Cariporide potentiates the effects of epinephrine and vasopressin by nonvascular mechanisms during closed-chest resuscitation.
BACKGROUND
The efficacy of vasopressor therapy during closed-chest resuscitation is limited and decreases over time. We previously reported that sodium-hydrogen exchanger isoform-1 inhibition during ventricular fibrillation (VF) using cariporide ameliorates ischemic contracture and enhances the efficacy of chest compression. We currently investigated whether cariporide could potentiate pressor responses to epinephrine and vasopressin.


METHODS
VF was induced and left untreated for 12 min in two series of 16 rats each. Chest compression was then started and the depth adjusted within the initial 2 min to attain an aortic diastolic pressure between 26 and 28 mm Hg. In one series, rats received boluses of epinephrine (150 microg/kg); in the other series, rats received boluses of vasopressin (0.8 U/kg) to maintain the aortic diastolic pressure > 25 mm Hg. Within each series, rats were randomized to receive a 3 mg/kg bolus of cariporide or 0.9% NaCl immediately before starting chest compression. Defibrillation was attempted at 20 min of VF (8 min of chest compression).


RESULTS
Cariporide prompted higher and more sustained coronary perfusion pressures in both the epinephrine group (37 +/- 5 mm Hg vs 29 +/- 7 mm Hg, p < 0.05) and the vasopressin group (36 +/- 5 mm Hg vs 28 +/- 6 mm Hg +/- SD, p < 0.02) even though fewer additional vasopressor doses were required. After resuscitation, cariporide-treated rats had less ventricular ectopic activity, better hemodynamic function, and improved survival scores. In separate experiments, in situ perfusion of the aorta excluded a vascular-mediated effect of cariporide.


CONCLUSIONS
Cariporide enhanced the hemodynamic efficacy of vasopressor agents and improved resuscitation outcomes probably as a result of enhanced forward blood flow without effect on the peripheral vasculature.
Kolarova
Julieta
J
Medical Service (111F), North Chicago VA Medical Center, 3001 Green Bay Rd, North Chicago, IL 60064, USA.
Yi
Zhong
Z
Ayoub
Iyad M
IM
Gazmuri
Raúl J
RJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D004357:Drug Synergism; D004837:Epinephrine / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods; D013450:Sulfones / Q000627:therapeutic use*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*; D014667:Vasopressins / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D013450:Sulfones; D014662:Vasoconstrictor Agents; D014667:Vasopressins; C093373:cariporide; D004837:Epinephrine