title: Enhancement of crystalloid cardioplegic protection by structural analogs of apelin-12.
abstract: 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.
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russia. Electronic address: olpi@cardio.ru.
authors.forename: Oleg I
authors.initials: OI
authors.lastname: Pisarenko
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russia.
authors.forename: Valentin S
authors.initials: VS
authors.lastname: Shulzhenko
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russia.
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Pelogeykina
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russia.
authors.forename: Irina M
authors.initials: IM
authors.lastname: Studneva
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000077324:Crystalloid Solutions; D006324:Heart Arrest, Induced; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007552:Isotonic Solutions / Q000737:chemistry*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000077324:Crystalloid Solutions; D036341:Intercellular Signaling Peptides and Proteins; D007552:Isotonic Solutions; C495200:apelin-12 peptide; D007770:L-Lactate Dehydrogenase
keywords: Cardiac function; Crystalloid cardioplegia; Isolated working rat heart; Myocardial metabolism; Structural analogs of apelin-12