title: Cariporide minimizes adverse myocardial effects of epinephrine during resuscitation from ventricular fibrillation.
abstract: OBJECTIVE
  Epinephrine given during closed-chest resuscitation increases blood flow across the coronary and cerebral circuits. However, epinephrine worsens reperfusion arrhythmias and intensifies postresuscitation myocardial dysfunction. We investigated whether cariporide-a selective sodium-hydrogen exchanger isoform-1 inhibitor-could ameliorate such adverse effects without diminishing its vasopressor actions.
  
  
  METHODS
  Randomized animal study.
  
  
  METHODS
  University-based animal laboratory.
  
  
  METHODS
  Twenty-four anesthetized male domestic pigs (29-43 kg).
  
  
  METHODS
  Ventricular fibrillation was electrically induced and left untreated for 8 mins. Pigs were randomized to receive after 2 mins of chest compression a 3 mg/kg bolus of cariporide (n = 8), a 0.02 mg/kg bolus of epinephrine (n = 8), or a combination of cariporide and epinephrine (n = 8). Additional doses of epinephrine were given if the coronary perfusion pressure decreased below 15 mm Hg. Successfully resuscitated pigs were observed for 72 hrs.
  
  
  RESULTS
  The averaged coronary perfusion pressure was higher in the epinephrine (34 +/- 11 mm Hg, p = .001) and cariporide/epinephrine (35 +/- 10 mm Hg, p < .001) groups compared with the cariporide group (15 +/- 6 mm Hg). All pigs in the epinephrine and cariporide/epinephrine groups but only six in the cariporide group were successfully resuscitated and survived 72 hrs. During the immediate postresuscitation period, four of eight pigs in the epinephrine group had episodes of recurrent ventricular fibrillation or pulseless ventricular tachycardia requiring additional electrical shocks (7.0 +/- 6.4) but none in the cariporide and cariporide/epinephrine groups (chi-square, p = .008). Myocardial dysfunction occurred early after return of spontaneous circulation but only in the epinephrine group.
  
  
  CONCLUSIONS
  The combined administration of cariporide and epinephrine prompted adequate pressor effects during chest compression and facilitated reestablishment of cardiac activity without episodes of recurrent ventricular fibrillation or transient myocardial dysfunction as with epinephrine alone.
authors.affiliation: Department of Medicine, Rosalind Franklin University of Medicine and Science, USA.
authors.forename: Iyad M
authors.initials: IM
authors.lastname: Ayoub
authors.forename: Julieta
authors.initials: J
authors.lastname: Kolarova
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Kantola
authors.forename: Robert
authors.initials: R
authors.lastname: Sanders
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Gazmuri
mesh_terms: D000318:Adrenergic beta-Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004837:Epinephrine / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D012151:Resuscitation / Q000379:methods*; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D014693:Ventricular Fibrillation / Q000188:drug therapy*
chemical_list: D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D013450:Sulfones; C093373:cariporide; D004837:Epinephrine