Experimental paperCariporide given during resuscitation promotes return of electrically stable and mechanically competent cardiac activity☆
Introduction
Ventricular arrhythmias commonly occur after successful resuscitation from cardiac arrest with a reported incidence of ventricular fibrillation (VF) as high as 79%.1 Some studies have reported an inverse relationship between the number of VF episodes and survival.1 These episodes were noted to occur within a time window of 23–115 s with a median of 45 s after the return of spontaneous circulation.1 The prevailing concept is that post-resuscitation ventricular arrhythmias, including episodes of VF are to a large extent a manifestation of cytosolic Ca2+ accumulation in cardiomyocytes.2, 3, 4 Such Ca2+ accumulation is a central manifestation of ischemia and reperfusion injury and reflects in part increased sarcolemmal Na+ entry followed by cytosolic Ca2+ overload consequent to reverse mode operation of the sarcolemmal Na+–Ca2+ exchanger.5, 6 One mechanism of sarcolemmal Na+ entry and cytosolic Na+ accumulation during ischemia and reperfusion is activation of the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) with concomitant inactivation of the Na+–K+ ATPase activity.7, 8
Along with reperfusion arrhythmias, the myocardium during the post-resuscitation period also suffers varying degrees of global dysfunction that can compromise hemodynamic function.9, 10 These electrical and mechanical abnormalities occur early in the post-resuscitation phase, coinciding with the prehospital phase and may account for the nearly 40% deaths that have been reported before hospital admission in initially resuscitated victims.11 Thus, treatments that could provide initial electrical and mechanical stability could have potential beneficial survival effects on victims of out-of-hospital cardiac arrest. In this study we examined the effects of NHE-1 inhibition using cariporide on post-resuscitation ventricular arrhythmias and myocardial dysfunction using a pig model of VF and closed-chest resuscitation.
Section snippets
Methods
The studies were approved by our Institutional Animal Care and Utilization Committee and conducted according to institutional guidelines.
Results
No differences in hemodynamic variables were observed between groups at baseline. From the 2nd to the 8th minute of closed-chest resuscitation the averaged coronary perfusion pressure was 16 ± 4 mmHg in pigs treated with cariporide and 15 ± 3 mmHg in control pigs. During the same interval the PETCO2 was higher in the cariporide group (30 ± 6 vs. 27 ± 6 mmHg) but the difference was not statistically significant.
Seven of 10 pigs in each group were successfully resuscitated. Failure to resuscitate was
Discussion
Cariporide in this pig model of electrically induced VF and closed-chest resuscitation attenuated post-resuscitation myocardial dysfunction enabling greater post-resuscitation hemodynamic stability. Additionally, there was a trend favoring less post-resuscitation episodes of VF in cariporide-treated pigs.
Conclusions
Cariporide in this study promoted early post-resuscitation electrical and mechanical cardiac stability. These favorable effects may allow safer transfer of initially resuscitated victims of cardiac arrest to a receiving hospital.
Conflict of interest statement
Authors have no conflict of interest.
Acknowledgements
Work supported by National Institutes of Health grant R01 HL71728-01 entitled “Myocardial Protection by NHE-1 Inhibition,” VA Merit Review Grant entitled “Myocardial Protection during VF”.
The authors wish to acknowledge the logistic support of Biomedical Engineering; Pharmacy Services, and the Supply, Processing, and Distribution Center at the North Chicago VA Medical Center.
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A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2009.09.013.