Reports expanded from these preliminary findings with exogenously utilized urocortin demonstrated unequivocally that urocortin shields primary cardiomyocytes from apoptotic cell death, calculated using both Annexin V surface discoloration and TUNEL positivity. More over, these cardio-protective peptides were MAPK inhibitors also able to protect the complete heart ex vivo by reducing infarct size within the Langendorff perfusion model and in vivo. These studies have been recently extended to show that Ucn III and Ucn II were also effective cardio-protective agents, in-vitro and ex vivo. The power of its homologues and urocortin to protect the heart from I/R injury is currently overwhelmingly recognized. Nevertheless, the particular mechanism of action of those cardioprotective agents is less well-understood. The vast majority of mechanistic studies of cardioprotection has been conducted on urocortin. In these studies, it became evident early-on that urocortins cardioprotective mechanism of action was complicated, requiring service of many Meristem various kinases for the severe effects of urocortin, and necessitating altered gene expression for the later effects of urocortin, because some of the cardioprotection induced by urocortin was lost in the presence of cyclohexamide. Several significant kinase pathways are influenced by urocortin treatment. Numerous early reports using primary cardiomyocyte arrangements implicated MAPK as being involved in one cardioprotective route utilized by urocortin. A subfamily of MAPK, the MAPK, is phosphorylated and activated by the MAPK kinase. Apparently, particular pharmacological inhibition of MEK1/2 by PD 98059 canceled when assayed by TUNEL positivity, Annexin V, and trypan blue exclusion cardioprotection developed by urocortin. This abolition of urocortins cardioprotective effect was observed when PD 98059 was given during ischemia, but also when (-)-MK 801 given during reperfusion. While studies using primary cardiomyocyte supplements are important, it’s essential to extend studies to the whole heart. Again, we see that the inhibitor of the MEK1/2 process PD 98059 eliminates the ability of urocortin to reduce infarct size during I/R in a ex vivo center design using the Langendorff perfusion apparatus. These studies were also seen for the two urocortin homologues, SRP and SCP, in both in-vitro studies and studies employing the Langendorff perfused ex vivo heart model, indicating that three of the urocortins, at-least partly, possess a comparable mechanism of action, via the service of the MEK1/2 process. Additional to the MEK1/2 and p42/44MAPK pathway, activation of the serine threonine Akt and the phosphatidyl inositol 3 OH kinase, its downstream effector, has additionally been shown to maintain cardiac func-tion and to become involved in cardioprotection created by urocortin during I/R.