Cariporide minimizes adverse myocardial effects of epinephrine during resuscitation from ventricular fibrillation

• Published in: Critical care medicine Vol. 33; no. 11; pp. 2599 - 2605
• Main Authors: Ayoub, Iyad M, Kolarova, Julieta, Kantola, Ronald L, Sanders, Robert, Gazmuri, Raúl J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD by the Society of Critical Care Medicine and Lippincott Williams & Wilkins 01-11-2005; Lippincott
• Subjects: Adrenergic beta-Agonists - adverse effects; Adrenergic beta-Agonists - therapeutic use; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anti-Arrhythmia Agents - pharmacology; Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care; Epinephrine - adverse effects; Epinephrine - antagonists & inhibitors; Epinephrine - therapeutic use; Guanidines - pharmacology; Heart; Intensive care medicine; Male; Medical sciences; Myocardial Ischemia - chemically induced; Myocardial Ischemia - prevention & control; Resuscitation - methods; Sulfones - pharmacology; Swine; Ventricular Fibrillation - drug therapy; Epinephrine; Intensive care; Arrhythmia; Hydrogen; Cardioprotective agent; Cariporide; Cardiovascular disease; Myocardial ischemia; Catecholamine; sodium-hydrogen antiporter; Coronary heart disease; Myocardial disease; Excitability disorder; Ventricular fibrillation; Vascular disease; cardiopulmonary resuscitation; Sodium; Resuscitation
• ISSN: 0090-3493; 1530-0293
• DOI: 10.1097/01.CCM.0000186773.88576.83

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.
DESIGN:Randomized animal study.
SETTING:University-based animal laboratory.
SUBJECTS:Twenty-four anesthetized male domestic pigs (29–43 kg).
INTERVENTIONS: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.
MEASUREMENTS AND MAIN 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.