BACKGROUND: C-terminal fragments of adipokine apelin are able to attenuate 
myocardial ischemia-reperfusion (I/R) injury, but whether their effects are 
manifested during cardioplegic arrest remain obscure. This study was designed to 
evaluate the efficacy of natural apelin-12 
(H-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe-OH, A12) and its novel 
structural analogs 
(H-(N(α)Me)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH, AI, and 
N(G)-Arg(N(G)NO2)-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-NH2, AII) as 
additives to crystalloid cardioplegia and explore benefits of early reperfusion 
with these peptides.
METHODS: Isolated working rat hearts subjected to normothermic global ischemia 
and further reperfusion were used. St. Thomas' Hospital cardioplegic solution 
No.2 (STH2) containing 140 μM A12, AI, or AII was infused for 5 min at 25 °C 
before ischemia. In separate series, peptide administration was used for 5 min 
after ischemia. Metabolic state of the hearts was evaluated by myocardial 
content of high energy phosphates and lactate. Lactate dehydrogenase (LDH) 
leakage was assessed in myocardial effluent on early reperfusion.
RESULTS: Addition of the peptides to STH2 enhanced functional and metabolic 
recovery of reperfused hearts compared with those of control (STH2 without 
additives). Cardioplegia with analog AII was the most effective and accompanied 
by a reduction of postischemic LDH leakage. Infusion of A12, AI, or AII after 
ischemia improved the majority indices of cardiac function and metabolic state 
of the heart by the end of reperfusion. However, the overall protective effect 
of the peptides was less than when they were added to STH2.
CONCLUSIONS: Enhancement of apelin bioavailability may minimize myocardial I/R 
damage during cardiac surgery. Structural analogs of A12 are promising 
components of clinical cardioplegic solutions.