title: Sodium-hydrogen exchange inhibition during ventricular fibrillation: Beneficial effects on ischemic contracture, action potential duration, reperfusion arrhythmias, myocardial function, and resuscitability.
abstract: BACKGROUND
  Inhibition of the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) is emerging as a promising novel strategy for ameliorating myocardial injury associated with ischemia and reperfusion. We investigated whether NHE-1 inhibition (with cariporide) could minimize mechanical and electrical myocardial abnormalities that develop during ventricular fibrillation (VF) and improve outcome using a porcine model of closed-chest resuscitation.
  
  
  RESULTS
  Two groups of 8 pigs each were subjected to 8 minutes of untreated VF and randomized to receive either a 3-mg/kg bolus of cariporide or 0.9% NaCl immediately before an 8-minute interval of conventional closed-chest resuscitation. Cariporide prevented progressive increases in left ventricular free-wall thickness (from 1.0+/-0.2 to 1.5+/-0.3 cm with NaCl, P<0.001 versus 0.9+/-0.1 to 1.1+/-0.3 cm with cariporide, P=NS), maintained the coronary perfusion pressure above resuscitability thresholds (10+/-8 versus 19+/-3 mm Hg before attempting defibrillation, P<0.05), and increased resuscitability (2 of 8 versus 8 of 8, P<0.005). In 2 additional groups of 4 pigs each subjected to a briefer interval of untreated VF, cariporide ameliorated postresuscitation shortening of the action potential duration (APD) at 30%, 60%, and 90% repolarization (ie, APD60 at 2 minutes after resuscitation; 75+/-29 versus 226+/-16 ms, P<0.05), minimized postresuscitation ventricular ectopic activity preventing recurrent VF, and lessened postresuscitation myocardial dysfunction.
  
  
  CONCLUSIONS
  NHE-1 inhibition may represent a highly potent novel strategy for resuscitation from VF that can ameliorate myocardial manifestations of ischemic injury and improve the effectiveness and outcome of closed-chest resuscitation.
authors.affiliation: Medical Service, North Chicago VA Medical Center and Department of Medicine, Finch University of Health Sciences, The Chicago Medical School, North Chicago, Ill 60064, USA.
authors.forename: Iyad M
authors.initials: IM
authors.lastname: Ayoub
authors.forename: Julieta
authors.initials: J
authors.lastname: Kolarova
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yi
authors.forename: Atul
authors.initials: A
authors.lastname: Trevedi
authors.forename: Hanumant
authors.initials: H
authors.lastname: Deshmukh
authors.forename: David L
authors.initials: DL
authors.lastname: Lubell
authors.forename: Michael R
authors.initials: MR
authors.lastname: Franz
authors.forename: Frank A
authors.initials: FA
authors.lastname: Maldonado
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Gazmuri
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D003131:Combined Modality Therapy; D017548:Echocardiography, Transesophageal; D006146:Guanidines / Q000627:therapeutic use; D006321:Heart / Q000503:physiopathology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012151:Resuscitation; D055502:Secondary Prevention; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000627:therapeutic use; D013552:Swine; D014693:Ventricular Fibrillation / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D016277:Ventricular Function, Left
chemical_list: D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C069139:growth factor-activatable Na-H exchanger NHE-1; C093373:cariporide