia were investigated separately by pre-perfusion with either -amanitin or cycloheximide. Our results demonstrate that cardioplegia partially ameliorates the effects of global ischemia and that cardioprotection is modulated by RNA and protein dependent mechanisms. Transcriptomic and proteomic enrichment analysis indicated that global ischemia down-regulates genes/proteins associated with the mitochondrion function and energy production and cofactor catabolism, generation of precursor metabolites of energy. In contrast, cardioplegia significantly increases differentially expressed genes/proteins associated with the mitochondrion and mitochondrial function and significantly up-regulates the biological processes of muscle contraction, involuntary muscle contraction, carboxylic acid and fatty acid catabolic processes, fatty acid beta-oxidation and fatty acid metabolic processes.