title: Acidic infusion in early reperfusion affects the activity of antioxidant enzymes in postischemic isolated rat heart.
abstract: BACKGROUND
  Acidic perfusion (AP) performed at the onset of reperfusion (i.e., acid postconditioning) is cardioprotective. We investigated the effect of AP on postischemic cardiac function and on the activity of endogenous superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase. The role of exogenous CAT or SOD on AP cardioprotection was also investigated. Phosphorylation of redox-sensitive survival kinases (protein kinase C [PKC] ε and extracellular signal-regulated kinase [ERK] 1/2) was also checked.
  
  
  METHODS
  Isolated rat hearts underwent ischemia and reperfusion (I/R) for 30 and 120 min, respectively. AP was obtained by lowering [HCO3(-)] in the perfusion buffer. Infarct size and left ventricular pressure were measured. Protocols include I/R only, I/R plus acidic perfusion in early reperfusion (I/R + AP), and I/R plus AP and CAT (I/R + AP + CAT) or SOD (I/R + AP + SOD). I/R + SOD and I/R + CAT additional hearts served as controls. AP and/or antioxidants were given in the initial 3 min of reperfusion. Enzyme activities were studied in postischemic phase (seventh minute of reperfusion) in I/R or I/R + AP and Sham (buffer-perfused) hearts.
  
  
  RESULTS
  AP with (I/R + AP + CAT or I/R + AP + SOD) or without (I/R + AP) antioxidant enzymes resulted in a larger reduction of infarct size compared with I/R, I/R + SOD, or I/R + CAT. Compared with I/R, the postischemic systolic and diastolic recoveries of the cardiac function were markedly improved by the addition of AP and a lesser extent by AP + SOD or AP + CAT. AP increased the postischemic activity of CAT and lowered that of SOD and glutathione peroxidase compared with I/R only. Also, the phosphorylation and activity of ERK1/2 and PKCε were increased by AP.
  
  
  CONCLUSIONS
  Acid postconditioning affects the activity of endogenous antioxidant enzymes, activates ERK1/2-PKCε pathways, and protects against myocardial I/R injury. The combination of AP and exogenous SOD or CAT still provides cardioprotection. It is likely that intracellular (not extracellular) redox condition plays a pivotal role in acidic protection.
authors: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors: Claudia
authors: C
authors: Penna
authors: Maria-Giulia
authors: MG
authors: Perrelli
authors: Francesca
authors: F
authors: Tullio
authors: Carmelina
authors: C
authors: Angotti
authors: Pasquale
authors: P
authors: Pagliaro
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003971:Diastole; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006334:Heart Function Tests; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013599:Systole; D014325:Tromethamine / Q000494:pharmacology
chemical_list: D000975:Antioxidants; C074097:Krebs-Henseleit solution; D014325:Tromethamine; D002374:Catalase; D013482:Superoxide Dismutase; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D005978:Glutathione; D005947:Glucose