title: Na(+)/H(+) exchange inhibitor cariporide attenuates cell injury predominantly during ischemia and not at onset of reperfusion in porcine hearts with low residual blood flow.
abstract: BACKGROUND
  This study investigated whether myocardial protection by inhibition of Na(+)/H(+) exchange (NHE) occurs during ischemia and/or during reperfusion.
  
  
  RESULTS
  The left anterior descending coronary artery was occluded in 32 pigs for 60 minutes and then reperfused for 24 hours. Infarct sizes (nitroblue tetrazolium [NBT] stain, histology) were determined at the end of the experiments. An extracorporeal bypass was used to achieve a constant residual blood flow of 3 mL/min in the myocardium at risk during ischemia. The NHE-1 inhibitor cariporide or distilled water was infused into the extracorporeal bypass system. In group 1, active treatment was administered from the onset of ischemia until 10 minutes of reperfusion (n=8). In group 2, active treatment was infused during the first 30 minutes of ischemia only (n=8). The group 3 animals (n=8) received intracoronary cariporide after 45 minutes of ischemia until 10 minutes of reperfusion. The control animals (group 4, n=7) were treated similarly to group 1 animals, with the cariporide solution being replaced by distilled water. Infarct sizes of group 1 (NBT stain, 41.5+/-20%; histology, 44. 6+/-12%) and group 2 (NBT stain, 33.5+/-14%; histology 34.9+/-15%) differed significantly (at least P:=0.012) from infarct sizes of group 3 (NBT stain, 71.6+/-15%; histology, 69.2+/-12%) and the control group (NBT stain, 76+/-9%; histology 72.4+/-12%). Cariporide treatment in group 1 and group 2 significantly improved functional recovery after 24 hours of reperfusion.
  
  
  CONCLUSIONS
  Myocardial protection by cariporide is predominantly achieved by NHE inhibition during ischemia and not during early reperfusion.
authors.affiliation: Division of Cardiology, Städt Krankenanstalten Idar-Oberstein GmbH, Germany, FRG.
authors.forename: H H
authors.initials: HH
authors.lastname: Klein
authors.forename: S
authors.initials: S
authors.lastname: Pich
authors.forename: R M
authors.initials: RM
authors.lastname: Bohle
authors.forename: S
authors.initials: S
authors.lastname: Lindert-Heimberg
authors.forename: K
authors.initials: K
authors.lastname: Nebendahl
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D003326:Coronary Circulation / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007261:Infusions, Intra-Arterial; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013450:Sulfones / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013552:Swine
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide