Cariporide given during resuscitation promotes return of electrically stable and mechanically competent cardiac activity

Resuscitation Institute at Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Resuscitation (Impact Factor: 4.17). 10/2009; 81(1):106-10. DOI: 10.1016/j.resuscitation.2009.09.013
Source: PubMed


Episodes of ventricular fibrillation (VF) and myocardial dysfunction commonly occur after cardiac resuscitation compromising the return of stable circulation. We investigated in a pig model of VF whether limiting Na(+)-induced cytosolic Ca(2+) overload using the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) inhibitor cariporide promotes resuscitation with stable circulation.
VF was electrically induced in 20 male pigs and left untreated for 6 min after which CPR was initiated and continued for 8 min before attempting defibrillation. Pigs were randomized to receive 3-mg/kg cariporide (n=10) or 0.9%-NaCl (n=10) before chest compression.
Seven of 10 pigs in each group were successfully resuscitated and survived 2h. Cariporide ameliorated post-resuscitation ventricular ectopic activity such that fewer singlets (5+/-5 vs. 26+/-21; p<0.05) and fewer bigemini (1+/-3 vs. 33+/-25; p<0.05) were observed during the initial 5 min post-resuscitation. Additionally, cariporide-treated pigs did not require additional post-resuscitation shocks for ventricular tachycardia or recurrent VF (0.0+/-0.0 vs. 5.3+/-7.8 shocks; p=0.073). During the initial 60 min cariporide-treated pigs had higher, cardiac index (6.1+/-0.7 vs. 4.4+/-1.1L/min/m(2); p<0.01), left ventricular stroke work index (45+/-9 vs. 36+/-10 gmm/beat/m(2); p<0.05), and numerically higher mean aortic pressure (104+/-11 vs. 91+/-12 mmHg; p=0.054).
Cariporide administered at the start of chest compression may help restore electrically and mechanically stable circulation after resuscitation from cardiac arrest.

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    • "In general, NHE-1 inhibition is thought to be a pharmacological tool for the treatment of various detrimental cardiac conditions such as ischemia/reperfusion injury, arrhythmias, hypertrophy, and HF. In many pre-clinical studies, NHE-1 inhibition has been shown to reduce ischemia/reperfusion injury (Lee et al., 2005; Ayoub et al., 2010). In clinical trials, however, the cardioprotective effects of NHE-1 inhibition were less clear and the treatment with the NHE-1 inhibitor cariporide was associated with significantly greater incidence of stroke (Fliegel and Karmazyn, 2004). "
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