Abstract

Background: The identification of serum biomarkers of ischemic injury could provide a means of assessing interventions designed to limit reperfusion injury after return of spontaneous circulation (ROSC). We sought to characterize the early post-ROSC timecourse of two candidate biomarkers of ischemic injury (cytochrome- c and IL-6) in a swine model of ventricular fibrillation (VF). We hypothesized that these two biomarkers would be elevated immediately after ROSC. Methods: Twenty-five mixed breed domestic swine were anesthetized and instrumented with ECG, temperature probe, and aortic and right atrial pressure transducers. VF was induced with a transthoracic shock and untreated for 8 minutes. Then mechanical CPR was done for 2 minutes, before drugs were given (epinephrine, vasopressin, and propranolol) with 3 additional minutes of CPR (first defibrillation attempt at 13 minutes of VF). Blood samples were drawn at the end of instrumentation (i.e. just prior to VF), and at 20, 40, and 60 minutes after ROSC. Samples were centrifuged and serum extracted. Cytochrome- c was analyzed via Western immunoblotting. IL-6 was analyzed with ELISA. Results: No cytochrome- c was detected in any animal, at any timepoint through 60 min. IL-6 was similar to baseline levels through 40 min, but was 121% of baseline at 60. Conclusions: Neither biomarker was elevated immediately after ROSC. Mitochondrial damage (as indicated by the absence of cytochrome- c ) may be delayed by as much as an hour after ROSC, hinting at a possible therapeutic window for interventions like hypothermia. Likewise, inflammatory cascades (as indicated by IL-6) may not begin immediately post-ROSC, but might by one hour.

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